Acute hospital care is fast becoming acute geriatric care: people aged 65 years or older are only 13% of the population but account for 44% of days of care in nonfederal hospitals and 38% of discharges.¹ In general, the elderly have longer hospital stays, incur greater costs, and have a higher risk of adverse outcomes than do their younger counterparts.²

Among the most common surgical procedures for patients older than 65 are percutaneous coronary intervention with stenting, coronary artery bypass graft surgery, and open reduction internal fixation for hip fracture; the latter is the most common operation in patients aged 85 years or older.³

Elderly patients frequently pose many challenges perioperatively that are not often seen in younger patients. Dementia, frailty, impaired ability to care for oneself, and malnourishment may be present at baseline and are likely to worsen postoperatively. The elderly are at increased risk of acute delirium and cognitive impairment post­operatively, which often complicates recovery and discharge placement.

This article uses a case study to review perioperative problems commonly encountered in elderly surgical patients, particularly those undergoing hip surgery. As the case is presented, I will review strategies to assess risks and prevent and mitigate postoperative cognitive dysfunction and other barriers to recovery.

CASE: AN 82-YEAR-OLD WOMAN WITH HIP FRACTURE

An 82-year-old woman is admitted to undergo open reduction internal fixation for hip fracture. She has a history of osteoarthritis, systolic hypertension, and visual impairment (20/70). Her medications include a beta-blocker, a thiazide diuretic, analgesics as needed, and a multivitamin. She was independent in all activities of daily living before the fracture. She is a social drinker and does not smoke. She has no known cardiovascular, lung, or renal disease.

Her laboratory test results are as follows:

• Blood urea nitrogen (BUN), 24 mg/dL
• Creatinine, 1.0 mg/dL
• Hemoglobin, 12.8 g/dL
• Albumin, 3.8 gm/dL
• Normal levels of thyroid-stimulating hormone and vitamin B₁₂.

Thus, her lab results are normal except for the BUN:creatinine ratio being a bit high, at 24:1 (normal is 10:1, with ratios greater than 18:1 being associated with an increased risk of delirium⁴).

ASSESSING COGNITIVE RISK: POSTOPERATIVE COGNITIVE DYSFUNCTION VS DELIRIUM

Question: Which of these statements about this patient is most correct?

A. She is at high risk (> 40%) of postoperative cognitive dysfunction

B. Her risk of postoperative delirium is 5% to 10%

C. Postoperative delirium cannot be prevented

D. Preoperative haloperidol (1.5 mg/day for 3 days) will reduce the risk of delirium by 25%

The best answer is A. Postoperative cognitive dysfunction is different from delirium, though it is part of a spectrum of cognitive impairment that may occur after surgery and even persist for a prolonged period. The patient’s risk of postoperative delirium is actually a bit higher than 10% (see “Estimating the risk of delirium” below). Some evidence shows that postoperative delirium can be prevented, at least in hip fracture patients. Kalisvaart et al found that preoperative treatment with low-dose haloperidol reduced the duration and severity of delirium in elderly patients following hip surgery but did not reduce its incidence.⁵

Cognitive dysfunction often follows surgery

Postoperative cognitive dysfunction has long been recognized and was first described in patients after cardiac surgery, especially following coronary artery bypass graft procedures. In the last several years, we have recognized that it also occurs in patients who undergo noncardiac surgery. Post­operative cognitive dysfunction, which may persist for weeks to months, may not be obvious but can be detected by standard neuropsychological testing.⁶

Postoperative cognitive dysfunction is different from the “emergence delirium” that may immediately follow surgery and that is often associated with the wearing off of anesthesia. It is also distinct from “incident delirium,” which sometimes occurs over the first few postoperative days (discussed below).

Postoperative dysfunction is especially persistent in the elderly

A recent study found cognitive dysfunction to be common at hospital discharge after major noncardiac surgery in adults of all ages: rates at discharge were 36.6% in patients aged 18 to 39 years, 30.4% in those aged 40 to 59, and 41.4% in those 60 or older.⁷ Notably, however, the oldest group was most likely to have persistent symptoms. Three months after surgery, 12.7% of patients aged 60 or older continued to have postoperative cognitive dysfunction, which was more than double the rates in the young and middle-aged patient groups (5.7% and 5.6%, respectively).⁷

Although the cause of postoperative cognitive dysfunction is not well understood, predisposing factors in addition to advanced age include metabolic problems, lower educational level, and previous cerebral vascular accident.⁷ When elective surgery is considered by elderly patients, the decision should take into account their risk of postoperative cognitive dysfunction and the impact it may have on their quality of life.

PREDICTING AND PREVENTING DELIRIUM

Delirium is easily recognized

Delirium is a common complication of surgery. Unlike postoperative cognitive dysfunction, delirium is easy to detect clinically. It is a disorder of attention and cognition and classically presents as an acute change in mental status accompanied by the following⁸:

• Fluctuation in awareness
• Memory impairment
• Inattention (inability to stay on task, distractibility)
• Disorganized or illogical thinking
• Altered level of consciousness—ie, hyperalertness (agitation, pulling out intravenous lines, etc) or hypoalertness (“quiet delirium”).

Estimating the risk of delirium

Marcantonio and colleagues developed a model to predict the likelihood that delirium will develop in patients undergoing elective surgery.⁹ The model assigns points to various risk factors as follows:

• Age ≥ 70 years (1 point)
• History of alcohol abuse (1 point)
• Baseline cognitive impairment (1 point)
• Severe physical impairment (reduced ability to walk or perform daily activities) (1 point)
• Abnormal preoperative blood levels of electrolytes or glucose (1 point)
• Noncardiac thoracic surgery (1 point)
• Abdominal aortic aneurysm surgery (2 points).

The study to validate this model found that a score of 0 points is associated with only a 2% risk of developing postoperative delirium. A score of 3 or more points is associated with a 50% risk of postoperative delirium. A score of 1 or 2 points (as for the patient in our case study) is associated with an 11% risk, according to this Marcantonio model.⁹

Additionally, well-designed cohort studies of medical patients¹⁰ have identified four major independent predictors of incident delirium:

• Severe illness (eg, high fever, complicated infections)

• Baseline dementia
• Dehydration (high BUN:creatinine ratio)
• Sensory impairments (particularly visual).

Kalisvaart et al conducted a prospective cohort study to determine whether these risk factors in medical patients are applicable to elderly patients undergoing hip surgery.¹¹ They found that the incidence of delirium was low (4%) in hip surgery patients with none of these factors, increased to 11% in patients with one or two of these factors, and increased to 37% in patients with three or four factors. These findings suggest that hip surgery patients (like our case patient) may be at greater risk of pos­toperative delirium than is reflected in the Marcantonio model discussed above,⁹ which was validated in a study of patients undergoing elective (not emergent) surgery.

 

 

Several drug classes raise dementia risk

Anticholinergic medications and other drugs with anticholinergic properties, ie, benzodiazepines and the opioid agent meperidine, also raise the risk for delirium. In general, the older an elderly patient is, the less appropriate these agents are. Many drugs that are not typically recognized as anticholinergics may have potent anticholinergic activity, including tricyclic antidepressants, first-generation antihistamines (eg, diphenhydramine), and high-dose H₂-receptor blockers (particularly cimetidine); these agents too should be avoided in elderly patients.¹²

Strategies to reduce postoperative delirium risk

How can we lower the risk of postoperative delirium in elderly hip fracture patients? Marcantonio et al¹³ randomized 126 patients undergoing hip fracture repair to receive usual care alone or supplemented with the following additional measures:

• Supplemental oxygen during surgery
• Optimization of electrolytes and blood glucose preoperatively
• Discontinuation of high-risk medications
• Adequate nutritional intake (by parenteral route if necessary)
• Encouragement to get out of bed on the first postoperative day
• Treatment of severe pain.

The incidence of delirium was reduced from 50% in the usual-care group to 32% in the intervention group, and the incidence of severe delirium was reduced even more, from 29% to 12%, respectively.¹³

OTHER BEST PRACTICES IN PERIOPERATIVE HIP FRACTURE MANAGEMENT

In a systematic literature review to identify best practices for perioperative management of elderly patients with hip fracture, Beaupre et al¹⁴ found the following measures to be among those with the strongest evidence of benefit:

• Use of spinal or local anesthesia rather than general anesthesia
• Use of pressure-relieving mattresses to prevent pressure ulcers
• Perioperative administration of antibiotics
• Deep vein thrombosis prophylaxis.

The review concluded that providing nutritional supplementation also is probably helpful although the evidence is not robust. Additionally, it was unclear whether minimizing the delay between hospital admission and surgery has any impact on mortality.¹⁴

Is early surgery better?

Early studies suggested that the sooner a hip fracture patient goes to surgery, the lower the mortality, but this has not been supported in well-controlled trials: no difference in mortality has been found whether the patient’s conditions are first optimized to reduce the risk of surgery or if the operation commences within 24 hours.

Although mortality does not appear to be affected, avoiding delay of hip fracture repair yields improvement in other outcomes. In a well-designed prospective cohort study, Orosz et al found that medically stable patients with hip fracture (mean age, 82 years) who underwent surgery within 24 hours had fewer days of pain and less intense pain postoperatively than those whose surgery was delayed beyond 24 hours.¹⁵ The early-surgery group also had a 1.94-day reduction in average length of stay compared with the late-surgery group.

A role for clinical pathways

To determine how the application of evidence-based peri­operative practices affects actual outcomes in elderly hip fracture patients, Beaupre et al used a pre/post study design to evaluate the impact of an evidence-based clinical pathway at their institution.¹⁶ Though there were no differences in in-hospital mortality or the overall costs of inpatient care in elderly hip surgery patients before and after pathway implementation, the patients undergoing surgery after pathway implementation were significantly less likely to have postoperative delirium, heart failure, pressure ulcers, and urinary tract infections compared with those under­going surgery before implementation. The outcomes benefits of this type of multimodal intervention are likely to extend to abdominal surgical procedures as well.

CASE CONTINUED: POSTOP DAY 2―PATIENT IS CONFUSED AND CRYING IN PAIN

On the second postoperative day, our patient appears weak and slightly confused. She is not eating and is crying in pain. Her neurological exam is normal.

Question: Which is the most appropriate next step?

A. Increase physical therapy

B. Begin an antidepressant

C. Insert a nasoenteric feeding tube

D. Increase doses of analgesics

The best answer is D. With no prior history of depression, an antidepressant would probably not be useful. It is premature to recommend nasoenteric feeding. Because pain hampers physical therapy, an increase in physical therapy would likewise be premature. Because we know the patient is in pain, the correct answer perhaps seems obvious. But keep in mind that relieving pain also has many other positive ramifications: intense pain can be a cause of delirium or at least worsen its symptoms, and pain relief is a pre­requisite for the physical therapy that this patient needs.

Strategies for pain control

In general, the treatment of choice for postoperative pain is low-dose morphine sulfate (eg, 1–4 mg every 2 hours, titrated as needed). Acetaminophen can be given safely to virtually all patients. Patient-controlled analgesia is reasonable for select patients but not for older patients with cognitive impairment. Nonsteroidal anti-inflammatory drugs might be helpful in younger patients and even in robust elderly patients, but they must be used very cautiously in the older population because of the risk of gastric ulcers and bleeding, acute kidney injury, fluid retention, and exacerbation of congestive heart failure.

POSTOP DAY 3: PATIENT REPORTS LONG-STANDING FATIGUE

On postoperative day 3, the patient is weak and complains of fatigue. She says that before the fracture, she was experiencing mild weight loss, fatigue, and reduced activity.

Question: What is the most likely reason for her symptoms before the fracture?

A. Frailty

B. Occult heart failure

C. Adverse drug reaction to her beta-blocker

D. Clinical depression

The best answer is A. Occult heart failure is a reasonable second choice, as it is very common in older patients and the diagnosis is easy to miss unless florid pulmonary edema or associated symptoms (eg, chest pain) are present. But this patient had no history of heart disease and was only on medications for hypertension. An adverse drug reaction, such as to the beta-blocker, is unlikely and would probably not cause weight loss. The patient had no history of depression, so clinical depression is unlikely. That said, all the choices are reasonable to consider in elderly patients reporting fatigue and weakness.

 

 

Frailty is important to recognize

It is important to identify frailty and to aggressively manage frail patients postoperatively. Although frailty is not clearly defined, Fried et al¹⁷ identified five clinical features that correlate with its underlying pathophysiology:

• Minimal physical activity (ie, “doing less”)
• Generalized (not focal) muscle weakness
• Slowed performance (eg, walking short distances takes longer)
• Fatigue or poor endurance
• Unintentional weight loss.

The presence of three or more of these features meets the criteria for frailty and is associated with increased risk for mortality over the next 3 years with or without surgery,¹⁷ although surgery probably increases the risk.

Frailty is believed to be a failure over time of the homeostatic mechanisms that keep our organ systems functioning in the face of a stress. Decline in the ability of organ systems to maintain normal function is probably caused by inflammation, chronic disease, and normal aging, and has been termed homeostenosis. As a person ages and physiologic reserves are reduced, adding a stress such as surgery or severe infection can result in organ failure—usually multiple-system organ failure. In any intensive care unit, one is likely to see elderly patients who were admitted with one medical or surgical problem and soon end up having renal, liver, or brain dysfunction as well.

Looked at another way, strength normally declines gradually during aging. An acute illness or surgery causes a precipitous decline in strength, and if it is too severe, the threshold of frailty is crossed (Figure 1). Early mobilization and early and persistent physical therapy can help patients regain strength, thereby preventing frailty.

Physical therapy immediately after hip fracture surgery is associated with significantly better locomotion 2 months later.¹⁸ A number of exercises are effective: range-of-motion exercises, low-impact aerobic activities, and exercises starting with low-intensity resistance (using bands, tubes, and weights) and progressing as tolerated to high-intensity resistance (with machines and pulleys) for an extended period of time.

Nutrition supplementation

Malnourishment can contribute to frailty, yet evidence for the benefits of supplementing nutrition is not strong, as noted above. However, meta-analyses of studies of nutritional interventions with meal supplementation (usually canned supplements) show that meal supplementation can improve mortality risk and reduce morbidity such as pressure ulcers in hospitalized elderly patients.^19,20 The patients most likely to benefit are those who are undernourished at baseline and aged 75 years or older.

CASE CONTINUED: WHAT HAPPENS POST-DISCHARGE?

Following surgery, our patient wonders, “Where will I go next? What will my lifestyle be like?”

These are important questions to consider when first evaluating whether an elderly patient should undergo surgery. In the case of hip fracture, standard thinking is that without surgery, the patient will never recover the ability to independently walk and perform activities of daily living. But we also must recognize the considerable risks of surgery in the elderly population, particularly those aged 75 years or older.

Comprehensive discharge planning

Early and intensive discharge management enhances quality of life and may help reduce hospital costs. A good model of care involves collaboration of orthopedic surgeons, hospitalists, general internists, geriatricians, and dietitians to address procedures, diet and nutrition, mobility and activities of daily living, and pain medications.²¹ A case manager such as a social worker should start addressing care transition the day after surgery—planning ahead is imperative.

Following hip surgery, patients are routinely sent to skilled nursing facilities as soon as possible so they can start intensive physical therapy. Patients with significant functional impairment or who had delirium are more likely to require a prolonged hospital stay.

Naylor et al examined the effectiveness of comprehensive discharge planning in a study that randomized hospitalized patients (including surgical patients) 65 years or older to either usual discharge planning or intensive discharge planning with advanced practice nurses beginning early in hospitalization.²² The intervention group was followed by home care nurses for up to 4 weeks and had continuous telephone access to the nurses. Patients who received the intervention had a significantly lower risk of hospital readmission, and those who were readmitted had significantly shorter hospital stays. The total cost of care was also significantly lower in the intervention group.

Family conferences aid decision making

Family conferences can be very useful for working through the many questions and challenges that surgery in an elderly person can pose, including whether the patient should undergo the operation, postoperative management, and postdischarge placement.²³ For patients with an uncertain prognosis because of unclear or multiple concurrent diseases, a family conference can help clarify the goals of therapy, inform the family about likely outcomes, and help determine the patient’s wishes and values. Such issues should be revisited as the postoperative course proceeds.

Family conferences also provide a good opportunity to review advanced directives, the need for life support, and possible transfers to intensive care. Family conferences can also help resolve conflicts in care management, as family members may not agree with the need for surgery, how aggressive treatment should be, or where to send the patient for rehabilitation. Differences among family members on these questions are especially common with elderly patients. Working out such issues will improve patient care, especially when done early in the hospitalization.

 

 

DISCUSSION

Question from the audience: In our preoperative clinic, we are trying to intervene to reduce delirium and postoperative cognitive dysfunction. How can we quickly screen for the most important predictors and act to reduce the risk?

Dr. Palmer: The most important risk factor for delirium is age, which obviously can’t be changed. Ask patients about alcohol use and depression. Check on nutritional status and begin supplementation if indicated. Discontinue high-risk medications. Check on electrolytes and their state of hydration; ideally, an electrolyte imbalance can be corrected preoperatively. In addition, other than in patients with end-stage renal disease, try to keep the hemoglobin above 7.5 g/dL, which appears to be associated with better outcomes and less risk of delirium.

It’s also important to remind the family to bring in the patient’s visual aids, hearing devices, and cane or walker so that they’re available right after the operation.

Intraoperative factors that are important for preventing delirium include maintaining good blood pressure levels, giving supplemental oxygen, minimizing the time under general anesthesia, and using local anesthesia if possible.

Question from the audience: How strong is the evidence for using spinal anesthesia as opposed to general anesthesia in preventing postoperative cognitive dysfunction and delirium, especially in the setting of hip fracture repair?

Dr. Palmer: The evidence is fairly soft. For patients undergoing either hip or knee arthroplasty who were randomized to receive either spinal (or local) or general anesthesia, the risk of delirium was similar, but complications such as prolonged bed rest, pressure ulcers, and catheter-related urinary tract infections were somewhat reduced in the spinal/local group.¹⁴ The relative risk of developing postoperative cognitive dysfunction is unclear—no randomized controlled trials have been conducted to answer that question.

Question from the audience: How do you use antipsychotic drugs, especially with the concerns from epidemiologic studies about an increased risk of death?

Dr. Palmer: No antipsychotic agents, including haloperidol, have a specific Food and Drug Administration–approved indication for treating agitation, dementia, or delirium. In general, they should not be used without a clear indication. That said, the usual off-label use is for patients who are severely agitated and are at risk of harming themselves or others. In an ICU setting, where patients have multiple lines, the use of these agents can be considered for a very agitated patient. Alternatives exist, but antipsychotics like haloperidol have the advantage that they can be given in small increments very rapidly and achieve good control of severe agitation.

Antipsychotic agents should only be used with great caution and for the shortest duration needed. As delirium resolves, they should be tapered fairly rapidly over a few days and ideally should be discontinued by the time of hospital discharge.

None of the antipsychotic agents—including those in the first generation and the newer atypical agents—is free of this risk of increased mortality. The mechanism is not understood; it may be torsades de pointes or hypotension leading to stroke or sudden cardiac death.

Question from the audience: What is the most efficient way to assess cognitive and physical functioning preoperatively? 

Dr. Palmer: There may be a documented history of dementia, or family members may tell you if there has been memory loss or some decline in the patient’s self-care abilities. For patients without dementia, you can ask them directly if they can perform basic activities of daily living, such as getting out of bed or dressing. To assess higher-level function, ask if they can manage their own medications, pay bills, or handle their finances. If not, they might have cognitive impairment and are at higher risk for postoperative delirium. These are rather sensitive measures. There are instruments to assess this more precisely, but few clinicians have time to use them.

Quick bedside tests can help assess for delirium postoperatively. We see if patients are “alert and oriented times three” (“Do you know who you are, where you are, and the date?”). We test for attention by asking them to repeat a random string of numbers spoken 1 second apart in monotone; people who are delirious and many patients with severe dementia can’t repeat more than three numbers. A patient who is alert and oriented, has a good attention span (more than three numbers in correct order), and has no history of dementia probably doesn’t have delirium or dementia.

For physical function, ask if they can walk, get out of bed to a chair, and ambulate. If they don’t give clear answers, observe them get out of bed or a chair, walk 10 feet, and return to bed. If they can do that with good balance, especially within 10 to 15 seconds, they probably have reasonably normal mobility and are at lower risk for postoperative complications such as falls with injury.

Acute hospital care is fast becoming acute geriatric care: people aged 65 years or older are only 13% of the population but account for 44% of days of care in nonfederal hospitals and 38% of discharges.¹ In general, the elderly have longer hospital stays, incur greater costs, and have a higher risk of adverse outcomes than do their younger counterparts.²

Among the most common surgical procedures for patients older than 65 are percutaneous coronary intervention with stenting, coronary artery bypass graft surgery, and open reduction internal fixation for hip fracture; the latter is the most common operation in patients aged 85 years or older.³

Elderly patients frequently pose many challenges perioperatively that are not often seen in younger patients. Dementia, frailty, impaired ability to care for oneself, and malnourishment may be present at baseline and are likely to worsen postoperatively. The elderly are at increased risk of acute delirium and cognitive impairment post­operatively, which often complicates recovery and discharge placement.

This article uses a case study to review perioperative problems commonly encountered in elderly surgical patients, particularly those undergoing hip surgery. As the case is presented, I will review strategies to assess risks and prevent and mitigate postoperative cognitive dysfunction and other barriers to recovery.

CASE: AN 82-YEAR-OLD WOMAN WITH HIP FRACTURE

An 82-year-old woman is admitted to undergo open reduction internal fixation for hip fracture. She has a history of osteoarthritis, systolic hypertension, and visual impairment (20/70). Her medications include a beta-blocker, a thiazide diuretic, analgesics as needed, and a multivitamin. She was independent in all activities of daily living before the fracture. She is a social drinker and does not smoke. She has no known cardiovascular, lung, or renal disease.

Her laboratory test results are as follows:

• Blood urea nitrogen (BUN), 24 mg/dL
• Creatinine, 1.0 mg/dL
• Hemoglobin, 12.8 g/dL
• Albumin, 3.8 gm/dL
• Normal levels of thyroid-stimulating hormone and vitamin B₁₂.

Thus, her lab results are normal except for the BUN:creatinine ratio being a bit high, at 24:1 (normal is 10:1, with ratios greater than 18:1 being associated with an increased risk of delirium⁴).

ASSESSING COGNITIVE RISK: POSTOPERATIVE COGNITIVE DYSFUNCTION VS DELIRIUM

Question: Which of these statements about this patient is most correct?

A. She is at high risk (> 40%) of postoperative cognitive dysfunction

B. Her risk of postoperative delirium is 5% to 10%

C. Postoperative delirium cannot be prevented

D. Preoperative haloperidol (1.5 mg/day for 3 days) will reduce the risk of delirium by 25%

The best answer is A. Postoperative cognitive dysfunction is different from delirium, though it is part of a spectrum of cognitive impairment that may occur after surgery and even persist for a prolonged period. The patient’s risk of postoperative delirium is actually a bit higher than 10% (see “Estimating the risk of delirium” below). Some evidence shows that postoperative delirium can be prevented, at least in hip fracture patients. Kalisvaart et al found that preoperative treatment with low-dose haloperidol reduced the duration and severity of delirium in elderly patients following hip surgery but did not reduce its incidence.⁵

Cognitive dysfunction often follows surgery

Postoperative cognitive dysfunction has long been recognized and was first described in patients after cardiac surgery, especially following coronary artery bypass graft procedures. In the last several years, we have recognized that it also occurs in patients who undergo noncardiac surgery. Post­operative cognitive dysfunction, which may persist for weeks to months, may not be obvious but can be detected by standard neuropsychological testing.⁶

Postoperative cognitive dysfunction is different from the “emergence delirium” that may immediately follow surgery and that is often associated with the wearing off of anesthesia. It is also distinct from “incident delirium,” which sometimes occurs over the first few postoperative days (discussed below).

Postoperative dysfunction is especially persistent in the elderly

A recent study found cognitive dysfunction to be common at hospital discharge after major noncardiac surgery in adults of all ages: rates at discharge were 36.6% in patients aged 18 to 39 years, 30.4% in those aged 40 to 59, and 41.4% in those 60 or older.⁷ Notably, however, the oldest group was most likely to have persistent symptoms. Three months after surgery, 12.7% of patients aged 60 or older continued to have postoperative cognitive dysfunction, which was more than double the rates in the young and middle-aged patient groups (5.7% and 5.6%, respectively).⁷

Although the cause of postoperative cognitive dysfunction is not well understood, predisposing factors in addition to advanced age include metabolic problems, lower educational level, and previous cerebral vascular accident.⁷ When elective surgery is considered by elderly patients, the decision should take into account their risk of postoperative cognitive dysfunction and the impact it may have on their quality of life.

PREDICTING AND PREVENTING DELIRIUM

Delirium is easily recognized

Delirium is a common complication of surgery. Unlike postoperative cognitive dysfunction, delirium is easy to detect clinically. It is a disorder of attention and cognition and classically presents as an acute change in mental status accompanied by the following⁸:

• Fluctuation in awareness
• Memory impairment
• Inattention (inability to stay on task, distractibility)
• Disorganized or illogical thinking
• Altered level of consciousness—ie, hyperalertness (agitation, pulling out intravenous lines, etc) or hypoalertness (“quiet delirium”).

Estimating the risk of delirium

Marcantonio and colleagues developed a model to predict the likelihood that delirium will develop in patients undergoing elective surgery.⁹ The model assigns points to various risk factors as follows:

• Age ≥ 70 years (1 point)
• History of alcohol abuse (1 point)
• Baseline cognitive impairment (1 point)
• Severe physical impairment (reduced ability to walk or perform daily activities) (1 point)
• Abnormal preoperative blood levels of electrolytes or glucose (1 point)
• Noncardiac thoracic surgery (1 point)
• Abdominal aortic aneurysm surgery (2 points).

The study to validate this model found that a score of 0 points is associated with only a 2% risk of developing postoperative delirium. A score of 3 or more points is associated with a 50% risk of postoperative delirium. A score of 1 or 2 points (as for the patient in our case study) is associated with an 11% risk, according to this Marcantonio model.⁹

Additionally, well-designed cohort studies of medical patients¹⁰ have identified four major independent predictors of incident delirium:

• Severe illness (eg, high fever, complicated infections)

• Baseline dementia
• Dehydration (high BUN:creatinine ratio)
• Sensory impairments (particularly visual).

Kalisvaart et al conducted a prospective cohort study to determine whether these risk factors in medical patients are applicable to elderly patients undergoing hip surgery.¹¹ They found that the incidence of delirium was low (4%) in hip surgery patients with none of these factors, increased to 11% in patients with one or two of these factors, and increased to 37% in patients with three or four factors. These findings suggest that hip surgery patients (like our case patient) may be at greater risk of pos­toperative delirium than is reflected in the Marcantonio model discussed above,⁹ which was validated in a study of patients undergoing elective (not emergent) surgery.

 

 

Several drug classes raise dementia risk

Anticholinergic medications and other drugs with anticholinergic properties, ie, benzodiazepines and the opioid agent meperidine, also raise the risk for delirium. In general, the older an elderly patient is, the less appropriate these agents are. Many drugs that are not typically recognized as anticholinergics may have potent anticholinergic activity, including tricyclic antidepressants, first-generation antihistamines (eg, diphenhydramine), and high-dose H₂-receptor blockers (particularly cimetidine); these agents too should be avoided in elderly patients.¹²

Strategies to reduce postoperative delirium risk

How can we lower the risk of postoperative delirium in elderly hip fracture patients? Marcantonio et al¹³ randomized 126 patients undergoing hip fracture repair to receive usual care alone or supplemented with the following additional measures:

• Supplemental oxygen during surgery
• Optimization of electrolytes and blood glucose preoperatively
• Discontinuation of high-risk medications
• Adequate nutritional intake (by parenteral route if necessary)
• Encouragement to get out of bed on the first postoperative day
• Treatment of severe pain.

The incidence of delirium was reduced from 50% in the usual-care group to 32% in the intervention group, and the incidence of severe delirium was reduced even more, from 29% to 12%, respectively.¹³

OTHER BEST PRACTICES IN PERIOPERATIVE HIP FRACTURE MANAGEMENT

In a systematic literature review to identify best practices for perioperative management of elderly patients with hip fracture, Beaupre et al¹⁴ found the following measures to be among those with the strongest evidence of benefit:

• Use of spinal or local anesthesia rather than general anesthesia
• Use of pressure-relieving mattresses to prevent pressure ulcers
• Perioperative administration of antibiotics
• Deep vein thrombosis prophylaxis.

The review concluded that providing nutritional supplementation also is probably helpful although the evidence is not robust. Additionally, it was unclear whether minimizing the delay between hospital admission and surgery has any impact on mortality.¹⁴

Is early surgery better?

Early studies suggested that the sooner a hip fracture patient goes to surgery, the lower the mortality, but this has not been supported in well-controlled trials: no difference in mortality has been found whether the patient’s conditions are first optimized to reduce the risk of surgery or if the operation commences within 24 hours.

Although mortality does not appear to be affected, avoiding delay of hip fracture repair yields improvement in other outcomes. In a well-designed prospective cohort study, Orosz et al found that medically stable patients with hip fracture (mean age, 82 years) who underwent surgery within 24 hours had fewer days of pain and less intense pain postoperatively than those whose surgery was delayed beyond 24 hours.¹⁵ The early-surgery group also had a 1.94-day reduction in average length of stay compared with the late-surgery group.

A role for clinical pathways

To determine how the application of evidence-based peri­operative practices affects actual outcomes in elderly hip fracture patients, Beaupre et al used a pre/post study design to evaluate the impact of an evidence-based clinical pathway at their institution.¹⁶ Though there were no differences in in-hospital mortality or the overall costs of inpatient care in elderly hip surgery patients before and after pathway implementation, the patients undergoing surgery after pathway implementation were significantly less likely to have postoperative delirium, heart failure, pressure ulcers, and urinary tract infections compared with those under­going surgery before implementation. The outcomes benefits of this type of multimodal intervention are likely to extend to abdominal surgical procedures as well.

CASE CONTINUED: POSTOP DAY 2―PATIENT IS CONFUSED AND CRYING IN PAIN

On the second postoperative day, our patient appears weak and slightly confused. She is not eating and is crying in pain. Her neurological exam is normal.

Question: Which is the most appropriate next step?

A. Increase physical therapy

B. Begin an antidepressant

C. Insert a nasoenteric feeding tube

D. Increase doses of analgesics

The best answer is D. With no prior history of depression, an antidepressant would probably not be useful. It is premature to recommend nasoenteric feeding. Because pain hampers physical therapy, an increase in physical therapy would likewise be premature. Because we know the patient is in pain, the correct answer perhaps seems obvious. But keep in mind that relieving pain also has many other positive ramifications: intense pain can be a cause of delirium or at least worsen its symptoms, and pain relief is a pre­requisite for the physical therapy that this patient needs.

Strategies for pain control

In general, the treatment of choice for postoperative pain is low-dose morphine sulfate (eg, 1–4 mg every 2 hours, titrated as needed). Acetaminophen can be given safely to virtually all patients. Patient-controlled analgesia is reasonable for select patients but not for older patients with cognitive impairment. Nonsteroidal anti-inflammatory drugs might be helpful in younger patients and even in robust elderly patients, but they must be used very cautiously in the older population because of the risk of gastric ulcers and bleeding, acute kidney injury, fluid retention, and exacerbation of congestive heart failure.

POSTOP DAY 3: PATIENT REPORTS LONG-STANDING FATIGUE

On postoperative day 3, the patient is weak and complains of fatigue. She says that before the fracture, she was experiencing mild weight loss, fatigue, and reduced activity.

Question: What is the most likely reason for her symptoms before the fracture?

A. Frailty

B. Occult heart failure

C. Adverse drug reaction to her beta-blocker

D. Clinical depression

The best answer is A. Occult heart failure is a reasonable second choice, as it is very common in older patients and the diagnosis is easy to miss unless florid pulmonary edema or associated symptoms (eg, chest pain) are present. But this patient had no history of heart disease and was only on medications for hypertension. An adverse drug reaction, such as to the beta-blocker, is unlikely and would probably not cause weight loss. The patient had no history of depression, so clinical depression is unlikely. That said, all the choices are reasonable to consider in elderly patients reporting fatigue and weakness.

 

 

Frailty is important to recognize

It is important to identify frailty and to aggressively manage frail patients postoperatively. Although frailty is not clearly defined, Fried et al¹⁷ identified five clinical features that correlate with its underlying pathophysiology:

• Minimal physical activity (ie, “doing less”)
• Generalized (not focal) muscle weakness
• Slowed performance (eg, walking short distances takes longer)
• Fatigue or poor endurance
• Unintentional weight loss.

The presence of three or more of these features meets the criteria for frailty and is associated with increased risk for mortality over the next 3 years with or without surgery,¹⁷ although surgery probably increases the risk.

Frailty is believed to be a failure over time of the homeostatic mechanisms that keep our organ systems functioning in the face of a stress. Decline in the ability of organ systems to maintain normal function is probably caused by inflammation, chronic disease, and normal aging, and has been termed homeostenosis. As a person ages and physiologic reserves are reduced, adding a stress such as surgery or severe infection can result in organ failure—usually multiple-system organ failure. In any intensive care unit, one is likely to see elderly patients who were admitted with one medical or surgical problem and soon end up having renal, liver, or brain dysfunction as well.

Looked at another way, strength normally declines gradually during aging. An acute illness or surgery causes a precipitous decline in strength, and if it is too severe, the threshold of frailty is crossed (Figure 1). Early mobilization and early and persistent physical therapy can help patients regain strength, thereby preventing frailty.

Physical therapy immediately after hip fracture surgery is associated with significantly better locomotion 2 months later.¹⁸ A number of exercises are effective: range-of-motion exercises, low-impact aerobic activities, and exercises starting with low-intensity resistance (using bands, tubes, and weights) and progressing as tolerated to high-intensity resistance (with machines and pulleys) for an extended period of time.

Nutrition supplementation

Malnourishment can contribute to frailty, yet evidence for the benefits of supplementing nutrition is not strong, as noted above. However, meta-analyses of studies of nutritional interventions with meal supplementation (usually canned supplements) show that meal supplementation can improve mortality risk and reduce morbidity such as pressure ulcers in hospitalized elderly patients.^19,20 The patients most likely to benefit are those who are undernourished at baseline and aged 75 years or older.

CASE CONTINUED: WHAT HAPPENS POST-DISCHARGE?

Following surgery, our patient wonders, “Where will I go next? What will my lifestyle be like?”

These are important questions to consider when first evaluating whether an elderly patient should undergo surgery. In the case of hip fracture, standard thinking is that without surgery, the patient will never recover the ability to independently walk and perform activities of daily living. But we also must recognize the considerable risks of surgery in the elderly population, particularly those aged 75 years or older.

Comprehensive discharge planning

Early and intensive discharge management enhances quality of life and may help reduce hospital costs. A good model of care involves collaboration of orthopedic surgeons, hospitalists, general internists, geriatricians, and dietitians to address procedures, diet and nutrition, mobility and activities of daily living, and pain medications.²¹ A case manager such as a social worker should start addressing care transition the day after surgery—planning ahead is imperative.

Following hip surgery, patients are routinely sent to skilled nursing facilities as soon as possible so they can start intensive physical therapy. Patients with significant functional impairment or who had delirium are more likely to require a prolonged hospital stay.

Naylor et al examined the effectiveness of comprehensive discharge planning in a study that randomized hospitalized patients (including surgical patients) 65 years or older to either usual discharge planning or intensive discharge planning with advanced practice nurses beginning early in hospitalization.²² The intervention group was followed by home care nurses for up to 4 weeks and had continuous telephone access to the nurses. Patients who received the intervention had a significantly lower risk of hospital readmission, and those who were readmitted had significantly shorter hospital stays. The total cost of care was also significantly lower in the intervention group.

Family conferences aid decision making

Family conferences can be very useful for working through the many questions and challenges that surgery in an elderly person can pose, including whether the patient should undergo the operation, postoperative management, and postdischarge placement.²³ For patients with an uncertain prognosis because of unclear or multiple concurrent diseases, a family conference can help clarify the goals of therapy, inform the family about likely outcomes, and help determine the patient’s wishes and values. Such issues should be revisited as the postoperative course proceeds.

Family conferences also provide a good opportunity to review advanced directives, the need for life support, and possible transfers to intensive care. Family conferences can also help resolve conflicts in care management, as family members may not agree with the need for surgery, how aggressive treatment should be, or where to send the patient for rehabilitation. Differences among family members on these questions are especially common with elderly patients. Working out such issues will improve patient care, especially when done early in the hospitalization.

 

 

DISCUSSION

Question from the audience: In our preoperative clinic, we are trying to intervene to reduce delirium and postoperative cognitive dysfunction. How can we quickly screen for the most important predictors and act to reduce the risk?

Dr. Palmer: The most important risk factor for delirium is age, which obviously can’t be changed. Ask patients about alcohol use and depression. Check on nutritional status and begin supplementation if indicated. Discontinue high-risk medications. Check on electrolytes and their state of hydration; ideally, an electrolyte imbalance can be corrected preoperatively. In addition, other than in patients with end-stage renal disease, try to keep the hemoglobin above 7.5 g/dL, which appears to be associated with better outcomes and less risk of delirium.

It’s also important to remind the family to bring in the patient’s visual aids, hearing devices, and cane or walker so that they’re available right after the operation.

Intraoperative factors that are important for preventing delirium include maintaining good blood pressure levels, giving supplemental oxygen, minimizing the time under general anesthesia, and using local anesthesia if possible.

Question from the audience: How strong is the evidence for using spinal anesthesia as opposed to general anesthesia in preventing postoperative cognitive dysfunction and delirium, especially in the setting of hip fracture repair?

Dr. Palmer: The evidence is fairly soft. For patients undergoing either hip or knee arthroplasty who were randomized to receive either spinal (or local) or general anesthesia, the risk of delirium was similar, but complications such as prolonged bed rest, pressure ulcers, and catheter-related urinary tract infections were somewhat reduced in the spinal/local group.¹⁴ The relative risk of developing postoperative cognitive dysfunction is unclear—no randomized controlled trials have been conducted to answer that question.

Question from the audience: How do you use antipsychotic drugs, especially with the concerns from epidemiologic studies about an increased risk of death?

Dr. Palmer: No antipsychotic agents, including haloperidol, have a specific Food and Drug Administration–approved indication for treating agitation, dementia, or delirium. In general, they should not be used without a clear indication. That said, the usual off-label use is for patients who are severely agitated and are at risk of harming themselves or others. In an ICU setting, where patients have multiple lines, the use of these agents can be considered for a very agitated patient. Alternatives exist, but antipsychotics like haloperidol have the advantage that they can be given in small increments very rapidly and achieve good control of severe agitation.

Antipsychotic agents should only be used with great caution and for the shortest duration needed. As delirium resolves, they should be tapered fairly rapidly over a few days and ideally should be discontinued by the time of hospital discharge.

None of the antipsychotic agents—including those in the first generation and the newer atypical agents—is free of this risk of increased mortality. The mechanism is not understood; it may be torsades de pointes or hypotension leading to stroke or sudden cardiac death.

Question from the audience: What is the most efficient way to assess cognitive and physical functioning preoperatively? 

Dr. Palmer: There may be a documented history of dementia, or family members may tell you if there has been memory loss or some decline in the patient’s self-care abilities. For patients without dementia, you can ask them directly if they can perform basic activities of daily living, such as getting out of bed or dressing. To assess higher-level function, ask if they can manage their own medications, pay bills, or handle their finances. If not, they might have cognitive impairment and are at higher risk for postoperative delirium. These are rather sensitive measures. There are instruments to assess this more precisely, but few clinicians have time to use them.

Quick bedside tests can help assess for delirium postoperatively. We see if patients are “alert and oriented times three” (“Do you know who you are, where you are, and the date?”). We test for attention by asking them to repeat a random string of numbers spoken 1 second apart in monotone; people who are delirious and many patients with severe dementia can’t repeat more than three numbers. A patient who is alert and oriented, has a good attention span (more than three numbers in correct order), and has no history of dementia probably doesn’t have delirium or dementia.

For physical function, ask if they can walk, get out of bed to a chair, and ambulate. If they don’t give clear answers, observe them get out of bed or a chair, walk 10 feet, and return to bed. If they can do that with good balance, especially within 10 to 15 seconds, they probably have reasonably normal mobility and are at lower risk for postoperative complications such as falls with injury.

Acute hospital care is fast becoming acute geriatric care: people aged 65 years or older are only 13% of the population but account for 44% of days of care in nonfederal hospitals and 38% of discharges.¹ In general, the elderly have longer hospital stays, incur greater costs, and have a higher risk of adverse outcomes than do their younger counterparts.²

Among the most common surgical procedures for patients older than 65 are percutaneous coronary intervention with stenting, coronary artery bypass graft surgery, and open reduction internal fixation for hip fracture; the latter is the most common operation in patients aged 85 years or older.³

Elderly patients frequently pose many challenges perioperatively that are not often seen in younger patients. Dementia, frailty, impaired ability to care for oneself, and malnourishment may be present at baseline and are likely to worsen postoperatively. The elderly are at increased risk of acute delirium and cognitive impairment post­operatively, which often complicates recovery and discharge placement.

This article uses a case study to review perioperative problems commonly encountered in elderly surgical patients, particularly those undergoing hip surgery. As the case is presented, I will review strategies to assess risks and prevent and mitigate postoperative cognitive dysfunction and other barriers to recovery.

CASE: AN 82-YEAR-OLD WOMAN WITH HIP FRACTURE

An 82-year-old woman is admitted to undergo open reduction internal fixation for hip fracture. She has a history of osteoarthritis, systolic hypertension, and visual impairment (20/70). Her medications include a beta-blocker, a thiazide diuretic, analgesics as needed, and a multivitamin. She was independent in all activities of daily living before the fracture. She is a social drinker and does not smoke. She has no known cardiovascular, lung, or renal disease.

Her laboratory test results are as follows:

• Blood urea nitrogen (BUN), 24 mg/dL
• Creatinine, 1.0 mg/dL
• Hemoglobin, 12.8 g/dL
• Albumin, 3.8 gm/dL
• Normal levels of thyroid-stimulating hormone and vitamin B₁₂.

Thus, her lab results are normal except for the BUN:creatinine ratio being a bit high, at 24:1 (normal is 10:1, with ratios greater than 18:1 being associated with an increased risk of delirium⁴).

ASSESSING COGNITIVE RISK: POSTOPERATIVE COGNITIVE DYSFUNCTION VS DELIRIUM

Question: Which of these statements about this patient is most correct?

A. She is at high risk (> 40%) of postoperative cognitive dysfunction

B. Her risk of postoperative delirium is 5% to 10%

C. Postoperative delirium cannot be prevented

D. Preoperative haloperidol (1.5 mg/day for 3 days) will reduce the risk of delirium by 25%

The best answer is A. Postoperative cognitive dysfunction is different from delirium, though it is part of a spectrum of cognitive impairment that may occur after surgery and even persist for a prolonged period. The patient’s risk of postoperative delirium is actually a bit higher than 10% (see “Estimating the risk of delirium” below). Some evidence shows that postoperative delirium can be prevented, at least in hip fracture patients. Kalisvaart et al found that preoperative treatment with low-dose haloperidol reduced the duration and severity of delirium in elderly patients following hip surgery but did not reduce its incidence.⁵

Cognitive dysfunction often follows surgery

Postoperative cognitive dysfunction has long been recognized and was first described in patients after cardiac surgery, especially following coronary artery bypass graft procedures. In the last several years, we have recognized that it also occurs in patients who undergo noncardiac surgery. Post­operative cognitive dysfunction, which may persist for weeks to months, may not be obvious but can be detected by standard neuropsychological testing.⁶

Postoperative cognitive dysfunction is different from the “emergence delirium” that may immediately follow surgery and that is often associated with the wearing off of anesthesia. It is also distinct from “incident delirium,” which sometimes occurs over the first few postoperative days (discussed below).

Postoperative dysfunction is especially persistent in the elderly

A recent study found cognitive dysfunction to be common at hospital discharge after major noncardiac surgery in adults of all ages: rates at discharge were 36.6% in patients aged 18 to 39 years, 30.4% in those aged 40 to 59, and 41.4% in those 60 or older.⁷ Notably, however, the oldest group was most likely to have persistent symptoms. Three months after surgery, 12.7% of patients aged 60 or older continued to have postoperative cognitive dysfunction, which was more than double the rates in the young and middle-aged patient groups (5.7% and 5.6%, respectively).⁷

Although the cause of postoperative cognitive dysfunction is not well understood, predisposing factors in addition to advanced age include metabolic problems, lower educational level, and previous cerebral vascular accident.⁷ When elective surgery is considered by elderly patients, the decision should take into account their risk of postoperative cognitive dysfunction and the impact it may have on their quality of life.

PREDICTING AND PREVENTING DELIRIUM

Delirium is easily recognized

Delirium is a common complication of surgery. Unlike postoperative cognitive dysfunction, delirium is easy to detect clinically. It is a disorder of attention and cognition and classically presents as an acute change in mental status accompanied by the following⁸:

• Fluctuation in awareness
• Memory impairment
• Inattention (inability to stay on task, distractibility)
• Disorganized or illogical thinking
• Altered level of consciousness—ie, hyperalertness (agitation, pulling out intravenous lines, etc) or hypoalertness (“quiet delirium”).

Estimating the risk of delirium

Marcantonio and colleagues developed a model to predict the likelihood that delirium will develop in patients undergoing elective surgery.⁹ The model assigns points to various risk factors as follows:

• Age ≥ 70 years (1 point)
• History of alcohol abuse (1 point)
• Baseline cognitive impairment (1 point)
• Severe physical impairment (reduced ability to walk or perform daily activities) (1 point)
• Abnormal preoperative blood levels of electrolytes or glucose (1 point)
• Noncardiac thoracic surgery (1 point)
• Abdominal aortic aneurysm surgery (2 points).

The study to validate this model found that a score of 0 points is associated with only a 2% risk of developing postoperative delirium. A score of 3 or more points is associated with a 50% risk of postoperative delirium. A score of 1 or 2 points (as for the patient in our case study) is associated with an 11% risk, according to this Marcantonio model.⁹

Additionally, well-designed cohort studies of medical patients¹⁰ have identified four major independent predictors of incident delirium:

• Severe illness (eg, high fever, complicated infections)

• Baseline dementia
• Dehydration (high BUN:creatinine ratio)
• Sensory impairments (particularly visual).

Kalisvaart et al conducted a prospective cohort study to determine whether these risk factors in medical patients are applicable to elderly patients undergoing hip surgery.¹¹ They found that the incidence of delirium was low (4%) in hip surgery patients with none of these factors, increased to 11% in patients with one or two of these factors, and increased to 37% in patients with three or four factors. These findings suggest that hip surgery patients (like our case patient) may be at greater risk of pos­toperative delirium than is reflected in the Marcantonio model discussed above,⁹ which was validated in a study of patients undergoing elective (not emergent) surgery.

 

 

Several drug classes raise dementia risk

Anticholinergic medications and other drugs with anticholinergic properties, ie, benzodiazepines and the opioid agent meperidine, also raise the risk for delirium. In general, the older an elderly patient is, the less appropriate these agents are. Many drugs that are not typically recognized as anticholinergics may have potent anticholinergic activity, including tricyclic antidepressants, first-generation antihistamines (eg, diphenhydramine), and high-dose H₂-receptor blockers (particularly cimetidine); these agents too should be avoided in elderly patients.¹²

Strategies to reduce postoperative delirium risk

How can we lower the risk of postoperative delirium in elderly hip fracture patients? Marcantonio et al¹³ randomized 126 patients undergoing hip fracture repair to receive usual care alone or supplemented with the following additional measures:

• Supplemental oxygen during surgery
• Optimization of electrolytes and blood glucose preoperatively
• Discontinuation of high-risk medications
• Adequate nutritional intake (by parenteral route if necessary)
• Encouragement to get out of bed on the first postoperative day
• Treatment of severe pain.

The incidence of delirium was reduced from 50% in the usual-care group to 32% in the intervention group, and the incidence of severe delirium was reduced even more, from 29% to 12%, respectively.¹³

OTHER BEST PRACTICES IN PERIOPERATIVE HIP FRACTURE MANAGEMENT

In a systematic literature review to identify best practices for perioperative management of elderly patients with hip fracture, Beaupre et al¹⁴ found the following measures to be among those with the strongest evidence of benefit:

• Use of spinal or local anesthesia rather than general anesthesia
• Use of pressure-relieving mattresses to prevent pressure ulcers
• Perioperative administration of antibiotics
• Deep vein thrombosis prophylaxis.

The review concluded that providing nutritional supplementation also is probably helpful although the evidence is not robust. Additionally, it was unclear whether minimizing the delay between hospital admission and surgery has any impact on mortality.¹⁴

Is early surgery better?

Early studies suggested that the sooner a hip fracture patient goes to surgery, the lower the mortality, but this has not been supported in well-controlled trials: no difference in mortality has been found whether the patient’s conditions are first optimized to reduce the risk of surgery or if the operation commences within 24 hours.

Although mortality does not appear to be affected, avoiding delay of hip fracture repair yields improvement in other outcomes. In a well-designed prospective cohort study, Orosz et al found that medically stable patients with hip fracture (mean age, 82 years) who underwent surgery within 24 hours had fewer days of pain and less intense pain postoperatively than those whose surgery was delayed beyond 24 hours.¹⁵ The early-surgery group also had a 1.94-day reduction in average length of stay compared with the late-surgery group.

A role for clinical pathways

To determine how the application of evidence-based peri­operative practices affects actual outcomes in elderly hip fracture patients, Beaupre et al used a pre/post study design to evaluate the impact of an evidence-based clinical pathway at their institution.¹⁶ Though there were no differences in in-hospital mortality or the overall costs of inpatient care in elderly hip surgery patients before and after pathway implementation, the patients undergoing surgery after pathway implementation were significantly less likely to have postoperative delirium, heart failure, pressure ulcers, and urinary tract infections compared with those under­going surgery before implementation. The outcomes benefits of this type of multimodal intervention are likely to extend to abdominal surgical procedures as well.

CASE CONTINUED: POSTOP DAY 2―PATIENT IS CONFUSED AND CRYING IN PAIN

On the second postoperative day, our patient appears weak and slightly confused. She is not eating and is crying in pain. Her neurological exam is normal.

Question: Which is the most appropriate next step?

A. Increase physical therapy

B. Begin an antidepressant

C. Insert a nasoenteric feeding tube

D. Increase doses of analgesics

The best answer is D. With no prior history of depression, an antidepressant would probably not be useful. It is premature to recommend nasoenteric feeding. Because pain hampers physical therapy, an increase in physical therapy would likewise be premature. Because we know the patient is in pain, the correct answer perhaps seems obvious. But keep in mind that relieving pain also has many other positive ramifications: intense pain can be a cause of delirium or at least worsen its symptoms, and pain relief is a pre­requisite for the physical therapy that this patient needs.

Strategies for pain control

In general, the treatment of choice for postoperative pain is low-dose morphine sulfate (eg, 1–4 mg every 2 hours, titrated as needed). Acetaminophen can be given safely to virtually all patients. Patient-controlled analgesia is reasonable for select patients but not for older patients with cognitive impairment. Nonsteroidal anti-inflammatory drugs might be helpful in younger patients and even in robust elderly patients, but they must be used very cautiously in the older population because of the risk of gastric ulcers and bleeding, acute kidney injury, fluid retention, and exacerbation of congestive heart failure.

POSTOP DAY 3: PATIENT REPORTS LONG-STANDING FATIGUE

On postoperative day 3, the patient is weak and complains of fatigue. She says that before the fracture, she was experiencing mild weight loss, fatigue, and reduced activity.

Question: What is the most likely reason for her symptoms before the fracture?

A. Frailty

B. Occult heart failure

C. Adverse drug reaction to her beta-blocker

D. Clinical depression

The best answer is A. Occult heart failure is a reasonable second choice, as it is very common in older patients and the diagnosis is easy to miss unless florid pulmonary edema or associated symptoms (eg, chest pain) are present. But this patient had no history of heart disease and was only on medications for hypertension. An adverse drug reaction, such as to the beta-blocker, is unlikely and would probably not cause weight loss. The patient had no history of depression, so clinical depression is unlikely. That said, all the choices are reasonable to consider in elderly patients reporting fatigue and weakness.

 

 

Frailty is important to recognize

It is important to identify frailty and to aggressively manage frail patients postoperatively. Although frailty is not clearly defined, Fried et al¹⁷ identified five clinical features that correlate with its underlying pathophysiology:

• Minimal physical activity (ie, “doing less”)
• Generalized (not focal) muscle weakness
• Slowed performance (eg, walking short distances takes longer)
• Fatigue or poor endurance
• Unintentional weight loss.

The presence of three or more of these features meets the criteria for frailty and is associated with increased risk for mortality over the next 3 years with or without surgery,¹⁷ although surgery probably increases the risk.

Frailty is believed to be a failure over time of the homeostatic mechanisms that keep our organ systems functioning in the face of a stress. Decline in the ability of organ systems to maintain normal function is probably caused by inflammation, chronic disease, and normal aging, and has been termed homeostenosis. As a person ages and physiologic reserves are reduced, adding a stress such as surgery or severe infection can result in organ failure—usually multiple-system organ failure. In any intensive care unit, one is likely to see elderly patients who were admitted with one medical or surgical problem and soon end up having renal, liver, or brain dysfunction as well.

Looked at another way, strength normally declines gradually during aging. An acute illness or surgery causes a precipitous decline in strength, and if it is too severe, the threshold of frailty is crossed (Figure 1). Early mobilization and early and persistent physical therapy can help patients regain strength, thereby preventing frailty.

Physical therapy immediately after hip fracture surgery is associated with significantly better locomotion 2 months later.¹⁸ A number of exercises are effective: range-of-motion exercises, low-impact aerobic activities, and exercises starting with low-intensity resistance (using bands, tubes, and weights) and progressing as tolerated to high-intensity resistance (with machines and pulleys) for an extended period of time.

Nutrition supplementation

Malnourishment can contribute to frailty, yet evidence for the benefits of supplementing nutrition is not strong, as noted above. However, meta-analyses of studies of nutritional interventions with meal supplementation (usually canned supplements) show that meal supplementation can improve mortality risk and reduce morbidity such as pressure ulcers in hospitalized elderly patients.^19,20 The patients most likely to benefit are those who are undernourished at baseline and aged 75 years or older.

CASE CONTINUED: WHAT HAPPENS POST-DISCHARGE?

Following surgery, our patient wonders, “Where will I go next? What will my lifestyle be like?”

These are important questions to consider when first evaluating whether an elderly patient should undergo surgery. In the case of hip fracture, standard thinking is that without surgery, the patient will never recover the ability to independently walk and perform activities of daily living. But we also must recognize the considerable risks of surgery in the elderly population, particularly those aged 75 years or older.

Comprehensive discharge planning

Early and intensive discharge management enhances quality of life and may help reduce hospital costs. A good model of care involves collaboration of orthopedic surgeons, hospitalists, general internists, geriatricians, and dietitians to address procedures, diet and nutrition, mobility and activities of daily living, and pain medications.²¹ A case manager such as a social worker should start addressing care transition the day after surgery—planning ahead is imperative.

Following hip surgery, patients are routinely sent to skilled nursing facilities as soon as possible so they can start intensive physical therapy. Patients with significant functional impairment or who had delirium are more likely to require a prolonged hospital stay.

Naylor et al examined the effectiveness of comprehensive discharge planning in a study that randomized hospitalized patients (including surgical patients) 65 years or older to either usual discharge planning or intensive discharge planning with advanced practice nurses beginning early in hospitalization.²² The intervention group was followed by home care nurses for up to 4 weeks and had continuous telephone access to the nurses. Patients who received the intervention had a significantly lower risk of hospital readmission, and those who were readmitted had significantly shorter hospital stays. The total cost of care was also significantly lower in the intervention group.

Family conferences aid decision making

Family conferences can be very useful for working through the many questions and challenges that surgery in an elderly person can pose, including whether the patient should undergo the operation, postoperative management, and postdischarge placement.²³ For patients with an uncertain prognosis because of unclear or multiple concurrent diseases, a family conference can help clarify the goals of therapy, inform the family about likely outcomes, and help determine the patient’s wishes and values. Such issues should be revisited as the postoperative course proceeds.

Family conferences also provide a good opportunity to review advanced directives, the need for life support, and possible transfers to intensive care. Family conferences can also help resolve conflicts in care management, as family members may not agree with the need for surgery, how aggressive treatment should be, or where to send the patient for rehabilitation. Differences among family members on these questions are especially common with elderly patients. Working out such issues will improve patient care, especially when done early in the hospitalization.

 

 

DISCUSSION

Question from the audience: In our preoperative clinic, we are trying to intervene to reduce delirium and postoperative cognitive dysfunction. How can we quickly screen for the most important predictors and act to reduce the risk?

Dr. Palmer: The most important risk factor for delirium is age, which obviously can’t be changed. Ask patients about alcohol use and depression. Check on nutritional status and begin supplementation if indicated. Discontinue high-risk medications. Check on electrolytes and their state of hydration; ideally, an electrolyte imbalance can be corrected preoperatively. In addition, other than in patients with end-stage renal disease, try to keep the hemoglobin above 7.5 g/dL, which appears to be associated with better outcomes and less risk of delirium.

It’s also important to remind the family to bring in the patient’s visual aids, hearing devices, and cane or walker so that they’re available right after the operation.

Intraoperative factors that are important for preventing delirium include maintaining good blood pressure levels, giving supplemental oxygen, minimizing the time under general anesthesia, and using local anesthesia if possible.

Question from the audience: How strong is the evidence for using spinal anesthesia as opposed to general anesthesia in preventing postoperative cognitive dysfunction and delirium, especially in the setting of hip fracture repair?

Dr. Palmer: The evidence is fairly soft. For patients undergoing either hip or knee arthroplasty who were randomized to receive either spinal (or local) or general anesthesia, the risk of delirium was similar, but complications such as prolonged bed rest, pressure ulcers, and catheter-related urinary tract infections were somewhat reduced in the spinal/local group.¹⁴ The relative risk of developing postoperative cognitive dysfunction is unclear—no randomized controlled trials have been conducted to answer that question.

Question from the audience: How do you use antipsychotic drugs, especially with the concerns from epidemiologic studies about an increased risk of death?

Dr. Palmer: No antipsychotic agents, including haloperidol, have a specific Food and Drug Administration–approved indication for treating agitation, dementia, or delirium. In general, they should not be used without a clear indication. That said, the usual off-label use is for patients who are severely agitated and are at risk of harming themselves or others. In an ICU setting, where patients have multiple lines, the use of these agents can be considered for a very agitated patient. Alternatives exist, but antipsychotics like haloperidol have the advantage that they can be given in small increments very rapidly and achieve good control of severe agitation.

Antipsychotic agents should only be used with great caution and for the shortest duration needed. As delirium resolves, they should be tapered fairly rapidly over a few days and ideally should be discontinued by the time of hospital discharge.

None of the antipsychotic agents—including those in the first generation and the newer atypical agents—is free of this risk of increased mortality. The mechanism is not understood; it may be torsades de pointes or hypotension leading to stroke or sudden cardiac death.

Question from the audience: What is the most efficient way to assess cognitive and physical functioning preoperatively? 

Dr. Palmer: There may be a documented history of dementia, or family members may tell you if there has been memory loss or some decline in the patient’s self-care abilities. For patients without dementia, you can ask them directly if they can perform basic activities of daily living, such as getting out of bed or dressing. To assess higher-level function, ask if they can manage their own medications, pay bills, or handle their finances. If not, they might have cognitive impairment and are at higher risk for postoperative delirium. These are rather sensitive measures. There are instruments to assess this more precisely, but few clinicians have time to use them.

Quick bedside tests can help assess for delirium postoperatively. We see if patients are “alert and oriented times three” (“Do you know who you are, where you are, and the date?”). We test for attention by asking them to repeat a random string of numbers spoken 1 second apart in monotone; people who are delirious and many patients with severe dementia can’t repeat more than three numbers. A patient who is alert and oriented, has a good attention span (more than three numbers in correct order), and has no history of dementia probably doesn’t have delirium or dementia.

For physical function, ask if they can walk, get out of bed to a chair, and ambulate. If they don’t give clear answers, observe them get out of bed or a chair, walk 10 feet, and return to bed. If they can do that with good balance, especially within 10 to 15 seconds, they probably have reasonably normal mobility and are at lower risk for postoperative complications such as falls with injury.

Routine presurgical assessment of patients with a standard battery of tests not only is wasteful but can lead to more unnecessary expense, delay, and even risk to the patient and physician. Any abnormal tests results, even if likely to be clinically unimportant to the upcoming surgery, will need to be followed up to rule out a significant abnormality that may have later implications. This review will outline strategies for making decisions about which tests are clinically useful for preoperative assessment of a given patient and also discuss the value of preoperative evaluation centers in promoting appropriate preoperative testing.

PREOPERATIVE EVALUATION SHOULD BE CLEARLY DIRECTED

Most patients scheduled for surgery at Brigham and Women’s Hospital are assessed by the staff at our preoperative evaluation center. We take a medical history and conduct a physical examination, review the medical records, order laboratory tests or other studies as indicated, and determine which patients need further work-up or consultations. The goals are to evaluate patient readiness for anesthesia and surgery, optimize patient health before surgery, enhance the quality of perioperative care, reduce the morbidity of surgery and length of stay, and return the patient to normal functioning.^1,2

The above goals are generally achieved by directed laboratory testing, managing the patient’s medications, stabilizing disorders when possible, and creating plans for postoperative care and pain management. Communication among the surgeon, the anesthesiology team, and the preoperative medical consultant (if there is one) is critical.^1,2

In contrast, “clearing the patient for surgery” is not a legitimate goal of consultation. The real issues to be taken up in a consult are:

• What is the patient’s risk of complications (cardiac and noncardiac)?
• Would further risk stratification alter patient management?
• Can anything be done to reduce the patient’s risk?

If indicated, a consult should cover the entire perioperative period, offering opinions on operative risk and suggesting treatments that affect long-term patient outcomes. Rarely is preoperative intervention necessary just to lower the risk of surgery. Most interventions that are needed should be done regardless of the surgery.

Everyone on the medical team should have the goal of efficient resource utilization, including avoidance of unnecessary visits, laboratory testing, and consultations.

PREOPERATIVE TESTING: WHAT IS NEEDED?

Preoperative testing is extremely expensive: even more than 20 years ago, preoperative medical testing for all types of surgery accounted for approximately $30 billion in US health care costs annually.³ The likelihood of abnormal test results increases with age, and the more tests performed, the more likely a false positive will occur, further driving up costs.

Preoperative testing should generally be directed by a targeted history and physical examination, and the relevance of any tests should be considered in light of the type of procedure that is planned, particularly the hemodynamic changes and blood loss involved. Before ordering a test, physicians should be sure that there is a good reason for the test, that it is consistent with established guidelines, and that the results will be useful (ie, have the potential to change management).

Case study: Inguinal surgery in a healthy elderly man

A 72-year-old man is being evaluated prior to a right inguinal herniorrhaphy. He has osteoarthritis but is otherwise healthy and jogs 3 to 5 miles several times a week. He takes no medications and has no known drug allergies.

Question: Which of the following tests is necessary prior to surgery?

A. Complete blood cell count (CBC)

B. Prothrombin time and partial thromboplastin time

C. Electrocardiogram (ECG)

D. All of the above

E. None of the above

The correct answer is E (none of the above), for the reasons laid out in the following section.

Unnecessary testing may cause more harm than good

Untargeted testing should be avoided. An unexpected result will probably not be clinically significant for the surgery and will only lead to more needless testing, unnecessary anxiety for the patient, and delays in proceeding to the operating room.⁴ The more tests that are ordered, the higher the likelihood of having an abnormal result by chance: for a test with 95% specificity, results for 1 out of 13 ordered tests will likely be abnormal without there being a true underlying physiologic abnormality.

Researchers at Johns Hopkins University assessed the value of routine preoperative medical testing in a randomized study of nearly 20,000 patients undergoing elective cataract surgery whose preoperative history and physical examination was either preceded or not preceded by a standard battery of tests, including ECG, CBC, electrolytes, urea nitrogen, creatinine, and glucose.⁵ This was an ideal study population, given the relatively noninvasive nature of the procedure (with minimal hemodynamic changes) and cataract patients’ relatively advanced age and resulting likelihood of comorbidities. Notably, there were no differences between the two groups in the overall rate of complications (approximately 3%), which led the researchers to conclude that routine preoperative medical testing does not increase the safety of cataract procedures. These results could be applied to other low-risk cases.

Unnecessary testing is also expensive. Researchers at Stanford University Hospital retrospectively compared preoperative test orders during 6-month periods before and 1 year after development of an anesthesia preoperative evaluation clinic.⁶ They found a 55% reduction in the number of preoperative tests ordered from the period before the clinic was established, when tests were ordered by surgeons and primary care physicians, to the period after the clinic was established, when test ordering was transferred to anesthesiologists at the clinic. This reduction in the number of tests ordered resulted in a 59% reduction in the hospital’s expenditures for preoperative tests, yielding $112 in cost savings per patient. No operating room cancellations, delays, or adverse patient events were reported as a result of the change.

Similar results were reported more recently by researchers at a Canadian hospital, who found that selective preoperative test ordering by staff anesthesiologists reduced the number and cost of preoperative studies compared with usual practice without a resulting increase in complications.⁷

What are the real legal risks?

Many surgeons express the fear that they will be sued if they do not routinely order preoperative tests. My view is that from a medicolegal standpoint, it is usually better not to order an unnecessary test if the next step to take in the event of an abnormal result would be unclear. The legal risk is greater for not following an abnormal test result than for not ordering a test that was not indicated. One may uncover an abnormal laboratory test finding that is not likely to be clinically significant but that could result in legal action if it were not evaluated further. A complication that may not be related to the abnormal result may develop at some point in the future and be blamed on the lack of follow-up. At our center, we insist that when a physician orders a test, he or she is responsible for the results and for following up on abnormalities.

 

 

Should testing be based on age?

Using age as a criterion for preoperative testing is controversial. There is no doubt that the older a patient is, the more likely he or she is to have abnormal test results: patients aged 70 years or older have about a 10% chance of having abnormal levels of serum creatinine, hemoglobin, or glucose⁸ and a 75% chance of having at least one abnormality on their ECG (and a 50% chance of having a major ECG abnormality).⁹ However, these factors were found not to be predictive of postoperative complications. In contrast, predictive factors for this age group are an American Society of Anesthesiologists (ASA) physical status classification of at least 3 (indicating severe systemic disease), the risk of the surgical procedure, and a history of congestive heart failure.^8,9

Guidelines for testing—and for not testing

About 10 years ago, the ASA attempted to develop a practice guideline for routine preoperative testing. The available data were so inconsistent, however, that the ASA could not reach a consensus and instead issued a practice advisory.¹⁰

Even so, there are a number of general principles for avoiding unnecessary preoperative testing:

• Routine laboratory tests are not good screening devices and should not be used to screen for disease
• Repetition should be avoided: there is no need to repeat a recent test
• Healthy patients may not need testing
• Patients undergoing minimally invasive procedures may not need testing
• A test should be ordered only if its results will influence management.

Table 1 lists four criteria for making an educated decision about whether a preoperative test is indicated.¹¹ In general, a test that meets only one or none of the four criteria is probably not a good test, and if it meets three or four of the criteria, it is a very good test (meeting two criteria would be borderline). These criteria should always be considered when ordering a laboratory test, an ECG, a stress test, or an additional consult.

A CLOSER LOOK AT A FEW SPECIFIC TESTS

Question: Which of the following tests is most likely to provide useful information to aid clinical decision-making during a preoperative evaluation for laparoscopic cholecystectomy?

A. A chest radiograph in a 43-year-old woman with asthma

B. An ECG in a 71-year-old man with hypertension

C. A pregnancy test in an 18-year-old woman with amenorrhea

D. A prothrombin time in a 51-year-old man with anemia

E. A urinalysis in a 67-year-old woman with diabetes

The best answer is C (pregnancy test); an ECG in the 71-year-old man would be less useful (see below). The remaining choices—chest radiograph, prothrombin time, and urinalysis—are even less appropriate. A chest radiograph in an asthmatic patient is not likely to yield more information than what is obtained from the history and physical exam. Patients with anemia are not likely to have abnormal coagulation, and the role of urinalysis in detecting glucose and protein in asymptomatic diabetic patients is limited.

Routine pregnancy testing is justifiable

There are a number of reasons to justify a low threshold for preoperative pregnancy testing¹⁰:

• Patients, especially adolescents, are often unreliable in suspecting that they might be pregnant (in several studies of routine preoperative pregnancy screening, 0.3% to 2.2% of tests were positive)
• History and physical examination are often insufficient to determine early pregnancy
• Management usually changes if it is discovered that a patient is pregnant.

Using the four criteria from Table 1, pregnancy testing rates high as a useful test: it would identify “abnormality,” it would determine a diagnosis, and it would likely change management.

Routine ECG has limited utility

In contrast, routine preoperative ECG is not well supported. A recent study from the Netherlands assessed the added value of a preoperative ECG in predicting myocardial infarction and death following noncardiac surgery among 2,422 patients older than age 50 years.¹² It showed that ECG findings were no more predictive of complications than findings from the history and physical examination and the patient’s activity level.

From our own data at Brigham and Women’s Hospital,¹³ we found that the presence of any of the following six risk factors predicted all but 0.44% of ECG abnormalities in patients aged 50 years or older presenting for preoperative evaluation:

• Age greater than 65 years
• Congestive heart failure
• High cholesterol
• Angina
• Myocardial infarction
• Severe valvular disease.

The 2007 guidelines on perioperative risk assessment from the American College of Cardiology and American Heart Association (ACC/AHA) do not consider ECG to be indicated in asymptomatic patients undergoing low-risk noncardiac procedures regardless of patient age,¹⁴ like the 71-year-old man with hypertension in the above case question. These guidelines also state that evidence for routine ECG orders is not well established in patients with at least one clinical risk factor undergoing intermediate-risk procedures.

The aforementioned ASA practice advisory acknowledges that the likelihood of ECG abnormalities rises with increasing patient age, but the ASA was unable to reach consensus on a minimum age for routinely ordering an ECG in surgical candidates.¹⁰ The advisory recommends taking into account other factors, such as cardiac risk factors, the presence of cardiocirculatory or respiratory disease, and the type and invasiveness of the surgical procedure.¹⁰ 

In recommendations not specific to the perioperative setting, the US Preventive Services Task Force advises against routine screening for coronary heart disease with ECG or exercise treadmill testing.¹⁵ It gives routine screening a “D” recommendation, indicating that risk is greater than benefit because of the potential for unnecessary invasive procedures, overtreatment, and mislabeling of patients.

Our group at Brigham and Women’s Hospital recently surveyed anesthesiology program directors at US teaching hospitals to determine their preoperative test-ordering practices.¹⁶ Among the 75 respondents (58% response rate), 95% said their institutions have no requirements for ordering ECGs unless indicated based on age, history, or surgery type; 71% said their institutions have age-based requirements for ordering ECGs (usually > 50 years). Most respondents reported that their institutions are ordering fewer ECGs since the publication of the 2007 ACC/AHA guidelines on perioperative evaluation.

Whether or not age should be used as a criterion for ECG testing is controversial, and editorials on this subject abound.^17–19 They point out that clinicians must be careful before abandoning routine ECGs in elderly patients, for several reasons:

• An abnormal ECG (or abnormal lab test results) may modify a patient’s ASA classification (which is predictive of complications)
• At least one-quarter of myocardial infarctions in elderly persons are “silent” or clinically unrecognized
• A preoperative ECG provides a useful baseline if the patient should develop ECG changes, chest pain, or cardiac complications during the perioperative period.

Most institutions use age as a criterion for ordering tests, especially for ECGs. If such a policy is used, a threshold of 60 years or older is probably most appropriate. However, a patient with good functional capacity who is undergoing a low-risk procedure does not need cardiac testing.^14,20

An additional consideration is cost. Although the cost of a single ECG is modest, the cumulative cost of preoperative ECGs for all older surgical patients is significant over the course of a year. Because the Centers for Medicare and Medicaid Services (CMS) no longer cover routine preoperative ECGs, routine testing can be very costly to an institution over time.

 

 

COST AND REGULATORY BENEFITS OF PREOPERATIVE CENTERS

Preoperative evaluation centers tend to be cost-effective, as they keep consultations and redundant provider interviews to a minimum, encourage more appropriate targeting of tests, and help to avoid last-minute operating room delays and cancellations.^21,22 They also provide an efficient means of compiling the chart for the operating room.

The merits of standardization

Preoperative evaluation centers likewise encourage more standardized preoperative assessment, which can facilitate compliance with surgical quality measures such as those from the National Surgical Quality Improvement Program and the Leapfrog Group. Standardization also fosters more efficient and consistent regulatory documentation, making it easier to follow requirements from CMS (often linked to reimbursement) and the Joint Commission. It also tends to improve reimbursement by encouraging more appropriate coding under CMS’ diagnosis-related group (DRG) system to indicate that whatever testing is ordered is related to the surgical diagnosis or to relevant comorbidities.

No excessive dictates from Joint Commission or CMS

Contrary to what many believe, the Joint Commission does not require excessive preoperative testing. The Joint Commission has no mandate for routine diagnostic tests but requires only what is necessary for determining a patient’s health care needs.²³

CMS provides no guidance as to what to do or not do in a preoperative assessment, but it does not reimburse for routine screening tests or for age-based testing.²⁴ Reimbursement for a preoperative ECG, for example, requires documentation of the patient’s signs or symptoms; for an ECG that is indicated, reimbursement includes review and interpretation by the physician.²⁵

A new partner for proper preoperative assessment

Appropriate preoperative evaluation and testing is one of the goals promoted by the recently formed Society for Perioperative Assessment and Quality Improvement (SPAQI). The mission of this international nonprofit organization is to optimize surgical outcomes by sharing best practices and promoting research and communication among health professionals across multiple disciplines. More information is available at www.spaqi.org.

DISCUSSION

Question from the audience: At my hospital, we teach residents about limiting the preoperative tests they order, but surgeons routinely expect many of these tests, including chest x-rays in patients with pulmonary conditions. Are any surgical societies involved in efforts to reduce preoperative testing? Or are surgical societies’ recommendations actually driving some of the unnecessary testing?

Dr. Hepner: I’m not aware of recommendations from surgical societies regarding preoperative testing. Many surgeons believe that the more testing that’s done, the likelier they are to uncover an occult disease. They also often want baseline information, which may actually be warranted in some cases.

Question from the audience: If you’re already ordering a “type and screen” or “type and hold” for a patient, isn’t it worthwhile to just add on a CBC? The patient is already getting the phlebotomy, so isn’t there a cost benefit to getting other routine tests done at the same time rather than calling the patient back for more tests if another indication arises?

Dr. Hepner: Charges are generally assessed for each individual test, not for drawing blood, so I would only get the tests that are indicated.

Question from the audience: In institutions without a preoperative clinic, sometimes the surgeons do the work-up without discussing the case with the primary doctor, and the surgeons want an ECG so that the case isn’t cancelled at the last minute. Can you give straightforward criteria in such cases, such as an age threshold, or would you not order an ECG for anyone?

Dr. Hepner: Based on our most recent data, 60 years seems to be a reasonable cutoff if you are going to use age as a criterion.

Question from the audience: What criteria do you use for preoperative screening with pregnancy tests?

Dr. Hepner: If you have an unreliable patient population, general screening should be done. We don’t have such a requirement, but we have a very low threshold. If a patient appears very reliable, knowing the exact date of her last menstrual period, we’ll go by that. If a patient is unsure, we’ll do a pregnancy test.

Question from the audience: My hospital doesn’t have a preoperative clinic, and until recently, the anesthesiology department has helped surgeons with ordering of pre­operative tests. We followed a guideline protocol for about 20 years. Now the newer surgeons say they don’t want to be responsible for abnormal test results. Yet we anesthesiologists aren’t seeing the patients, so we can’t use clinical judgment; we can only go by the guidelines. The surgeons are the only physicians on the case who actually do the history and physical exam. So who should sign the test orders and be responsible for abnormal results?

Dr. Hepner: In our preoperative test center, we tell the surgical team that if they are uncertain about which tests to order, we will handle it. And if we order a test, we follow up on the results. You must ensure that orders are signed and not rubber-stamped; that way, the person who orders a test will get called with any abnormal results. If you order it, you own it.

Question from the audience: I agree that no testing is needed for the 72-year-old man you presented who was undergoing surgery for inguinal hernia, but it always worries me not to do an ECG since part of the standard of care for anesthesia is intraoperative ECG monitoring. If we see some sort of unusual arrhythmia when we take the patient in, we might cancel the case if we don’t know whether it was present at baseline. Surgeons will ask me, “Why didn’t you order a baseline if you’re going to monitor the ECG in the operating room? If you’re not going to order a baseline, then why monitor the ECG?” These are medicolegal issues that I haven’t seen addressed.

Dr. Hepner: A case like you describe will be addressed in the upcoming medicolegal session (see page S119). You make a good point that many times just having a baseline is helpful, but I would argue that it is more helpful for intermediate- or high-risk cases.

Routine presurgical assessment of patients with a standard battery of tests not only is wasteful but can lead to more unnecessary expense, delay, and even risk to the patient and physician. Any abnormal tests results, even if likely to be clinically unimportant to the upcoming surgery, will need to be followed up to rule out a significant abnormality that may have later implications. This review will outline strategies for making decisions about which tests are clinically useful for preoperative assessment of a given patient and also discuss the value of preoperative evaluation centers in promoting appropriate preoperative testing.

PREOPERATIVE EVALUATION SHOULD BE CLEARLY DIRECTED

Most patients scheduled for surgery at Brigham and Women’s Hospital are assessed by the staff at our preoperative evaluation center. We take a medical history and conduct a physical examination, review the medical records, order laboratory tests or other studies as indicated, and determine which patients need further work-up or consultations. The goals are to evaluate patient readiness for anesthesia and surgery, optimize patient health before surgery, enhance the quality of perioperative care, reduce the morbidity of surgery and length of stay, and return the patient to normal functioning.^1,2

The above goals are generally achieved by directed laboratory testing, managing the patient’s medications, stabilizing disorders when possible, and creating plans for postoperative care and pain management. Communication among the surgeon, the anesthesiology team, and the preoperative medical consultant (if there is one) is critical.^1,2

In contrast, “clearing the patient for surgery” is not a legitimate goal of consultation. The real issues to be taken up in a consult are:

• What is the patient’s risk of complications (cardiac and noncardiac)?
• Would further risk stratification alter patient management?
• Can anything be done to reduce the patient’s risk?

If indicated, a consult should cover the entire perioperative period, offering opinions on operative risk and suggesting treatments that affect long-term patient outcomes. Rarely is preoperative intervention necessary just to lower the risk of surgery. Most interventions that are needed should be done regardless of the surgery.

Everyone on the medical team should have the goal of efficient resource utilization, including avoidance of unnecessary visits, laboratory testing, and consultations.

PREOPERATIVE TESTING: WHAT IS NEEDED?

Preoperative testing is extremely expensive: even more than 20 years ago, preoperative medical testing for all types of surgery accounted for approximately $30 billion in US health care costs annually.³ The likelihood of abnormal test results increases with age, and the more tests performed, the more likely a false positive will occur, further driving up costs.

Preoperative testing should generally be directed by a targeted history and physical examination, and the relevance of any tests should be considered in light of the type of procedure that is planned, particularly the hemodynamic changes and blood loss involved. Before ordering a test, physicians should be sure that there is a good reason for the test, that it is consistent with established guidelines, and that the results will be useful (ie, have the potential to change management).

Case study: Inguinal surgery in a healthy elderly man

A 72-year-old man is being evaluated prior to a right inguinal herniorrhaphy. He has osteoarthritis but is otherwise healthy and jogs 3 to 5 miles several times a week. He takes no medications and has no known drug allergies.

Question: Which of the following tests is necessary prior to surgery?

A. Complete blood cell count (CBC)

B. Prothrombin time and partial thromboplastin time

C. Electrocardiogram (ECG)

D. All of the above

E. None of the above

The correct answer is E (none of the above), for the reasons laid out in the following section.

Unnecessary testing may cause more harm than good

Untargeted testing should be avoided. An unexpected result will probably not be clinically significant for the surgery and will only lead to more needless testing, unnecessary anxiety for the patient, and delays in proceeding to the operating room.⁴ The more tests that are ordered, the higher the likelihood of having an abnormal result by chance: for a test with 95% specificity, results for 1 out of 13 ordered tests will likely be abnormal without there being a true underlying physiologic abnormality.

Researchers at Johns Hopkins University assessed the value of routine preoperative medical testing in a randomized study of nearly 20,000 patients undergoing elective cataract surgery whose preoperative history and physical examination was either preceded or not preceded by a standard battery of tests, including ECG, CBC, electrolytes, urea nitrogen, creatinine, and glucose.⁵ This was an ideal study population, given the relatively noninvasive nature of the procedure (with minimal hemodynamic changes) and cataract patients’ relatively advanced age and resulting likelihood of comorbidities. Notably, there were no differences between the two groups in the overall rate of complications (approximately 3%), which led the researchers to conclude that routine preoperative medical testing does not increase the safety of cataract procedures. These results could be applied to other low-risk cases.

Unnecessary testing is also expensive. Researchers at Stanford University Hospital retrospectively compared preoperative test orders during 6-month periods before and 1 year after development of an anesthesia preoperative evaluation clinic.⁶ They found a 55% reduction in the number of preoperative tests ordered from the period before the clinic was established, when tests were ordered by surgeons and primary care physicians, to the period after the clinic was established, when test ordering was transferred to anesthesiologists at the clinic. This reduction in the number of tests ordered resulted in a 59% reduction in the hospital’s expenditures for preoperative tests, yielding $112 in cost savings per patient. No operating room cancellations, delays, or adverse patient events were reported as a result of the change.

Similar results were reported more recently by researchers at a Canadian hospital, who found that selective preoperative test ordering by staff anesthesiologists reduced the number and cost of preoperative studies compared with usual practice without a resulting increase in complications.⁷

What are the real legal risks?

Many surgeons express the fear that they will be sued if they do not routinely order preoperative tests. My view is that from a medicolegal standpoint, it is usually better not to order an unnecessary test if the next step to take in the event of an abnormal result would be unclear. The legal risk is greater for not following an abnormal test result than for not ordering a test that was not indicated. One may uncover an abnormal laboratory test finding that is not likely to be clinically significant but that could result in legal action if it were not evaluated further. A complication that may not be related to the abnormal result may develop at some point in the future and be blamed on the lack of follow-up. At our center, we insist that when a physician orders a test, he or she is responsible for the results and for following up on abnormalities.

 

 

Should testing be based on age?

Using age as a criterion for preoperative testing is controversial. There is no doubt that the older a patient is, the more likely he or she is to have abnormal test results: patients aged 70 years or older have about a 10% chance of having abnormal levels of serum creatinine, hemoglobin, or glucose⁸ and a 75% chance of having at least one abnormality on their ECG (and a 50% chance of having a major ECG abnormality).⁹ However, these factors were found not to be predictive of postoperative complications. In contrast, predictive factors for this age group are an American Society of Anesthesiologists (ASA) physical status classification of at least 3 (indicating severe systemic disease), the risk of the surgical procedure, and a history of congestive heart failure.^8,9

Guidelines for testing—and for not testing

About 10 years ago, the ASA attempted to develop a practice guideline for routine preoperative testing. The available data were so inconsistent, however, that the ASA could not reach a consensus and instead issued a practice advisory.¹⁰

Even so, there are a number of general principles for avoiding unnecessary preoperative testing:

• Routine laboratory tests are not good screening devices and should not be used to screen for disease
• Repetition should be avoided: there is no need to repeat a recent test
• Healthy patients may not need testing
• Patients undergoing minimally invasive procedures may not need testing
• A test should be ordered only if its results will influence management.

Table 1 lists four criteria for making an educated decision about whether a preoperative test is indicated.¹¹ In general, a test that meets only one or none of the four criteria is probably not a good test, and if it meets three or four of the criteria, it is a very good test (meeting two criteria would be borderline). These criteria should always be considered when ordering a laboratory test, an ECG, a stress test, or an additional consult.

A CLOSER LOOK AT A FEW SPECIFIC TESTS

Question: Which of the following tests is most likely to provide useful information to aid clinical decision-making during a preoperative evaluation for laparoscopic cholecystectomy?

A. A chest radiograph in a 43-year-old woman with asthma

B. An ECG in a 71-year-old man with hypertension

C. A pregnancy test in an 18-year-old woman with amenorrhea

D. A prothrombin time in a 51-year-old man with anemia

E. A urinalysis in a 67-year-old woman with diabetes

The best answer is C (pregnancy test); an ECG in the 71-year-old man would be less useful (see below). The remaining choices—chest radiograph, prothrombin time, and urinalysis—are even less appropriate. A chest radiograph in an asthmatic patient is not likely to yield more information than what is obtained from the history and physical exam. Patients with anemia are not likely to have abnormal coagulation, and the role of urinalysis in detecting glucose and protein in asymptomatic diabetic patients is limited.

Routine pregnancy testing is justifiable

There are a number of reasons to justify a low threshold for preoperative pregnancy testing¹⁰:

• Patients, especially adolescents, are often unreliable in suspecting that they might be pregnant (in several studies of routine preoperative pregnancy screening, 0.3% to 2.2% of tests were positive)
• History and physical examination are often insufficient to determine early pregnancy
• Management usually changes if it is discovered that a patient is pregnant.

Using the four criteria from Table 1, pregnancy testing rates high as a useful test: it would identify “abnormality,” it would determine a diagnosis, and it would likely change management.

Routine ECG has limited utility

In contrast, routine preoperative ECG is not well supported. A recent study from the Netherlands assessed the added value of a preoperative ECG in predicting myocardial infarction and death following noncardiac surgery among 2,422 patients older than age 50 years.¹² It showed that ECG findings were no more predictive of complications than findings from the history and physical examination and the patient’s activity level.

From our own data at Brigham and Women’s Hospital,¹³ we found that the presence of any of the following six risk factors predicted all but 0.44% of ECG abnormalities in patients aged 50 years or older presenting for preoperative evaluation:

• Age greater than 65 years
• Congestive heart failure
• High cholesterol
• Angina
• Myocardial infarction
• Severe valvular disease.

The 2007 guidelines on perioperative risk assessment from the American College of Cardiology and American Heart Association (ACC/AHA) do not consider ECG to be indicated in asymptomatic patients undergoing low-risk noncardiac procedures regardless of patient age,¹⁴ like the 71-year-old man with hypertension in the above case question. These guidelines also state that evidence for routine ECG orders is not well established in patients with at least one clinical risk factor undergoing intermediate-risk procedures.

The aforementioned ASA practice advisory acknowledges that the likelihood of ECG abnormalities rises with increasing patient age, but the ASA was unable to reach consensus on a minimum age for routinely ordering an ECG in surgical candidates.¹⁰ The advisory recommends taking into account other factors, such as cardiac risk factors, the presence of cardiocirculatory or respiratory disease, and the type and invasiveness of the surgical procedure.¹⁰ 

In recommendations not specific to the perioperative setting, the US Preventive Services Task Force advises against routine screening for coronary heart disease with ECG or exercise treadmill testing.¹⁵ It gives routine screening a “D” recommendation, indicating that risk is greater than benefit because of the potential for unnecessary invasive procedures, overtreatment, and mislabeling of patients.

Our group at Brigham and Women’s Hospital recently surveyed anesthesiology program directors at US teaching hospitals to determine their preoperative test-ordering practices.¹⁶ Among the 75 respondents (58% response rate), 95% said their institutions have no requirements for ordering ECGs unless indicated based on age, history, or surgery type; 71% said their institutions have age-based requirements for ordering ECGs (usually > 50 years). Most respondents reported that their institutions are ordering fewer ECGs since the publication of the 2007 ACC/AHA guidelines on perioperative evaluation.

Whether or not age should be used as a criterion for ECG testing is controversial, and editorials on this subject abound.^17–19 They point out that clinicians must be careful before abandoning routine ECGs in elderly patients, for several reasons:

• An abnormal ECG (or abnormal lab test results) may modify a patient’s ASA classification (which is predictive of complications)
• At least one-quarter of myocardial infarctions in elderly persons are “silent” or clinically unrecognized
• A preoperative ECG provides a useful baseline if the patient should develop ECG changes, chest pain, or cardiac complications during the perioperative period.

Most institutions use age as a criterion for ordering tests, especially for ECGs. If such a policy is used, a threshold of 60 years or older is probably most appropriate. However, a patient with good functional capacity who is undergoing a low-risk procedure does not need cardiac testing.^14,20

An additional consideration is cost. Although the cost of a single ECG is modest, the cumulative cost of preoperative ECGs for all older surgical patients is significant over the course of a year. Because the Centers for Medicare and Medicaid Services (CMS) no longer cover routine preoperative ECGs, routine testing can be very costly to an institution over time.

 

 

COST AND REGULATORY BENEFITS OF PREOPERATIVE CENTERS

Preoperative evaluation centers tend to be cost-effective, as they keep consultations and redundant provider interviews to a minimum, encourage more appropriate targeting of tests, and help to avoid last-minute operating room delays and cancellations.^21,22 They also provide an efficient means of compiling the chart for the operating room.

The merits of standardization

Preoperative evaluation centers likewise encourage more standardized preoperative assessment, which can facilitate compliance with surgical quality measures such as those from the National Surgical Quality Improvement Program and the Leapfrog Group. Standardization also fosters more efficient and consistent regulatory documentation, making it easier to follow requirements from CMS (often linked to reimbursement) and the Joint Commission. It also tends to improve reimbursement by encouraging more appropriate coding under CMS’ diagnosis-related group (DRG) system to indicate that whatever testing is ordered is related to the surgical diagnosis or to relevant comorbidities.

No excessive dictates from Joint Commission or CMS

Contrary to what many believe, the Joint Commission does not require excessive preoperative testing. The Joint Commission has no mandate for routine diagnostic tests but requires only what is necessary for determining a patient’s health care needs.²³

CMS provides no guidance as to what to do or not do in a preoperative assessment, but it does not reimburse for routine screening tests or for age-based testing.²⁴ Reimbursement for a preoperative ECG, for example, requires documentation of the patient’s signs or symptoms; for an ECG that is indicated, reimbursement includes review and interpretation by the physician.²⁵

A new partner for proper preoperative assessment

Appropriate preoperative evaluation and testing is one of the goals promoted by the recently formed Society for Perioperative Assessment and Quality Improvement (SPAQI). The mission of this international nonprofit organization is to optimize surgical outcomes by sharing best practices and promoting research and communication among health professionals across multiple disciplines. More information is available at www.spaqi.org.

DISCUSSION

Question from the audience: At my hospital, we teach residents about limiting the preoperative tests they order, but surgeons routinely expect many of these tests, including chest x-rays in patients with pulmonary conditions. Are any surgical societies involved in efforts to reduce preoperative testing? Or are surgical societies’ recommendations actually driving some of the unnecessary testing?

Dr. Hepner: I’m not aware of recommendations from surgical societies regarding preoperative testing. Many surgeons believe that the more testing that’s done, the likelier they are to uncover an occult disease. They also often want baseline information, which may actually be warranted in some cases.

Question from the audience: If you’re already ordering a “type and screen” or “type and hold” for a patient, isn’t it worthwhile to just add on a CBC? The patient is already getting the phlebotomy, so isn’t there a cost benefit to getting other routine tests done at the same time rather than calling the patient back for more tests if another indication arises?

Dr. Hepner: Charges are generally assessed for each individual test, not for drawing blood, so I would only get the tests that are indicated.

Question from the audience: In institutions without a preoperative clinic, sometimes the surgeons do the work-up without discussing the case with the primary doctor, and the surgeons want an ECG so that the case isn’t cancelled at the last minute. Can you give straightforward criteria in such cases, such as an age threshold, or would you not order an ECG for anyone?

Dr. Hepner: Based on our most recent data, 60 years seems to be a reasonable cutoff if you are going to use age as a criterion.

Question from the audience: What criteria do you use for preoperative screening with pregnancy tests?

Dr. Hepner: If you have an unreliable patient population, general screening should be done. We don’t have such a requirement, but we have a very low threshold. If a patient appears very reliable, knowing the exact date of her last menstrual period, we’ll go by that. If a patient is unsure, we’ll do a pregnancy test.

Question from the audience: My hospital doesn’t have a preoperative clinic, and until recently, the anesthesiology department has helped surgeons with ordering of pre­operative tests. We followed a guideline protocol for about 20 years. Now the newer surgeons say they don’t want to be responsible for abnormal test results. Yet we anesthesiologists aren’t seeing the patients, so we can’t use clinical judgment; we can only go by the guidelines. The surgeons are the only physicians on the case who actually do the history and physical exam. So who should sign the test orders and be responsible for abnormal results?

Dr. Hepner: In our preoperative test center, we tell the surgical team that if they are uncertain about which tests to order, we will handle it. And if we order a test, we follow up on the results. You must ensure that orders are signed and not rubber-stamped; that way, the person who orders a test will get called with any abnormal results. If you order it, you own it.

Question from the audience: I agree that no testing is needed for the 72-year-old man you presented who was undergoing surgery for inguinal hernia, but it always worries me not to do an ECG since part of the standard of care for anesthesia is intraoperative ECG monitoring. If we see some sort of unusual arrhythmia when we take the patient in, we might cancel the case if we don’t know whether it was present at baseline. Surgeons will ask me, “Why didn’t you order a baseline if you’re going to monitor the ECG in the operating room? If you’re not going to order a baseline, then why monitor the ECG?” These are medicolegal issues that I haven’t seen addressed.

Dr. Hepner: A case like you describe will be addressed in the upcoming medicolegal session (see page S119). You make a good point that many times just having a baseline is helpful, but I would argue that it is more helpful for intermediate- or high-risk cases.

Routine presurgical assessment of patients with a standard battery of tests not only is wasteful but can lead to more unnecessary expense, delay, and even risk to the patient and physician. Any abnormal tests results, even if likely to be clinically unimportant to the upcoming surgery, will need to be followed up to rule out a significant abnormality that may have later implications. This review will outline strategies for making decisions about which tests are clinically useful for preoperative assessment of a given patient and also discuss the value of preoperative evaluation centers in promoting appropriate preoperative testing.

PREOPERATIVE EVALUATION SHOULD BE CLEARLY DIRECTED

Most patients scheduled for surgery at Brigham and Women’s Hospital are assessed by the staff at our preoperative evaluation center. We take a medical history and conduct a physical examination, review the medical records, order laboratory tests or other studies as indicated, and determine which patients need further work-up or consultations. The goals are to evaluate patient readiness for anesthesia and surgery, optimize patient health before surgery, enhance the quality of perioperative care, reduce the morbidity of surgery and length of stay, and return the patient to normal functioning.^1,2

The above goals are generally achieved by directed laboratory testing, managing the patient’s medications, stabilizing disorders when possible, and creating plans for postoperative care and pain management. Communication among the surgeon, the anesthesiology team, and the preoperative medical consultant (if there is one) is critical.^1,2

In contrast, “clearing the patient for surgery” is not a legitimate goal of consultation. The real issues to be taken up in a consult are:

• What is the patient’s risk of complications (cardiac and noncardiac)?
• Would further risk stratification alter patient management?
• Can anything be done to reduce the patient’s risk?

If indicated, a consult should cover the entire perioperative period, offering opinions on operative risk and suggesting treatments that affect long-term patient outcomes. Rarely is preoperative intervention necessary just to lower the risk of surgery. Most interventions that are needed should be done regardless of the surgery.

Everyone on the medical team should have the goal of efficient resource utilization, including avoidance of unnecessary visits, laboratory testing, and consultations.

PREOPERATIVE TESTING: WHAT IS NEEDED?

Preoperative testing is extremely expensive: even more than 20 years ago, preoperative medical testing for all types of surgery accounted for approximately $30 billion in US health care costs annually.³ The likelihood of abnormal test results increases with age, and the more tests performed, the more likely a false positive will occur, further driving up costs.

Preoperative testing should generally be directed by a targeted history and physical examination, and the relevance of any tests should be considered in light of the type of procedure that is planned, particularly the hemodynamic changes and blood loss involved. Before ordering a test, physicians should be sure that there is a good reason for the test, that it is consistent with established guidelines, and that the results will be useful (ie, have the potential to change management).

Case study: Inguinal surgery in a healthy elderly man

A 72-year-old man is being evaluated prior to a right inguinal herniorrhaphy. He has osteoarthritis but is otherwise healthy and jogs 3 to 5 miles several times a week. He takes no medications and has no known drug allergies.

Question: Which of the following tests is necessary prior to surgery?

A. Complete blood cell count (CBC)

B. Prothrombin time and partial thromboplastin time

C. Electrocardiogram (ECG)

D. All of the above

E. None of the above

The correct answer is E (none of the above), for the reasons laid out in the following section.

Unnecessary testing may cause more harm than good

Untargeted testing should be avoided. An unexpected result will probably not be clinically significant for the surgery and will only lead to more needless testing, unnecessary anxiety for the patient, and delays in proceeding to the operating room.⁴ The more tests that are ordered, the higher the likelihood of having an abnormal result by chance: for a test with 95% specificity, results for 1 out of 13 ordered tests will likely be abnormal without there being a true underlying physiologic abnormality.

Researchers at Johns Hopkins University assessed the value of routine preoperative medical testing in a randomized study of nearly 20,000 patients undergoing elective cataract surgery whose preoperative history and physical examination was either preceded or not preceded by a standard battery of tests, including ECG, CBC, electrolytes, urea nitrogen, creatinine, and glucose.⁵ This was an ideal study population, given the relatively noninvasive nature of the procedure (with minimal hemodynamic changes) and cataract patients’ relatively advanced age and resulting likelihood of comorbidities. Notably, there were no differences between the two groups in the overall rate of complications (approximately 3%), which led the researchers to conclude that routine preoperative medical testing does not increase the safety of cataract procedures. These results could be applied to other low-risk cases.

Unnecessary testing is also expensive. Researchers at Stanford University Hospital retrospectively compared preoperative test orders during 6-month periods before and 1 year after development of an anesthesia preoperative evaluation clinic.⁶ They found a 55% reduction in the number of preoperative tests ordered from the period before the clinic was established, when tests were ordered by surgeons and primary care physicians, to the period after the clinic was established, when test ordering was transferred to anesthesiologists at the clinic. This reduction in the number of tests ordered resulted in a 59% reduction in the hospital’s expenditures for preoperative tests, yielding $112 in cost savings per patient. No operating room cancellations, delays, or adverse patient events were reported as a result of the change.

Similar results were reported more recently by researchers at a Canadian hospital, who found that selective preoperative test ordering by staff anesthesiologists reduced the number and cost of preoperative studies compared with usual practice without a resulting increase in complications.⁷

What are the real legal risks?

Many surgeons express the fear that they will be sued if they do not routinely order preoperative tests. My view is that from a medicolegal standpoint, it is usually better not to order an unnecessary test if the next step to take in the event of an abnormal result would be unclear. The legal risk is greater for not following an abnormal test result than for not ordering a test that was not indicated. One may uncover an abnormal laboratory test finding that is not likely to be clinically significant but that could result in legal action if it were not evaluated further. A complication that may not be related to the abnormal result may develop at some point in the future and be blamed on the lack of follow-up. At our center, we insist that when a physician orders a test, he or she is responsible for the results and for following up on abnormalities.

 

 

Should testing be based on age?

Using age as a criterion for preoperative testing is controversial. There is no doubt that the older a patient is, the more likely he or she is to have abnormal test results: patients aged 70 years or older have about a 10% chance of having abnormal levels of serum creatinine, hemoglobin, or glucose⁸ and a 75% chance of having at least one abnormality on their ECG (and a 50% chance of having a major ECG abnormality).⁹ However, these factors were found not to be predictive of postoperative complications. In contrast, predictive factors for this age group are an American Society of Anesthesiologists (ASA) physical status classification of at least 3 (indicating severe systemic disease), the risk of the surgical procedure, and a history of congestive heart failure.^8,9

Guidelines for testing—and for not testing

About 10 years ago, the ASA attempted to develop a practice guideline for routine preoperative testing. The available data were so inconsistent, however, that the ASA could not reach a consensus and instead issued a practice advisory.¹⁰

Even so, there are a number of general principles for avoiding unnecessary preoperative testing:

• Routine laboratory tests are not good screening devices and should not be used to screen for disease
• Repetition should be avoided: there is no need to repeat a recent test
• Healthy patients may not need testing
• Patients undergoing minimally invasive procedures may not need testing
• A test should be ordered only if its results will influence management.

Table 1 lists four criteria for making an educated decision about whether a preoperative test is indicated.¹¹ In general, a test that meets only one or none of the four criteria is probably not a good test, and if it meets three or four of the criteria, it is a very good test (meeting two criteria would be borderline). These criteria should always be considered when ordering a laboratory test, an ECG, a stress test, or an additional consult.

A CLOSER LOOK AT A FEW SPECIFIC TESTS

Question: Which of the following tests is most likely to provide useful information to aid clinical decision-making during a preoperative evaluation for laparoscopic cholecystectomy?

A. A chest radiograph in a 43-year-old woman with asthma

B. An ECG in a 71-year-old man with hypertension

C. A pregnancy test in an 18-year-old woman with amenorrhea

D. A prothrombin time in a 51-year-old man with anemia

E. A urinalysis in a 67-year-old woman with diabetes

The best answer is C (pregnancy test); an ECG in the 71-year-old man would be less useful (see below). The remaining choices—chest radiograph, prothrombin time, and urinalysis—are even less appropriate. A chest radiograph in an asthmatic patient is not likely to yield more information than what is obtained from the history and physical exam. Patients with anemia are not likely to have abnormal coagulation, and the role of urinalysis in detecting glucose and protein in asymptomatic diabetic patients is limited.

Routine pregnancy testing is justifiable

There are a number of reasons to justify a low threshold for preoperative pregnancy testing¹⁰:

• Patients, especially adolescents, are often unreliable in suspecting that they might be pregnant (in several studies of routine preoperative pregnancy screening, 0.3% to 2.2% of tests were positive)
• History and physical examination are often insufficient to determine early pregnancy
• Management usually changes if it is discovered that a patient is pregnant.

Using the four criteria from Table 1, pregnancy testing rates high as a useful test: it would identify “abnormality,” it would determine a diagnosis, and it would likely change management.

Routine ECG has limited utility

In contrast, routine preoperative ECG is not well supported. A recent study from the Netherlands assessed the added value of a preoperative ECG in predicting myocardial infarction and death following noncardiac surgery among 2,422 patients older than age 50 years.¹² It showed that ECG findings were no more predictive of complications than findings from the history and physical examination and the patient’s activity level.

From our own data at Brigham and Women’s Hospital,¹³ we found that the presence of any of the following six risk factors predicted all but 0.44% of ECG abnormalities in patients aged 50 years or older presenting for preoperative evaluation:

• Age greater than 65 years
• Congestive heart failure
• High cholesterol
• Angina
• Myocardial infarction
• Severe valvular disease.

The 2007 guidelines on perioperative risk assessment from the American College of Cardiology and American Heart Association (ACC/AHA) do not consider ECG to be indicated in asymptomatic patients undergoing low-risk noncardiac procedures regardless of patient age,¹⁴ like the 71-year-old man with hypertension in the above case question. These guidelines also state that evidence for routine ECG orders is not well established in patients with at least one clinical risk factor undergoing intermediate-risk procedures.

The aforementioned ASA practice advisory acknowledges that the likelihood of ECG abnormalities rises with increasing patient age, but the ASA was unable to reach consensus on a minimum age for routinely ordering an ECG in surgical candidates.¹⁰ The advisory recommends taking into account other factors, such as cardiac risk factors, the presence of cardiocirculatory or respiratory disease, and the type and invasiveness of the surgical procedure.¹⁰ 

In recommendations not specific to the perioperative setting, the US Preventive Services Task Force advises against routine screening for coronary heart disease with ECG or exercise treadmill testing.¹⁵ It gives routine screening a “D” recommendation, indicating that risk is greater than benefit because of the potential for unnecessary invasive procedures, overtreatment, and mislabeling of patients.

Our group at Brigham and Women’s Hospital recently surveyed anesthesiology program directors at US teaching hospitals to determine their preoperative test-ordering practices.¹⁶ Among the 75 respondents (58% response rate), 95% said their institutions have no requirements for ordering ECGs unless indicated based on age, history, or surgery type; 71% said their institutions have age-based requirements for ordering ECGs (usually > 50 years). Most respondents reported that their institutions are ordering fewer ECGs since the publication of the 2007 ACC/AHA guidelines on perioperative evaluation.

Whether or not age should be used as a criterion for ECG testing is controversial, and editorials on this subject abound.^17–19 They point out that clinicians must be careful before abandoning routine ECGs in elderly patients, for several reasons:

• An abnormal ECG (or abnormal lab test results) may modify a patient’s ASA classification (which is predictive of complications)
• At least one-quarter of myocardial infarctions in elderly persons are “silent” or clinically unrecognized
• A preoperative ECG provides a useful baseline if the patient should develop ECG changes, chest pain, or cardiac complications during the perioperative period.

Most institutions use age as a criterion for ordering tests, especially for ECGs. If such a policy is used, a threshold of 60 years or older is probably most appropriate. However, a patient with good functional capacity who is undergoing a low-risk procedure does not need cardiac testing.^14,20

An additional consideration is cost. Although the cost of a single ECG is modest, the cumulative cost of preoperative ECGs for all older surgical patients is significant over the course of a year. Because the Centers for Medicare and Medicaid Services (CMS) no longer cover routine preoperative ECGs, routine testing can be very costly to an institution over time.

 

 

COST AND REGULATORY BENEFITS OF PREOPERATIVE CENTERS

Preoperative evaluation centers tend to be cost-effective, as they keep consultations and redundant provider interviews to a minimum, encourage more appropriate targeting of tests, and help to avoid last-minute operating room delays and cancellations.^21,22 They also provide an efficient means of compiling the chart for the operating room.

The merits of standardization

Preoperative evaluation centers likewise encourage more standardized preoperative assessment, which can facilitate compliance with surgical quality measures such as those from the National Surgical Quality Improvement Program and the Leapfrog Group. Standardization also fosters more efficient and consistent regulatory documentation, making it easier to follow requirements from CMS (often linked to reimbursement) and the Joint Commission. It also tends to improve reimbursement by encouraging more appropriate coding under CMS’ diagnosis-related group (DRG) system to indicate that whatever testing is ordered is related to the surgical diagnosis or to relevant comorbidities.

No excessive dictates from Joint Commission or CMS

Contrary to what many believe, the Joint Commission does not require excessive preoperative testing. The Joint Commission has no mandate for routine diagnostic tests but requires only what is necessary for determining a patient’s health care needs.²³

CMS provides no guidance as to what to do or not do in a preoperative assessment, but it does not reimburse for routine screening tests or for age-based testing.²⁴ Reimbursement for a preoperative ECG, for example, requires documentation of the patient’s signs or symptoms; for an ECG that is indicated, reimbursement includes review and interpretation by the physician.²⁵

A new partner for proper preoperative assessment

Appropriate preoperative evaluation and testing is one of the goals promoted by the recently formed Society for Perioperative Assessment and Quality Improvement (SPAQI). The mission of this international nonprofit organization is to optimize surgical outcomes by sharing best practices and promoting research and communication among health professionals across multiple disciplines. More information is available at www.spaqi.org.

DISCUSSION

Question from the audience: At my hospital, we teach residents about limiting the preoperative tests they order, but surgeons routinely expect many of these tests, including chest x-rays in patients with pulmonary conditions. Are any surgical societies involved in efforts to reduce preoperative testing? Or are surgical societies’ recommendations actually driving some of the unnecessary testing?

Dr. Hepner: I’m not aware of recommendations from surgical societies regarding preoperative testing. Many surgeons believe that the more testing that’s done, the likelier they are to uncover an occult disease. They also often want baseline information, which may actually be warranted in some cases.

Question from the audience: If you’re already ordering a “type and screen” or “type and hold” for a patient, isn’t it worthwhile to just add on a CBC? The patient is already getting the phlebotomy, so isn’t there a cost benefit to getting other routine tests done at the same time rather than calling the patient back for more tests if another indication arises?

Dr. Hepner: Charges are generally assessed for each individual test, not for drawing blood, so I would only get the tests that are indicated.

Question from the audience: In institutions without a preoperative clinic, sometimes the surgeons do the work-up without discussing the case with the primary doctor, and the surgeons want an ECG so that the case isn’t cancelled at the last minute. Can you give straightforward criteria in such cases, such as an age threshold, or would you not order an ECG for anyone?

Dr. Hepner: Based on our most recent data, 60 years seems to be a reasonable cutoff if you are going to use age as a criterion.

Question from the audience: What criteria do you use for preoperative screening with pregnancy tests?

Dr. Hepner: If you have an unreliable patient population, general screening should be done. We don’t have such a requirement, but we have a very low threshold. If a patient appears very reliable, knowing the exact date of her last menstrual period, we’ll go by that. If a patient is unsure, we’ll do a pregnancy test.

Question from the audience: My hospital doesn’t have a preoperative clinic, and until recently, the anesthesiology department has helped surgeons with ordering of pre­operative tests. We followed a guideline protocol for about 20 years. Now the newer surgeons say they don’t want to be responsible for abnormal test results. Yet we anesthesiologists aren’t seeing the patients, so we can’t use clinical judgment; we can only go by the guidelines. The surgeons are the only physicians on the case who actually do the history and physical exam. So who should sign the test orders and be responsible for abnormal results?

Dr. Hepner: In our preoperative test center, we tell the surgical team that if they are uncertain about which tests to order, we will handle it. And if we order a test, we follow up on the results. You must ensure that orders are signed and not rubber-stamped; that way, the person who orders a test will get called with any abnormal results. If you order it, you own it.

Question from the audience: I agree that no testing is needed for the 72-year-old man you presented who was undergoing surgery for inguinal hernia, but it always worries me not to do an ECG since part of the standard of care for anesthesia is intraoperative ECG monitoring. If we see some sort of unusual arrhythmia when we take the patient in, we might cancel the case if we don’t know whether it was present at baseline. Surgeons will ask me, “Why didn’t you order a baseline if you’re going to monitor the ECG in the operating room? If you’re not going to order a baseline, then why monitor the ECG?” These are medicolegal issues that I haven’t seen addressed.

Dr. Hepner: A case like you describe will be addressed in the upcoming medicolegal session (see page S119). You make a good point that many times just having a baseline is helpful, but I would argue that it is more helpful for intermediate- or high-risk cases.

Perioperative fluid management remains controversial. Until recently, fluid management was guided by targets such as urine output, static pressures, blood pressure, and other physiologic variables. Such physiologic signs, however, are inadequate for detecting subclinical hypovolemia. This has prompted the emergence of an approach to fluid administration based on stroke volume and cardiac output—a “flow-guided” approach—designed to overcome the inadequacies of conventional physiologic signs and improve outcomes. Recent technological advances are permitting noninvasive guidance of intravenous fluid therapy to optimize intravascular volume status.

This article reviews the rationale for perioperative fluid management, strategies for perioperative fluid therapy and their associated outcomes, the types of volume expanders used, and considerations for improving perioperative fluid administration.

WHY FLUID MANAGEMENT MATTERS

Postoperative complications predict survival

In 2005, Khuri et al published a study of survival after major surgery that starkly illustrated the prognostic importance of postoperative complications.¹ In an effort to identify predictors of long-term survival, they analyzed a National Surgical Quality Improvement Program database of 105,951 patients who underwent eight common operations at Veterans Administration facilities. They found that the most important determinant of reduced postoperative survival over 8 years of follow-up was the occurrence of a complication within 30 days after surgery. The presence of a postoperative complication was a stronger predictor of death than any intraoperative or preoperative risk factor.

Fluid management is key to preventing complications

Optimizing perioperative fluid management is essential to reducing the risk of postoperative complications and mortality. Surgical patients are more likely to have serious complications and die if they have limited physiologic reserve. Adequate fluid administration may reduce the stress response to surgical trauma and support recovery.

Building on early work showing that survivors of major surgery have consistently higher postoperative cardiac output and oxygen delivery (DO₂) than do nonsurvivors,^2,3 a seminal study by Shoemaker et al showed that these types of blood flow–related parameters are predictive of both survival and complication-free survival.⁴ Specifically, Shoemaker and his team showed that a protocol designed to achieve DO₂ of at least 600 mL/min/m² was associated with reductions in both postoperative complications and death.⁴

PROBLEMS WITH PERIOPERATIVE FLUID THERAPY―AND EFFORTS TO OVERCOME THEM

Despite the utility of fluid management in reducing postoperative complications, perioperative fluid therapy is fraught with several fundamental problems:

• Blood volume cannot be evaluated accurately.
• Fluid overload cannot be identified accurately, apart from tissue edema as a result of gross fluid overload.
• Hypovolemia cannot be identified accurately. Commonly measured variables (heart rate, blood pressure, base excess, lactate) are late markers, and the patient’s status upon admission to the operating room is often unknown.
• Tissue perfusion cannot be evaluated accurately. Although lactate and venous oxygen saturation are surrogate markers, genuinely accurate markers for tissue perfusion are lacking.

For these reasons, fluids are commonly administered without the guidance of direct markers of fluid status.

Assessing flow-guided fluid therapy

These shortcomings prompted me and several other researchers to assess the evidence regarding a flow-guided approach to fluid administration, which aims to achieve maximal cardiac output and stroke volume while avoiding excess fluid administration. We conducted a systematic literature search for randomized controlled trials evaluating the postsurgical effects of perioperative fluid therapy to increase global blood flow to explicitly defined goals, after which we performed a meta-analysis of the 22 qualifying studies.⁵ The trials collectively included 4,546 patients undergoing relatively high-risk elective or emergency surgery, consisting of general, vascular, cardiac, orthopedic, and urologic procedures. Overall mortality in these trials was 10.6% (481 deaths). The primary outcome assessed was mortality; secondary outcomes included morbidity and length of stay in the hospital and in the intensive care unit. Outcomes were assessed according to the timing of the intervention, the fluid type, and explicit measured goals. Fluids were given to all patients, usually as a dynamic bolus, using a flow-guided approach above and beyond that of the control group.

Our analysis found that a flow-guided protocol was associated with a significant reduction in mortality compared with control protocols (odds ratio = 0.82 [95% CI, 0.67–0.99]; P = .04).⁵ However, sensitivity analysis showed that the largest and best-designed studies tended to yield no significant differences in mortality between the groups, which highlights the remaining need for larger studies to more definitively clarify the effect on mortality.

Timing of administration (ie, whether fluid was given pre-, intra-, or postoperatively) influenced the primary outcome: compared with control, flow-guided fluid therapy was associated with a significant reduction in mortality only when administered intraoperatively, but not when given preoperatively or postoperatively.⁵

Length of hospital stay was reduced by approximately 1.6 days with flow-guided therapy compared with control (P < .00001), but there was no significant difference between approaches in terms of intensive care unit stay.⁵

Postoperative complication rates are difficult to compare, given the lack of a uniform definition of a complication and the relative importance of different complications. Nevertheless, when grouped as a whole, the rate of complications was 48% lower (P < .00001) with flow-guided therapy compared with control. Of all outcomes assessed, the effect on complications was the most consistent among all the studies in the analysis. To provide an example using one easily defined complication, the incidence of renal failure was reduced by 35% with flow-guided therapy compared with control (P = .002).⁵

COLLOID OR CRYSTALLOID?

Two pharmacologically distinct classes

Intravenous fluids can be broadly classified into colloid and crystalloid solutions, and the relative merits of these two fluid classes are at the center of an enduring debate that predates the advent of flow-based fluid administration. Despite fundamental differences in their pharmacokinetics and other characteristics, colloids and crystalloids are often not sufficiently distinguished from one another in discussions of perioperative fluid therapy.

The effect of a colloid depends on its molecular weight. Ninety minutes following administration, a significant proportion of a colloid with a high molecular weight (eg, hydroxyethyl starch) will be retained in the circulation. In contrast, crystalloid solutions (eg, 0.9% saline) readily disappear from the circulation, owing to the ease with which they travel across the cell membrane.⁶

No evidence of outcome differences

A systematic literature review by Choi et al reflects the current state of knowledge on the relative effects of colloids and crystalloids for fluid resuscitation.⁷ It concluded that there are no apparent differences between these fluid classes in their effects on pulmonary edema, mortality, or length of stay. The authors noted that methodologic limitations of the available comparative studies prevent meaningful conclusions and that larger randomized controlled trials are needed to detect any differences in outcomes between the two classes.

Although using a crystalloid for fluid resuscitation probably results in a greater volume of fluid given, a study known as SAFE (Saline versus Albumin Fluid Evaluation),⁸ published after the Choi analysis, showed no differences in 28-day all-cause mortality or other significant outcomes between patients randomized to the colloid (4% albumin) and those assigned to the crystalloid (0.9% saline). Patients receiving the colloid had a higher central venous pressure at all time points, a lower heart rate at the end of the first day, and less overall volume on days 1 and 2 compared with patients receiving the crystalloid. While SAFE was conducted in critically ill patients, these physiologic advantages of the colloid may have implications for results in the perioperative arena, although this remains speculative.

 

 

INTRAOPERATIVE MONITORING TO OPTIMIZE FLUID THERAPY

Another important issue is the emergence of minimally invasive technologies for monitoring hemodynamic measures intraoperatively. The aim is to enable more precise tailoring of fluid therapy to meet patient needs on a case-by-case basis.

One of the simplest of these techniques is esophageal Doppler monitoring to measure descending aortic blood flow using Doppler ultrasonography. The technique is used to titrate repeated boluses of fluid based on continuous estimations of stroke volume and surrogate markers of preload indices. Typical protocols for esophageal Doppler monitoring call for administration of colloid to maintain a descending thoracic corrected flow time of no more than 0.35 seconds and stroke volume increments of 10%.

Phan et al recently published a meta-analysis to assess the effect of intraoperative esophageal Doppler monitoring in guiding fluid therapy to optimize intravascular volume status.⁹ The analysis, which included nine randomized controlled trials in a total of 920 patients, found statistically significant reductions in the rate of complications and in length of hospital stay with the use of esophageal Doppler monitoring; there was no difference in mortality. Use of Doppler monitoring was associated with an increase (+671 mL) in the volume of colloid administered and a decrease (–156 mL) in the volume of crystalloid.

Timing of fluid administration can be critical

One of the trials in the above meta-analysis illustrated that the timing of fluid administration might be more critical than the volume of fluid given. Noblett et al placed an esophageal Doppler probe in each of a series of 108 patients undergoing colorectal resection;¹⁰ the control group received perioperative fluid at the anesthesiologist’s discretion, whereas the intervention group received additional colloid boluses based on Doppler assessment. While the overall volume of colloid given was comparable between the two groups, the intervention group received nearly 100% of the total volume during the first quarter of surgery. The intervention group had significantly fewer postoperative complications than the control group as well as a 2-day reduction in average length of stay. Circulating levels of interleukin-6 and cytokines also were significantly lower in the intervention group, which suggests that the intervention blunted the inflammatory response to surgery.

Fluid management must be individualized

Intraoperative fluid needs are highly variable and patient-specific. Parker et al tested an approach in which they universally administered 500 mL of a gelatin colloid solution prior to hip fracture surgery and compared it with a conventional intravenous saline crystalloid solution; neither approach used invasive intraoperative monitoring.¹¹ They found no significant difference in length of stay, 30-day mortality, or postoperative complications between the two study arms. They concluded that more invasive investigation of patients before or during surgery may have been able to identify a subgroup in whom the colloid therapy or more precise fluid control would have been beneficial.

THE ROAD AHEAD

Fluid management remains suboptimal

Despite being a fundamental component of surgical and perioperative care, fluid management remains suboptimal in clinical practice. I can speak most directly to the practice of fluid management in the United Kingdom (UK), but the same types of shortcomings apply broadly to the United States as well.

In 1999, the UK’s National Confidential Enquiry into Patient Outcome and Death examined perioperative death in the UK, concluding that patients were dying as a result of too much or too little perioperative fluid administration.¹² Their report cited staff inexperience as an important contributor to the problem, as junior physicians order and deliver the majority of postoperative fluid regimens.

This cautionary report from 10 years ago appears not to have produced substantial improvements in practice, at least according to a recent study by Walsh et al.¹³ These researchers prospectively audited postoperative fluid management practices in 106 consecutive patients undergoing laparotomy in a UK general surgical unit over a 6-month period in 2003. They found no correlation between available fluid balance data and the quantities of fluids prescribed, suggesting that physicians routinely ignore such data when prescribing. Fifty-four percent of the patients developed at least one fluid-related complication. Patients routinely received significantly greater amounts of fluid and sodium than were physiologically needed, and multivariate analysis showed that mean daily fluid load predicted development of fluid-related complications.

Guidance from a new British consensus document

Where can clinicians turn for a good synthesis of current evidence to guide better perioperative fluid management? I would recommend the newly released British Consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical Patients,¹⁴ which are available on the Evidence Based Peri-Operative Medicine Web site (http://www.ebpom.org). These guidelines were developed by a multidisciplinary team of clinicians to improve perioperative fluid prescribing. They cover principles of preoperative, intraoperative, and postoperative fluid management, as well as fluid therapy in acute kidney injury. They pre­sent 28 recommendations in all, at least 12 of which are based on high-level (grade 1a or 1b) evidence.

DISCUSSION

Question from the audience: What is the relationship between perioperative fluid management, gut edema from perioperative fluid use, and postoperative ileus?

Dr. Hamilton: There’s no easy answer. Excessive administration of sodium and fluid does predispose to gut and tissue fluid edema. Many of the enhanced surgery recovery programs require no preoperative fasting. There’s no bowel prep. The enteral route is used primarily as quickly as possible. In the UK, we no longer use nasogastric tubes for many of those programs. But there’s no doubt that tissue edema still occurs with excess fluid therapy.

The premise for individualizing fluid therapy is that less is not more but that more is not the right approach either. The stroke volume approaches or the corrected flow time approaches have been related to return of gastrointestinal function and return of flatus, which is a function of gastrointestinal recovery.

Question from the audience: Can you comment on the perioperative use of the Swan-Ganz catheter for fluid management?

Dr. Hamilton: I don’t use it intraoperatively, and not many hospitals in the UK use it apart from liver resection surgery. Having said that, Swan-Ganz catheters were the predominant monitor for 30% to 40% of the original studies of hemodynamic optimization. I cannot give you intraoperative data to support the use of Swan-Ganz catheters for monitoring, but if you lift evidence from the other methods of monitoring hemodynamics, if you’re optimizing flow in a bolus and dynamic fashion, then you should see the kinds of improvements in outcomes that are associated with the other modalities.

The drawback with the Swan-Ganz catheter, obviously, is the morbidity associated with its insertion and its interpretation. But if you’re confident in doing those things, I think it’s a perfectly good monitor.

Perioperative fluid management remains controversial. Until recently, fluid management was guided by targets such as urine output, static pressures, blood pressure, and other physiologic variables. Such physiologic signs, however, are inadequate for detecting subclinical hypovolemia. This has prompted the emergence of an approach to fluid administration based on stroke volume and cardiac output—a “flow-guided” approach—designed to overcome the inadequacies of conventional physiologic signs and improve outcomes. Recent technological advances are permitting noninvasive guidance of intravenous fluid therapy to optimize intravascular volume status.

This article reviews the rationale for perioperative fluid management, strategies for perioperative fluid therapy and their associated outcomes, the types of volume expanders used, and considerations for improving perioperative fluid administration.

WHY FLUID MANAGEMENT MATTERS

Postoperative complications predict survival

In 2005, Khuri et al published a study of survival after major surgery that starkly illustrated the prognostic importance of postoperative complications.¹ In an effort to identify predictors of long-term survival, they analyzed a National Surgical Quality Improvement Program database of 105,951 patients who underwent eight common operations at Veterans Administration facilities. They found that the most important determinant of reduced postoperative survival over 8 years of follow-up was the occurrence of a complication within 30 days after surgery. The presence of a postoperative complication was a stronger predictor of death than any intraoperative or preoperative risk factor.

Fluid management is key to preventing complications

Optimizing perioperative fluid management is essential to reducing the risk of postoperative complications and mortality. Surgical patients are more likely to have serious complications and die if they have limited physiologic reserve. Adequate fluid administration may reduce the stress response to surgical trauma and support recovery.

Building on early work showing that survivors of major surgery have consistently higher postoperative cardiac output and oxygen delivery (DO₂) than do nonsurvivors,^2,3 a seminal study by Shoemaker et al showed that these types of blood flow–related parameters are predictive of both survival and complication-free survival.⁴ Specifically, Shoemaker and his team showed that a protocol designed to achieve DO₂ of at least 600 mL/min/m² was associated with reductions in both postoperative complications and death.⁴

PROBLEMS WITH PERIOPERATIVE FLUID THERAPY―AND EFFORTS TO OVERCOME THEM

Despite the utility of fluid management in reducing postoperative complications, perioperative fluid therapy is fraught with several fundamental problems:

• Blood volume cannot be evaluated accurately.
• Fluid overload cannot be identified accurately, apart from tissue edema as a result of gross fluid overload.
• Hypovolemia cannot be identified accurately. Commonly measured variables (heart rate, blood pressure, base excess, lactate) are late markers, and the patient’s status upon admission to the operating room is often unknown.
• Tissue perfusion cannot be evaluated accurately. Although lactate and venous oxygen saturation are surrogate markers, genuinely accurate markers for tissue perfusion are lacking.

For these reasons, fluids are commonly administered without the guidance of direct markers of fluid status.

Assessing flow-guided fluid therapy

These shortcomings prompted me and several other researchers to assess the evidence regarding a flow-guided approach to fluid administration, which aims to achieve maximal cardiac output and stroke volume while avoiding excess fluid administration. We conducted a systematic literature search for randomized controlled trials evaluating the postsurgical effects of perioperative fluid therapy to increase global blood flow to explicitly defined goals, after which we performed a meta-analysis of the 22 qualifying studies.⁵ The trials collectively included 4,546 patients undergoing relatively high-risk elective or emergency surgery, consisting of general, vascular, cardiac, orthopedic, and urologic procedures. Overall mortality in these trials was 10.6% (481 deaths). The primary outcome assessed was mortality; secondary outcomes included morbidity and length of stay in the hospital and in the intensive care unit. Outcomes were assessed according to the timing of the intervention, the fluid type, and explicit measured goals. Fluids were given to all patients, usually as a dynamic bolus, using a flow-guided approach above and beyond that of the control group.

Our analysis found that a flow-guided protocol was associated with a significant reduction in mortality compared with control protocols (odds ratio = 0.82 [95% CI, 0.67–0.99]; P = .04).⁵ However, sensitivity analysis showed that the largest and best-designed studies tended to yield no significant differences in mortality between the groups, which highlights the remaining need for larger studies to more definitively clarify the effect on mortality.

Timing of administration (ie, whether fluid was given pre-, intra-, or postoperatively) influenced the primary outcome: compared with control, flow-guided fluid therapy was associated with a significant reduction in mortality only when administered intraoperatively, but not when given preoperatively or postoperatively.⁵

Length of hospital stay was reduced by approximately 1.6 days with flow-guided therapy compared with control (P < .00001), but there was no significant difference between approaches in terms of intensive care unit stay.⁵

Postoperative complication rates are difficult to compare, given the lack of a uniform definition of a complication and the relative importance of different complications. Nevertheless, when grouped as a whole, the rate of complications was 48% lower (P < .00001) with flow-guided therapy compared with control. Of all outcomes assessed, the effect on complications was the most consistent among all the studies in the analysis. To provide an example using one easily defined complication, the incidence of renal failure was reduced by 35% with flow-guided therapy compared with control (P = .002).⁵

COLLOID OR CRYSTALLOID?

Two pharmacologically distinct classes

Intravenous fluids can be broadly classified into colloid and crystalloid solutions, and the relative merits of these two fluid classes are at the center of an enduring debate that predates the advent of flow-based fluid administration. Despite fundamental differences in their pharmacokinetics and other characteristics, colloids and crystalloids are often not sufficiently distinguished from one another in discussions of perioperative fluid therapy.

The effect of a colloid depends on its molecular weight. Ninety minutes following administration, a significant proportion of a colloid with a high molecular weight (eg, hydroxyethyl starch) will be retained in the circulation. In contrast, crystalloid solutions (eg, 0.9% saline) readily disappear from the circulation, owing to the ease with which they travel across the cell membrane.⁶

No evidence of outcome differences

A systematic literature review by Choi et al reflects the current state of knowledge on the relative effects of colloids and crystalloids for fluid resuscitation.⁷ It concluded that there are no apparent differences between these fluid classes in their effects on pulmonary edema, mortality, or length of stay. The authors noted that methodologic limitations of the available comparative studies prevent meaningful conclusions and that larger randomized controlled trials are needed to detect any differences in outcomes between the two classes.

Although using a crystalloid for fluid resuscitation probably results in a greater volume of fluid given, a study known as SAFE (Saline versus Albumin Fluid Evaluation),⁸ published after the Choi analysis, showed no differences in 28-day all-cause mortality or other significant outcomes between patients randomized to the colloid (4% albumin) and those assigned to the crystalloid (0.9% saline). Patients receiving the colloid had a higher central venous pressure at all time points, a lower heart rate at the end of the first day, and less overall volume on days 1 and 2 compared with patients receiving the crystalloid. While SAFE was conducted in critically ill patients, these physiologic advantages of the colloid may have implications for results in the perioperative arena, although this remains speculative.

 

 

INTRAOPERATIVE MONITORING TO OPTIMIZE FLUID THERAPY

Another important issue is the emergence of minimally invasive technologies for monitoring hemodynamic measures intraoperatively. The aim is to enable more precise tailoring of fluid therapy to meet patient needs on a case-by-case basis.

One of the simplest of these techniques is esophageal Doppler monitoring to measure descending aortic blood flow using Doppler ultrasonography. The technique is used to titrate repeated boluses of fluid based on continuous estimations of stroke volume and surrogate markers of preload indices. Typical protocols for esophageal Doppler monitoring call for administration of colloid to maintain a descending thoracic corrected flow time of no more than 0.35 seconds and stroke volume increments of 10%.

Phan et al recently published a meta-analysis to assess the effect of intraoperative esophageal Doppler monitoring in guiding fluid therapy to optimize intravascular volume status.⁹ The analysis, which included nine randomized controlled trials in a total of 920 patients, found statistically significant reductions in the rate of complications and in length of hospital stay with the use of esophageal Doppler monitoring; there was no difference in mortality. Use of Doppler monitoring was associated with an increase (+671 mL) in the volume of colloid administered and a decrease (–156 mL) in the volume of crystalloid.

Timing of fluid administration can be critical

One of the trials in the above meta-analysis illustrated that the timing of fluid administration might be more critical than the volume of fluid given. Noblett et al placed an esophageal Doppler probe in each of a series of 108 patients undergoing colorectal resection;¹⁰ the control group received perioperative fluid at the anesthesiologist’s discretion, whereas the intervention group received additional colloid boluses based on Doppler assessment. While the overall volume of colloid given was comparable between the two groups, the intervention group received nearly 100% of the total volume during the first quarter of surgery. The intervention group had significantly fewer postoperative complications than the control group as well as a 2-day reduction in average length of stay. Circulating levels of interleukin-6 and cytokines also were significantly lower in the intervention group, which suggests that the intervention blunted the inflammatory response to surgery.

Fluid management must be individualized

Intraoperative fluid needs are highly variable and patient-specific. Parker et al tested an approach in which they universally administered 500 mL of a gelatin colloid solution prior to hip fracture surgery and compared it with a conventional intravenous saline crystalloid solution; neither approach used invasive intraoperative monitoring.¹¹ They found no significant difference in length of stay, 30-day mortality, or postoperative complications between the two study arms. They concluded that more invasive investigation of patients before or during surgery may have been able to identify a subgroup in whom the colloid therapy or more precise fluid control would have been beneficial.

THE ROAD AHEAD

Fluid management remains suboptimal

Despite being a fundamental component of surgical and perioperative care, fluid management remains suboptimal in clinical practice. I can speak most directly to the practice of fluid management in the United Kingdom (UK), but the same types of shortcomings apply broadly to the United States as well.

In 1999, the UK’s National Confidential Enquiry into Patient Outcome and Death examined perioperative death in the UK, concluding that patients were dying as a result of too much or too little perioperative fluid administration.¹² Their report cited staff inexperience as an important contributor to the problem, as junior physicians order and deliver the majority of postoperative fluid regimens.

This cautionary report from 10 years ago appears not to have produced substantial improvements in practice, at least according to a recent study by Walsh et al.¹³ These researchers prospectively audited postoperative fluid management practices in 106 consecutive patients undergoing laparotomy in a UK general surgical unit over a 6-month period in 2003. They found no correlation between available fluid balance data and the quantities of fluids prescribed, suggesting that physicians routinely ignore such data when prescribing. Fifty-four percent of the patients developed at least one fluid-related complication. Patients routinely received significantly greater amounts of fluid and sodium than were physiologically needed, and multivariate analysis showed that mean daily fluid load predicted development of fluid-related complications.

Guidance from a new British consensus document

Where can clinicians turn for a good synthesis of current evidence to guide better perioperative fluid management? I would recommend the newly released British Consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical Patients,¹⁴ which are available on the Evidence Based Peri-Operative Medicine Web site (http://www.ebpom.org). These guidelines were developed by a multidisciplinary team of clinicians to improve perioperative fluid prescribing. They cover principles of preoperative, intraoperative, and postoperative fluid management, as well as fluid therapy in acute kidney injury. They pre­sent 28 recommendations in all, at least 12 of which are based on high-level (grade 1a or 1b) evidence.

DISCUSSION

Question from the audience: What is the relationship between perioperative fluid management, gut edema from perioperative fluid use, and postoperative ileus?

Dr. Hamilton: There’s no easy answer. Excessive administration of sodium and fluid does predispose to gut and tissue fluid edema. Many of the enhanced surgery recovery programs require no preoperative fasting. There’s no bowel prep. The enteral route is used primarily as quickly as possible. In the UK, we no longer use nasogastric tubes for many of those programs. But there’s no doubt that tissue edema still occurs with excess fluid therapy.

The premise for individualizing fluid therapy is that less is not more but that more is not the right approach either. The stroke volume approaches or the corrected flow time approaches have been related to return of gastrointestinal function and return of flatus, which is a function of gastrointestinal recovery.

Question from the audience: Can you comment on the perioperative use of the Swan-Ganz catheter for fluid management?

Dr. Hamilton: I don’t use it intraoperatively, and not many hospitals in the UK use it apart from liver resection surgery. Having said that, Swan-Ganz catheters were the predominant monitor for 30% to 40% of the original studies of hemodynamic optimization. I cannot give you intraoperative data to support the use of Swan-Ganz catheters for monitoring, but if you lift evidence from the other methods of monitoring hemodynamics, if you’re optimizing flow in a bolus and dynamic fashion, then you should see the kinds of improvements in outcomes that are associated with the other modalities.

The drawback with the Swan-Ganz catheter, obviously, is the morbidity associated with its insertion and its interpretation. But if you’re confident in doing those things, I think it’s a perfectly good monitor.

Perioperative fluid management remains controversial. Until recently, fluid management was guided by targets such as urine output, static pressures, blood pressure, and other physiologic variables. Such physiologic signs, however, are inadequate for detecting subclinical hypovolemia. This has prompted the emergence of an approach to fluid administration based on stroke volume and cardiac output—a “flow-guided” approach—designed to overcome the inadequacies of conventional physiologic signs and improve outcomes. Recent technological advances are permitting noninvasive guidance of intravenous fluid therapy to optimize intravascular volume status.

This article reviews the rationale for perioperative fluid management, strategies for perioperative fluid therapy and their associated outcomes, the types of volume expanders used, and considerations for improving perioperative fluid administration.

WHY FLUID MANAGEMENT MATTERS

Postoperative complications predict survival

In 2005, Khuri et al published a study of survival after major surgery that starkly illustrated the prognostic importance of postoperative complications.¹ In an effort to identify predictors of long-term survival, they analyzed a National Surgical Quality Improvement Program database of 105,951 patients who underwent eight common operations at Veterans Administration facilities. They found that the most important determinant of reduced postoperative survival over 8 years of follow-up was the occurrence of a complication within 30 days after surgery. The presence of a postoperative complication was a stronger predictor of death than any intraoperative or preoperative risk factor.

Fluid management is key to preventing complications

Optimizing perioperative fluid management is essential to reducing the risk of postoperative complications and mortality. Surgical patients are more likely to have serious complications and die if they have limited physiologic reserve. Adequate fluid administration may reduce the stress response to surgical trauma and support recovery.

Building on early work showing that survivors of major surgery have consistently higher postoperative cardiac output and oxygen delivery (DO₂) than do nonsurvivors,^2,3 a seminal study by Shoemaker et al showed that these types of blood flow–related parameters are predictive of both survival and complication-free survival.⁴ Specifically, Shoemaker and his team showed that a protocol designed to achieve DO₂ of at least 600 mL/min/m² was associated with reductions in both postoperative complications and death.⁴

PROBLEMS WITH PERIOPERATIVE FLUID THERAPY―AND EFFORTS TO OVERCOME THEM

Despite the utility of fluid management in reducing postoperative complications, perioperative fluid therapy is fraught with several fundamental problems:

• Blood volume cannot be evaluated accurately.
• Fluid overload cannot be identified accurately, apart from tissue edema as a result of gross fluid overload.
• Hypovolemia cannot be identified accurately. Commonly measured variables (heart rate, blood pressure, base excess, lactate) are late markers, and the patient’s status upon admission to the operating room is often unknown.
• Tissue perfusion cannot be evaluated accurately. Although lactate and venous oxygen saturation are surrogate markers, genuinely accurate markers for tissue perfusion are lacking.

For these reasons, fluids are commonly administered without the guidance of direct markers of fluid status.

Assessing flow-guided fluid therapy

These shortcomings prompted me and several other researchers to assess the evidence regarding a flow-guided approach to fluid administration, which aims to achieve maximal cardiac output and stroke volume while avoiding excess fluid administration. We conducted a systematic literature search for randomized controlled trials evaluating the postsurgical effects of perioperative fluid therapy to increase global blood flow to explicitly defined goals, after which we performed a meta-analysis of the 22 qualifying studies.⁵ The trials collectively included 4,546 patients undergoing relatively high-risk elective or emergency surgery, consisting of general, vascular, cardiac, orthopedic, and urologic procedures. Overall mortality in these trials was 10.6% (481 deaths). The primary outcome assessed was mortality; secondary outcomes included morbidity and length of stay in the hospital and in the intensive care unit. Outcomes were assessed according to the timing of the intervention, the fluid type, and explicit measured goals. Fluids were given to all patients, usually as a dynamic bolus, using a flow-guided approach above and beyond that of the control group.

Our analysis found that a flow-guided protocol was associated with a significant reduction in mortality compared with control protocols (odds ratio = 0.82 [95% CI, 0.67–0.99]; P = .04).⁵ However, sensitivity analysis showed that the largest and best-designed studies tended to yield no significant differences in mortality between the groups, which highlights the remaining need for larger studies to more definitively clarify the effect on mortality.

Timing of administration (ie, whether fluid was given pre-, intra-, or postoperatively) influenced the primary outcome: compared with control, flow-guided fluid therapy was associated with a significant reduction in mortality only when administered intraoperatively, but not when given preoperatively or postoperatively.⁵

Length of hospital stay was reduced by approximately 1.6 days with flow-guided therapy compared with control (P < .00001), but there was no significant difference between approaches in terms of intensive care unit stay.⁵

Postoperative complication rates are difficult to compare, given the lack of a uniform definition of a complication and the relative importance of different complications. Nevertheless, when grouped as a whole, the rate of complications was 48% lower (P < .00001) with flow-guided therapy compared with control. Of all outcomes assessed, the effect on complications was the most consistent among all the studies in the analysis. To provide an example using one easily defined complication, the incidence of renal failure was reduced by 35% with flow-guided therapy compared with control (P = .002).⁵

COLLOID OR CRYSTALLOID?

Two pharmacologically distinct classes

Intravenous fluids can be broadly classified into colloid and crystalloid solutions, and the relative merits of these two fluid classes are at the center of an enduring debate that predates the advent of flow-based fluid administration. Despite fundamental differences in their pharmacokinetics and other characteristics, colloids and crystalloids are often not sufficiently distinguished from one another in discussions of perioperative fluid therapy.

The effect of a colloid depends on its molecular weight. Ninety minutes following administration, a significant proportion of a colloid with a high molecular weight (eg, hydroxyethyl starch) will be retained in the circulation. In contrast, crystalloid solutions (eg, 0.9% saline) readily disappear from the circulation, owing to the ease with which they travel across the cell membrane.⁶

No evidence of outcome differences

A systematic literature review by Choi et al reflects the current state of knowledge on the relative effects of colloids and crystalloids for fluid resuscitation.⁷ It concluded that there are no apparent differences between these fluid classes in their effects on pulmonary edema, mortality, or length of stay. The authors noted that methodologic limitations of the available comparative studies prevent meaningful conclusions and that larger randomized controlled trials are needed to detect any differences in outcomes between the two classes.

Although using a crystalloid for fluid resuscitation probably results in a greater volume of fluid given, a study known as SAFE (Saline versus Albumin Fluid Evaluation),⁸ published after the Choi analysis, showed no differences in 28-day all-cause mortality or other significant outcomes between patients randomized to the colloid (4% albumin) and those assigned to the crystalloid (0.9% saline). Patients receiving the colloid had a higher central venous pressure at all time points, a lower heart rate at the end of the first day, and less overall volume on days 1 and 2 compared with patients receiving the crystalloid. While SAFE was conducted in critically ill patients, these physiologic advantages of the colloid may have implications for results in the perioperative arena, although this remains speculative.

 

 

INTRAOPERATIVE MONITORING TO OPTIMIZE FLUID THERAPY

Another important issue is the emergence of minimally invasive technologies for monitoring hemodynamic measures intraoperatively. The aim is to enable more precise tailoring of fluid therapy to meet patient needs on a case-by-case basis.

One of the simplest of these techniques is esophageal Doppler monitoring to measure descending aortic blood flow using Doppler ultrasonography. The technique is used to titrate repeated boluses of fluid based on continuous estimations of stroke volume and surrogate markers of preload indices. Typical protocols for esophageal Doppler monitoring call for administration of colloid to maintain a descending thoracic corrected flow time of no more than 0.35 seconds and stroke volume increments of 10%.

Phan et al recently published a meta-analysis to assess the effect of intraoperative esophageal Doppler monitoring in guiding fluid therapy to optimize intravascular volume status.⁹ The analysis, which included nine randomized controlled trials in a total of 920 patients, found statistically significant reductions in the rate of complications and in length of hospital stay with the use of esophageal Doppler monitoring; there was no difference in mortality. Use of Doppler monitoring was associated with an increase (+671 mL) in the volume of colloid administered and a decrease (–156 mL) in the volume of crystalloid.

Timing of fluid administration can be critical

One of the trials in the above meta-analysis illustrated that the timing of fluid administration might be more critical than the volume of fluid given. Noblett et al placed an esophageal Doppler probe in each of a series of 108 patients undergoing colorectal resection;¹⁰ the control group received perioperative fluid at the anesthesiologist’s discretion, whereas the intervention group received additional colloid boluses based on Doppler assessment. While the overall volume of colloid given was comparable between the two groups, the intervention group received nearly 100% of the total volume during the first quarter of surgery. The intervention group had significantly fewer postoperative complications than the control group as well as a 2-day reduction in average length of stay. Circulating levels of interleukin-6 and cytokines also were significantly lower in the intervention group, which suggests that the intervention blunted the inflammatory response to surgery.

Fluid management must be individualized

Intraoperative fluid needs are highly variable and patient-specific. Parker et al tested an approach in which they universally administered 500 mL of a gelatin colloid solution prior to hip fracture surgery and compared it with a conventional intravenous saline crystalloid solution; neither approach used invasive intraoperative monitoring.¹¹ They found no significant difference in length of stay, 30-day mortality, or postoperative complications between the two study arms. They concluded that more invasive investigation of patients before or during surgery may have been able to identify a subgroup in whom the colloid therapy or more precise fluid control would have been beneficial.

THE ROAD AHEAD

Fluid management remains suboptimal

Despite being a fundamental component of surgical and perioperative care, fluid management remains suboptimal in clinical practice. I can speak most directly to the practice of fluid management in the United Kingdom (UK), but the same types of shortcomings apply broadly to the United States as well.

In 1999, the UK’s National Confidential Enquiry into Patient Outcome and Death examined perioperative death in the UK, concluding that patients were dying as a result of too much or too little perioperative fluid administration.¹² Their report cited staff inexperience as an important contributor to the problem, as junior physicians order and deliver the majority of postoperative fluid regimens.

This cautionary report from 10 years ago appears not to have produced substantial improvements in practice, at least according to a recent study by Walsh et al.¹³ These researchers prospectively audited postoperative fluid management practices in 106 consecutive patients undergoing laparotomy in a UK general surgical unit over a 6-month period in 2003. They found no correlation between available fluid balance data and the quantities of fluids prescribed, suggesting that physicians routinely ignore such data when prescribing. Fifty-four percent of the patients developed at least one fluid-related complication. Patients routinely received significantly greater amounts of fluid and sodium than were physiologically needed, and multivariate analysis showed that mean daily fluid load predicted development of fluid-related complications.

Guidance from a new British consensus document

Where can clinicians turn for a good synthesis of current evidence to guide better perioperative fluid management? I would recommend the newly released British Consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical Patients,¹⁴ which are available on the Evidence Based Peri-Operative Medicine Web site (http://www.ebpom.org). These guidelines were developed by a multidisciplinary team of clinicians to improve perioperative fluid prescribing. They cover principles of preoperative, intraoperative, and postoperative fluid management, as well as fluid therapy in acute kidney injury. They pre­sent 28 recommendations in all, at least 12 of which are based on high-level (grade 1a or 1b) evidence.

DISCUSSION

Question from the audience: What is the relationship between perioperative fluid management, gut edema from perioperative fluid use, and postoperative ileus?

Dr. Hamilton: There’s no easy answer. Excessive administration of sodium and fluid does predispose to gut and tissue fluid edema. Many of the enhanced surgery recovery programs require no preoperative fasting. There’s no bowel prep. The enteral route is used primarily as quickly as possible. In the UK, we no longer use nasogastric tubes for many of those programs. But there’s no doubt that tissue edema still occurs with excess fluid therapy.

The premise for individualizing fluid therapy is that less is not more but that more is not the right approach either. The stroke volume approaches or the corrected flow time approaches have been related to return of gastrointestinal function and return of flatus, which is a function of gastrointestinal recovery.

Question from the audience: Can you comment on the perioperative use of the Swan-Ganz catheter for fluid management?

Dr. Hamilton: I don’t use it intraoperatively, and not many hospitals in the UK use it apart from liver resection surgery. Having said that, Swan-Ganz catheters were the predominant monitor for 30% to 40% of the original studies of hemodynamic optimization. I cannot give you intraoperative data to support the use of Swan-Ganz catheters for monitoring, but if you lift evidence from the other methods of monitoring hemodynamics, if you’re optimizing flow in a bolus and dynamic fashion, then you should see the kinds of improvements in outcomes that are associated with the other modalities.

The drawback with the Swan-Ganz catheter, obviously, is the morbidity associated with its insertion and its interpretation. But if you’re confident in doing those things, I think it’s a perfectly good monitor.

The ideal preoperative medical consultation (consult) is useful to the whole surgical team, ensures maximal patient readiness for surgery, and promotes optimal perioperative care of the patient. Too often, however, consults are ignored or, even worse, set the stage for legal problems. This article identifies problems frequently seen in preoperative consults, particularly from the perspective of anesthesiologists, and gives guidance to those who write consults—hospitalists, internists, cardiologists, and other medical consultants—on providing the information that is most needed by those who use them. 

A WIDE RANGE OF END USERS

Anesthesiologists are most often the primary users of the information in preoperative consults, but many other members of the surgical and perioperative team benefit from a well-developed consult, including surgeons, intensivists, nurses, and pain management specialists. Most important, patients stand to benefit, as a good consult helps to ensure that the full breadth of relevant patient-specific information is brought to bear to anticipate potential difficulties and promote optimal care.

Purpose of a consult is in the eye of the beholder

The literature on medical consults in the perioperative arena is scant. The only fairly recent assessment of physician attitudes toward the role of consults was reported by Katz et al in 1998.¹ These researchers surveyed attitudes about the various perceived purposes of preoperative cardiology consults, and received rather different responses from anesthesiologists, cardiologists, and surgeons. 

There was consensus among all three specialties that two particular functions of a consult are important:

• Treating an inadequately managed cardiac condition before surgery
• Providing data to use in anesthetic management.

Additionally, all three specialties deemed the suggestion of intraoperative treatment modalities to be reasonably important when such suggestions were specifically included in the consult request, although anesthesiologists assigned less importance to this function.¹

In contrast, anesthesiologists considered suggestions about intraoperative treatment generally unimportant when not specifically requested, and they viewed suggestions of intraoperative monitoring and advice on the safest type of anesthesia as even less important. Anesthesiologists also deemed “clearing the patient for surgery” as an unimportant function of the consult. Cardiologists rated all of these functions as more important than anesthesiologists did and in some cases as considerably more important. To many of the survey questions, surgeons responded that a specific purpose of a consult was “neither important nor unimportant.”¹ That may be because the surgeon’s purpose in obtaining the consult is often simply to address the concerns of the anesthesiologist, who might otherwise delay or cancel a needed surgery.

Consult deficiencies: Vagueness, illegibility, dictating anesthetic choice

The survey by Katz et al also assessed each specialty’s perceptions of the most common deficiencies of pre­operative cardiology consults. The deficiencies deemed most common were failure to give specific facts, illegible handwriting, and attempts to dictate the type of anesthesia to be used. Anesthesiologists considered each of the deficiencies assessed as occurring more commonly than their cardiologist or surgeon colleagues did.¹

The requester–user disconnect

The differing perceptions of preoperative consults by anesthesiologists and surgeons underscore a fundamental problem: the primary requesters of consults (surgeons) are different from the primary users of consults (anesthesiologists).

Ideally, preoperative consults should be requested by anesthesiologists. Unless and until the ordering of consults changes on a wide scale, however, our advice is for consultants to ask the anesthesiologist what he or she needs to know, in addition to any questions directed to the requesting surgeon. Communication between the surgeon and anesthesiologist should be encouraged as much as possible, and consultants should keep both the anesthesiologist and surgeon in mind when writing consult notes.

A final end user: The plaintiff’s attorney

It is wise to keep in mind one more potential user of your consult: a plaintiff’s attorney. A poorly written consult may benefit plaintiffs’ lawyers. Consults should never give absolute instructions; it is better to use such phrases as “Strongly consider…” or “The current literature strongly suggests…” Otherwise, the surgical team is placed in an awkward position if it does not follow your recommendations, even if for good reason. If a certain recommendation absolutely must be followed, then direct oral communication from the consultant to the attending anesthesiologist (or surgeon) is best.

CONSIDER THE PRIMARY USER: WHAT ANESTHESIOLOGISTS ALREADY KNOW

For the purpose of preoperative consults, it is helpful to think of anesthesiologists as experts in acute medical care. Their 4-year training consists of the following:

• 1 year of internship, often in medicine, including 6 months of basic patient care in the ward or clinic (the last time they will manage chronic disease)
• 4 months in the intensive care unit (ICU) and 1 month in the recovery room, which yields solid intensivist training
• 3 months in pain management, covering acute and chronic pain and regional blocks
• ~24 months in the operating room, often devoted to care of complex problems in surgical subspecialties (obstetric, pediatric, neurologic, cardiothoracic, vascular)
• 1 month of preoperative screening and consultations (a recent requirement).

An optional fifth year may be spent in a subspecialty.

Since the large part of anesthesiologists’ training is in acute care, they generally do not need advice about the acute treatment of any ailment. Consults should not advise anesthesiologists on subjects in which they have considerable expertise. They already have well-established ideas about addressing hypertension, myocardial ischemia, heart failure, arrhythmias (unless unusual therapies are needed), bronchospasm, glucose levels, and pain in the operating room, so they are apt to ignore advice on such topics.

There are several additional topics in which anesthesiologists have considerable expertise and do not need guidance in consults:

• Choice of anesthetic type and its impact on outcome
• Choice of invasive or noninvasive monitoring for any comorbidity and operation
• Postoperative patient disposition (ie, whether to send a patient home, to the postanesthesia care unit, to the ICU, or to a step-down unit)
• Impact of optimizing organ function on perioperative outcome
• Cardiovascular and respiratory physiology
• Pharmacology of intravenous agents.

 

 

WHAT ANESTHESIOLOGISTS MAY NOT KNOW―AND NEED FROM CONSULTANTS

How to manage chronic diseases

Preoperative consults should concentrate on matters in which anesthesiologists are not well trained (Table 1). These largely involve optimizing the preoperative treatment of chronic diseases—eg, hypertension, diabetes, coronary artery disease, renal failure, malnutrition, hepatic dysfunction, asthma/chronic obstructive pulmonary disease—and managing oral drug regimens. Anesthesiologists generally do not need help, however, in optimizing the function of an organ system once the patient is in the operating room. Advice on preoperative optimization should include guidance on how long the optimization is likely to take.

Follow-up care (eg, for poorly controlled diabetes or hypertension) often can wait until after the operation, and a consultant’s opinion about that is appreciated. It is especially helpful to know that the patient will be followed without the surgeon or anesthesiologist having to arrange for it.

New evidence-based guidance from the literature

One case when recommendations on acute medical management should be provided is when they involve new information from the literature—ie, important data or guidelines published within the prior 5 years or so. It can take time for new information and recommendations to reach all clinicians even within a single specialty. Moreover, important information, such as on the perioperative use of beta-blockers and statins, is not necessarily published in the anesthesiology literature. It is critical to relay information such as the recent recommendation not to withdraw statins prior to surgery, as the current editions of most anesthesiology textbooks have incorrect information suggesting discontinuation. Thus, consultants should include pertinent recent data and guideline recommendations, especially if they go against previous dogma.

Rare diseases, blood disorders, other special cases

As outlined in Table 1, advice on perioperative management is appreciated for patients with rare diseases, coagulation disorders or other blood disorders, and brittle diabetes and other endocrine disorders, as most anesthesiologists are not intimately familiar with these conditions. Anesthesiologists also need, but often do not get, basic details on coronary stents and other implanted devices (see Table 1), as well as guidance on the latest anticoagulation recommendations, with which it is difficult to keep up to date.

A sensitivity to audience and context

It is always appropriate to ask the surgeon requesting a consult—and the anesthesiologist assigned to the case, if known—what he or she wants to know from the consult. If guidance on specific cases is impractical, it is appropriate to ask the chair of the anesthesiology department, or several anesthesiologists collectively, for general guidance on what they look for from preoperative consults.

Anesthesiologists, like consultants, comprise a broad range of people, and it is always important to be sensitive to context. Generalists who work mainly on healthy patients or in a community setting may have forgotten some of their training in acute medicine and are more likely to appreciate advice on intraoperative care. On the other hand, an anesthesiologist who trained in a cardiothoracic subspecialty fellowship, who routinely deals with issues such as left ventricular assist devices and heart transplants, would not benefit from such advice.

WHAT A CONSULT SHOULD―AND SHOULD NOT―BE

The above advice can be distilled into a few principles:

• A consult is an opportunity for the medical consultant to provide helpful management suggestions to the operative team.
• A fundamental objective of a consult is to optimize a patient’s underlying disease before it is compounded by the insult of surgery.
• The purpose of a consult is never to “clear” a patient for surgery. Whether or not to proceed to surgery is a question for the anesthesiologist, surgeon, and patient to decide after weighing the risks and benefits once the patient’s comorbidities are optimally managed. The consult is an important contributing factor to this decision, but it should never be the mechanism of the decision. Though the note from the surgeon requesting a consult may routinely be written as, “Clear the patient for surgery,” consultants should recognize this for what it is—the surgeon’s attempt to avoid having the anesthesiologist cancel the operation—and refrain from weighing in on “clearance” one way or the other.

CASE STUDY: CARDIAC CONSULT REQUESTED BEFORE FEM-POP BYPASS SURGERY

Cardiovascular problems are the most common reasons for requesting preoperative consults. The following case illustrates a typical scenario for a cardiac consult request and presents examples of good and bad notes requesting consults and good and bad consults written in response.

The case

A 47-year-old man is scheduled for femoral-popliteal bypass surgery. His medical history is significant for diabetes, a myocardial infarction (MI) 3 years ago followed by placement of a stent, and a limited ability to assess exercise tolerance. Evidence of an anteroseptal MI is present on 12-lead electrocardiography. His medications include metoprolol 25 mg twice daily and an oral hypoglycemic agent. His blood pressure is 152/89 mm Hg, heart rate 81 beats per minute, respiratory rate 14 breaths per minute, and arterial oxygen saturation 96% on room air.

The consult request: Bad and good examples

A bad consult request in this case would be, “Clear the patient for surgery.” Although this type of request is routinely written, it is routinely useless.

For this complex surgery with significant fluid requirements, a much better consult request would include several specific requests and questions and might read as follows:

—Please evaluate patient’s post-MI therapy for his CAD. Is further therapy required to optimize CAD treatment?

—Do his blood pressure or diabetic regimens need modification? If so, can this be done postoperatively?

—Please evaluate patient’s myocardial function in light of a lack of info on exercise tolerance. Is an echo indicated?

—Are other tests, therapies, or interventions warranted pre- or postoperatively?

Example of a bad consult

A poorly written consult in a case like this may:

• Include a brief history repeating facts that are already known and noting that “the patient is at his baseline without obvious ischemia.”
• State that the patient is cleared for “spinal” anesthesia. “Clearing a patient for anesthesia” is useless to begin with, but clearing for a certain type of anesthesia places the anesthesiologist in a terrible medicolegal position if general anesthesia turns out to be needed. Moreover, there are no proven major outcome differences related to the type of anesthetic chosen.
• Recommend that “a pulmonary artery catheter might be indicated to monitor hemodynamics.” Besides the fact that such catheters probably do more harm than good, such a recommendation is unnecessary since the anesthesiologist is already expert in managing perioperative care.
• Recommend that “the anesthesia team should monitor the patient carefully in the perioperative arena for hypoxia and hypotension.” Qualitative advice, such as “avoid hypoxia, hypotension, and tachycardia,” is not useful, but quantitative information, such as “during ischemic stress testing, the patient exhibited ischemia when his heart rate went to 142,” can be very helpful.
• State that the patient be sent to the ICU following surgery. Mandating an ICU stay in advance makes no sense unless the operation itself demands ICU care, which is the call of the surgeon and anesthesiologist anyway.

A consult like this doesn’t tell the perioperative team anything that it didn’t already know. Such a consult not only is unhelpful but also actually creates more work since much of the advice needs to be “undone” lest a lawyer see the chart and it not be clear why the consultant’s recommendations were not followed.

Example of a good consult

In contrast, a good consult for this case would involve:

• A detailed history examining the potential for silent ischemia associated with the diabetes, as well as the relationship of the hypertension and beta-blocker therapy to episodes of ischemia. The level of ischemia should be clearly categorized. If it cannot be determined, this should be noted; if it can be determined only that the ischemia is not New York Heart Association class III or IV, note this as well (the perioperative outcomes literature suggests that no preoperative ischemia testing is needed with class I or II angina).
• Guidance on blood pressure optimization in light of the relative urgency of the procedure. Blood pressure need not be normalized preoperatively in this case, but if the operation were totally elective and the consultant felt it could make a difference, it would be appropriate to suggest that blood pressure be optimized beforehand.
• A recommendation on whether and when to change the beta-blocker dosage. If the dosage needs to be increased, the anesthesiologist will want to know how many doses are needed to reach a new steady state. Joint guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA)² recommend 7 to 30 days, but this time frame is unrealistic in this setting, so more practical advice would be appreciated. A good consult notes any deviation from established guidelines, however, and explains the rationale for such deviation.
• Evaluation of the myocardium at risk. This is especially important with left main disease, as it influences the decision whether to test or intervene versus proceeding with careful beta-blocker titration.
• Evaluation of myocardial function and, if appropriate, a therapy suggestion for optimization.
• Notation of the heart rate or blood pressure thresholds at which ischemia develops if a stress test is performed.

 

 

GOOD GUIDANCE FROM THE ACC/AHA GUIDELINES

Our advice here is broadly consistent with the aforementioned 2007 ACC/AHA guidelines on perioperative cardiovascular evaluation for noncardiac surgery.² The following observation on cardiac evaluations from these guidelines applies to preoperative consults in general:

The purpose of preoperative evaluation is not to give medical clearance but rather to perform an evaluation of the patient’s current medical status; make recommendations concerning the evaluation, management, and risk of cardiac problems over the entire perioperative period; and provide a clinical risk profile that [can be used] in making treatment decisions that may influence short- and long-term cardiac outcomes.²

These guidelines contain a good description of the ideal preoperative evaluation and consult in a short section (Section II, “General Approach to the Patient”)² that is worthy of wide dissemination.

DISCUSSION

Question from the audience: Many consults are written more for the surgical team than for the anesthesiologists, hence advice such as managing intraoperative diabetes. Isn’t that appropriate?

Dr. Lubarsky: There are a variety of users of the information in a consult note. I focused on the anesthesiologist, but certainly the surgical staff and house staff would benefit from suggestions about postoperative management. However, they would not benefit from suggestions on intraoperative management; surgeons simply do not need this information and the anesthesiologist will have his or her own regimen. But if there is a specific type of insulin infusion that’s been shown to be best in the specific patient at hand, then detailing that obviously is beneficial.

Question from the audience: We all agree that communication is key, but how does the consultant reach the anesthesiologist to find out what he or she wants to know when the anesthesiologist isn’t usually assigned to the case until a day before surgery?

Dr. Lubarsky: If no anesthesiologist is yet assigned to a case, the consultant can discuss the case with the chief of the anesthesiology department. The discussion should be documented in the note. But it’s important that the system be changed so that anesthesiologists are assigned to cases well in advance. I instituted such a policy at my previous hospital. Many hospitals schedule surgeries 3 months in advance, and many anesthesiology departments have schedules made at least 1 month and often 2 to 3 months in advance. The department could assign a specific anesthesiologist to a future scheduled case with ease.

Question from the audience: How do anesthesiologists educate all the various people we rely on for consults when we can’t get them in one place at one time?

Dr. Lubarsky: It’s a challenge. I try many things, such as going to cardiology rounds, but there are always new people coming through. A good monograph or a set of guidelines with examples would help. If each specialty educates the other and speaks at each other’s conferences more often, that should help. Anesthesiologists would benefit from hearing about the challenges medical consultants face; we may not be doing all we can to optimize perioperative care. There’s room for improvement through communication on both sides. I should also emphasize that we’re all trying to do the right thing. Doctors try to be accommodating, but that doesn’t always make for good decisions. Recently a consultant in my hospital did a preoperative stress test on a patient who didn’t need one. When I asked why, he said, “Because the surgeon asked me to.”

Question from the audience: But don’t you agree that many anesthesiologists would like to see that negative stress test, even if a stress test is not indicated by the guidelines? Cardiologists know that the anesthesiologists are often looking for that on the morning of surgery.

Dr. Lubarsky: The point is that physicians should be responsible for what they have expertise in. When I am asked to intubate a patient, my response as an expert in intubation might be, “Actually, he doesn’t need to be intubated right now.” In the case of this unnecessary stress test, the cardiologist probably should have called the surgeon and said, “It’s really not indicated because the patient had a negative stress test 2 years ago, there’s been no change in symptoms and no angina since then, and he operates well above 4 metabolic equivalents. There’s a clear-cut reason not to do it.” If the surgeon still wanted the test done just to be reassured, that’s simply a poor use of society’s resources. We depend on experts to identify the tests that are indicated to evaluate a patient’s disease and not just do tests for the sake of doing them.

The ideal preoperative medical consultation (consult) is useful to the whole surgical team, ensures maximal patient readiness for surgery, and promotes optimal perioperative care of the patient. Too often, however, consults are ignored or, even worse, set the stage for legal problems. This article identifies problems frequently seen in preoperative consults, particularly from the perspective of anesthesiologists, and gives guidance to those who write consults—hospitalists, internists, cardiologists, and other medical consultants—on providing the information that is most needed by those who use them. 

A WIDE RANGE OF END USERS

Anesthesiologists are most often the primary users of the information in preoperative consults, but many other members of the surgical and perioperative team benefit from a well-developed consult, including surgeons, intensivists, nurses, and pain management specialists. Most important, patients stand to benefit, as a good consult helps to ensure that the full breadth of relevant patient-specific information is brought to bear to anticipate potential difficulties and promote optimal care.

Purpose of a consult is in the eye of the beholder

The literature on medical consults in the perioperative arena is scant. The only fairly recent assessment of physician attitudes toward the role of consults was reported by Katz et al in 1998.¹ These researchers surveyed attitudes about the various perceived purposes of preoperative cardiology consults, and received rather different responses from anesthesiologists, cardiologists, and surgeons. 

There was consensus among all three specialties that two particular functions of a consult are important:

• Treating an inadequately managed cardiac condition before surgery
• Providing data to use in anesthetic management.

Additionally, all three specialties deemed the suggestion of intraoperative treatment modalities to be reasonably important when such suggestions were specifically included in the consult request, although anesthesiologists assigned less importance to this function.¹

In contrast, anesthesiologists considered suggestions about intraoperative treatment generally unimportant when not specifically requested, and they viewed suggestions of intraoperative monitoring and advice on the safest type of anesthesia as even less important. Anesthesiologists also deemed “clearing the patient for surgery” as an unimportant function of the consult. Cardiologists rated all of these functions as more important than anesthesiologists did and in some cases as considerably more important. To many of the survey questions, surgeons responded that a specific purpose of a consult was “neither important nor unimportant.”¹ That may be because the surgeon’s purpose in obtaining the consult is often simply to address the concerns of the anesthesiologist, who might otherwise delay or cancel a needed surgery.

Consult deficiencies: Vagueness, illegibility, dictating anesthetic choice

The survey by Katz et al also assessed each specialty’s perceptions of the most common deficiencies of pre­operative cardiology consults. The deficiencies deemed most common were failure to give specific facts, illegible handwriting, and attempts to dictate the type of anesthesia to be used. Anesthesiologists considered each of the deficiencies assessed as occurring more commonly than their cardiologist or surgeon colleagues did.¹

The requester–user disconnect

The differing perceptions of preoperative consults by anesthesiologists and surgeons underscore a fundamental problem: the primary requesters of consults (surgeons) are different from the primary users of consults (anesthesiologists).

Ideally, preoperative consults should be requested by anesthesiologists. Unless and until the ordering of consults changes on a wide scale, however, our advice is for consultants to ask the anesthesiologist what he or she needs to know, in addition to any questions directed to the requesting surgeon. Communication between the surgeon and anesthesiologist should be encouraged as much as possible, and consultants should keep both the anesthesiologist and surgeon in mind when writing consult notes.

A final end user: The plaintiff’s attorney

It is wise to keep in mind one more potential user of your consult: a plaintiff’s attorney. A poorly written consult may benefit plaintiffs’ lawyers. Consults should never give absolute instructions; it is better to use such phrases as “Strongly consider…” or “The current literature strongly suggests…” Otherwise, the surgical team is placed in an awkward position if it does not follow your recommendations, even if for good reason. If a certain recommendation absolutely must be followed, then direct oral communication from the consultant to the attending anesthesiologist (or surgeon) is best.

CONSIDER THE PRIMARY USER: WHAT ANESTHESIOLOGISTS ALREADY KNOW

For the purpose of preoperative consults, it is helpful to think of anesthesiologists as experts in acute medical care. Their 4-year training consists of the following:

• 1 year of internship, often in medicine, including 6 months of basic patient care in the ward or clinic (the last time they will manage chronic disease)
• 4 months in the intensive care unit (ICU) and 1 month in the recovery room, which yields solid intensivist training
• 3 months in pain management, covering acute and chronic pain and regional blocks
• ~24 months in the operating room, often devoted to care of complex problems in surgical subspecialties (obstetric, pediatric, neurologic, cardiothoracic, vascular)
• 1 month of preoperative screening and consultations (a recent requirement).

An optional fifth year may be spent in a subspecialty.

Since the large part of anesthesiologists’ training is in acute care, they generally do not need advice about the acute treatment of any ailment. Consults should not advise anesthesiologists on subjects in which they have considerable expertise. They already have well-established ideas about addressing hypertension, myocardial ischemia, heart failure, arrhythmias (unless unusual therapies are needed), bronchospasm, glucose levels, and pain in the operating room, so they are apt to ignore advice on such topics.

There are several additional topics in which anesthesiologists have considerable expertise and do not need guidance in consults:

• Choice of anesthetic type and its impact on outcome
• Choice of invasive or noninvasive monitoring for any comorbidity and operation
• Postoperative patient disposition (ie, whether to send a patient home, to the postanesthesia care unit, to the ICU, or to a step-down unit)
• Impact of optimizing organ function on perioperative outcome
• Cardiovascular and respiratory physiology
• Pharmacology of intravenous agents.

 

 

WHAT ANESTHESIOLOGISTS MAY NOT KNOW―AND NEED FROM CONSULTANTS

How to manage chronic diseases

Preoperative consults should concentrate on matters in which anesthesiologists are not well trained (Table 1). These largely involve optimizing the preoperative treatment of chronic diseases—eg, hypertension, diabetes, coronary artery disease, renal failure, malnutrition, hepatic dysfunction, asthma/chronic obstructive pulmonary disease—and managing oral drug regimens. Anesthesiologists generally do not need help, however, in optimizing the function of an organ system once the patient is in the operating room. Advice on preoperative optimization should include guidance on how long the optimization is likely to take.

Follow-up care (eg, for poorly controlled diabetes or hypertension) often can wait until after the operation, and a consultant’s opinion about that is appreciated. It is especially helpful to know that the patient will be followed without the surgeon or anesthesiologist having to arrange for it.

New evidence-based guidance from the literature

One case when recommendations on acute medical management should be provided is when they involve new information from the literature—ie, important data or guidelines published within the prior 5 years or so. It can take time for new information and recommendations to reach all clinicians even within a single specialty. Moreover, important information, such as on the perioperative use of beta-blockers and statins, is not necessarily published in the anesthesiology literature. It is critical to relay information such as the recent recommendation not to withdraw statins prior to surgery, as the current editions of most anesthesiology textbooks have incorrect information suggesting discontinuation. Thus, consultants should include pertinent recent data and guideline recommendations, especially if they go against previous dogma.

Rare diseases, blood disorders, other special cases

As outlined in Table 1, advice on perioperative management is appreciated for patients with rare diseases, coagulation disorders or other blood disorders, and brittle diabetes and other endocrine disorders, as most anesthesiologists are not intimately familiar with these conditions. Anesthesiologists also need, but often do not get, basic details on coronary stents and other implanted devices (see Table 1), as well as guidance on the latest anticoagulation recommendations, with which it is difficult to keep up to date.

A sensitivity to audience and context

It is always appropriate to ask the surgeon requesting a consult—and the anesthesiologist assigned to the case, if known—what he or she wants to know from the consult. If guidance on specific cases is impractical, it is appropriate to ask the chair of the anesthesiology department, or several anesthesiologists collectively, for general guidance on what they look for from preoperative consults.

Anesthesiologists, like consultants, comprise a broad range of people, and it is always important to be sensitive to context. Generalists who work mainly on healthy patients or in a community setting may have forgotten some of their training in acute medicine and are more likely to appreciate advice on intraoperative care. On the other hand, an anesthesiologist who trained in a cardiothoracic subspecialty fellowship, who routinely deals with issues such as left ventricular assist devices and heart transplants, would not benefit from such advice.

WHAT A CONSULT SHOULD―AND SHOULD NOT―BE

The above advice can be distilled into a few principles:

• A consult is an opportunity for the medical consultant to provide helpful management suggestions to the operative team.
• A fundamental objective of a consult is to optimize a patient’s underlying disease before it is compounded by the insult of surgery.
• The purpose of a consult is never to “clear” a patient for surgery. Whether or not to proceed to surgery is a question for the anesthesiologist, surgeon, and patient to decide after weighing the risks and benefits once the patient’s comorbidities are optimally managed. The consult is an important contributing factor to this decision, but it should never be the mechanism of the decision. Though the note from the surgeon requesting a consult may routinely be written as, “Clear the patient for surgery,” consultants should recognize this for what it is—the surgeon’s attempt to avoid having the anesthesiologist cancel the operation—and refrain from weighing in on “clearance” one way or the other.

CASE STUDY: CARDIAC CONSULT REQUESTED BEFORE FEM-POP BYPASS SURGERY

Cardiovascular problems are the most common reasons for requesting preoperative consults. The following case illustrates a typical scenario for a cardiac consult request and presents examples of good and bad notes requesting consults and good and bad consults written in response.

The case

A 47-year-old man is scheduled for femoral-popliteal bypass surgery. His medical history is significant for diabetes, a myocardial infarction (MI) 3 years ago followed by placement of a stent, and a limited ability to assess exercise tolerance. Evidence of an anteroseptal MI is present on 12-lead electrocardiography. His medications include metoprolol 25 mg twice daily and an oral hypoglycemic agent. His blood pressure is 152/89 mm Hg, heart rate 81 beats per minute, respiratory rate 14 breaths per minute, and arterial oxygen saturation 96% on room air.

The consult request: Bad and good examples

A bad consult request in this case would be, “Clear the patient for surgery.” Although this type of request is routinely written, it is routinely useless.

For this complex surgery with significant fluid requirements, a much better consult request would include several specific requests and questions and might read as follows:

—Please evaluate patient’s post-MI therapy for his CAD. Is further therapy required to optimize CAD treatment?

—Do his blood pressure or diabetic regimens need modification? If so, can this be done postoperatively?

—Please evaluate patient’s myocardial function in light of a lack of info on exercise tolerance. Is an echo indicated?

—Are other tests, therapies, or interventions warranted pre- or postoperatively?

Example of a bad consult

A poorly written consult in a case like this may:

• Include a brief history repeating facts that are already known and noting that “the patient is at his baseline without obvious ischemia.”
• State that the patient is cleared for “spinal” anesthesia. “Clearing a patient for anesthesia” is useless to begin with, but clearing for a certain type of anesthesia places the anesthesiologist in a terrible medicolegal position if general anesthesia turns out to be needed. Moreover, there are no proven major outcome differences related to the type of anesthetic chosen.
• Recommend that “a pulmonary artery catheter might be indicated to monitor hemodynamics.” Besides the fact that such catheters probably do more harm than good, such a recommendation is unnecessary since the anesthesiologist is already expert in managing perioperative care.
• Recommend that “the anesthesia team should monitor the patient carefully in the perioperative arena for hypoxia and hypotension.” Qualitative advice, such as “avoid hypoxia, hypotension, and tachycardia,” is not useful, but quantitative information, such as “during ischemic stress testing, the patient exhibited ischemia when his heart rate went to 142,” can be very helpful.
• State that the patient be sent to the ICU following surgery. Mandating an ICU stay in advance makes no sense unless the operation itself demands ICU care, which is the call of the surgeon and anesthesiologist anyway.

A consult like this doesn’t tell the perioperative team anything that it didn’t already know. Such a consult not only is unhelpful but also actually creates more work since much of the advice needs to be “undone” lest a lawyer see the chart and it not be clear why the consultant’s recommendations were not followed.

Example of a good consult

In contrast, a good consult for this case would involve:

• A detailed history examining the potential for silent ischemia associated with the diabetes, as well as the relationship of the hypertension and beta-blocker therapy to episodes of ischemia. The level of ischemia should be clearly categorized. If it cannot be determined, this should be noted; if it can be determined only that the ischemia is not New York Heart Association class III or IV, note this as well (the perioperative outcomes literature suggests that no preoperative ischemia testing is needed with class I or II angina).
• Guidance on blood pressure optimization in light of the relative urgency of the procedure. Blood pressure need not be normalized preoperatively in this case, but if the operation were totally elective and the consultant felt it could make a difference, it would be appropriate to suggest that blood pressure be optimized beforehand.
• A recommendation on whether and when to change the beta-blocker dosage. If the dosage needs to be increased, the anesthesiologist will want to know how many doses are needed to reach a new steady state. Joint guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA)² recommend 7 to 30 days, but this time frame is unrealistic in this setting, so more practical advice would be appreciated. A good consult notes any deviation from established guidelines, however, and explains the rationale for such deviation.
• Evaluation of the myocardium at risk. This is especially important with left main disease, as it influences the decision whether to test or intervene versus proceeding with careful beta-blocker titration.
• Evaluation of myocardial function and, if appropriate, a therapy suggestion for optimization.
• Notation of the heart rate or blood pressure thresholds at which ischemia develops if a stress test is performed.

 

 

GOOD GUIDANCE FROM THE ACC/AHA GUIDELINES

Our advice here is broadly consistent with the aforementioned 2007 ACC/AHA guidelines on perioperative cardiovascular evaluation for noncardiac surgery.² The following observation on cardiac evaluations from these guidelines applies to preoperative consults in general:

The purpose of preoperative evaluation is not to give medical clearance but rather to perform an evaluation of the patient’s current medical status; make recommendations concerning the evaluation, management, and risk of cardiac problems over the entire perioperative period; and provide a clinical risk profile that [can be used] in making treatment decisions that may influence short- and long-term cardiac outcomes.²

These guidelines contain a good description of the ideal preoperative evaluation and consult in a short section (Section II, “General Approach to the Patient”)² that is worthy of wide dissemination.

DISCUSSION

Question from the audience: Many consults are written more for the surgical team than for the anesthesiologists, hence advice such as managing intraoperative diabetes. Isn’t that appropriate?

Dr. Lubarsky: There are a variety of users of the information in a consult note. I focused on the anesthesiologist, but certainly the surgical staff and house staff would benefit from suggestions about postoperative management. However, they would not benefit from suggestions on intraoperative management; surgeons simply do not need this information and the anesthesiologist will have his or her own regimen. But if there is a specific type of insulin infusion that’s been shown to be best in the specific patient at hand, then detailing that obviously is beneficial.

Question from the audience: We all agree that communication is key, but how does the consultant reach the anesthesiologist to find out what he or she wants to know when the anesthesiologist isn’t usually assigned to the case until a day before surgery?

Dr. Lubarsky: If no anesthesiologist is yet assigned to a case, the consultant can discuss the case with the chief of the anesthesiology department. The discussion should be documented in the note. But it’s important that the system be changed so that anesthesiologists are assigned to cases well in advance. I instituted such a policy at my previous hospital. Many hospitals schedule surgeries 3 months in advance, and many anesthesiology departments have schedules made at least 1 month and often 2 to 3 months in advance. The department could assign a specific anesthesiologist to a future scheduled case with ease.

Question from the audience: How do anesthesiologists educate all the various people we rely on for consults when we can’t get them in one place at one time?

Dr. Lubarsky: It’s a challenge. I try many things, such as going to cardiology rounds, but there are always new people coming through. A good monograph or a set of guidelines with examples would help. If each specialty educates the other and speaks at each other’s conferences more often, that should help. Anesthesiologists would benefit from hearing about the challenges medical consultants face; we may not be doing all we can to optimize perioperative care. There’s room for improvement through communication on both sides. I should also emphasize that we’re all trying to do the right thing. Doctors try to be accommodating, but that doesn’t always make for good decisions. Recently a consultant in my hospital did a preoperative stress test on a patient who didn’t need one. When I asked why, he said, “Because the surgeon asked me to.”

Question from the audience: But don’t you agree that many anesthesiologists would like to see that negative stress test, even if a stress test is not indicated by the guidelines? Cardiologists know that the anesthesiologists are often looking for that on the morning of surgery.

Dr. Lubarsky: The point is that physicians should be responsible for what they have expertise in. When I am asked to intubate a patient, my response as an expert in intubation might be, “Actually, he doesn’t need to be intubated right now.” In the case of this unnecessary stress test, the cardiologist probably should have called the surgeon and said, “It’s really not indicated because the patient had a negative stress test 2 years ago, there’s been no change in symptoms and no angina since then, and he operates well above 4 metabolic equivalents. There’s a clear-cut reason not to do it.” If the surgeon still wanted the test done just to be reassured, that’s simply a poor use of society’s resources. We depend on experts to identify the tests that are indicated to evaluate a patient’s disease and not just do tests for the sake of doing them.

The ideal preoperative medical consultation (consult) is useful to the whole surgical team, ensures maximal patient readiness for surgery, and promotes optimal perioperative care of the patient. Too often, however, consults are ignored or, even worse, set the stage for legal problems. This article identifies problems frequently seen in preoperative consults, particularly from the perspective of anesthesiologists, and gives guidance to those who write consults—hospitalists, internists, cardiologists, and other medical consultants—on providing the information that is most needed by those who use them. 

A WIDE RANGE OF END USERS

Anesthesiologists are most often the primary users of the information in preoperative consults, but many other members of the surgical and perioperative team benefit from a well-developed consult, including surgeons, intensivists, nurses, and pain management specialists. Most important, patients stand to benefit, as a good consult helps to ensure that the full breadth of relevant patient-specific information is brought to bear to anticipate potential difficulties and promote optimal care.

Purpose of a consult is in the eye of the beholder

The literature on medical consults in the perioperative arena is scant. The only fairly recent assessment of physician attitudes toward the role of consults was reported by Katz et al in 1998.¹ These researchers surveyed attitudes about the various perceived purposes of preoperative cardiology consults, and received rather different responses from anesthesiologists, cardiologists, and surgeons. 

There was consensus among all three specialties that two particular functions of a consult are important:

• Treating an inadequately managed cardiac condition before surgery
• Providing data to use in anesthetic management.

Additionally, all three specialties deemed the suggestion of intraoperative treatment modalities to be reasonably important when such suggestions were specifically included in the consult request, although anesthesiologists assigned less importance to this function.¹

In contrast, anesthesiologists considered suggestions about intraoperative treatment generally unimportant when not specifically requested, and they viewed suggestions of intraoperative monitoring and advice on the safest type of anesthesia as even less important. Anesthesiologists also deemed “clearing the patient for surgery” as an unimportant function of the consult. Cardiologists rated all of these functions as more important than anesthesiologists did and in some cases as considerably more important. To many of the survey questions, surgeons responded that a specific purpose of a consult was “neither important nor unimportant.”¹ That may be because the surgeon’s purpose in obtaining the consult is often simply to address the concerns of the anesthesiologist, who might otherwise delay or cancel a needed surgery.

Consult deficiencies: Vagueness, illegibility, dictating anesthetic choice

The survey by Katz et al also assessed each specialty’s perceptions of the most common deficiencies of pre­operative cardiology consults. The deficiencies deemed most common were failure to give specific facts, illegible handwriting, and attempts to dictate the type of anesthesia to be used. Anesthesiologists considered each of the deficiencies assessed as occurring more commonly than their cardiologist or surgeon colleagues did.¹

The requester–user disconnect

The differing perceptions of preoperative consults by anesthesiologists and surgeons underscore a fundamental problem: the primary requesters of consults (surgeons) are different from the primary users of consults (anesthesiologists).

Ideally, preoperative consults should be requested by anesthesiologists. Unless and until the ordering of consults changes on a wide scale, however, our advice is for consultants to ask the anesthesiologist what he or she needs to know, in addition to any questions directed to the requesting surgeon. Communication between the surgeon and anesthesiologist should be encouraged as much as possible, and consultants should keep both the anesthesiologist and surgeon in mind when writing consult notes.

A final end user: The plaintiff’s attorney

It is wise to keep in mind one more potential user of your consult: a plaintiff’s attorney. A poorly written consult may benefit plaintiffs’ lawyers. Consults should never give absolute instructions; it is better to use such phrases as “Strongly consider…” or “The current literature strongly suggests…” Otherwise, the surgical team is placed in an awkward position if it does not follow your recommendations, even if for good reason. If a certain recommendation absolutely must be followed, then direct oral communication from the consultant to the attending anesthesiologist (or surgeon) is best.

CONSIDER THE PRIMARY USER: WHAT ANESTHESIOLOGISTS ALREADY KNOW

For the purpose of preoperative consults, it is helpful to think of anesthesiologists as experts in acute medical care. Their 4-year training consists of the following:

• 1 year of internship, often in medicine, including 6 months of basic patient care in the ward or clinic (the last time they will manage chronic disease)
• 4 months in the intensive care unit (ICU) and 1 month in the recovery room, which yields solid intensivist training
• 3 months in pain management, covering acute and chronic pain and regional blocks
• ~24 months in the operating room, often devoted to care of complex problems in surgical subspecialties (obstetric, pediatric, neurologic, cardiothoracic, vascular)
• 1 month of preoperative screening and consultations (a recent requirement).

An optional fifth year may be spent in a subspecialty.

Since the large part of anesthesiologists’ training is in acute care, they generally do not need advice about the acute treatment of any ailment. Consults should not advise anesthesiologists on subjects in which they have considerable expertise. They already have well-established ideas about addressing hypertension, myocardial ischemia, heart failure, arrhythmias (unless unusual therapies are needed), bronchospasm, glucose levels, and pain in the operating room, so they are apt to ignore advice on such topics.

There are several additional topics in which anesthesiologists have considerable expertise and do not need guidance in consults:

• Choice of anesthetic type and its impact on outcome
• Choice of invasive or noninvasive monitoring for any comorbidity and operation
• Postoperative patient disposition (ie, whether to send a patient home, to the postanesthesia care unit, to the ICU, or to a step-down unit)
• Impact of optimizing organ function on perioperative outcome
• Cardiovascular and respiratory physiology
• Pharmacology of intravenous agents.

 

 

WHAT ANESTHESIOLOGISTS MAY NOT KNOW―AND NEED FROM CONSULTANTS

How to manage chronic diseases

Preoperative consults should concentrate on matters in which anesthesiologists are not well trained (Table 1). These largely involve optimizing the preoperative treatment of chronic diseases—eg, hypertension, diabetes, coronary artery disease, renal failure, malnutrition, hepatic dysfunction, asthma/chronic obstructive pulmonary disease—and managing oral drug regimens. Anesthesiologists generally do not need help, however, in optimizing the function of an organ system once the patient is in the operating room. Advice on preoperative optimization should include guidance on how long the optimization is likely to take.

Follow-up care (eg, for poorly controlled diabetes or hypertension) often can wait until after the operation, and a consultant’s opinion about that is appreciated. It is especially helpful to know that the patient will be followed without the surgeon or anesthesiologist having to arrange for it.

New evidence-based guidance from the literature

One case when recommendations on acute medical management should be provided is when they involve new information from the literature—ie, important data or guidelines published within the prior 5 years or so. It can take time for new information and recommendations to reach all clinicians even within a single specialty. Moreover, important information, such as on the perioperative use of beta-blockers and statins, is not necessarily published in the anesthesiology literature. It is critical to relay information such as the recent recommendation not to withdraw statins prior to surgery, as the current editions of most anesthesiology textbooks have incorrect information suggesting discontinuation. Thus, consultants should include pertinent recent data and guideline recommendations, especially if they go against previous dogma.

Rare diseases, blood disorders, other special cases

As outlined in Table 1, advice on perioperative management is appreciated for patients with rare diseases, coagulation disorders or other blood disorders, and brittle diabetes and other endocrine disorders, as most anesthesiologists are not intimately familiar with these conditions. Anesthesiologists also need, but often do not get, basic details on coronary stents and other implanted devices (see Table 1), as well as guidance on the latest anticoagulation recommendations, with which it is difficult to keep up to date.

A sensitivity to audience and context

It is always appropriate to ask the surgeon requesting a consult—and the anesthesiologist assigned to the case, if known—what he or she wants to know from the consult. If guidance on specific cases is impractical, it is appropriate to ask the chair of the anesthesiology department, or several anesthesiologists collectively, for general guidance on what they look for from preoperative consults.

Anesthesiologists, like consultants, comprise a broad range of people, and it is always important to be sensitive to context. Generalists who work mainly on healthy patients or in a community setting may have forgotten some of their training in acute medicine and are more likely to appreciate advice on intraoperative care. On the other hand, an anesthesiologist who trained in a cardiothoracic subspecialty fellowship, who routinely deals with issues such as left ventricular assist devices and heart transplants, would not benefit from such advice.

WHAT A CONSULT SHOULD―AND SHOULD NOT―BE

The above advice can be distilled into a few principles:

• A consult is an opportunity for the medical consultant to provide helpful management suggestions to the operative team.
• A fundamental objective of a consult is to optimize a patient’s underlying disease before it is compounded by the insult of surgery.
• The purpose of a consult is never to “clear” a patient for surgery. Whether or not to proceed to surgery is a question for the anesthesiologist, surgeon, and patient to decide after weighing the risks and benefits once the patient’s comorbidities are optimally managed. The consult is an important contributing factor to this decision, but it should never be the mechanism of the decision. Though the note from the surgeon requesting a consult may routinely be written as, “Clear the patient for surgery,” consultants should recognize this for what it is—the surgeon’s attempt to avoid having the anesthesiologist cancel the operation—and refrain from weighing in on “clearance” one way or the other.

CASE STUDY: CARDIAC CONSULT REQUESTED BEFORE FEM-POP BYPASS SURGERY

Cardiovascular problems are the most common reasons for requesting preoperative consults. The following case illustrates a typical scenario for a cardiac consult request and presents examples of good and bad notes requesting consults and good and bad consults written in response.

The case

A 47-year-old man is scheduled for femoral-popliteal bypass surgery. His medical history is significant for diabetes, a myocardial infarction (MI) 3 years ago followed by placement of a stent, and a limited ability to assess exercise tolerance. Evidence of an anteroseptal MI is present on 12-lead electrocardiography. His medications include metoprolol 25 mg twice daily and an oral hypoglycemic agent. His blood pressure is 152/89 mm Hg, heart rate 81 beats per minute, respiratory rate 14 breaths per minute, and arterial oxygen saturation 96% on room air.

The consult request: Bad and good examples

A bad consult request in this case would be, “Clear the patient for surgery.” Although this type of request is routinely written, it is routinely useless.

For this complex surgery with significant fluid requirements, a much better consult request would include several specific requests and questions and might read as follows:

—Please evaluate patient’s post-MI therapy for his CAD. Is further therapy required to optimize CAD treatment?

—Do his blood pressure or diabetic regimens need modification? If so, can this be done postoperatively?

—Please evaluate patient’s myocardial function in light of a lack of info on exercise tolerance. Is an echo indicated?

—Are other tests, therapies, or interventions warranted pre- or postoperatively?

Example of a bad consult

A poorly written consult in a case like this may:

• Include a brief history repeating facts that are already known and noting that “the patient is at his baseline without obvious ischemia.”
• State that the patient is cleared for “spinal” anesthesia. “Clearing a patient for anesthesia” is useless to begin with, but clearing for a certain type of anesthesia places the anesthesiologist in a terrible medicolegal position if general anesthesia turns out to be needed. Moreover, there are no proven major outcome differences related to the type of anesthetic chosen.
• Recommend that “a pulmonary artery catheter might be indicated to monitor hemodynamics.” Besides the fact that such catheters probably do more harm than good, such a recommendation is unnecessary since the anesthesiologist is already expert in managing perioperative care.
• Recommend that “the anesthesia team should monitor the patient carefully in the perioperative arena for hypoxia and hypotension.” Qualitative advice, such as “avoid hypoxia, hypotension, and tachycardia,” is not useful, but quantitative information, such as “during ischemic stress testing, the patient exhibited ischemia when his heart rate went to 142,” can be very helpful.
• State that the patient be sent to the ICU following surgery. Mandating an ICU stay in advance makes no sense unless the operation itself demands ICU care, which is the call of the surgeon and anesthesiologist anyway.

A consult like this doesn’t tell the perioperative team anything that it didn’t already know. Such a consult not only is unhelpful but also actually creates more work since much of the advice needs to be “undone” lest a lawyer see the chart and it not be clear why the consultant’s recommendations were not followed.

Example of a good consult

In contrast, a good consult for this case would involve:

• A detailed history examining the potential for silent ischemia associated with the diabetes, as well as the relationship of the hypertension and beta-blocker therapy to episodes of ischemia. The level of ischemia should be clearly categorized. If it cannot be determined, this should be noted; if it can be determined only that the ischemia is not New York Heart Association class III or IV, note this as well (the perioperative outcomes literature suggests that no preoperative ischemia testing is needed with class I or II angina).
• Guidance on blood pressure optimization in light of the relative urgency of the procedure. Blood pressure need not be normalized preoperatively in this case, but if the operation were totally elective and the consultant felt it could make a difference, it would be appropriate to suggest that blood pressure be optimized beforehand.
• A recommendation on whether and when to change the beta-blocker dosage. If the dosage needs to be increased, the anesthesiologist will want to know how many doses are needed to reach a new steady state. Joint guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA)² recommend 7 to 30 days, but this time frame is unrealistic in this setting, so more practical advice would be appreciated. A good consult notes any deviation from established guidelines, however, and explains the rationale for such deviation.
• Evaluation of the myocardium at risk. This is especially important with left main disease, as it influences the decision whether to test or intervene versus proceeding with careful beta-blocker titration.
• Evaluation of myocardial function and, if appropriate, a therapy suggestion for optimization.
• Notation of the heart rate or blood pressure thresholds at which ischemia develops if a stress test is performed.

 

 

GOOD GUIDANCE FROM THE ACC/AHA GUIDELINES

Our advice here is broadly consistent with the aforementioned 2007 ACC/AHA guidelines on perioperative cardiovascular evaluation for noncardiac surgery.² The following observation on cardiac evaluations from these guidelines applies to preoperative consults in general:

The purpose of preoperative evaluation is not to give medical clearance but rather to perform an evaluation of the patient’s current medical status; make recommendations concerning the evaluation, management, and risk of cardiac problems over the entire perioperative period; and provide a clinical risk profile that [can be used] in making treatment decisions that may influence short- and long-term cardiac outcomes.²

These guidelines contain a good description of the ideal preoperative evaluation and consult in a short section (Section II, “General Approach to the Patient”)² that is worthy of wide dissemination.

DISCUSSION

Question from the audience: Many consults are written more for the surgical team than for the anesthesiologists, hence advice such as managing intraoperative diabetes. Isn’t that appropriate?

Dr. Lubarsky: There are a variety of users of the information in a consult note. I focused on the anesthesiologist, but certainly the surgical staff and house staff would benefit from suggestions about postoperative management. However, they would not benefit from suggestions on intraoperative management; surgeons simply do not need this information and the anesthesiologist will have his or her own regimen. But if there is a specific type of insulin infusion that’s been shown to be best in the specific patient at hand, then detailing that obviously is beneficial.

Question from the audience: We all agree that communication is key, but how does the consultant reach the anesthesiologist to find out what he or she wants to know when the anesthesiologist isn’t usually assigned to the case until a day before surgery?

Dr. Lubarsky: If no anesthesiologist is yet assigned to a case, the consultant can discuss the case with the chief of the anesthesiology department. The discussion should be documented in the note. But it’s important that the system be changed so that anesthesiologists are assigned to cases well in advance. I instituted such a policy at my previous hospital. Many hospitals schedule surgeries 3 months in advance, and many anesthesiology departments have schedules made at least 1 month and often 2 to 3 months in advance. The department could assign a specific anesthesiologist to a future scheduled case with ease.

Question from the audience: How do anesthesiologists educate all the various people we rely on for consults when we can’t get them in one place at one time?

Dr. Lubarsky: It’s a challenge. I try many things, such as going to cardiology rounds, but there are always new people coming through. A good monograph or a set of guidelines with examples would help. If each specialty educates the other and speaks at each other’s conferences more often, that should help. Anesthesiologists would benefit from hearing about the challenges medical consultants face; we may not be doing all we can to optimize perioperative care. There’s room for improvement through communication on both sides. I should also emphasize that we’re all trying to do the right thing. Doctors try to be accommodating, but that doesn’t always make for good decisions. Recently a consultant in my hospital did a preoperative stress test on a patient who didn’t need one. When I asked why, he said, “Because the surgeon asked me to.”

Question from the audience: But don’t you agree that many anesthesiologists would like to see that negative stress test, even if a stress test is not indicated by the guidelines? Cardiologists know that the anesthesiologists are often looking for that on the morning of surgery.

Dr. Lubarsky: The point is that physicians should be responsible for what they have expertise in. When I am asked to intubate a patient, my response as an expert in intubation might be, “Actually, he doesn’t need to be intubated right now.” In the case of this unnecessary stress test, the cardiologist probably should have called the surgeon and said, “It’s really not indicated because the patient had a negative stress test 2 years ago, there’s been no change in symptoms and no angina since then, and he operates well above 4 metabolic equivalents. There’s a clear-cut reason not to do it.” If the surgeon still wanted the test done just to be reassured, that’s simply a poor use of society’s resources. We depend on experts to identify the tests that are indicated to evaluate a patient’s disease and not just do tests for the sake of doing them.

Perioperative management of surgical patients who require temporary discontinuation of vitamin K antagonists (warfarin) or antiplatelet drugs is complicated. The risk of a thrombotic event during interruption of anticoagulant or antiplatelet therapy must be weighed against the risk of bleeding when such therapy is used in close proximity to a surgical procedure. This balancing of risks is guided by the patient’s individual risk for thromboembolism or bleeding and underlying conditions such as the presence of a mechanical heart valve or a coronary stent.

High-profile adverse events have made anticoagulant and antiplatelet management one of the most highly litigated aspects of perioperative medicine. Moreover, there is a paucity of randomized clinical trial data and definitive guidelines to address the perioperative needs of patients on antithrombotic therapy. Treatment protocols vary depending on many underlying factors, such as the presence of mechanical heart valves, comorbidities, stent type and location, patient age and medical history, and type of surgical procedure. While recent attention has focused on genetic variations that result in higher or lower sensitivity to warfarin in some patients, routine genetic testing for warfarin sensitivity is controversial and not part of widespread practice at this time.

The first portion of this article explores key issues and principles in the perioperative management of surgical patients on warfarin therapy, and the second portion does the same for surgical patients on antiplatelet therapy.

ACCP RECOMMENDATIONS FOR PERIOPERATIVE ANTICOAGULANT MANAGEMENT

In 2008 the American College of Chest Physicians (ACCP) published the latest update of its consensus guidelines for the perioperative management of patients receiving antithrombotic therapy.¹ The guidelines’ recommendations for anticoagulant management are based on stratification of patients into risk categories (Table 1) according to their underlying indication for long-term anticoagulation—ie, presence of a mechanical heart valve, history of atrial fibrillation, or history of venous thromboembolism (VTE).

Patients with mechanical valves who are at high risk for perioperative thromboembolism include those with any mechanical mitral valve, an older valve, or a history of stroke or transient ischemic attack (TIA). Patients with atrial fibrillation who are at high risk include those with a recent stroke or TIA, rheumatic valvular heart disease, or a CHADS₂ score of 5 or 6. (The CHADS₂ scoring system assigns one point each for a history of congestive heart failure, hypertension, age greater than 75 years, or diabetes, and two points for history of stroke or TIA.) Patients with a history of VTE within the prior 3 months are also considered high risk.

Bridging anticoagulation (bridge therapy)—ie, the temporary use of intravenous unfractionated heparin (IV UFH) or low-molecular-weight heparin (LMWH) prior to surgery—is central to the ACCP’s recommendations for perioperative management in patients on long-term anticoagulant therapy. Key ACCP recommendations¹ for these patients, according to their risk for thromboembolism (Table 1), are as follows:

• High risk—bridging anticoagulation with therapeutic-dose subcutaneous LMWH or IV UFH
• Moderate risk—bridging anticoagulation with therapeutic-dose subcutaneous LMWH, therapeutic-dose IV UFH, or low-dose subcutaneous LMWH
• Low risk—bridging anticoagulation with low-dose subcutaneous LMWH or no bridging.

ASSESSING RISKS: DETERMINING WHETHER TO BRIDGE

Considerations in bridge therapy include balancing the risk of thromboembolism against the risk of bleeding, either of which can lead to catastrophic results.² Though the objective of bridge therapy is to avoid bleeding complications associated with invasive procedures, the bridge protocol itself can introduce additional serious complications. Figure 1 presents an algorithm for identifying patient and surgical risk factors for patients on anticoagulation therapy who are undergoing elective surgery.

Patient-specific risk factors

Patient risk factors include the indication for anti­coagulation, as detailed above, as well as other individual risks for thromboembolism, as discussed in the article by Michota on preventing VTE on page S45 of this supplement.

If anticoagulation is indicated because the patient has a mechanical heart valve, the valve type and position must be considered because these factors affect thrombo­embolic risk, as reflected in Table 1. For instance, the risk of thromboembolism is greater when the valve is in the mitral position than in the aortic position, and is also greater with an older caged-ball valve than with a newer-generation bileaflet valve.³

In patients receiving anticoagulation because of atrial fibrillation, annual stroke risk can be estimated using the validated CHADS₂ scoring system, as presented in Table 2.⁴ Generally, patients with atrial fibrillation who have a CHADS₂ score of 3 or higher should receive bridge therapy, while those with a CHADS₂ score of 2 or lower probably should not.

Procedure-related risk factors

Surgical risks factors include the type of surgery and its associated risks of bleeding and thromboembolism, as well as the expected time that anticoagulation will be interrupted. Estimating thromboembolic risk is complicated, however, and reliable results are generally not achieved with simplistic calculations or formulas. Such calculations tend not to appropriately account for the hypercoagulable state induced by surgery itself, as the risk of VTE is estimated to be 100 times greater during the perioperative period than in the nonoperative setting, owing to increased levels of plasminogen activator inhibitor-1. Moreover, multiple studies have demonstrated increases in coagulation factors that suggest that a “rebound hypercoagulability” may occur shortly after discontinuation of oral anti­coagulant therapy.^5–8

Net benefit vs risk in trials of bridge therapy

Several prospective studies of bridge therapy have been conducted in more than 2,700 surgical patients with mechanical heart valves, atrial fibrillation, or prior VTE.^9–14 Warfarin was discontinued in these patients and replaced with LMWH as bridge therapy. As shown in Table 3, the rate of thromboembolism at follow-up (2 weeks to 90 days) in these studies averaged approximately 1%, while the risk of major bleeding was approximately 3.5%.^9–14

In an analysis of data from observational studies, Kearon and Hirsh estimated the relative risk reduction for thromboembolism with bridge therapy to be 66% to 80%, depending on the indication for anticoagulation.⁸ Thus, if a patient’s risk of developing thromboembolism is 1.5%, bridge therapy reduces the risk to 0.5% or less.

Weigh relative consequences of an event with the patient

Determining whether and how to initiate bridge therapy ultimately depends on the consequences of an event. Recurrent VTE is fatal in 5% to 10% of cases,¹⁵ and arterial thromboembolism is fatal in 20% of cases and causes permanent disability in at least 50% of cases.¹⁶ While 9% to 13% of major bleeding events are fatal, bleeding rarely causes permanent disability.¹⁷ Thus, whereas a patient who bleeds can be resuscitated, a patient who develops a thrombo­embolism may be permanently disabled. These considerations should be shared with the patient, and patient preference should factor into the management strategy. Though the risk of bleeding with anticoagulation may be much higher than the risk of stroke without it, many patients will be more concerned about stroke risk.

 

 

CHOICE OF AGENT FOR BRIDGE THERAPY

LMWH appears to offer cost advantage over UFH

For cost reasons, managed care organizations often recommend LMWH, which can be administered sub­cutaneously in outpatient settings, over IV UFH administered in the hospital. A retrospective analysis of medical costs from the 1990s in a managed care organization found that bridge therapy with LMWH prior to elective surgery cost an average of $13,114 less per patient (in total cost of care) than did bridge therapy with UFH.¹⁸

LMWH safety issues in valve patients are a myth

Clinical outcomes were not statistically significantly different for patients receiving LMWH or UFH in the above study.¹⁸ Nevertheless, there is a widely held notion that LMWH is not safe to use as bridge therapy for patients with mechanical heart valves. Recent prospective bridge studies do not support that view, demonstrating that LMWH used as bridge therapy is associated with low risks for thromboembolism and major bleeding even in patients with mechanical valves.^9,10,12–14 In contrast, recent data on the use of IV UFH for bridging is minimal, with most bridge studies dating to the 1970s. Accordingly, the latest ACCP guidelines for perioperative management of patients on antithrombotic therapy recommend therapeutic-dose LMWH over IV UFH for bridge therapy, including in patients with mechanical heart valves.¹ Likewise, 2006 guidelines from the American College of Cardiology and American Heart Association on management of patients with valvular heart disease endorse LMWH as an option for bridge therapy.¹⁹

A PRACTICAL APPROACH TO BRIDGE THERAPY

A bridge therapy protocol for patients receiving warfarin has been successfully used at the Cleveland Clinic, where I previously practiced. Essentials of the protocol²⁰ are summarized here, followed by commentary that draws on additional sources.

Before surgery

• Discontinue warfarin 5 days before surgery (ie, hold four doses) if the preoperative international normalized ratio (INR) is 2 to 3, and 6 days before surgery (hold five doses) if the INR is 3 to 4.5.
• For bridge therapy, start LMWH (enoxaparin 1 mg/kg or dalteparin 100 IU/kg subcutaneously every 12 hours) beginning 36 hours after the last dose of warfarin.
• Give the last dose of LMWH approximately 24 hours prior to surgery.

After surgery

• For minor surgery, reinitiate LMWH at full dose approximately 24 hours after surgery. For major surgery and for patients at high risk of bleeding, consider using prophylactic doses on the first two postoperative days.
• Discuss the timing of anticoagulant reinitiation with the surgeon.
• Restart warfarin at preoperative dose 1 day after surgery. 
• Order daily prothrombin time/INR tests until the patient is discharged and periodically after discharge until the INR is within the therapeutic range.
• Order a complete blood cell count with platelets on days 3 and 7.
• Discontinue LMWH when the INR is between 2 and 3 for 2 consecutive days.

Additionally, the plan should be discussed in advance with the patient, surgeon, and anesthesiologist, along with the risks and benefits associated with LMWH. The patient should receive written instructions for self-administration and information about signs and symptoms of bleeding and thromboembolism.

When to stop warfarin

Warfarin should be discontinued far enough in advance of surgery to achieve a preoperative target INR of less than 1.2.²¹ Patients with an initial INR of 2 to 3 tend to achieve that target after discontinuation of warfarin for about 5 days (four doses). A longer wait (6 days, or five doses) is necessary for patients with an initial INR of 3 to 4. Age is associated with a slower rate of decrease in the INR, and there is wide interpatient variation. The INR should always be checked prior to surgery.²¹

Warfarin need not be stopped for all procedures

It is commonly assumed that warfarin should be discontinued for any procedure, including minor surgery. But several procedures, listed in Table 4, can be performed safely without discontinuing long-term anticoagulation, as suggested by several literature reviews and comparative studies.^22–25 Additionally, a 2003 systematic review concluded that major bleeding with continuation of therapeutic oral anticoagulation was rare for patients undergoing dental procedures, arthrocentesis, cataract surgery, upper endoscopy, or colonoscopy.²⁶

If warfarin is stopped for minor procedures, bridging may be counterproductive

At the same time, a recent prospective observational study evaluated the effects of brief (≤ 5 days) interruption of warfarin among more than 1,000 patients undergoing minor outpatient procedures and found low rates of both thromboembolism (0.7%) and major bleeding (0.6%).²⁷ The risk of major bleeding was significantly higher among the small proportion of patients who received bridge therapy with UFH or LMWH. The study concluded that interrupting warfarin for 5 days or less for minor outpatient procedures carries a low risk of thromboembolism and that the risk of clinically significant bleeding should be weighed before bridge therapy is considered in this setting.

When to stop bridge therapy preoperatively

Bridge therapy with LMWH is commonly discontinued 12 hours before surgery, but it is preferable to discontinue 24 hours before surgery. In a study of preoperative anticoagulant activity in 80 patients, LMWH (enoxaparin 1 mg/kg) was administered twice daily and discontinued the night before surgery.²⁸ Blood anti–factor Xa levels were measured shortly before surgery, at which time 68% of patients still had therapeutic levels of anti–Xa. This suggests that discontinuing LMWH too close to the time of surgery can increase the risk of bleeding.

Consistent with these findings, consensus guidelines from the American Society of Regional Anesthesia and Pain Medicine (ASRA) recommend that needle placement for regional anesthesia take place 12 hours after the last dose of LMWH if prophylactic dosing is used and 24 hours after the last dose of LMWH if therapeutic dosing is used (ie, ≥ 1 mg/kg of enoxaparin every 12 hours).²⁹

Dosing and timing of postoperative bridge therapy

Postoperative use of full-dose bridge therapy is associated with increased risks of bleeding, according to a multicenter study of approximately 500 patients who received various doses of UFH or LMWH for bridge therapy.¹⁴ Patients who received full-dose LMWH or UFH after surgery had a fivefold to sixfold increase in the incidence of major bleeding compared with patients who received prophylactic doses. The study centers that frequently used full-dose bridge protocols were four times as likely to report major bleeding events. In light of these findings, waiting a couple of days after surgery to initiate full-dose bridge therapy is recommended, and prophylactic dosing may be considered in the interim.

The ASRA consensus guidelines recommend that indwelling catheters be removed prior to postoperative reinitiation of twice-daily dosing of LMWH. The first dose of LMWH should be given no sooner than 2 hours after catheter removal. Once-daily dosing of LMWH (European dosing) is acceptable under the ASRA guidelines, but the first dose should be given 6 to 8 hours after surgery and the second dose no sooner than 24 hours later. The guidelines state that once-daily (but not twice-daily) LMWH dosing is acceptable in patients with indwelling catheters; neurological status should be monitored in these patients, and the catheter should be removed 12 to 24 hours after the last dose of LMWH.²⁹

 

 

PERIOPERATIVE MANAGEMENT OF ANTIPLATELET THERAPY: TYPE OF AGENT MATTERS

Unlike the considerations with warfarin, the timing of preoperative discontinuation of antiplatelet therapy in patients undergoing noncardiac surgery depends on the type of agent used and its pharmacokinetic actions. Commonly used antiplatelet drugs include aspirin, the thienopyridine agent clopidogrel, and nonsteroidal anti-inflammatory drugs (NSAIDs).

Aspirin works by irreversibly inhibiting platelet cyclooxygenase. The circulating platelet pool is replaced every 7 to 10 days, so aspirin therapy should be discontinued 7 to 10 days before surgery.¹

NSAIDs reversibly inhibit platelet cyclooxygenase. Knowing whether a patient is using short- or long-acting NSAIDs is important for determining when to discontinue therapy. For a short-acting NSAID such as ibuprofen, discontinuation 24 hours before surgery may be adequate to normalize platelet function.^1,30

Thienopyridines inhibit adenosine diphosphate receptor–mediated platelet activation and aggregation. Short-acting thienopyridines may be discontinued 24 hours before surgery, but long-acting agents such as clopidogrel should be stopped 7 days prior to surgery (including when used with aspirin as dual antiplatelet therapy),¹ although some outcomes data suggest that 5 days may be sufficient.³¹

All of these agents should be resumed as soon as adequate hemostasis is achieved after surgery. The ACCP guidelines on perioperative management of antithrombotic therapy recommend resumption of aspirin at the usual maintenance dose the day after surgery, but they make no specific recommendations on when to resume other antiplatelet drugs.¹

ANTIPLATELET THERAPY: SPECIAL CONSIDERATIONS IN PATIENTS WITH STENTS

Patients who are on antiplatelet therapy because they have a coronary stent merit special consideration due to the high risk of thrombosis if therapy is interrupted. The risk of stent thrombosis is especially elevated in the postoperative period, particularly if surgery follows soon after stent placement.

Optimal preoperative management of patients with coronary artery stents depends on many factors, as outlined in Table 5. Some patients carry a wallet card that provides some of this crucial information, such as the type of stent and the date and location of its placement, but speaking with the patient’s cardiologist is always recommended. This information, determined in conjunction with the cardiologist, should be used to inform the key perioperative considerations in this setting:

• Relative risks and benefits of stopping versus continuing antiplatelet therapy
• Identification of patients at high risk for a perioperative event after cessation of antiplatelet therapy
• Identification of patients at high risk of bleeding.

Bleeding vs stent thrombosis: Consider relative consequences

The risk of bleeding varies by individual patient. No laboratory tests are available to determine individual bleeding risk, but the risk of perioperative bleeding increases when two or more antiplatelet agents are used, as in dual antiplatelet therapy with aspirin and clopidogrel.³¹

When balancing risks of bleeding versus thrombotic events, the relative consequences of each event again must be considered. Bleeding is rarely life-threatening in comparison with the potential consequences of stent thrombosis. In a prospective observational study of 2,229 patients who received drug-eluting stents, 29 (1.3%) developed stent thrombosis during 9-month follow-up.³² Among these patients, 20 (69%) had a nonfatal myocardial infarction and 13 (45%) died. The most significant independent risk factor for stent thrombosis was premature discontinuation of antiplatelet therapy (hazard ratio = 89.78 [95% CI, 29.90–260.60]; P < .001). Other independent risk factors included renal failure, bifurcation lesions, diabetes, and low ejection fraction.

Premature interruption of antiplatelet therapy: Why it matters

Abrupt discontinuation of antiplatelet therapy can lead to a rebound effect marked by an inflammatory prothrombotic state, increased platelet adhesion and aggregation, and excessive thromboxane A₂ activity. Surgery further increases the prothrombotic and inflammatory state, which, combined with incompletely endothelialized drug-eluting stents, can lead to stent thrombosis and, consequently, myocardial infarction and/or death.³³

Timing of surgery after stenting: Getting it right

The US Food and Drug Administration recommends that dual antiplatelet therapy be continued for at least 3 months after placement of a sirolimus-eluting stent and at least 6 months after placement of a paclitaxel-eluting stent. Recent data suggest, however, that this duration of antiplatelet therapy may not be sufficient and that at least 1 year of therapy may be needed.³⁴

A recent joint science advisory from the American College of Cardiology (ACC) and the American Heart Association (AHA) emphasizes the importance of educating providers about the “potentially catastrophic” risks of premature stopping of thienopyridine therapy in patients with coronary stents.³⁴ In addition to recommendations in this joint advisory, the ACC and AHA issued updated guidelines in 2007 on perioperative cardiovascular evaluation and care for noncardiac surgery.³⁵ Below is a summary of recommendations on the timing of surgery following stenting in light of these and other sources:

• Following placement of a bare metal stent, elective and nonurgent procedures should be delayed for at least 1 month, according to the ACC/AHA joint advisory,³⁴ or at least 6 weeks, according to the ACC/AHA guidelines.³⁵ Newer data suggest that the optimal interval for delay is likely to be 3 months.^36,37
• For patients with recent (< 6 weeks) bare metal stent placement who require urgent surgery, dual antiplatelet therapy should be continued during the perioperative period.¹
• Following placement of a drug-eluting stent, elective and nonurgent procedures should be delayed for at least 12 months.^34,35
• For patients with recent drug-eluting stent placement in whom surgery cannot be delayed, dual antiplatelet therapy should be continued without interruption if the stent was placed within the prior 6 months.^1,35 If the stent was placed more than 6 months before urgent surgery, aspirin should be continued without interruption (at ≥ 81 mg/day) and clopidogrel should be continued until 5 days before surgery and resumed as soon as possible after surgery (at a loading dose of 300 mg followed by 75 mg/day). If the surgeon is comfortable continuing dual antiplatelet therapy in a patient whose stent was placed 6 to 12 months earlier, that course should be considered.¹

It is important to note that the ACC/AHA joint advisory³⁴ and other documents have medicolegal implications, so delaying nonurgent surgery for the periods recommended is the most prudent approach.

 

 

CONCLUSIONS

Perioperative management of anticoagulant and antiplatelet therapy is complicated by the paucity of randomized clinical trial data and the risk for serious adverse events. The underlying indications for anticoagulant and antiplatelet therapy vary widely, so the best approach to perioperative management is to involve all members of the health care team—hospitalist, surgeon, cardiologist, and anesthesiologist, together with the patient—to ensure that care is individualized and all relevant considerations are accounted for. Patient and surgical risks can be identified and quantified to some extent, but patients often have greater concerns about the risk of stroke than the risk of bleeding. Ideally, nonemergency surgeries should be scheduled to allow enough time to thoroughly plan the management protocol, reducing risks for bleeding and thrombotic events as much as possible.

DISCUSSION

Question from the audience: If a patient’s INR is 1.3 or 1.4, rather than the recommended 1.2, is it necessary to cancel a planned epidural?

Dr. Jaffer: It depends on how comfortable the surgeon or anesthesiologist is with the INR level. Generally, an INR less than 1.5 is probably acceptable, but it depends on the procedure. For a craniotomy, for example, 1.2 is recommended.

Question from the audience: Is it necessary to use anti–Xa levels to guide bridge therapy when administering LMWH or UFH in a patient with a mechanical heart valve?

Dr. Jaffer: It’s not generally necessary, except for pregnant women. For most patients, doses are calculated as milligrams of LMWH per kilogram body weight or as International Units of LMWH per kilogram.

Question from the audience: You mentioned medico­legal disputes arising from adverse events associated with bridge therapy, drug discontinuation, or related issues. Who has final responsibility for making decisions about discontinuation of antiplatelet therapy, for example?

Dr. Jaffer: I don’t know if it ultimately comes down to just one person. Several physicians should be involved in the decision, and communication protocols within an institution should be very clear. It’s important to make certain everyone involved in the decision is reviewing the same literature. The final decision has to be something everyone involved can accept and support.

Perioperative management of surgical patients who require temporary discontinuation of vitamin K antagonists (warfarin) or antiplatelet drugs is complicated. The risk of a thrombotic event during interruption of anticoagulant or antiplatelet therapy must be weighed against the risk of bleeding when such therapy is used in close proximity to a surgical procedure. This balancing of risks is guided by the patient’s individual risk for thromboembolism or bleeding and underlying conditions such as the presence of a mechanical heart valve or a coronary stent.

High-profile adverse events have made anticoagulant and antiplatelet management one of the most highly litigated aspects of perioperative medicine. Moreover, there is a paucity of randomized clinical trial data and definitive guidelines to address the perioperative needs of patients on antithrombotic therapy. Treatment protocols vary depending on many underlying factors, such as the presence of mechanical heart valves, comorbidities, stent type and location, patient age and medical history, and type of surgical procedure. While recent attention has focused on genetic variations that result in higher or lower sensitivity to warfarin in some patients, routine genetic testing for warfarin sensitivity is controversial and not part of widespread practice at this time.

The first portion of this article explores key issues and principles in the perioperative management of surgical patients on warfarin therapy, and the second portion does the same for surgical patients on antiplatelet therapy.

ACCP RECOMMENDATIONS FOR PERIOPERATIVE ANTICOAGULANT MANAGEMENT

In 2008 the American College of Chest Physicians (ACCP) published the latest update of its consensus guidelines for the perioperative management of patients receiving antithrombotic therapy.¹ The guidelines’ recommendations for anticoagulant management are based on stratification of patients into risk categories (Table 1) according to their underlying indication for long-term anticoagulation—ie, presence of a mechanical heart valve, history of atrial fibrillation, or history of venous thromboembolism (VTE).

Patients with mechanical valves who are at high risk for perioperative thromboembolism include those with any mechanical mitral valve, an older valve, or a history of stroke or transient ischemic attack (TIA). Patients with atrial fibrillation who are at high risk include those with a recent stroke or TIA, rheumatic valvular heart disease, or a CHADS₂ score of 5 or 6. (The CHADS₂ scoring system assigns one point each for a history of congestive heart failure, hypertension, age greater than 75 years, or diabetes, and two points for history of stroke or TIA.) Patients with a history of VTE within the prior 3 months are also considered high risk.

Bridging anticoagulation (bridge therapy)—ie, the temporary use of intravenous unfractionated heparin (IV UFH) or low-molecular-weight heparin (LMWH) prior to surgery—is central to the ACCP’s recommendations for perioperative management in patients on long-term anticoagulant therapy. Key ACCP recommendations¹ for these patients, according to their risk for thromboembolism (Table 1), are as follows:

• High risk—bridging anticoagulation with therapeutic-dose subcutaneous LMWH or IV UFH
• Moderate risk—bridging anticoagulation with therapeutic-dose subcutaneous LMWH, therapeutic-dose IV UFH, or low-dose subcutaneous LMWH
• Low risk—bridging anticoagulation with low-dose subcutaneous LMWH or no bridging.

ASSESSING RISKS: DETERMINING WHETHER TO BRIDGE

Considerations in bridge therapy include balancing the risk of thromboembolism against the risk of bleeding, either of which can lead to catastrophic results.² Though the objective of bridge therapy is to avoid bleeding complications associated with invasive procedures, the bridge protocol itself can introduce additional serious complications. Figure 1 presents an algorithm for identifying patient and surgical risk factors for patients on anticoagulation therapy who are undergoing elective surgery.

Patient-specific risk factors

Patient risk factors include the indication for anti­coagulation, as detailed above, as well as other individual risks for thromboembolism, as discussed in the article by Michota on preventing VTE on page S45 of this supplement.

If anticoagulation is indicated because the patient has a mechanical heart valve, the valve type and position must be considered because these factors affect thrombo­embolic risk, as reflected in Table 1. For instance, the risk of thromboembolism is greater when the valve is in the mitral position than in the aortic position, and is also greater with an older caged-ball valve than with a newer-generation bileaflet valve.³

In patients receiving anticoagulation because of atrial fibrillation, annual stroke risk can be estimated using the validated CHADS₂ scoring system, as presented in Table 2.⁴ Generally, patients with atrial fibrillation who have a CHADS₂ score of 3 or higher should receive bridge therapy, while those with a CHADS₂ score of 2 or lower probably should not.

Procedure-related risk factors

Surgical risks factors include the type of surgery and its associated risks of bleeding and thromboembolism, as well as the expected time that anticoagulation will be interrupted. Estimating thromboembolic risk is complicated, however, and reliable results are generally not achieved with simplistic calculations or formulas. Such calculations tend not to appropriately account for the hypercoagulable state induced by surgery itself, as the risk of VTE is estimated to be 100 times greater during the perioperative period than in the nonoperative setting, owing to increased levels of plasminogen activator inhibitor-1. Moreover, multiple studies have demonstrated increases in coagulation factors that suggest that a “rebound hypercoagulability” may occur shortly after discontinuation of oral anti­coagulant therapy.^5–8

Net benefit vs risk in trials of bridge therapy

Several prospective studies of bridge therapy have been conducted in more than 2,700 surgical patients with mechanical heart valves, atrial fibrillation, or prior VTE.^9–14 Warfarin was discontinued in these patients and replaced with LMWH as bridge therapy. As shown in Table 3, the rate of thromboembolism at follow-up (2 weeks to 90 days) in these studies averaged approximately 1%, while the risk of major bleeding was approximately 3.5%.^9–14

In an analysis of data from observational studies, Kearon and Hirsh estimated the relative risk reduction for thromboembolism with bridge therapy to be 66% to 80%, depending on the indication for anticoagulation.⁸ Thus, if a patient’s risk of developing thromboembolism is 1.5%, bridge therapy reduces the risk to 0.5% or less.

Weigh relative consequences of an event with the patient

Determining whether and how to initiate bridge therapy ultimately depends on the consequences of an event. Recurrent VTE is fatal in 5% to 10% of cases,¹⁵ and arterial thromboembolism is fatal in 20% of cases and causes permanent disability in at least 50% of cases.¹⁶ While 9% to 13% of major bleeding events are fatal, bleeding rarely causes permanent disability.¹⁷ Thus, whereas a patient who bleeds can be resuscitated, a patient who develops a thrombo­embolism may be permanently disabled. These considerations should be shared with the patient, and patient preference should factor into the management strategy. Though the risk of bleeding with anticoagulation may be much higher than the risk of stroke without it, many patients will be more concerned about stroke risk.

 

 

CHOICE OF AGENT FOR BRIDGE THERAPY

LMWH appears to offer cost advantage over UFH

For cost reasons, managed care organizations often recommend LMWH, which can be administered sub­cutaneously in outpatient settings, over IV UFH administered in the hospital. A retrospective analysis of medical costs from the 1990s in a managed care organization found that bridge therapy with LMWH prior to elective surgery cost an average of $13,114 less per patient (in total cost of care) than did bridge therapy with UFH.¹⁸

LMWH safety issues in valve patients are a myth

Clinical outcomes were not statistically significantly different for patients receiving LMWH or UFH in the above study.¹⁸ Nevertheless, there is a widely held notion that LMWH is not safe to use as bridge therapy for patients with mechanical heart valves. Recent prospective bridge studies do not support that view, demonstrating that LMWH used as bridge therapy is associated with low risks for thromboembolism and major bleeding even in patients with mechanical valves.^9,10,12–14 In contrast, recent data on the use of IV UFH for bridging is minimal, with most bridge studies dating to the 1970s. Accordingly, the latest ACCP guidelines for perioperative management of patients on antithrombotic therapy recommend therapeutic-dose LMWH over IV UFH for bridge therapy, including in patients with mechanical heart valves.¹ Likewise, 2006 guidelines from the American College of Cardiology and American Heart Association on management of patients with valvular heart disease endorse LMWH as an option for bridge therapy.¹⁹

A PRACTICAL APPROACH TO BRIDGE THERAPY

A bridge therapy protocol for patients receiving warfarin has been successfully used at the Cleveland Clinic, where I previously practiced. Essentials of the protocol²⁰ are summarized here, followed by commentary that draws on additional sources.

Before surgery

• Discontinue warfarin 5 days before surgery (ie, hold four doses) if the preoperative international normalized ratio (INR) is 2 to 3, and 6 days before surgery (hold five doses) if the INR is 3 to 4.5.
• For bridge therapy, start LMWH (enoxaparin 1 mg/kg or dalteparin 100 IU/kg subcutaneously every 12 hours) beginning 36 hours after the last dose of warfarin.
• Give the last dose of LMWH approximately 24 hours prior to surgery.

After surgery

• For minor surgery, reinitiate LMWH at full dose approximately 24 hours after surgery. For major surgery and for patients at high risk of bleeding, consider using prophylactic doses on the first two postoperative days.
• Discuss the timing of anticoagulant reinitiation with the surgeon.
• Restart warfarin at preoperative dose 1 day after surgery. 
• Order daily prothrombin time/INR tests until the patient is discharged and periodically after discharge until the INR is within the therapeutic range.
• Order a complete blood cell count with platelets on days 3 and 7.
• Discontinue LMWH when the INR is between 2 and 3 for 2 consecutive days.

Additionally, the plan should be discussed in advance with the patient, surgeon, and anesthesiologist, along with the risks and benefits associated with LMWH. The patient should receive written instructions for self-administration and information about signs and symptoms of bleeding and thromboembolism.

When to stop warfarin

Warfarin should be discontinued far enough in advance of surgery to achieve a preoperative target INR of less than 1.2.²¹ Patients with an initial INR of 2 to 3 tend to achieve that target after discontinuation of warfarin for about 5 days (four doses). A longer wait (6 days, or five doses) is necessary for patients with an initial INR of 3 to 4. Age is associated with a slower rate of decrease in the INR, and there is wide interpatient variation. The INR should always be checked prior to surgery.²¹

Warfarin need not be stopped for all procedures

It is commonly assumed that warfarin should be discontinued for any procedure, including minor surgery. But several procedures, listed in Table 4, can be performed safely without discontinuing long-term anticoagulation, as suggested by several literature reviews and comparative studies.^22–25 Additionally, a 2003 systematic review concluded that major bleeding with continuation of therapeutic oral anticoagulation was rare for patients undergoing dental procedures, arthrocentesis, cataract surgery, upper endoscopy, or colonoscopy.²⁶

If warfarin is stopped for minor procedures, bridging may be counterproductive

At the same time, a recent prospective observational study evaluated the effects of brief (≤ 5 days) interruption of warfarin among more than 1,000 patients undergoing minor outpatient procedures and found low rates of both thromboembolism (0.7%) and major bleeding (0.6%).²⁷ The risk of major bleeding was significantly higher among the small proportion of patients who received bridge therapy with UFH or LMWH. The study concluded that interrupting warfarin for 5 days or less for minor outpatient procedures carries a low risk of thromboembolism and that the risk of clinically significant bleeding should be weighed before bridge therapy is considered in this setting.

When to stop bridge therapy preoperatively

Bridge therapy with LMWH is commonly discontinued 12 hours before surgery, but it is preferable to discontinue 24 hours before surgery. In a study of preoperative anticoagulant activity in 80 patients, LMWH (enoxaparin 1 mg/kg) was administered twice daily and discontinued the night before surgery.²⁸ Blood anti–factor Xa levels were measured shortly before surgery, at which time 68% of patients still had therapeutic levels of anti–Xa. This suggests that discontinuing LMWH too close to the time of surgery can increase the risk of bleeding.

Consistent with these findings, consensus guidelines from the American Society of Regional Anesthesia and Pain Medicine (ASRA) recommend that needle placement for regional anesthesia take place 12 hours after the last dose of LMWH if prophylactic dosing is used and 24 hours after the last dose of LMWH if therapeutic dosing is used (ie, ≥ 1 mg/kg of enoxaparin every 12 hours).²⁹

Dosing and timing of postoperative bridge therapy

Postoperative use of full-dose bridge therapy is associated with increased risks of bleeding, according to a multicenter study of approximately 500 patients who received various doses of UFH or LMWH for bridge therapy.¹⁴ Patients who received full-dose LMWH or UFH after surgery had a fivefold to sixfold increase in the incidence of major bleeding compared with patients who received prophylactic doses. The study centers that frequently used full-dose bridge protocols were four times as likely to report major bleeding events. In light of these findings, waiting a couple of days after surgery to initiate full-dose bridge therapy is recommended, and prophylactic dosing may be considered in the interim.

The ASRA consensus guidelines recommend that indwelling catheters be removed prior to postoperative reinitiation of twice-daily dosing of LMWH. The first dose of LMWH should be given no sooner than 2 hours after catheter removal. Once-daily dosing of LMWH (European dosing) is acceptable under the ASRA guidelines, but the first dose should be given 6 to 8 hours after surgery and the second dose no sooner than 24 hours later. The guidelines state that once-daily (but not twice-daily) LMWH dosing is acceptable in patients with indwelling catheters; neurological status should be monitored in these patients, and the catheter should be removed 12 to 24 hours after the last dose of LMWH.²⁹

 

 

PERIOPERATIVE MANAGEMENT OF ANTIPLATELET THERAPY: TYPE OF AGENT MATTERS

Unlike the considerations with warfarin, the timing of preoperative discontinuation of antiplatelet therapy in patients undergoing noncardiac surgery depends on the type of agent used and its pharmacokinetic actions. Commonly used antiplatelet drugs include aspirin, the thienopyridine agent clopidogrel, and nonsteroidal anti-inflammatory drugs (NSAIDs).

Aspirin works by irreversibly inhibiting platelet cyclooxygenase. The circulating platelet pool is replaced every 7 to 10 days, so aspirin therapy should be discontinued 7 to 10 days before surgery.¹

NSAIDs reversibly inhibit platelet cyclooxygenase. Knowing whether a patient is using short- or long-acting NSAIDs is important for determining when to discontinue therapy. For a short-acting NSAID such as ibuprofen, discontinuation 24 hours before surgery may be adequate to normalize platelet function.^1,30

Thienopyridines inhibit adenosine diphosphate receptor–mediated platelet activation and aggregation. Short-acting thienopyridines may be discontinued 24 hours before surgery, but long-acting agents such as clopidogrel should be stopped 7 days prior to surgery (including when used with aspirin as dual antiplatelet therapy),¹ although some outcomes data suggest that 5 days may be sufficient.³¹

All of these agents should be resumed as soon as adequate hemostasis is achieved after surgery. The ACCP guidelines on perioperative management of antithrombotic therapy recommend resumption of aspirin at the usual maintenance dose the day after surgery, but they make no specific recommendations on when to resume other antiplatelet drugs.¹

ANTIPLATELET THERAPY: SPECIAL CONSIDERATIONS IN PATIENTS WITH STENTS

Patients who are on antiplatelet therapy because they have a coronary stent merit special consideration due to the high risk of thrombosis if therapy is interrupted. The risk of stent thrombosis is especially elevated in the postoperative period, particularly if surgery follows soon after stent placement.

Optimal preoperative management of patients with coronary artery stents depends on many factors, as outlined in Table 5. Some patients carry a wallet card that provides some of this crucial information, such as the type of stent and the date and location of its placement, but speaking with the patient’s cardiologist is always recommended. This information, determined in conjunction with the cardiologist, should be used to inform the key perioperative considerations in this setting:

• Relative risks and benefits of stopping versus continuing antiplatelet therapy
• Identification of patients at high risk for a perioperative event after cessation of antiplatelet therapy
• Identification of patients at high risk of bleeding.

Bleeding vs stent thrombosis: Consider relative consequences

The risk of bleeding varies by individual patient. No laboratory tests are available to determine individual bleeding risk, but the risk of perioperative bleeding increases when two or more antiplatelet agents are used, as in dual antiplatelet therapy with aspirin and clopidogrel.³¹

When balancing risks of bleeding versus thrombotic events, the relative consequences of each event again must be considered. Bleeding is rarely life-threatening in comparison with the potential consequences of stent thrombosis. In a prospective observational study of 2,229 patients who received drug-eluting stents, 29 (1.3%) developed stent thrombosis during 9-month follow-up.³² Among these patients, 20 (69%) had a nonfatal myocardial infarction and 13 (45%) died. The most significant independent risk factor for stent thrombosis was premature discontinuation of antiplatelet therapy (hazard ratio = 89.78 [95% CI, 29.90–260.60]; P < .001). Other independent risk factors included renal failure, bifurcation lesions, diabetes, and low ejection fraction.

Premature interruption of antiplatelet therapy: Why it matters

Abrupt discontinuation of antiplatelet therapy can lead to a rebound effect marked by an inflammatory prothrombotic state, increased platelet adhesion and aggregation, and excessive thromboxane A₂ activity. Surgery further increases the prothrombotic and inflammatory state, which, combined with incompletely endothelialized drug-eluting stents, can lead to stent thrombosis and, consequently, myocardial infarction and/or death.³³

Timing of surgery after stenting: Getting it right

The US Food and Drug Administration recommends that dual antiplatelet therapy be continued for at least 3 months after placement of a sirolimus-eluting stent and at least 6 months after placement of a paclitaxel-eluting stent. Recent data suggest, however, that this duration of antiplatelet therapy may not be sufficient and that at least 1 year of therapy may be needed.³⁴

A recent joint science advisory from the American College of Cardiology (ACC) and the American Heart Association (AHA) emphasizes the importance of educating providers about the “potentially catastrophic” risks of premature stopping of thienopyridine therapy in patients with coronary stents.³⁴ In addition to recommendations in this joint advisory, the ACC and AHA issued updated guidelines in 2007 on perioperative cardiovascular evaluation and care for noncardiac surgery.³⁵ Below is a summary of recommendations on the timing of surgery following stenting in light of these and other sources:

• Following placement of a bare metal stent, elective and nonurgent procedures should be delayed for at least 1 month, according to the ACC/AHA joint advisory,³⁴ or at least 6 weeks, according to the ACC/AHA guidelines.³⁵ Newer data suggest that the optimal interval for delay is likely to be 3 months.^36,37
• For patients with recent (< 6 weeks) bare metal stent placement who require urgent surgery, dual antiplatelet therapy should be continued during the perioperative period.¹
• Following placement of a drug-eluting stent, elective and nonurgent procedures should be delayed for at least 12 months.^34,35
• For patients with recent drug-eluting stent placement in whom surgery cannot be delayed, dual antiplatelet therapy should be continued without interruption if the stent was placed within the prior 6 months.^1,35 If the stent was placed more than 6 months before urgent surgery, aspirin should be continued without interruption (at ≥ 81 mg/day) and clopidogrel should be continued until 5 days before surgery and resumed as soon as possible after surgery (at a loading dose of 300 mg followed by 75 mg/day). If the surgeon is comfortable continuing dual antiplatelet therapy in a patient whose stent was placed 6 to 12 months earlier, that course should be considered.¹

It is important to note that the ACC/AHA joint advisory³⁴ and other documents have medicolegal implications, so delaying nonurgent surgery for the periods recommended is the most prudent approach.

 

 

CONCLUSIONS

Perioperative management of anticoagulant and antiplatelet therapy is complicated by the paucity of randomized clinical trial data and the risk for serious adverse events. The underlying indications for anticoagulant and antiplatelet therapy vary widely, so the best approach to perioperative management is to involve all members of the health care team—hospitalist, surgeon, cardiologist, and anesthesiologist, together with the patient—to ensure that care is individualized and all relevant considerations are accounted for. Patient and surgical risks can be identified and quantified to some extent, but patients often have greater concerns about the risk of stroke than the risk of bleeding. Ideally, nonemergency surgeries should be scheduled to allow enough time to thoroughly plan the management protocol, reducing risks for bleeding and thrombotic events as much as possible.

DISCUSSION

Question from the audience: If a patient’s INR is 1.3 or 1.4, rather than the recommended 1.2, is it necessary to cancel a planned epidural?

Dr. Jaffer: It depends on how comfortable the surgeon or anesthesiologist is with the INR level. Generally, an INR less than 1.5 is probably acceptable, but it depends on the procedure. For a craniotomy, for example, 1.2 is recommended.

Question from the audience: Is it necessary to use anti–Xa levels to guide bridge therapy when administering LMWH or UFH in a patient with a mechanical heart valve?

Dr. Jaffer: It’s not generally necessary, except for pregnant women. For most patients, doses are calculated as milligrams of LMWH per kilogram body weight or as International Units of LMWH per kilogram.

Question from the audience: You mentioned medico­legal disputes arising from adverse events associated with bridge therapy, drug discontinuation, or related issues. Who has final responsibility for making decisions about discontinuation of antiplatelet therapy, for example?

Dr. Jaffer: I don’t know if it ultimately comes down to just one person. Several physicians should be involved in the decision, and communication protocols within an institution should be very clear. It’s important to make certain everyone involved in the decision is reviewing the same literature. The final decision has to be something everyone involved can accept and support.

Perioperative management of surgical patients who require temporary discontinuation of vitamin K antagonists (warfarin) or antiplatelet drugs is complicated. The risk of a thrombotic event during interruption of anticoagulant or antiplatelet therapy must be weighed against the risk of bleeding when such therapy is used in close proximity to a surgical procedure. This balancing of risks is guided by the patient’s individual risk for thromboembolism or bleeding and underlying conditions such as the presence of a mechanical heart valve or a coronary stent.

High-profile adverse events have made anticoagulant and antiplatelet management one of the most highly litigated aspects of perioperative medicine. Moreover, there is a paucity of randomized clinical trial data and definitive guidelines to address the perioperative needs of patients on antithrombotic therapy. Treatment protocols vary depending on many underlying factors, such as the presence of mechanical heart valves, comorbidities, stent type and location, patient age and medical history, and type of surgical procedure. While recent attention has focused on genetic variations that result in higher or lower sensitivity to warfarin in some patients, routine genetic testing for warfarin sensitivity is controversial and not part of widespread practice at this time.

The first portion of this article explores key issues and principles in the perioperative management of surgical patients on warfarin therapy, and the second portion does the same for surgical patients on antiplatelet therapy.

ACCP RECOMMENDATIONS FOR PERIOPERATIVE ANTICOAGULANT MANAGEMENT

In 2008 the American College of Chest Physicians (ACCP) published the latest update of its consensus guidelines for the perioperative management of patients receiving antithrombotic therapy.¹ The guidelines’ recommendations for anticoagulant management are based on stratification of patients into risk categories (Table 1) according to their underlying indication for long-term anticoagulation—ie, presence of a mechanical heart valve, history of atrial fibrillation, or history of venous thromboembolism (VTE).

Patients with mechanical valves who are at high risk for perioperative thromboembolism include those with any mechanical mitral valve, an older valve, or a history of stroke or transient ischemic attack (TIA). Patients with atrial fibrillation who are at high risk include those with a recent stroke or TIA, rheumatic valvular heart disease, or a CHADS₂ score of 5 or 6. (The CHADS₂ scoring system assigns one point each for a history of congestive heart failure, hypertension, age greater than 75 years, or diabetes, and two points for history of stroke or TIA.) Patients with a history of VTE within the prior 3 months are also considered high risk.

Bridging anticoagulation (bridge therapy)—ie, the temporary use of intravenous unfractionated heparin (IV UFH) or low-molecular-weight heparin (LMWH) prior to surgery—is central to the ACCP’s recommendations for perioperative management in patients on long-term anticoagulant therapy. Key ACCP recommendations¹ for these patients, according to their risk for thromboembolism (Table 1), are as follows:

• High risk—bridging anticoagulation with therapeutic-dose subcutaneous LMWH or IV UFH
• Moderate risk—bridging anticoagulation with therapeutic-dose subcutaneous LMWH, therapeutic-dose IV UFH, or low-dose subcutaneous LMWH
• Low risk—bridging anticoagulation with low-dose subcutaneous LMWH or no bridging.

ASSESSING RISKS: DETERMINING WHETHER TO BRIDGE

Considerations in bridge therapy include balancing the risk of thromboembolism against the risk of bleeding, either of which can lead to catastrophic results.² Though the objective of bridge therapy is to avoid bleeding complications associated with invasive procedures, the bridge protocol itself can introduce additional serious complications. Figure 1 presents an algorithm for identifying patient and surgical risk factors for patients on anticoagulation therapy who are undergoing elective surgery.

Patient-specific risk factors

Patient risk factors include the indication for anti­coagulation, as detailed above, as well as other individual risks for thromboembolism, as discussed in the article by Michota on preventing VTE on page S45 of this supplement.

If anticoagulation is indicated because the patient has a mechanical heart valve, the valve type and position must be considered because these factors affect thrombo­embolic risk, as reflected in Table 1. For instance, the risk of thromboembolism is greater when the valve is in the mitral position than in the aortic position, and is also greater with an older caged-ball valve than with a newer-generation bileaflet valve.³

In patients receiving anticoagulation because of atrial fibrillation, annual stroke risk can be estimated using the validated CHADS₂ scoring system, as presented in Table 2.⁴ Generally, patients with atrial fibrillation who have a CHADS₂ score of 3 or higher should receive bridge therapy, while those with a CHADS₂ score of 2 or lower probably should not.

Procedure-related risk factors

Surgical risks factors include the type of surgery and its associated risks of bleeding and thromboembolism, as well as the expected time that anticoagulation will be interrupted. Estimating thromboembolic risk is complicated, however, and reliable results are generally not achieved with simplistic calculations or formulas. Such calculations tend not to appropriately account for the hypercoagulable state induced by surgery itself, as the risk of VTE is estimated to be 100 times greater during the perioperative period than in the nonoperative setting, owing to increased levels of plasminogen activator inhibitor-1. Moreover, multiple studies have demonstrated increases in coagulation factors that suggest that a “rebound hypercoagulability” may occur shortly after discontinuation of oral anti­coagulant therapy.^5–8

Net benefit vs risk in trials of bridge therapy

Several prospective studies of bridge therapy have been conducted in more than 2,700 surgical patients with mechanical heart valves, atrial fibrillation, or prior VTE.^9–14 Warfarin was discontinued in these patients and replaced with LMWH as bridge therapy. As shown in Table 3, the rate of thromboembolism at follow-up (2 weeks to 90 days) in these studies averaged approximately 1%, while the risk of major bleeding was approximately 3.5%.^9–14

In an analysis of data from observational studies, Kearon and Hirsh estimated the relative risk reduction for thromboembolism with bridge therapy to be 66% to 80%, depending on the indication for anticoagulation.⁸ Thus, if a patient’s risk of developing thromboembolism is 1.5%, bridge therapy reduces the risk to 0.5% or less.

Weigh relative consequences of an event with the patient

Determining whether and how to initiate bridge therapy ultimately depends on the consequences of an event. Recurrent VTE is fatal in 5% to 10% of cases,¹⁵ and arterial thromboembolism is fatal in 20% of cases and causes permanent disability in at least 50% of cases.¹⁶ While 9% to 13% of major bleeding events are fatal, bleeding rarely causes permanent disability.¹⁷ Thus, whereas a patient who bleeds can be resuscitated, a patient who develops a thrombo­embolism may be permanently disabled. These considerations should be shared with the patient, and patient preference should factor into the management strategy. Though the risk of bleeding with anticoagulation may be much higher than the risk of stroke without it, many patients will be more concerned about stroke risk.

 

 

CHOICE OF AGENT FOR BRIDGE THERAPY

LMWH appears to offer cost advantage over UFH

For cost reasons, managed care organizations often recommend LMWH, which can be administered sub­cutaneously in outpatient settings, over IV UFH administered in the hospital. A retrospective analysis of medical costs from the 1990s in a managed care organization found that bridge therapy with LMWH prior to elective surgery cost an average of $13,114 less per patient (in total cost of care) than did bridge therapy with UFH.¹⁸

LMWH safety issues in valve patients are a myth

Clinical outcomes were not statistically significantly different for patients receiving LMWH or UFH in the above study.¹⁸ Nevertheless, there is a widely held notion that LMWH is not safe to use as bridge therapy for patients with mechanical heart valves. Recent prospective bridge studies do not support that view, demonstrating that LMWH used as bridge therapy is associated with low risks for thromboembolism and major bleeding even in patients with mechanical valves.^9,10,12–14 In contrast, recent data on the use of IV UFH for bridging is minimal, with most bridge studies dating to the 1970s. Accordingly, the latest ACCP guidelines for perioperative management of patients on antithrombotic therapy recommend therapeutic-dose LMWH over IV UFH for bridge therapy, including in patients with mechanical heart valves.¹ Likewise, 2006 guidelines from the American College of Cardiology and American Heart Association on management of patients with valvular heart disease endorse LMWH as an option for bridge therapy.¹⁹

A PRACTICAL APPROACH TO BRIDGE THERAPY

A bridge therapy protocol for patients receiving warfarin has been successfully used at the Cleveland Clinic, where I previously practiced. Essentials of the protocol²⁰ are summarized here, followed by commentary that draws on additional sources.

Before surgery

• Discontinue warfarin 5 days before surgery (ie, hold four doses) if the preoperative international normalized ratio (INR) is 2 to 3, and 6 days before surgery (hold five doses) if the INR is 3 to 4.5.
• For bridge therapy, start LMWH (enoxaparin 1 mg/kg or dalteparin 100 IU/kg subcutaneously every 12 hours) beginning 36 hours after the last dose of warfarin.
• Give the last dose of LMWH approximately 24 hours prior to surgery.

After surgery

• For minor surgery, reinitiate LMWH at full dose approximately 24 hours after surgery. For major surgery and for patients at high risk of bleeding, consider using prophylactic doses on the first two postoperative days.
• Discuss the timing of anticoagulant reinitiation with the surgeon.
• Restart warfarin at preoperative dose 1 day after surgery. 
• Order daily prothrombin time/INR tests until the patient is discharged and periodically after discharge until the INR is within the therapeutic range.
• Order a complete blood cell count with platelets on days 3 and 7.
• Discontinue LMWH when the INR is between 2 and 3 for 2 consecutive days.

Additionally, the plan should be discussed in advance with the patient, surgeon, and anesthesiologist, along with the risks and benefits associated with LMWH. The patient should receive written instructions for self-administration and information about signs and symptoms of bleeding and thromboembolism.

When to stop warfarin

Warfarin should be discontinued far enough in advance of surgery to achieve a preoperative target INR of less than 1.2.²¹ Patients with an initial INR of 2 to 3 tend to achieve that target after discontinuation of warfarin for about 5 days (four doses). A longer wait (6 days, or five doses) is necessary for patients with an initial INR of 3 to 4. Age is associated with a slower rate of decrease in the INR, and there is wide interpatient variation. The INR should always be checked prior to surgery.²¹

Warfarin need not be stopped for all procedures

It is commonly assumed that warfarin should be discontinued for any procedure, including minor surgery. But several procedures, listed in Table 4, can be performed safely without discontinuing long-term anticoagulation, as suggested by several literature reviews and comparative studies.^22–25 Additionally, a 2003 systematic review concluded that major bleeding with continuation of therapeutic oral anticoagulation was rare for patients undergoing dental procedures, arthrocentesis, cataract surgery, upper endoscopy, or colonoscopy.²⁶

If warfarin is stopped for minor procedures, bridging may be counterproductive

At the same time, a recent prospective observational study evaluated the effects of brief (≤ 5 days) interruption of warfarin among more than 1,000 patients undergoing minor outpatient procedures and found low rates of both thromboembolism (0.7%) and major bleeding (0.6%).²⁷ The risk of major bleeding was significantly higher among the small proportion of patients who received bridge therapy with UFH or LMWH. The study concluded that interrupting warfarin for 5 days or less for minor outpatient procedures carries a low risk of thromboembolism and that the risk of clinically significant bleeding should be weighed before bridge therapy is considered in this setting.

When to stop bridge therapy preoperatively

Bridge therapy with LMWH is commonly discontinued 12 hours before surgery, but it is preferable to discontinue 24 hours before surgery. In a study of preoperative anticoagulant activity in 80 patients, LMWH (enoxaparin 1 mg/kg) was administered twice daily and discontinued the night before surgery.²⁸ Blood anti–factor Xa levels were measured shortly before surgery, at which time 68% of patients still had therapeutic levels of anti–Xa. This suggests that discontinuing LMWH too close to the time of surgery can increase the risk of bleeding.

Consistent with these findings, consensus guidelines from the American Society of Regional Anesthesia and Pain Medicine (ASRA) recommend that needle placement for regional anesthesia take place 12 hours after the last dose of LMWH if prophylactic dosing is used and 24 hours after the last dose of LMWH if therapeutic dosing is used (ie, ≥ 1 mg/kg of enoxaparin every 12 hours).²⁹

Dosing and timing of postoperative bridge therapy

Postoperative use of full-dose bridge therapy is associated with increased risks of bleeding, according to a multicenter study of approximately 500 patients who received various doses of UFH or LMWH for bridge therapy.¹⁴ Patients who received full-dose LMWH or UFH after surgery had a fivefold to sixfold increase in the incidence of major bleeding compared with patients who received prophylactic doses. The study centers that frequently used full-dose bridge protocols were four times as likely to report major bleeding events. In light of these findings, waiting a couple of days after surgery to initiate full-dose bridge therapy is recommended, and prophylactic dosing may be considered in the interim.

The ASRA consensus guidelines recommend that indwelling catheters be removed prior to postoperative reinitiation of twice-daily dosing of LMWH. The first dose of LMWH should be given no sooner than 2 hours after catheter removal. Once-daily dosing of LMWH (European dosing) is acceptable under the ASRA guidelines, but the first dose should be given 6 to 8 hours after surgery and the second dose no sooner than 24 hours later. The guidelines state that once-daily (but not twice-daily) LMWH dosing is acceptable in patients with indwelling catheters; neurological status should be monitored in these patients, and the catheter should be removed 12 to 24 hours after the last dose of LMWH.²⁹

 

 

PERIOPERATIVE MANAGEMENT OF ANTIPLATELET THERAPY: TYPE OF AGENT MATTERS

Unlike the considerations with warfarin, the timing of preoperative discontinuation of antiplatelet therapy in patients undergoing noncardiac surgery depends on the type of agent used and its pharmacokinetic actions. Commonly used antiplatelet drugs include aspirin, the thienopyridine agent clopidogrel, and nonsteroidal anti-inflammatory drugs (NSAIDs).

Aspirin works by irreversibly inhibiting platelet cyclooxygenase. The circulating platelet pool is replaced every 7 to 10 days, so aspirin therapy should be discontinued 7 to 10 days before surgery.¹

NSAIDs reversibly inhibit platelet cyclooxygenase. Knowing whether a patient is using short- or long-acting NSAIDs is important for determining when to discontinue therapy. For a short-acting NSAID such as ibuprofen, discontinuation 24 hours before surgery may be adequate to normalize platelet function.^1,30

Thienopyridines inhibit adenosine diphosphate receptor–mediated platelet activation and aggregation. Short-acting thienopyridines may be discontinued 24 hours before surgery, but long-acting agents such as clopidogrel should be stopped 7 days prior to surgery (including when used with aspirin as dual antiplatelet therapy),¹ although some outcomes data suggest that 5 days may be sufficient.³¹

All of these agents should be resumed as soon as adequate hemostasis is achieved after surgery. The ACCP guidelines on perioperative management of antithrombotic therapy recommend resumption of aspirin at the usual maintenance dose the day after surgery, but they make no specific recommendations on when to resume other antiplatelet drugs.¹

ANTIPLATELET THERAPY: SPECIAL CONSIDERATIONS IN PATIENTS WITH STENTS

Patients who are on antiplatelet therapy because they have a coronary stent merit special consideration due to the high risk of thrombosis if therapy is interrupted. The risk of stent thrombosis is especially elevated in the postoperative period, particularly if surgery follows soon after stent placement.

Optimal preoperative management of patients with coronary artery stents depends on many factors, as outlined in Table 5. Some patients carry a wallet card that provides some of this crucial information, such as the type of stent and the date and location of its placement, but speaking with the patient’s cardiologist is always recommended. This information, determined in conjunction with the cardiologist, should be used to inform the key perioperative considerations in this setting:

• Relative risks and benefits of stopping versus continuing antiplatelet therapy
• Identification of patients at high risk for a perioperative event after cessation of antiplatelet therapy
• Identification of patients at high risk of bleeding.

Bleeding vs stent thrombosis: Consider relative consequences

The risk of bleeding varies by individual patient. No laboratory tests are available to determine individual bleeding risk, but the risk of perioperative bleeding increases when two or more antiplatelet agents are used, as in dual antiplatelet therapy with aspirin and clopidogrel.³¹

When balancing risks of bleeding versus thrombotic events, the relative consequences of each event again must be considered. Bleeding is rarely life-threatening in comparison with the potential consequences of stent thrombosis. In a prospective observational study of 2,229 patients who received drug-eluting stents, 29 (1.3%) developed stent thrombosis during 9-month follow-up.³² Among these patients, 20 (69%) had a nonfatal myocardial infarction and 13 (45%) died. The most significant independent risk factor for stent thrombosis was premature discontinuation of antiplatelet therapy (hazard ratio = 89.78 [95% CI, 29.90–260.60]; P < .001). Other independent risk factors included renal failure, bifurcation lesions, diabetes, and low ejection fraction.

Premature interruption of antiplatelet therapy: Why it matters

Abrupt discontinuation of antiplatelet therapy can lead to a rebound effect marked by an inflammatory prothrombotic state, increased platelet adhesion and aggregation, and excessive thromboxane A₂ activity. Surgery further increases the prothrombotic and inflammatory state, which, combined with incompletely endothelialized drug-eluting stents, can lead to stent thrombosis and, consequently, myocardial infarction and/or death.³³

Timing of surgery after stenting: Getting it right

The US Food and Drug Administration recommends that dual antiplatelet therapy be continued for at least 3 months after placement of a sirolimus-eluting stent and at least 6 months after placement of a paclitaxel-eluting stent. Recent data suggest, however, that this duration of antiplatelet therapy may not be sufficient and that at least 1 year of therapy may be needed.³⁴

A recent joint science advisory from the American College of Cardiology (ACC) and the American Heart Association (AHA) emphasizes the importance of educating providers about the “potentially catastrophic” risks of premature stopping of thienopyridine therapy in patients with coronary stents.³⁴ In addition to recommendations in this joint advisory, the ACC and AHA issued updated guidelines in 2007 on perioperative cardiovascular evaluation and care for noncardiac surgery.³⁵ Below is a summary of recommendations on the timing of surgery following stenting in light of these and other sources:

• Following placement of a bare metal stent, elective and nonurgent procedures should be delayed for at least 1 month, according to the ACC/AHA joint advisory,³⁴ or at least 6 weeks, according to the ACC/AHA guidelines.³⁵ Newer data suggest that the optimal interval for delay is likely to be 3 months.^36,37
• For patients with recent (< 6 weeks) bare metal stent placement who require urgent surgery, dual antiplatelet therapy should be continued during the perioperative period.¹
• Following placement of a drug-eluting stent, elective and nonurgent procedures should be delayed for at least 12 months.^34,35
• For patients with recent drug-eluting stent placement in whom surgery cannot be delayed, dual antiplatelet therapy should be continued without interruption if the stent was placed within the prior 6 months.^1,35 If the stent was placed more than 6 months before urgent surgery, aspirin should be continued without interruption (at ≥ 81 mg/day) and clopidogrel should be continued until 5 days before surgery and resumed as soon as possible after surgery (at a loading dose of 300 mg followed by 75 mg/day). If the surgeon is comfortable continuing dual antiplatelet therapy in a patient whose stent was placed 6 to 12 months earlier, that course should be considered.¹

It is important to note that the ACC/AHA joint advisory³⁴ and other documents have medicolegal implications, so delaying nonurgent surgery for the periods recommended is the most prudent approach.

 

 

CONCLUSIONS

Perioperative management of anticoagulant and antiplatelet therapy is complicated by the paucity of randomized clinical trial data and the risk for serious adverse events. The underlying indications for anticoagulant and antiplatelet therapy vary widely, so the best approach to perioperative management is to involve all members of the health care team—hospitalist, surgeon, cardiologist, and anesthesiologist, together with the patient—to ensure that care is individualized and all relevant considerations are accounted for. Patient and surgical risks can be identified and quantified to some extent, but patients often have greater concerns about the risk of stroke than the risk of bleeding. Ideally, nonemergency surgeries should be scheduled to allow enough time to thoroughly plan the management protocol, reducing risks for bleeding and thrombotic events as much as possible.

DISCUSSION

Question from the audience: If a patient’s INR is 1.3 or 1.4, rather than the recommended 1.2, is it necessary to cancel a planned epidural?

Dr. Jaffer: It depends on how comfortable the surgeon or anesthesiologist is with the INR level. Generally, an INR less than 1.5 is probably acceptable, but it depends on the procedure. For a craniotomy, for example, 1.2 is recommended.

Question from the audience: Is it necessary to use anti–Xa levels to guide bridge therapy when administering LMWH or UFH in a patient with a mechanical heart valve?

Dr. Jaffer: It’s not generally necessary, except for pregnant women. For most patients, doses are calculated as milligrams of LMWH per kilogram body weight or as International Units of LMWH per kilogram.

Question from the audience: You mentioned medico­legal disputes arising from adverse events associated with bridge therapy, drug discontinuation, or related issues. Who has final responsibility for making decisions about discontinuation of antiplatelet therapy, for example?

Dr. Jaffer: I don’t know if it ultimately comes down to just one person. Several physicians should be involved in the decision, and communication protocols within an institution should be very clear. It’s important to make certain everyone involved in the decision is reviewing the same literature. The final decision has to be something everyone involved can accept and support.

Most surgical patients who require hospitalization should be considered at high risk for venous thromboembolism (VTE) and be given appropriate prophylaxis. For lower-risk procedures such as knee arthroscopy, prophylaxis is needed for those with individual risk factors such as morbid obesity, limited mobility after surgery, or a history of deep vein thrombosis (DVT) or malignancy. Too often, however, prophylaxis is not provided appropriately or not given at all.

This review surveys the essentials of perioperative VTE prophylaxis and important new developments in the field, which include the 2008 release of new evidence-based clinical practice guidelines on antithrombotic and thrombolytic therapy from the American College of Chest Physicians (ACCP). This 8th edition of the guidelines updates the previous edition, published in 2004, and includes a section by Geerts et al devoted to VTE prevention.¹ Other major guidelines are also discussed, as are developments in VTE-related quality measurement, management of special patient populations (those with renal impairment or morbid obesity), and emerging therapies for VTE prophylaxis.

IMPETUS FOR QUALITY IMPROVEMENT IN VTE

A new seriousness about VTE quality measures

The 8th edition of the ACCP guidelines recommends that every hospital develop a formal, active strategy to consistently identify medical and surgical patients at risk for VTE and to prevent VTE occurrence.¹ Although prior editions of the ACCP guidelines have made this recommendation for more than 2 decades, fewer than 1 in 10 acute care hospitals had any such strategy in place as recently as 5 years ago. Now, however, most US hospitals have implemented such a strategy, thanks to the growing national emphasis on health care quality measurement in recent years.

The Surgical Care Improvement Project (SCIP) has been at the forefront of this recent quality measures movement. SCIP, a joint project of the American Medical Association and federal government agencies, set a goal to reduce surgical complications in the United States by 25% from 2005 to 2010.² Two SCIP process measures relate to improving VTE prophylaxis^2,3:

• The proportion of surgical patients for whom recommended VTE prophylaxis is ordered
• The proportion of surgical patients who actually receive appropriate VTE prophylaxis within 24 hours before or after surgery.

The Joint Commission and the National Quality Forum recently endorsed these two SCIP performance measures for perioperative VTE prophylaxis along with several others relating to VTE treatment.

CMS raises the stakes with reimbursement restrictions

More significantly, the federal government’s Centers for Medicare and Medicaid Services (CMS) will soon refuse to reimburse for hospital treatment of a primary diagnosis of DVT or pulmonary embolism (PE) following recent (within 30 days) total hip or knee arthroplasty. Effective October 1, 2009, a primary VTE diagnosis following these joint replacement procedures will be added to CMS’ current list of “never events,” or hospital-acquired conditions for which CMS will not provide reimbursement because they are considered the result of preventable medical errors. (Notably, treatment of DVT or PE as a secondary diagnosis will still be reimbursed—for example, if a joint replacement patient develops nosocomial pneumonia, is transferred to the intensive care unit, and then develops VTE.) This addition of DVT and PE to the list is highly controversial since these events sometimes develop even if prophylactic therapy is appropriate and aggressive.

Strategies to promote best practices

In the update for the new 8th edition of its guidelines, the ACCP added recommendations on specific ways for hospitals to identify patients at high risk for VTE and ensure that they receive appropriate prophylaxis. These include the use of computer decision-support systems, preprinted orders, and periodic audit and feedback.¹

Researchers at Brigham and Women’s Hospital evaluated the effectiveness of a computer alert system for notifying physicians of newly hospitalized patients at risk for DVT who were not receiving prevention therapy within the first 24 hours of hospital admission.⁴ These patients presumably “fell through the cracks” and warranted prophylaxis but were otherwise not recognized by the health care team. Risk was determined by a scoring system based on multiple variables, including malignancy, previous DVT or PE, hypercoagulability, major surgery, advanced age, obesity, ordered bed rest, and treatment with hormone replacement therapy or oral contraceptives. Study physicians had to acknowledge having received the alert but could choose whether or not to order VTE prophylaxis. Prophylaxis was used in considerably more patients from the intervention group than from a control group of high-risk patients whose physicians did not receive alerts (34% vs 14%, respectively); accordingly, the risk of a symptomatic DVT or PE event at 90 days was reduced by 41% in the intervention group.

Despite this evidence of improved practice under the alert system, the study begs the question of why the percentage of patients at risk for VTE who were given prophylaxis was still so low (34%), demonstrating how much progress in improving practice remains to be achieved.

PROPHYLAXIS STRATEGIES: MATCHING THERAPY TO RISK

A fundamental consideration in determining the degree of VTE prophylaxis that a surgical patient may need is the thromboembolic risk of the procedure itself. Table 1 presents a procedure-based ranking of risk based on recommendations in the 8th edition of the ACCP guidelines.¹ As risk increases, so does the intensity of prophylaxis, with increasing reliance on pharmacologic strategies. The vast majority of patients who are hospitalized for surgery will fall into the moderate- or high-risk categories in Table 1.

A patient’s risk of thrombosis is also influenced by individual risk factors (Table 2),^1,5 many of which are nonmodifiable. A thorough preoperative evaluation is important to reveal “hidden” risk factors such as thrombo­philia and a family or personal history of VTE.

 

 

NONPHARMACOLOGIC PROPHYLAXIS STRATEGIES

Does ambulation prevent DVT?

Although it is commonly accepted that walking prevents DVT, this has never been directly tested. Walking may simply be a marker of health, and healthy people are less prone to develop thromboses. We have almost no evidence to show that forcing an unhealthy person to walk helps prevent DVT. Early ambulation offers many benefits and should be encouraged, but it should not be considered DVT prophylaxis; it is simply good hospital care.

Mechanical devices: Adherence is key

Amaragiri and Lees conducted a systematic literature review of randomized controlled trials evaluating the effectiveness of graduated compression stockings (elastic stockings) for preventing DVT in various groups of hospitalized patients.⁶ The analysis demonstrated a statistically significant reduction in DVT incidence with graduated compression stockings compared with control both among the nine trials in which stockings were used alone (odds ratio = 0.34) and among the seven trials in which stockings were used in addition to another method of thrombo­prophylaxis (odds ratio = 0.24). Although benefit was demonstrated, many of the trials in this review involved patients undergoing gynecologic surgery and date from the 1970s and 1980s (when obesity was less prevalent), so the applicability of their results today may be limited.

The 8th edition of the ACCP guidelines recommends that mechanical methods of VTE prophylaxis be used primarily in patients who are at high risk of bleeding and that careful attention be directed to ensuring their proper use and optimal adherence.¹ The latter point about adherence cannot be emphasized enough, as graduated compression stockings and other mechanical devices have been shown not to be effective unless they are worn at least 18 to 20 hours a day. This degree of adherence is difficult to achieve, as it can severely limit patient mobility and leave patients susceptible to develop­ment of pressure ulcers.

Mechanical compression should be initiated prior to induction of anesthesia and continue intraoperatively and then into the postanesthesia care unit. Orders for use of mechanical devices should include instructions in the patient’s medical chart specifying how—and for how many hours per day—they are to be worn. Not doing so leaves the physician vulnerable to litigation, especially as the ACCP guidelines include language on optimal adherence to these devices (“they should be removed for only a short time each day when the patient is actually walking or for bathing”¹).

Continuous external compression therapy

Newer mechanical device options include a continuous external compression therapy system that allows patients to be mobile while wearing it and provides rhythmic compression that results in good peak venous flows. Ideally such a device could be put on the patient preoperatively and worn during surgery, throughout the hospital stay, and even at home during recovery. Anecdotally, however, I see patients turn these new devices off at the side of the bed just as often as they do with traditional devices.

Vena caval interruption

Vena caval interruption involves placement of a retrievable vena cava filter before surgery and removal some time later; it offers the potential for VTE prophylaxis in patients who could not tolerate even minor amounts of bleeding, such as certain trauma patients. The Eastern Association for the Surgery of Trauma has put forth a consensus recommendation to consider vena caval interruption in high-risk trauma patients who cannot receive pharmacologic prophylaxis.⁷ A randomized trial evaluating the usefulness of vena caval interruption for patients undergoing surgery is needed. For now, this intervention should be regarded as experimental and considered only on a highly individualized basis.

PHARMACOLOGIC PROPHYLAXIS

The ACCP guidelines’ recommendations for pharmacologic VTE prophylaxis in surgical patients are lengthy, and many remain unchanged from prior editions, so this discussion will focus on broad principles and new recommendations adopted in the recent 8th edition.¹Table 3 lists notable new recommendations for patients undergoing specific surgical procedures.

Timing of initiation

Pharmacologic VTE prophylaxis generally should begin 8 to 24 hours postoperatively. Of course, adequate hemostasis is required before initiation, and the net risk/benefit tradeoff with regard to timing of anticoagulant initiation has still not been well studied in many surgical patient populations.

Extended prophylaxis

In the update for the 8th edition of its guidelines, the ACCP added an explicit recommendation for extended outpatient prophylaxis with low-molecular-weight heparin (LMWH) for up to 28 days postoperatively in selected high-risk patients undergoing general or gynecologic surgery, including those with cancer or a history of VTE.¹ This recommendation was based largely on studies of extended prophylaxis in patients with cancer undergoing colorectal surgery.⁸

Increased appreciation of the value of extended VTE prophylaxis after discharge is linked to a growing recognition that DVT and PE episodes in the community setting are often related to a recent hospital stay for either medical illness or surgery. A population-based study found that 59% of all community cases of a first lifetime VTE event in residents of Olmsted County, Minn., over a 15-year period could be linked to current or recent (< 30 days) hospitalization or nursing home residence.⁹ A similar population-based study in the Worcester, Mass., area found that three-fourths of all VTE events in a 3-year period occurred in the outpatient setting.¹⁰ Among patients with these outpatient VTE events, a large proportion had undergone surgery (23%) or hospitalization (37%) in the prior 3 months; among those, 67% experienced their VTE within 1 month of their time in the hospital.

These findings are no surprise, since surgery induces a hypercoagulable state that, when combined with individual risk factors such as obesity, old age, or poor heart function, cannot be assumed to return to baseline on postoperative day 4 or 5 just because the patient is being discharged.

Orthopedic surgery

For patients undergoing major orthopedic procedures, the ACCP guidelines recommend against routine screening for VTE with Doppler ultrasonography before discharge if the patient is asymptomatic.¹ Such screening is not considered cost-effective because asymptomatic clots often are found, for which treatment is uncertain, and proximal clots may be missed, giving a false sense of security.

ACCP recommendations for prophylaxis in patients undergoing orthopedic surgery are summarized in Table 4.¹ As shown, the recommended options for hip and knee replacement and hip fracture surgery are almost exclusively medication-based. The vast majority of patients undergoing these major orthopedic procedures need prophylaxis beyond their typical hospital stay of 3 or 4 days. About 90% of DVTs following knee replacement occur within 2 weeks of surgery, so 10 to 14 days of therapy is probably the best practice in this setting, although a longer period may be justified depending on the patient’s risk profile. For hip replacement, in contrast, 28 to 30 days of prophylaxis is often preferable, since about half of all DVTs in that setting occur more than 2 weeks after surgery.

New to the ACCP guidelines in the 8th edition is the recommendation that patients undergoing knee arthroscopy who have risk factors for VTE (or whose procedure is complicated) should receive 1 week of prophylaxis with LMWH.¹ Also new are recommendations for patients with risk factors undergoing single- or multilevel laminectomy (Table 4).

 

 

Recommendations unchanged in neurosurgery, spinal injury, trauma, burns

Recommendations for neurosurgery remain unchanged from the prior (2004) edition of the ACCP guidelines and are still based on the 2000 meta-analysis by Iorio and Agnelli of LMWH prophylaxis in neurosurgery cases.¹¹ In the United States, the standard is overwhelmingly to use mechanical devices for thromboprophylaxis in neurosurgery, even for patients with cancer.

For prophylaxis in surgical patients with spinal cord injury, multisystem trauma, or burns, LMWH is predominantly used, and the ACCP recommendations are unchanged from 2004.

Drug-specific considerations

LMWH vs vitamin K antagonist. Although vitamin K antagonists (warfarin) still appear in the latest ACCP recommendations,¹ LMWH is preferable. A 2004 meta-analysis of studies comparing vitamin K antagonists with LMWH for prophylaxis in patients undergoing orthopedic surgery found that vitamin K antagonists were associated with more episodes of total DVT (relative risk [RR] = 1.51; 95% CI, 1.27–1.79) and proximal DVT (RR = 1.51; 95% CI, 1.04–2.17) compared with LMWH.¹² No difference was found in rates of wound hematoma or major bleeding. This finding of inferiority for vitamin K antagonists came despite the likelihood that warfarin was more often administered correctly (ie, with dose adjustment to achieve an international normalized ratio [INR] of 2.0 to 3.0 within 72 hours after surgery) in the studies in this analysis than it is in real-world practice.

Fondaparinux. The indirect factor Xa–specific inhibitor fondaparinux has had a surprisingly limited clinical adoption despite having been widely studied and found to be safe and effective. This is likely attributable in part to its 17-hour half-life, which raises concerns that it may take 3 days for its effects to stop if a patient begins to bleed. Large phase 3 studies have found fondaparinux to be equivalent to LMWH in VTE prevention after hip replacement, marginally superior to LMWH after knee replacement, and superior to LMWH following hip fracture repair.¹³ Fondaparinux was associated with an increase in bleeding events and instances of transfusion requirement, but only in one of the studies, which was in the setting of knee replacement surgery.¹⁴

Aspirin not recommended by ACCP. Although aspirin reduces the risk of VTE, practice guidelines from both the ACCP¹ and the International Union of Angiology¹⁵ contain no recommendation for its use as prophylaxis because it is considered less effective and more risky than other therapies. In contrast, clinical practice guidelines from the American Academy of Orthopaedic Surgeons suggest that aspirin is reasonable for VTE prophylaxis.¹⁶ The varying recommendations reflect differences in perspective among these different specialties.

Aspirin has the advantages of ease of use and low cost, but it is clearly not the best evidence-based approach for VTE prophylaxis. The only recent randomized trial evidence in support of aspirin comes from the Pulmonary Embolism Prevention trial, a study with a flawed design involving more than 13,000 patients undergoing surgery for hip fracture or elective arthroplasty in five countries.¹⁷ Patients were randomized to receive aspirin 160 mg daily or placebo for 35 days along with any other prophylaxis deemed necessary (an important potential confounder). Aspirin was associated with an absolute reduction in symptomatic events of less than 1% relative to placebo, and no benefit was observed within the first week. The best results with aspirin were among patients with hip fracture. No benefit was shown among patients undergoing hip arthroplasty or knee arthroplasty; in those groups, both the aspirin and placebo recipients were also treated with LMWH. An absolute increase in rates of wound bleeding (0.6% increase) and gastrointestinal bleeding (1.0% increase) was observed in the aspirin group. The absolute increase in complications was greater than the absolute reduction in episodes of symptomatic DVT: for every episode of symptomatic DVT averted, one wound bleed and 10 gastrointestinal bleeds occurred.

SPECIAL PATIENT POPULATIONS

Renal impairment

The 8th edition of the ACCP guidelines recommends that renal function be kept in mind when considering LMWH, fondaparinux, and other antithrombotic drugs that are cleared by the kidneys. Fondaparinux and LMWH can bioaccumulate in patients with renal insufficiency, who have a higher risk of bleeding to begin with, thereby compounding the risk. Options for patients with renal compromise include avoiding drugs that bioaccumulate, using a lower dosage, and monitoring the drug level or anticoagulant effect.¹

Fondaparinux is explicitly contraindicated in patients with low body weight (< 50 kg) or renal impairment (creatinine clearance < 30 mL/min). Renal function should be assessed periodically in any patients receiving the drug.¹⁸

I also would not use fondaparinux or LMWH in patients with rapidly changing renal function. For patients with chronic, stable renal impairment, one can reduce the dose of LMWH empirically; one LMWH, enoxaparin, has specific dosing guidelines in its package insert (one-third reduction in dose), but this option does not hold for patients with rapidly changing renal function.¹⁹

Obesity

The 8th edition of the ACCP guidelines recommends weight-based dosing of thromboprophylactic agents in obese patients. The guidelines particularly recommend that patients undergoing inpatient bariatric surgery be given higher doses of LMWH or unfractionated heparin.^1,20

Frederiksen et al measured the anticoagulant effect of a single fixed dose of a LMWH (using anti-factor Xa heparin activity levels) and found that it was dependent on body weight.²¹ This suggests that fixed doses that are effective in normal-weight patients may have no detectable anti-coagulant effect in patients with very high body weight.

Weight-based dosing: mounting nonprospective evidence. Weight-based dosage adjustment for the morbidly obese has not been directly studied in a prospective, randomized fashion. A nonrandomized study by Scholten et al compared two regimens of enoxaparin (30 mg twice daily vs 40 mg twice daily) among 481 obese patients undergoing bariatric surgery; each regimen was used along with mechanical thromboprophylaxis.²² They found that the higher-dose regimen was associated with significantly fewer postoperative DVT complications (0.6% vs 5.4%; P < .01) without an increase in bleeding complications.

Separately, Shepherd et al used weight-adjusted doses of unfractionated heparin (started on the evening of surgery) to achieve subtherapeutic peak anti–factor Xa heparin activity levels of 0.11 to 0.25 IU/mL in a series of 700 patients undergoing laparoscopic gastric bypass surgery.²³ The resulting doses were greater than those in traditional fixed-rate protocols, but rates of bleeding and VTE events were low and comparable to those reported in patients receiving standard doses. 

Don’t rule out multimodal approaches. Multimodal prophylaxis can also be used in obese patients and need not be abandoned as a result of size considerations. For instance, two intermittent compression therapy devices can be pieced together with a Velcro binder if a single device is too small to be worn.

 

 

EMERGING ANTICOAGULANT OPTIONS

For many years, unfractionated heparin was the only available parenteral anticoagulant. While heparin has broad anticoagulant properties, it also has well-established limitations, including the need for parenteral delivery, recent problems related to contamination (it is derived from pig intestines), and of course heparin-induced thrombocytopenia (HIT). HIT is an immune-mediated form of platelet activation that can lead to widespread thrombosis throughout the body. It is more commonly associated with venous thrombosis, but arterial events with limb-threatening ischemia may also occur. LMWH is associated with a reduced risk of HIT, but LMWH does not avoid the risk entirely.

Beyond the issue of avoiding HIT, newer anticoagulant therapies are being developed with the aim of oral administration and more targeted inhibition of coagulation factors IIa (thrombin) and Xa.²⁴

Oral direct thrombin inhibitors

One of the two most promising classes of emerging anticoagulants is the direct thrombin inhibitors, most of which are being developed for oral administration. There were high hopes for the initial compound in this class, ximelagatran, but it was abandoned about 5 years ago because of hepatotoxicity.

Dabigatran is the direct thrombin inhibitor furthest along in development today. Currently approved in Europe for prevention of VTE in patients undergoing total hip or knee replacement surgery, dabigatran is likely to be available soon in the United States. It is administered orally, has a rapid onset of action (< 1 hour), and has a predictable anticoagulant response that requires no monitoring.²⁴ Because dabigatran is excreted essentially unchanged by the kidneys and may bioaccumulate, it should not be used in patients with renal impairment or rapidly changing renal function.

In phase 3 clinical trials for VTE prevention in knee replacement surgery, dabigatran was at least as effective as enoxaparin 40 mg once daily and had a comparable safety profile,²⁵ but it was slightly less effective than enoxaparin 30 mg twice daily.²⁶ In a phase 3 trial in patients under­going hip replacement surgery, dabigatran was equivalent in efficacy and safety to enoxaparin 40 mg once daily.²⁷

Oral direct factor Xa inhibitors

A key rationale for direct inhibition of factor Xa is that it results in inhibition of thrombin production on the activated platelet. Whereas fondaparinux is an indirect inhibitor of factor Xa, direct factor Xa inhibitors offer an advantage in that they inhibit factor Xa within the prothrombinase complex, which occurs on the surface of a platelet and is the main site for thrombin development (very little thrombin is actually produced on endothelial cells). Recall the adage that “thrombin begets more thrombin”: it activates not only platelets but the intrinsic and extrinsic pathways.²⁸

Factor Xa may be a better target than thrombin for a number of other reasons:

• Factor Xa is believed to have few functions (compared with thrombin) outside of coagulation

• In vitro studies show that factor Xa has a wider therapeutic window than thrombin, which translates to greater separation between drug levels that will confer efficacy and bleeding
• Thrombin inhibitors are associated with rebound thrombin generation (there is no evidence of this with factor Xa inhibitors)
• The efficacy of heparin-based anticoagulants improves as selectivity for factor Xa increases (unfractionated heparin is less effective than LMWH, which is less effective than fondaparinux).

Two direct factor Xa inhibitors—both administered orally—are far along in development, as detailed below.

Apixaban has shown promise, but the phase 3 ADVANCE-1 study of apixaban for VTE prevention in patients undergoing knee surgery did not meet statistical criteria for noninferiority compared with enoxaparin 30 mg twice daily.²⁹ This prompted a delay in regulatory filings for apixaban in the United States, and the drug’s prospects for approval for VTE prevention may be unclear until release of results from two other comparative phase 3 trials with enoxaparin in 2009 and 2010.

Rivaroxaban is more likely to become clinically available soon, in light of recent results from the phase 3 RECORD4 trial demonstrating that it was significantly superior to enoxaparin 30 mg twice daily in preventing VTE following knee replacement surgery with comparable rates of major bleeding.³⁰

DISCUSSION

Question from the audience: Some surgeons in my hospital prescribe warfarin immediately after surgery without a bridge of LMWH. Is that appropriate?

Dr. Michota: Warfarin is an option for prophylaxis in orthopedic surgery, beginning on the day of surgery. It could even be started the day before surgery, but the dose should be monitored to achieve an INR between 2.0 and 3.0 within 72 hours of the procedure. If the INR is not in this optimum range, prophylactic doses of LMWH can be given until it is therapeutic.

Follow-up question: In practice, do you actually encourage INR monitoring? Usually we just put patients on a certain dose without monitoring. When we do check the INR, it’s usually 1.4 or 1.5.

Dr. Michota: Warfarin was shown to be effective in reducing VTE risk in orthopedic surgery with dose adjustment based on INR monitoring. On that basis, warfarin remains in the guideline recommendations. Unmonitored, warfarin has not been shown to reduce risk, so to give it that way would not be evidence-based.

Question from the audience: I work with several plastic surgeons who use compression stockings intraoperatively because they’ve heard of several patients who developed a PE during surgery. Is there any benefit to using compression stockings for 2 to 3 hours and then sending the patient home?

Dr. Michota: I don’t know. Theoretically, a device that is on and working before induction may reduce stasis.

The plastic surgery societies do have guidelines. Risk depends on the type of plastic surgery procedure; for example, risk probably increases due to inflammation in procedures that involve scraping the fat pads.

This is an area where we don’t have much data. These patients may be at risk, but we don’t know the best way to mitigate it. It is important that risks be discussed with patients in the informed-consent process and be documented. If the surgeon thinks it is reasonable to give pharmacologic prophylaxis after surgery, I wouldn’t hesitate to do that, but any form of bleeding in the setting of plastic surgery is catastrophic because it defeats the reason for which the surgery was done in the first place.

Question from the audience: How do the guidelines address being aggressive with pharmacologic thromboprophylaxis when a patient is already taking dual antiplatelet therapy?

Dr. Michota: For patients with an indication for VTE prophylaxis in a setting for which there is a specific strategy, the ACCP guidelines recommend that they be put on that regimen whether they are on antiplatelet agents or not. For example, consider a high-risk patient having colorectal surgery who should get unfractionated heparin or LMWH postoperatively and who is currently taking clopidogrel and aspirin. There is no evidence that the dual aspirin–clopidogrel therapy alone is effective in decreasing the risk of DVT. However, we do know that if we add on additional agents, the risk of bleeding is increased. The guidelines consider risk and benefit, and they recommend adding the agents that we know work to prevent DVT.

Question from the audience: You briefly mentioned prophylaxis for knee arthroscopy, which is the most frequently performed orthopedic procedure. Do these recommendations apply to all patients undergoing knee arthroscopy?

Dr. Michota: No. Prophylaxis is indicated only for patients with what the ACCP considers to be additional risk factors for thrombosis. They didn’t specify which risk factors, but good indications for prophylaxis would include morbid obesity, limited mobility after the procedure, a personal history of DVT, features of stasis noted on physical examination, stasis dermatitis (or other features that could indicate prior thrombosis), advanced age, and malignancy. If a patient undergoing knee arthroscopy has other nonmodifiable risk factors, you should also think about prophylaxis. But the vast majority of patients do not need it.

Question from the audience: I’m an academic hospitalist who works closely with orthopedic surgeons. Certain surgeons will only use aspirin for prophylaxis, and it is nonnegotiable. Where does that leave me from a medicolegal standpoint? Our model is to follow ACCP recommendations, but these orthopedic surgeons still use only aspirin.

Dr. Michota: You must do everything you can to come to a consensus with your surgeon colleagues. If you are uncomfortable, as a group you must say to the surgeons, “We are uncomfortable. This is how we view the data. How do you view the data?” If they answer, “We’re doing it because it’s easy, and the American Academy of Orthopaedic Surgeons says we can do it,” I don’t have a good response. But it is more likely that their use of aspirin is based on their own observations; they may not see many clots. Of course, the problem with observational data is that the numbers are not large and they are not generated in a randomized and prospective fashion. Perhaps you can come to some middle ground, but you could always make the difficult choice and say, “I’m just not going to follow your patients.”

Most surgical patients who require hospitalization should be considered at high risk for venous thromboembolism (VTE) and be given appropriate prophylaxis. For lower-risk procedures such as knee arthroscopy, prophylaxis is needed for those with individual risk factors such as morbid obesity, limited mobility after surgery, or a history of deep vein thrombosis (DVT) or malignancy. Too often, however, prophylaxis is not provided appropriately or not given at all.

This review surveys the essentials of perioperative VTE prophylaxis and important new developments in the field, which include the 2008 release of new evidence-based clinical practice guidelines on antithrombotic and thrombolytic therapy from the American College of Chest Physicians (ACCP). This 8th edition of the guidelines updates the previous edition, published in 2004, and includes a section by Geerts et al devoted to VTE prevention.¹ Other major guidelines are also discussed, as are developments in VTE-related quality measurement, management of special patient populations (those with renal impairment or morbid obesity), and emerging therapies for VTE prophylaxis.

IMPETUS FOR QUALITY IMPROVEMENT IN VTE

A new seriousness about VTE quality measures

The 8th edition of the ACCP guidelines recommends that every hospital develop a formal, active strategy to consistently identify medical and surgical patients at risk for VTE and to prevent VTE occurrence.¹ Although prior editions of the ACCP guidelines have made this recommendation for more than 2 decades, fewer than 1 in 10 acute care hospitals had any such strategy in place as recently as 5 years ago. Now, however, most US hospitals have implemented such a strategy, thanks to the growing national emphasis on health care quality measurement in recent years.

The Surgical Care Improvement Project (SCIP) has been at the forefront of this recent quality measures movement. SCIP, a joint project of the American Medical Association and federal government agencies, set a goal to reduce surgical complications in the United States by 25% from 2005 to 2010.² Two SCIP process measures relate to improving VTE prophylaxis^2,3:

• The proportion of surgical patients for whom recommended VTE prophylaxis is ordered
• The proportion of surgical patients who actually receive appropriate VTE prophylaxis within 24 hours before or after surgery.

The Joint Commission and the National Quality Forum recently endorsed these two SCIP performance measures for perioperative VTE prophylaxis along with several others relating to VTE treatment.

CMS raises the stakes with reimbursement restrictions

More significantly, the federal government’s Centers for Medicare and Medicaid Services (CMS) will soon refuse to reimburse for hospital treatment of a primary diagnosis of DVT or pulmonary embolism (PE) following recent (within 30 days) total hip or knee arthroplasty. Effective October 1, 2009, a primary VTE diagnosis following these joint replacement procedures will be added to CMS’ current list of “never events,” or hospital-acquired conditions for which CMS will not provide reimbursement because they are considered the result of preventable medical errors. (Notably, treatment of DVT or PE as a secondary diagnosis will still be reimbursed—for example, if a joint replacement patient develops nosocomial pneumonia, is transferred to the intensive care unit, and then develops VTE.) This addition of DVT and PE to the list is highly controversial since these events sometimes develop even if prophylactic therapy is appropriate and aggressive.

Strategies to promote best practices

In the update for the new 8th edition of its guidelines, the ACCP added recommendations on specific ways for hospitals to identify patients at high risk for VTE and ensure that they receive appropriate prophylaxis. These include the use of computer decision-support systems, preprinted orders, and periodic audit and feedback.¹

Researchers at Brigham and Women’s Hospital evaluated the effectiveness of a computer alert system for notifying physicians of newly hospitalized patients at risk for DVT who were not receiving prevention therapy within the first 24 hours of hospital admission.⁴ These patients presumably “fell through the cracks” and warranted prophylaxis but were otherwise not recognized by the health care team. Risk was determined by a scoring system based on multiple variables, including malignancy, previous DVT or PE, hypercoagulability, major surgery, advanced age, obesity, ordered bed rest, and treatment with hormone replacement therapy or oral contraceptives. Study physicians had to acknowledge having received the alert but could choose whether or not to order VTE prophylaxis. Prophylaxis was used in considerably more patients from the intervention group than from a control group of high-risk patients whose physicians did not receive alerts (34% vs 14%, respectively); accordingly, the risk of a symptomatic DVT or PE event at 90 days was reduced by 41% in the intervention group.

Despite this evidence of improved practice under the alert system, the study begs the question of why the percentage of patients at risk for VTE who were given prophylaxis was still so low (34%), demonstrating how much progress in improving practice remains to be achieved.

PROPHYLAXIS STRATEGIES: MATCHING THERAPY TO RISK

A fundamental consideration in determining the degree of VTE prophylaxis that a surgical patient may need is the thromboembolic risk of the procedure itself. Table 1 presents a procedure-based ranking of risk based on recommendations in the 8th edition of the ACCP guidelines.¹ As risk increases, so does the intensity of prophylaxis, with increasing reliance on pharmacologic strategies. The vast majority of patients who are hospitalized for surgery will fall into the moderate- or high-risk categories in Table 1.

A patient’s risk of thrombosis is also influenced by individual risk factors (Table 2),^1,5 many of which are nonmodifiable. A thorough preoperative evaluation is important to reveal “hidden” risk factors such as thrombo­philia and a family or personal history of VTE.

 

 

NONPHARMACOLOGIC PROPHYLAXIS STRATEGIES

Does ambulation prevent DVT?

Although it is commonly accepted that walking prevents DVT, this has never been directly tested. Walking may simply be a marker of health, and healthy people are less prone to develop thromboses. We have almost no evidence to show that forcing an unhealthy person to walk helps prevent DVT. Early ambulation offers many benefits and should be encouraged, but it should not be considered DVT prophylaxis; it is simply good hospital care.

Mechanical devices: Adherence is key

Amaragiri and Lees conducted a systematic literature review of randomized controlled trials evaluating the effectiveness of graduated compression stockings (elastic stockings) for preventing DVT in various groups of hospitalized patients.⁶ The analysis demonstrated a statistically significant reduction in DVT incidence with graduated compression stockings compared with control both among the nine trials in which stockings were used alone (odds ratio = 0.34) and among the seven trials in which stockings were used in addition to another method of thrombo­prophylaxis (odds ratio = 0.24). Although benefit was demonstrated, many of the trials in this review involved patients undergoing gynecologic surgery and date from the 1970s and 1980s (when obesity was less prevalent), so the applicability of their results today may be limited.

The 8th edition of the ACCP guidelines recommends that mechanical methods of VTE prophylaxis be used primarily in patients who are at high risk of bleeding and that careful attention be directed to ensuring their proper use and optimal adherence.¹ The latter point about adherence cannot be emphasized enough, as graduated compression stockings and other mechanical devices have been shown not to be effective unless they are worn at least 18 to 20 hours a day. This degree of adherence is difficult to achieve, as it can severely limit patient mobility and leave patients susceptible to develop­ment of pressure ulcers.

Mechanical compression should be initiated prior to induction of anesthesia and continue intraoperatively and then into the postanesthesia care unit. Orders for use of mechanical devices should include instructions in the patient’s medical chart specifying how—and for how many hours per day—they are to be worn. Not doing so leaves the physician vulnerable to litigation, especially as the ACCP guidelines include language on optimal adherence to these devices (“they should be removed for only a short time each day when the patient is actually walking or for bathing”¹).

Continuous external compression therapy

Newer mechanical device options include a continuous external compression therapy system that allows patients to be mobile while wearing it and provides rhythmic compression that results in good peak venous flows. Ideally such a device could be put on the patient preoperatively and worn during surgery, throughout the hospital stay, and even at home during recovery. Anecdotally, however, I see patients turn these new devices off at the side of the bed just as often as they do with traditional devices.

Vena caval interruption

Vena caval interruption involves placement of a retrievable vena cava filter before surgery and removal some time later; it offers the potential for VTE prophylaxis in patients who could not tolerate even minor amounts of bleeding, such as certain trauma patients. The Eastern Association for the Surgery of Trauma has put forth a consensus recommendation to consider vena caval interruption in high-risk trauma patients who cannot receive pharmacologic prophylaxis.⁷ A randomized trial evaluating the usefulness of vena caval interruption for patients undergoing surgery is needed. For now, this intervention should be regarded as experimental and considered only on a highly individualized basis.

PHARMACOLOGIC PROPHYLAXIS

The ACCP guidelines’ recommendations for pharmacologic VTE prophylaxis in surgical patients are lengthy, and many remain unchanged from prior editions, so this discussion will focus on broad principles and new recommendations adopted in the recent 8th edition.¹Table 3 lists notable new recommendations for patients undergoing specific surgical procedures.

Timing of initiation

Pharmacologic VTE prophylaxis generally should begin 8 to 24 hours postoperatively. Of course, adequate hemostasis is required before initiation, and the net risk/benefit tradeoff with regard to timing of anticoagulant initiation has still not been well studied in many surgical patient populations.

Extended prophylaxis

In the update for the 8th edition of its guidelines, the ACCP added an explicit recommendation for extended outpatient prophylaxis with low-molecular-weight heparin (LMWH) for up to 28 days postoperatively in selected high-risk patients undergoing general or gynecologic surgery, including those with cancer or a history of VTE.¹ This recommendation was based largely on studies of extended prophylaxis in patients with cancer undergoing colorectal surgery.⁸

Increased appreciation of the value of extended VTE prophylaxis after discharge is linked to a growing recognition that DVT and PE episodes in the community setting are often related to a recent hospital stay for either medical illness or surgery. A population-based study found that 59% of all community cases of a first lifetime VTE event in residents of Olmsted County, Minn., over a 15-year period could be linked to current or recent (< 30 days) hospitalization or nursing home residence.⁹ A similar population-based study in the Worcester, Mass., area found that three-fourths of all VTE events in a 3-year period occurred in the outpatient setting.¹⁰ Among patients with these outpatient VTE events, a large proportion had undergone surgery (23%) or hospitalization (37%) in the prior 3 months; among those, 67% experienced their VTE within 1 month of their time in the hospital.

These findings are no surprise, since surgery induces a hypercoagulable state that, when combined with individual risk factors such as obesity, old age, or poor heart function, cannot be assumed to return to baseline on postoperative day 4 or 5 just because the patient is being discharged.

Orthopedic surgery

For patients undergoing major orthopedic procedures, the ACCP guidelines recommend against routine screening for VTE with Doppler ultrasonography before discharge if the patient is asymptomatic.¹ Such screening is not considered cost-effective because asymptomatic clots often are found, for which treatment is uncertain, and proximal clots may be missed, giving a false sense of security.

ACCP recommendations for prophylaxis in patients undergoing orthopedic surgery are summarized in Table 4.¹ As shown, the recommended options for hip and knee replacement and hip fracture surgery are almost exclusively medication-based. The vast majority of patients undergoing these major orthopedic procedures need prophylaxis beyond their typical hospital stay of 3 or 4 days. About 90% of DVTs following knee replacement occur within 2 weeks of surgery, so 10 to 14 days of therapy is probably the best practice in this setting, although a longer period may be justified depending on the patient’s risk profile. For hip replacement, in contrast, 28 to 30 days of prophylaxis is often preferable, since about half of all DVTs in that setting occur more than 2 weeks after surgery.

New to the ACCP guidelines in the 8th edition is the recommendation that patients undergoing knee arthroscopy who have risk factors for VTE (or whose procedure is complicated) should receive 1 week of prophylaxis with LMWH.¹ Also new are recommendations for patients with risk factors undergoing single- or multilevel laminectomy (Table 4).

 

 

Recommendations unchanged in neurosurgery, spinal injury, trauma, burns

Recommendations for neurosurgery remain unchanged from the prior (2004) edition of the ACCP guidelines and are still based on the 2000 meta-analysis by Iorio and Agnelli of LMWH prophylaxis in neurosurgery cases.¹¹ In the United States, the standard is overwhelmingly to use mechanical devices for thromboprophylaxis in neurosurgery, even for patients with cancer.

For prophylaxis in surgical patients with spinal cord injury, multisystem trauma, or burns, LMWH is predominantly used, and the ACCP recommendations are unchanged from 2004.

Drug-specific considerations

LMWH vs vitamin K antagonist. Although vitamin K antagonists (warfarin) still appear in the latest ACCP recommendations,¹ LMWH is preferable. A 2004 meta-analysis of studies comparing vitamin K antagonists with LMWH for prophylaxis in patients undergoing orthopedic surgery found that vitamin K antagonists were associated with more episodes of total DVT (relative risk [RR] = 1.51; 95% CI, 1.27–1.79) and proximal DVT (RR = 1.51; 95% CI, 1.04–2.17) compared with LMWH.¹² No difference was found in rates of wound hematoma or major bleeding. This finding of inferiority for vitamin K antagonists came despite the likelihood that warfarin was more often administered correctly (ie, with dose adjustment to achieve an international normalized ratio [INR] of 2.0 to 3.0 within 72 hours after surgery) in the studies in this analysis than it is in real-world practice.

Fondaparinux. The indirect factor Xa–specific inhibitor fondaparinux has had a surprisingly limited clinical adoption despite having been widely studied and found to be safe and effective. This is likely attributable in part to its 17-hour half-life, which raises concerns that it may take 3 days for its effects to stop if a patient begins to bleed. Large phase 3 studies have found fondaparinux to be equivalent to LMWH in VTE prevention after hip replacement, marginally superior to LMWH after knee replacement, and superior to LMWH following hip fracture repair.¹³ Fondaparinux was associated with an increase in bleeding events and instances of transfusion requirement, but only in one of the studies, which was in the setting of knee replacement surgery.¹⁴

Aspirin not recommended by ACCP. Although aspirin reduces the risk of VTE, practice guidelines from both the ACCP¹ and the International Union of Angiology¹⁵ contain no recommendation for its use as prophylaxis because it is considered less effective and more risky than other therapies. In contrast, clinical practice guidelines from the American Academy of Orthopaedic Surgeons suggest that aspirin is reasonable for VTE prophylaxis.¹⁶ The varying recommendations reflect differences in perspective among these different specialties.

Aspirin has the advantages of ease of use and low cost, but it is clearly not the best evidence-based approach for VTE prophylaxis. The only recent randomized trial evidence in support of aspirin comes from the Pulmonary Embolism Prevention trial, a study with a flawed design involving more than 13,000 patients undergoing surgery for hip fracture or elective arthroplasty in five countries.¹⁷ Patients were randomized to receive aspirin 160 mg daily or placebo for 35 days along with any other prophylaxis deemed necessary (an important potential confounder). Aspirin was associated with an absolute reduction in symptomatic events of less than 1% relative to placebo, and no benefit was observed within the first week. The best results with aspirin were among patients with hip fracture. No benefit was shown among patients undergoing hip arthroplasty or knee arthroplasty; in those groups, both the aspirin and placebo recipients were also treated with LMWH. An absolute increase in rates of wound bleeding (0.6% increase) and gastrointestinal bleeding (1.0% increase) was observed in the aspirin group. The absolute increase in complications was greater than the absolute reduction in episodes of symptomatic DVT: for every episode of symptomatic DVT averted, one wound bleed and 10 gastrointestinal bleeds occurred.

SPECIAL PATIENT POPULATIONS

Renal impairment

The 8th edition of the ACCP guidelines recommends that renal function be kept in mind when considering LMWH, fondaparinux, and other antithrombotic drugs that are cleared by the kidneys. Fondaparinux and LMWH can bioaccumulate in patients with renal insufficiency, who have a higher risk of bleeding to begin with, thereby compounding the risk. Options for patients with renal compromise include avoiding drugs that bioaccumulate, using a lower dosage, and monitoring the drug level or anticoagulant effect.¹

Fondaparinux is explicitly contraindicated in patients with low body weight (< 50 kg) or renal impairment (creatinine clearance < 30 mL/min). Renal function should be assessed periodically in any patients receiving the drug.¹⁸

I also would not use fondaparinux or LMWH in patients with rapidly changing renal function. For patients with chronic, stable renal impairment, one can reduce the dose of LMWH empirically; one LMWH, enoxaparin, has specific dosing guidelines in its package insert (one-third reduction in dose), but this option does not hold for patients with rapidly changing renal function.¹⁹

Obesity

The 8th edition of the ACCP guidelines recommends weight-based dosing of thromboprophylactic agents in obese patients. The guidelines particularly recommend that patients undergoing inpatient bariatric surgery be given higher doses of LMWH or unfractionated heparin.^1,20

Frederiksen et al measured the anticoagulant effect of a single fixed dose of a LMWH (using anti-factor Xa heparin activity levels) and found that it was dependent on body weight.²¹ This suggests that fixed doses that are effective in normal-weight patients may have no detectable anti-coagulant effect in patients with very high body weight.

Weight-based dosing: mounting nonprospective evidence. Weight-based dosage adjustment for the morbidly obese has not been directly studied in a prospective, randomized fashion. A nonrandomized study by Scholten et al compared two regimens of enoxaparin (30 mg twice daily vs 40 mg twice daily) among 481 obese patients undergoing bariatric surgery; each regimen was used along with mechanical thromboprophylaxis.²² They found that the higher-dose regimen was associated with significantly fewer postoperative DVT complications (0.6% vs 5.4%; P < .01) without an increase in bleeding complications.

Separately, Shepherd et al used weight-adjusted doses of unfractionated heparin (started on the evening of surgery) to achieve subtherapeutic peak anti–factor Xa heparin activity levels of 0.11 to 0.25 IU/mL in a series of 700 patients undergoing laparoscopic gastric bypass surgery.²³ The resulting doses were greater than those in traditional fixed-rate protocols, but rates of bleeding and VTE events were low and comparable to those reported in patients receiving standard doses. 

Don’t rule out multimodal approaches. Multimodal prophylaxis can also be used in obese patients and need not be abandoned as a result of size considerations. For instance, two intermittent compression therapy devices can be pieced together with a Velcro binder if a single device is too small to be worn.

 

 

EMERGING ANTICOAGULANT OPTIONS

For many years, unfractionated heparin was the only available parenteral anticoagulant. While heparin has broad anticoagulant properties, it also has well-established limitations, including the need for parenteral delivery, recent problems related to contamination (it is derived from pig intestines), and of course heparin-induced thrombocytopenia (HIT). HIT is an immune-mediated form of platelet activation that can lead to widespread thrombosis throughout the body. It is more commonly associated with venous thrombosis, but arterial events with limb-threatening ischemia may also occur. LMWH is associated with a reduced risk of HIT, but LMWH does not avoid the risk entirely.

Beyond the issue of avoiding HIT, newer anticoagulant therapies are being developed with the aim of oral administration and more targeted inhibition of coagulation factors IIa (thrombin) and Xa.²⁴

Oral direct thrombin inhibitors

One of the two most promising classes of emerging anticoagulants is the direct thrombin inhibitors, most of which are being developed for oral administration. There were high hopes for the initial compound in this class, ximelagatran, but it was abandoned about 5 years ago because of hepatotoxicity.

Dabigatran is the direct thrombin inhibitor furthest along in development today. Currently approved in Europe for prevention of VTE in patients undergoing total hip or knee replacement surgery, dabigatran is likely to be available soon in the United States. It is administered orally, has a rapid onset of action (< 1 hour), and has a predictable anticoagulant response that requires no monitoring.²⁴ Because dabigatran is excreted essentially unchanged by the kidneys and may bioaccumulate, it should not be used in patients with renal impairment or rapidly changing renal function.

In phase 3 clinical trials for VTE prevention in knee replacement surgery, dabigatran was at least as effective as enoxaparin 40 mg once daily and had a comparable safety profile,²⁵ but it was slightly less effective than enoxaparin 30 mg twice daily.²⁶ In a phase 3 trial in patients under­going hip replacement surgery, dabigatran was equivalent in efficacy and safety to enoxaparin 40 mg once daily.²⁷

Oral direct factor Xa inhibitors

A key rationale for direct inhibition of factor Xa is that it results in inhibition of thrombin production on the activated platelet. Whereas fondaparinux is an indirect inhibitor of factor Xa, direct factor Xa inhibitors offer an advantage in that they inhibit factor Xa within the prothrombinase complex, which occurs on the surface of a platelet and is the main site for thrombin development (very little thrombin is actually produced on endothelial cells). Recall the adage that “thrombin begets more thrombin”: it activates not only platelets but the intrinsic and extrinsic pathways.²⁸

Factor Xa may be a better target than thrombin for a number of other reasons:

• Factor Xa is believed to have few functions (compared with thrombin) outside of coagulation

• In vitro studies show that factor Xa has a wider therapeutic window than thrombin, which translates to greater separation between drug levels that will confer efficacy and bleeding
• Thrombin inhibitors are associated with rebound thrombin generation (there is no evidence of this with factor Xa inhibitors)
• The efficacy of heparin-based anticoagulants improves as selectivity for factor Xa increases (unfractionated heparin is less effective than LMWH, which is less effective than fondaparinux).

Two direct factor Xa inhibitors—both administered orally—are far along in development, as detailed below.

Apixaban has shown promise, but the phase 3 ADVANCE-1 study of apixaban for VTE prevention in patients undergoing knee surgery did not meet statistical criteria for noninferiority compared with enoxaparin 30 mg twice daily.²⁹ This prompted a delay in regulatory filings for apixaban in the United States, and the drug’s prospects for approval for VTE prevention may be unclear until release of results from two other comparative phase 3 trials with enoxaparin in 2009 and 2010.

Rivaroxaban is more likely to become clinically available soon, in light of recent results from the phase 3 RECORD4 trial demonstrating that it was significantly superior to enoxaparin 30 mg twice daily in preventing VTE following knee replacement surgery with comparable rates of major bleeding.³⁰

DISCUSSION

Question from the audience: Some surgeons in my hospital prescribe warfarin immediately after surgery without a bridge of LMWH. Is that appropriate?

Dr. Michota: Warfarin is an option for prophylaxis in orthopedic surgery, beginning on the day of surgery. It could even be started the day before surgery, but the dose should be monitored to achieve an INR between 2.0 and 3.0 within 72 hours of the procedure. If the INR is not in this optimum range, prophylactic doses of LMWH can be given until it is therapeutic.

Follow-up question: In practice, do you actually encourage INR monitoring? Usually we just put patients on a certain dose without monitoring. When we do check the INR, it’s usually 1.4 or 1.5.

Dr. Michota: Warfarin was shown to be effective in reducing VTE risk in orthopedic surgery with dose adjustment based on INR monitoring. On that basis, warfarin remains in the guideline recommendations. Unmonitored, warfarin has not been shown to reduce risk, so to give it that way would not be evidence-based.

Question from the audience: I work with several plastic surgeons who use compression stockings intraoperatively because they’ve heard of several patients who developed a PE during surgery. Is there any benefit to using compression stockings for 2 to 3 hours and then sending the patient home?

Dr. Michota: I don’t know. Theoretically, a device that is on and working before induction may reduce stasis.

The plastic surgery societies do have guidelines. Risk depends on the type of plastic surgery procedure; for example, risk probably increases due to inflammation in procedures that involve scraping the fat pads.

This is an area where we don’t have much data. These patients may be at risk, but we don’t know the best way to mitigate it. It is important that risks be discussed with patients in the informed-consent process and be documented. If the surgeon thinks it is reasonable to give pharmacologic prophylaxis after surgery, I wouldn’t hesitate to do that, but any form of bleeding in the setting of plastic surgery is catastrophic because it defeats the reason for which the surgery was done in the first place.

Question from the audience: How do the guidelines address being aggressive with pharmacologic thromboprophylaxis when a patient is already taking dual antiplatelet therapy?

Dr. Michota: For patients with an indication for VTE prophylaxis in a setting for which there is a specific strategy, the ACCP guidelines recommend that they be put on that regimen whether they are on antiplatelet agents or not. For example, consider a high-risk patient having colorectal surgery who should get unfractionated heparin or LMWH postoperatively and who is currently taking clopidogrel and aspirin. There is no evidence that the dual aspirin–clopidogrel therapy alone is effective in decreasing the risk of DVT. However, we do know that if we add on additional agents, the risk of bleeding is increased. The guidelines consider risk and benefit, and they recommend adding the agents that we know work to prevent DVT.

Question from the audience: You briefly mentioned prophylaxis for knee arthroscopy, which is the most frequently performed orthopedic procedure. Do these recommendations apply to all patients undergoing knee arthroscopy?

Dr. Michota: No. Prophylaxis is indicated only for patients with what the ACCP considers to be additional risk factors for thrombosis. They didn’t specify which risk factors, but good indications for prophylaxis would include morbid obesity, limited mobility after the procedure, a personal history of DVT, features of stasis noted on physical examination, stasis dermatitis (or other features that could indicate prior thrombosis), advanced age, and malignancy. If a patient undergoing knee arthroscopy has other nonmodifiable risk factors, you should also think about prophylaxis. But the vast majority of patients do not need it.

Question from the audience: I’m an academic hospitalist who works closely with orthopedic surgeons. Certain surgeons will only use aspirin for prophylaxis, and it is nonnegotiable. Where does that leave me from a medicolegal standpoint? Our model is to follow ACCP recommendations, but these orthopedic surgeons still use only aspirin.

Dr. Michota: You must do everything you can to come to a consensus with your surgeon colleagues. If you are uncomfortable, as a group you must say to the surgeons, “We are uncomfortable. This is how we view the data. How do you view the data?” If they answer, “We’re doing it because it’s easy, and the American Academy of Orthopaedic Surgeons says we can do it,” I don’t have a good response. But it is more likely that their use of aspirin is based on their own observations; they may not see many clots. Of course, the problem with observational data is that the numbers are not large and they are not generated in a randomized and prospective fashion. Perhaps you can come to some middle ground, but you could always make the difficult choice and say, “I’m just not going to follow your patients.”

Most surgical patients who require hospitalization should be considered at high risk for venous thromboembolism (VTE) and be given appropriate prophylaxis. For lower-risk procedures such as knee arthroscopy, prophylaxis is needed for those with individual risk factors such as morbid obesity, limited mobility after surgery, or a history of deep vein thrombosis (DVT) or malignancy. Too often, however, prophylaxis is not provided appropriately or not given at all.

This review surveys the essentials of perioperative VTE prophylaxis and important new developments in the field, which include the 2008 release of new evidence-based clinical practice guidelines on antithrombotic and thrombolytic therapy from the American College of Chest Physicians (ACCP). This 8th edition of the guidelines updates the previous edition, published in 2004, and includes a section by Geerts et al devoted to VTE prevention.¹ Other major guidelines are also discussed, as are developments in VTE-related quality measurement, management of special patient populations (those with renal impairment or morbid obesity), and emerging therapies for VTE prophylaxis.

IMPETUS FOR QUALITY IMPROVEMENT IN VTE

A new seriousness about VTE quality measures

The 8th edition of the ACCP guidelines recommends that every hospital develop a formal, active strategy to consistently identify medical and surgical patients at risk for VTE and to prevent VTE occurrence.¹ Although prior editions of the ACCP guidelines have made this recommendation for more than 2 decades, fewer than 1 in 10 acute care hospitals had any such strategy in place as recently as 5 years ago. Now, however, most US hospitals have implemented such a strategy, thanks to the growing national emphasis on health care quality measurement in recent years.

The Surgical Care Improvement Project (SCIP) has been at the forefront of this recent quality measures movement. SCIP, a joint project of the American Medical Association and federal government agencies, set a goal to reduce surgical complications in the United States by 25% from 2005 to 2010.² Two SCIP process measures relate to improving VTE prophylaxis^2,3:

• The proportion of surgical patients for whom recommended VTE prophylaxis is ordered
• The proportion of surgical patients who actually receive appropriate VTE prophylaxis within 24 hours before or after surgery.

The Joint Commission and the National Quality Forum recently endorsed these two SCIP performance measures for perioperative VTE prophylaxis along with several others relating to VTE treatment.

CMS raises the stakes with reimbursement restrictions

More significantly, the federal government’s Centers for Medicare and Medicaid Services (CMS) will soon refuse to reimburse for hospital treatment of a primary diagnosis of DVT or pulmonary embolism (PE) following recent (within 30 days) total hip or knee arthroplasty. Effective October 1, 2009, a primary VTE diagnosis following these joint replacement procedures will be added to CMS’ current list of “never events,” or hospital-acquired conditions for which CMS will not provide reimbursement because they are considered the result of preventable medical errors. (Notably, treatment of DVT or PE as a secondary diagnosis will still be reimbursed—for example, if a joint replacement patient develops nosocomial pneumonia, is transferred to the intensive care unit, and then develops VTE.) This addition of DVT and PE to the list is highly controversial since these events sometimes develop even if prophylactic therapy is appropriate and aggressive.

Strategies to promote best practices

In the update for the new 8th edition of its guidelines, the ACCP added recommendations on specific ways for hospitals to identify patients at high risk for VTE and ensure that they receive appropriate prophylaxis. These include the use of computer decision-support systems, preprinted orders, and periodic audit and feedback.¹

Researchers at Brigham and Women’s Hospital evaluated the effectiveness of a computer alert system for notifying physicians of newly hospitalized patients at risk for DVT who were not receiving prevention therapy within the first 24 hours of hospital admission.⁴ These patients presumably “fell through the cracks” and warranted prophylaxis but were otherwise not recognized by the health care team. Risk was determined by a scoring system based on multiple variables, including malignancy, previous DVT or PE, hypercoagulability, major surgery, advanced age, obesity, ordered bed rest, and treatment with hormone replacement therapy or oral contraceptives. Study physicians had to acknowledge having received the alert but could choose whether or not to order VTE prophylaxis. Prophylaxis was used in considerably more patients from the intervention group than from a control group of high-risk patients whose physicians did not receive alerts (34% vs 14%, respectively); accordingly, the risk of a symptomatic DVT or PE event at 90 days was reduced by 41% in the intervention group.

Despite this evidence of improved practice under the alert system, the study begs the question of why the percentage of patients at risk for VTE who were given prophylaxis was still so low (34%), demonstrating how much progress in improving practice remains to be achieved.

PROPHYLAXIS STRATEGIES: MATCHING THERAPY TO RISK

A fundamental consideration in determining the degree of VTE prophylaxis that a surgical patient may need is the thromboembolic risk of the procedure itself. Table 1 presents a procedure-based ranking of risk based on recommendations in the 8th edition of the ACCP guidelines.¹ As risk increases, so does the intensity of prophylaxis, with increasing reliance on pharmacologic strategies. The vast majority of patients who are hospitalized for surgery will fall into the moderate- or high-risk categories in Table 1.

A patient’s risk of thrombosis is also influenced by individual risk factors (Table 2),^1,5 many of which are nonmodifiable. A thorough preoperative evaluation is important to reveal “hidden” risk factors such as thrombo­philia and a family or personal history of VTE.

 

 

NONPHARMACOLOGIC PROPHYLAXIS STRATEGIES

Does ambulation prevent DVT?

Although it is commonly accepted that walking prevents DVT, this has never been directly tested. Walking may simply be a marker of health, and healthy people are less prone to develop thromboses. We have almost no evidence to show that forcing an unhealthy person to walk helps prevent DVT. Early ambulation offers many benefits and should be encouraged, but it should not be considered DVT prophylaxis; it is simply good hospital care.

Mechanical devices: Adherence is key

Amaragiri and Lees conducted a systematic literature review of randomized controlled trials evaluating the effectiveness of graduated compression stockings (elastic stockings) for preventing DVT in various groups of hospitalized patients.⁶ The analysis demonstrated a statistically significant reduction in DVT incidence with graduated compression stockings compared with control both among the nine trials in which stockings were used alone (odds ratio = 0.34) and among the seven trials in which stockings were used in addition to another method of thrombo­prophylaxis (odds ratio = 0.24). Although benefit was demonstrated, many of the trials in this review involved patients undergoing gynecologic surgery and date from the 1970s and 1980s (when obesity was less prevalent), so the applicability of their results today may be limited.

The 8th edition of the ACCP guidelines recommends that mechanical methods of VTE prophylaxis be used primarily in patients who are at high risk of bleeding and that careful attention be directed to ensuring their proper use and optimal adherence.¹ The latter point about adherence cannot be emphasized enough, as graduated compression stockings and other mechanical devices have been shown not to be effective unless they are worn at least 18 to 20 hours a day. This degree of adherence is difficult to achieve, as it can severely limit patient mobility and leave patients susceptible to develop­ment of pressure ulcers.

Mechanical compression should be initiated prior to induction of anesthesia and continue intraoperatively and then into the postanesthesia care unit. Orders for use of mechanical devices should include instructions in the patient’s medical chart specifying how—and for how many hours per day—they are to be worn. Not doing so leaves the physician vulnerable to litigation, especially as the ACCP guidelines include language on optimal adherence to these devices (“they should be removed for only a short time each day when the patient is actually walking or for bathing”¹).

Continuous external compression therapy

Newer mechanical device options include a continuous external compression therapy system that allows patients to be mobile while wearing it and provides rhythmic compression that results in good peak venous flows. Ideally such a device could be put on the patient preoperatively and worn during surgery, throughout the hospital stay, and even at home during recovery. Anecdotally, however, I see patients turn these new devices off at the side of the bed just as often as they do with traditional devices.

Vena caval interruption

Vena caval interruption involves placement of a retrievable vena cava filter before surgery and removal some time later; it offers the potential for VTE prophylaxis in patients who could not tolerate even minor amounts of bleeding, such as certain trauma patients. The Eastern Association for the Surgery of Trauma has put forth a consensus recommendation to consider vena caval interruption in high-risk trauma patients who cannot receive pharmacologic prophylaxis.⁷ A randomized trial evaluating the usefulness of vena caval interruption for patients undergoing surgery is needed. For now, this intervention should be regarded as experimental and considered only on a highly individualized basis.

PHARMACOLOGIC PROPHYLAXIS

The ACCP guidelines’ recommendations for pharmacologic VTE prophylaxis in surgical patients are lengthy, and many remain unchanged from prior editions, so this discussion will focus on broad principles and new recommendations adopted in the recent 8th edition.¹Table 3 lists notable new recommendations for patients undergoing specific surgical procedures.

Timing of initiation

Pharmacologic VTE prophylaxis generally should begin 8 to 24 hours postoperatively. Of course, adequate hemostasis is required before initiation, and the net risk/benefit tradeoff with regard to timing of anticoagulant initiation has still not been well studied in many surgical patient populations.

Extended prophylaxis

In the update for the 8th edition of its guidelines, the ACCP added an explicit recommendation for extended outpatient prophylaxis with low-molecular-weight heparin (LMWH) for up to 28 days postoperatively in selected high-risk patients undergoing general or gynecologic surgery, including those with cancer or a history of VTE.¹ This recommendation was based largely on studies of extended prophylaxis in patients with cancer undergoing colorectal surgery.⁸

Increased appreciation of the value of extended VTE prophylaxis after discharge is linked to a growing recognition that DVT and PE episodes in the community setting are often related to a recent hospital stay for either medical illness or surgery. A population-based study found that 59% of all community cases of a first lifetime VTE event in residents of Olmsted County, Minn., over a 15-year period could be linked to current or recent (< 30 days) hospitalization or nursing home residence.⁹ A similar population-based study in the Worcester, Mass., area found that three-fourths of all VTE events in a 3-year period occurred in the outpatient setting.¹⁰ Among patients with these outpatient VTE events, a large proportion had undergone surgery (23%) or hospitalization (37%) in the prior 3 months; among those, 67% experienced their VTE within 1 month of their time in the hospital.

These findings are no surprise, since surgery induces a hypercoagulable state that, when combined with individual risk factors such as obesity, old age, or poor heart function, cannot be assumed to return to baseline on postoperative day 4 or 5 just because the patient is being discharged.

Orthopedic surgery

For patients undergoing major orthopedic procedures, the ACCP guidelines recommend against routine screening for VTE with Doppler ultrasonography before discharge if the patient is asymptomatic.¹ Such screening is not considered cost-effective because asymptomatic clots often are found, for which treatment is uncertain, and proximal clots may be missed, giving a false sense of security.

ACCP recommendations for prophylaxis in patients undergoing orthopedic surgery are summarized in Table 4.¹ As shown, the recommended options for hip and knee replacement and hip fracture surgery are almost exclusively medication-based. The vast majority of patients undergoing these major orthopedic procedures need prophylaxis beyond their typical hospital stay of 3 or 4 days. About 90% of DVTs following knee replacement occur within 2 weeks of surgery, so 10 to 14 days of therapy is probably the best practice in this setting, although a longer period may be justified depending on the patient’s risk profile. For hip replacement, in contrast, 28 to 30 days of prophylaxis is often preferable, since about half of all DVTs in that setting occur more than 2 weeks after surgery.

New to the ACCP guidelines in the 8th edition is the recommendation that patients undergoing knee arthroscopy who have risk factors for VTE (or whose procedure is complicated) should receive 1 week of prophylaxis with LMWH.¹ Also new are recommendations for patients with risk factors undergoing single- or multilevel laminectomy (Table 4).

 

 

Recommendations unchanged in neurosurgery, spinal injury, trauma, burns

Recommendations for neurosurgery remain unchanged from the prior (2004) edition of the ACCP guidelines and are still based on the 2000 meta-analysis by Iorio and Agnelli of LMWH prophylaxis in neurosurgery cases.¹¹ In the United States, the standard is overwhelmingly to use mechanical devices for thromboprophylaxis in neurosurgery, even for patients with cancer.

For prophylaxis in surgical patients with spinal cord injury, multisystem trauma, or burns, LMWH is predominantly used, and the ACCP recommendations are unchanged from 2004.

Drug-specific considerations

LMWH vs vitamin K antagonist. Although vitamin K antagonists (warfarin) still appear in the latest ACCP recommendations,¹ LMWH is preferable. A 2004 meta-analysis of studies comparing vitamin K antagonists with LMWH for prophylaxis in patients undergoing orthopedic surgery found that vitamin K antagonists were associated with more episodes of total DVT (relative risk [RR] = 1.51; 95% CI, 1.27–1.79) and proximal DVT (RR = 1.51; 95% CI, 1.04–2.17) compared with LMWH.¹² No difference was found in rates of wound hematoma or major bleeding. This finding of inferiority for vitamin K antagonists came despite the likelihood that warfarin was more often administered correctly (ie, with dose adjustment to achieve an international normalized ratio [INR] of 2.0 to 3.0 within 72 hours after surgery) in the studies in this analysis than it is in real-world practice.

Fondaparinux. The indirect factor Xa–specific inhibitor fondaparinux has had a surprisingly limited clinical adoption despite having been widely studied and found to be safe and effective. This is likely attributable in part to its 17-hour half-life, which raises concerns that it may take 3 days for its effects to stop if a patient begins to bleed. Large phase 3 studies have found fondaparinux to be equivalent to LMWH in VTE prevention after hip replacement, marginally superior to LMWH after knee replacement, and superior to LMWH following hip fracture repair.¹³ Fondaparinux was associated with an increase in bleeding events and instances of transfusion requirement, but only in one of the studies, which was in the setting of knee replacement surgery.¹⁴

Aspirin not recommended by ACCP. Although aspirin reduces the risk of VTE, practice guidelines from both the ACCP¹ and the International Union of Angiology¹⁵ contain no recommendation for its use as prophylaxis because it is considered less effective and more risky than other therapies. In contrast, clinical practice guidelines from the American Academy of Orthopaedic Surgeons suggest that aspirin is reasonable for VTE prophylaxis.¹⁶ The varying recommendations reflect differences in perspective among these different specialties.

Aspirin has the advantages of ease of use and low cost, but it is clearly not the best evidence-based approach for VTE prophylaxis. The only recent randomized trial evidence in support of aspirin comes from the Pulmonary Embolism Prevention trial, a study with a flawed design involving more than 13,000 patients undergoing surgery for hip fracture or elective arthroplasty in five countries.¹⁷ Patients were randomized to receive aspirin 160 mg daily or placebo for 35 days along with any other prophylaxis deemed necessary (an important potential confounder). Aspirin was associated with an absolute reduction in symptomatic events of less than 1% relative to placebo, and no benefit was observed within the first week. The best results with aspirin were among patients with hip fracture. No benefit was shown among patients undergoing hip arthroplasty or knee arthroplasty; in those groups, both the aspirin and placebo recipients were also treated with LMWH. An absolute increase in rates of wound bleeding (0.6% increase) and gastrointestinal bleeding (1.0% increase) was observed in the aspirin group. The absolute increase in complications was greater than the absolute reduction in episodes of symptomatic DVT: for every episode of symptomatic DVT averted, one wound bleed and 10 gastrointestinal bleeds occurred.

SPECIAL PATIENT POPULATIONS

Renal impairment

The 8th edition of the ACCP guidelines recommends that renal function be kept in mind when considering LMWH, fondaparinux, and other antithrombotic drugs that are cleared by the kidneys. Fondaparinux and LMWH can bioaccumulate in patients with renal insufficiency, who have a higher risk of bleeding to begin with, thereby compounding the risk. Options for patients with renal compromise include avoiding drugs that bioaccumulate, using a lower dosage, and monitoring the drug level or anticoagulant effect.¹

Fondaparinux is explicitly contraindicated in patients with low body weight (< 50 kg) or renal impairment (creatinine clearance < 30 mL/min). Renal function should be assessed periodically in any patients receiving the drug.¹⁸

I also would not use fondaparinux or LMWH in patients with rapidly changing renal function. For patients with chronic, stable renal impairment, one can reduce the dose of LMWH empirically; one LMWH, enoxaparin, has specific dosing guidelines in its package insert (one-third reduction in dose), but this option does not hold for patients with rapidly changing renal function.¹⁹

Obesity

The 8th edition of the ACCP guidelines recommends weight-based dosing of thromboprophylactic agents in obese patients. The guidelines particularly recommend that patients undergoing inpatient bariatric surgery be given higher doses of LMWH or unfractionated heparin.^1,20

Frederiksen et al measured the anticoagulant effect of a single fixed dose of a LMWH (using anti-factor Xa heparin activity levels) and found that it was dependent on body weight.²¹ This suggests that fixed doses that are effective in normal-weight patients may have no detectable anti-coagulant effect in patients with very high body weight.

Weight-based dosing: mounting nonprospective evidence. Weight-based dosage adjustment for the morbidly obese has not been directly studied in a prospective, randomized fashion. A nonrandomized study by Scholten et al compared two regimens of enoxaparin (30 mg twice daily vs 40 mg twice daily) among 481 obese patients undergoing bariatric surgery; each regimen was used along with mechanical thromboprophylaxis.²² They found that the higher-dose regimen was associated with significantly fewer postoperative DVT complications (0.6% vs 5.4%; P < .01) without an increase in bleeding complications.

Separately, Shepherd et al used weight-adjusted doses of unfractionated heparin (started on the evening of surgery) to achieve subtherapeutic peak anti–factor Xa heparin activity levels of 0.11 to 0.25 IU/mL in a series of 700 patients undergoing laparoscopic gastric bypass surgery.²³ The resulting doses were greater than those in traditional fixed-rate protocols, but rates of bleeding and VTE events were low and comparable to those reported in patients receiving standard doses. 

Don’t rule out multimodal approaches. Multimodal prophylaxis can also be used in obese patients and need not be abandoned as a result of size considerations. For instance, two intermittent compression therapy devices can be pieced together with a Velcro binder if a single device is too small to be worn.

 

 

EMERGING ANTICOAGULANT OPTIONS

For many years, unfractionated heparin was the only available parenteral anticoagulant. While heparin has broad anticoagulant properties, it also has well-established limitations, including the need for parenteral delivery, recent problems related to contamination (it is derived from pig intestines), and of course heparin-induced thrombocytopenia (HIT). HIT is an immune-mediated form of platelet activation that can lead to widespread thrombosis throughout the body. It is more commonly associated with venous thrombosis, but arterial events with limb-threatening ischemia may also occur. LMWH is associated with a reduced risk of HIT, but LMWH does not avoid the risk entirely.

Beyond the issue of avoiding HIT, newer anticoagulant therapies are being developed with the aim of oral administration and more targeted inhibition of coagulation factors IIa (thrombin) and Xa.²⁴

Oral direct thrombin inhibitors

One of the two most promising classes of emerging anticoagulants is the direct thrombin inhibitors, most of which are being developed for oral administration. There were high hopes for the initial compound in this class, ximelagatran, but it was abandoned about 5 years ago because of hepatotoxicity.

Dabigatran is the direct thrombin inhibitor furthest along in development today. Currently approved in Europe for prevention of VTE in patients undergoing total hip or knee replacement surgery, dabigatran is likely to be available soon in the United States. It is administered orally, has a rapid onset of action (< 1 hour), and has a predictable anticoagulant response that requires no monitoring.²⁴ Because dabigatran is excreted essentially unchanged by the kidneys and may bioaccumulate, it should not be used in patients with renal impairment or rapidly changing renal function.

In phase 3 clinical trials for VTE prevention in knee replacement surgery, dabigatran was at least as effective as enoxaparin 40 mg once daily and had a comparable safety profile,²⁵ but it was slightly less effective than enoxaparin 30 mg twice daily.²⁶ In a phase 3 trial in patients under­going hip replacement surgery, dabigatran was equivalent in efficacy and safety to enoxaparin 40 mg once daily.²⁷

Oral direct factor Xa inhibitors

A key rationale for direct inhibition of factor Xa is that it results in inhibition of thrombin production on the activated platelet. Whereas fondaparinux is an indirect inhibitor of factor Xa, direct factor Xa inhibitors offer an advantage in that they inhibit factor Xa within the prothrombinase complex, which occurs on the surface of a platelet and is the main site for thrombin development (very little thrombin is actually produced on endothelial cells). Recall the adage that “thrombin begets more thrombin”: it activates not only platelets but the intrinsic and extrinsic pathways.²⁸

Factor Xa may be a better target than thrombin for a number of other reasons:

• Factor Xa is believed to have few functions (compared with thrombin) outside of coagulation

• In vitro studies show that factor Xa has a wider therapeutic window than thrombin, which translates to greater separation between drug levels that will confer efficacy and bleeding
• Thrombin inhibitors are associated with rebound thrombin generation (there is no evidence of this with factor Xa inhibitors)
• The efficacy of heparin-based anticoagulants improves as selectivity for factor Xa increases (unfractionated heparin is less effective than LMWH, which is less effective than fondaparinux).

Two direct factor Xa inhibitors—both administered orally—are far along in development, as detailed below.

Apixaban has shown promise, but the phase 3 ADVANCE-1 study of apixaban for VTE prevention in patients undergoing knee surgery did not meet statistical criteria for noninferiority compared with enoxaparin 30 mg twice daily.²⁹ This prompted a delay in regulatory filings for apixaban in the United States, and the drug’s prospects for approval for VTE prevention may be unclear until release of results from two other comparative phase 3 trials with enoxaparin in 2009 and 2010.

Rivaroxaban is more likely to become clinically available soon, in light of recent results from the phase 3 RECORD4 trial demonstrating that it was significantly superior to enoxaparin 30 mg twice daily in preventing VTE following knee replacement surgery with comparable rates of major bleeding.³⁰

DISCUSSION

Question from the audience: Some surgeons in my hospital prescribe warfarin immediately after surgery without a bridge of LMWH. Is that appropriate?

Dr. Michota: Warfarin is an option for prophylaxis in orthopedic surgery, beginning on the day of surgery. It could even be started the day before surgery, but the dose should be monitored to achieve an INR between 2.0 and 3.0 within 72 hours of the procedure. If the INR is not in this optimum range, prophylactic doses of LMWH can be given until it is therapeutic.

Follow-up question: In practice, do you actually encourage INR monitoring? Usually we just put patients on a certain dose without monitoring. When we do check the INR, it’s usually 1.4 or 1.5.

Dr. Michota: Warfarin was shown to be effective in reducing VTE risk in orthopedic surgery with dose adjustment based on INR monitoring. On that basis, warfarin remains in the guideline recommendations. Unmonitored, warfarin has not been shown to reduce risk, so to give it that way would not be evidence-based.

Question from the audience: I work with several plastic surgeons who use compression stockings intraoperatively because they’ve heard of several patients who developed a PE during surgery. Is there any benefit to using compression stockings for 2 to 3 hours and then sending the patient home?

Dr. Michota: I don’t know. Theoretically, a device that is on and working before induction may reduce stasis.

The plastic surgery societies do have guidelines. Risk depends on the type of plastic surgery procedure; for example, risk probably increases due to inflammation in procedures that involve scraping the fat pads.

This is an area where we don’t have much data. These patients may be at risk, but we don’t know the best way to mitigate it. It is important that risks be discussed with patients in the informed-consent process and be documented. If the surgeon thinks it is reasonable to give pharmacologic prophylaxis after surgery, I wouldn’t hesitate to do that, but any form of bleeding in the setting of plastic surgery is catastrophic because it defeats the reason for which the surgery was done in the first place.

Question from the audience: How do the guidelines address being aggressive with pharmacologic thromboprophylaxis when a patient is already taking dual antiplatelet therapy?

Dr. Michota: For patients with an indication for VTE prophylaxis in a setting for which there is a specific strategy, the ACCP guidelines recommend that they be put on that regimen whether they are on antiplatelet agents or not. For example, consider a high-risk patient having colorectal surgery who should get unfractionated heparin or LMWH postoperatively and who is currently taking clopidogrel and aspirin. There is no evidence that the dual aspirin–clopidogrel therapy alone is effective in decreasing the risk of DVT. However, we do know that if we add on additional agents, the risk of bleeding is increased. The guidelines consider risk and benefit, and they recommend adding the agents that we know work to prevent DVT.

Question from the audience: You briefly mentioned prophylaxis for knee arthroscopy, which is the most frequently performed orthopedic procedure. Do these recommendations apply to all patients undergoing knee arthroscopy?

Dr. Michota: No. Prophylaxis is indicated only for patients with what the ACCP considers to be additional risk factors for thrombosis. They didn’t specify which risk factors, but good indications for prophylaxis would include morbid obesity, limited mobility after the procedure, a personal history of DVT, features of stasis noted on physical examination, stasis dermatitis (or other features that could indicate prior thrombosis), advanced age, and malignancy. If a patient undergoing knee arthroscopy has other nonmodifiable risk factors, you should also think about prophylaxis. But the vast majority of patients do not need it.

Question from the audience: I’m an academic hospitalist who works closely with orthopedic surgeons. Certain surgeons will only use aspirin for prophylaxis, and it is nonnegotiable. Where does that leave me from a medicolegal standpoint? Our model is to follow ACCP recommendations, but these orthopedic surgeons still use only aspirin.

Dr. Michota: You must do everything you can to come to a consensus with your surgeon colleagues. If you are uncomfortable, as a group you must say to the surgeons, “We are uncomfortable. This is how we view the data. How do you view the data?” If they answer, “We’re doing it because it’s easy, and the American Academy of Orthopaedic Surgeons says we can do it,” I don’t have a good response. But it is more likely that their use of aspirin is based on their own observations; they may not see many clots. Of course, the problem with observational data is that the numbers are not large and they are not generated in a randomized and prospective fashion. Perhaps you can come to some middle ground, but you could always make the difficult choice and say, “I’m just not going to follow your patients.”

Diabetes confers an increased risk of perioperative morbidity and mortality, mostly from infection and cardiovascular events. It is not unusual for surgical patients with diabetes to have a number of comorbidities or underlying chronic vascular complications that put them at risk for cardiovascular events or an infectious complication. Silent ischemia, coronary artery disease, and autonomic neuropathy are common among patients with diabetes, and each can contribute to perioperative morbidity and mortality. These are important considerations since nearly one-fifth of surgical patients have diabetes and since a person with diabetes has a 50% risk of undergoing surgery at some point in his or her lifetime.¹

This article reviews the preoperative evaluation of patients with diabetes, discusses the relation between glycemic control and perioperative outcomes, and examines targets and strategies for glycemic control in patients with type 1 and type 2 diabetes throughout the perioperative period.

PREOPERATIVE EVALUATION

The preoperative evaluation must consider first and foremost the status of the patient’s diabetes and his or her surgical risk factors. Also important are the characteristics of the procedure to be performed, the method of anesthesia to be used, and select laboratory values.

Diabetes status

The type of diabetes and its treatment must be considered. Type 1 diabetes requires continuous insulin therapy to prevent ketoacidosis; patients with type 2 diabetes are usually treated with oral medications with or without insulin. Baseline control of blood glucose is a predictor of morbidity following surgery. Hypoglycemia is associated with increased morbidity in the inpatient setting, so a history of severe hypoglycemic events or of difficulty recognizing hypoglycemia (hypoglycemia unawareness) should be elicited in the preoperative evaluation. Complications of diabetes and other comorbidities also must be evaluated, along with their treatments.

Surgical risk factors

Patients with diabetes have surgical risk factors specific to their health—namely, cardiovascular risk factors that may or may not have been previously diagnosed. Patients with diabetes may have silent ischemia, atypical manifestations of coronary ischemia, or underlying cardiomyopathy. Many patients with type 2 diabetes have hypertension, which may complicate perioperative management. Other common surgical risk factors in this population include obesity, chronic kidney disease, and undiagnosed autonomic dysfunction, which may compromise hemodynamic stability in the perioperative period. Additionally, patients with long-standing diabetes experience reductions in pulmonary function (eg, forced expiratory volume, peak expiratory flow, and diffusion capacity for carbon monoxide) related to disease duration and vascular injury,² which may complicate weaning from ventilatory support.

Characteristics of the procedure and anesthetic

Both surgery and anesthesia may induce an increase in levels of stress hormones (epinephrine, cortisol, growth hormone) and inflammatory cytokines (interleukin-6 and tumor necrosis factor–alpha), resulting in insulin resistance and impaired insulin secretion (even among patients who present with adequate insulin secretion). These in turn contribute to lipolysis and protein catabolism, leading to hyperglycemia and, if a patient is severely insulin deficient, ketoacidosis. Other factors that particularly affect insulin resistance and secretion include cardiovascular bypass surgery, sepsis, the need for total parenteral nutrition, and steroid therapy.

The characteristics of the surgical procedure, including the type of surgery as well as its urgency, duration, and timing (morning vs later in the day), are important in planning for perioperative glycemic management. For example, a short, minor procedure may require only observation, whereas more extensive procedures warrant periodic monitoring and active glycemic management with insulin infusions.

The type of anesthesia should also be considered. Compared with epidural anesthesia, general anesthesia is associated with greater stimulation of the sympathetic nervous system and increased catecholamine levels, resulting in more pronounced hyperglycemia.³

Preoperative tests

Preoperative testing and laboratory evaluation should include, at minimum, an electrocardiogram, a basic metabolic panel to assess renal function, electrolyte levels, and hemoglobin A_1c measurement. For low-risk procedures in patients with adequate exercise tolerance, no diagnostic tests might be needed. In any case, knowledge of the hemoglobin A_1c level may help not only to classify perioperative risk but also to determine postoperative care, including the choice of antiglycemic medications at discharge.

IMPORTANCE OF GLYCEMIC CONTROL

Preoperative glycemic control has a significant impact on the risk of infectious complications—including pneumonia, wound infection, urinary tract infection, and sepsis—in patients with diabetes across a variety of surgical procedures.⁴ Similarly, postoperative glycemic control—to a mean blood glucose level less than 200 mg/dL in the immediate postoperative period—significantly reduces the incidence of deep sternal wound infection after open heart surgery.⁵

Among patients undergoing cardiothoracic surgery, both cardiac-related and overall mortality are greater with increasing postoperative blood glucose levels, although a cause-and-effect relationship has not been established.⁶

Glycemic control matters regardless of diabetes status

Hyperglycemia affects mortality regardless of diabetes status. In a study of 779 consecutive patients admitted for acute myocardial infarction, mortality at 180 days was highly associated with hyperglycemia on admission independent of a history of diabetes; the highest mortality was among hyperglycemic patients without previously known diabetes.⁷ Similarly, a large study of glycemic control in intensive care unit (ICU) patients receiving insulin found that mortality in nondiabetic patients increased with median glucose level and was higher than mortality in diabetic patients.⁸ These findings suggest a need for vigilance in the perioperative and critical care management of all patients with hyperglycemia, regardless of preadmission diabetes diagnosis, as they carry significant morbidity and mortality risk.

GLYCEMIC CONTROL IN THE CRITICALLY ILL: SOME SUPPORT FOR A MODIFIED TARGET, BUT VIGILANCE FOR HYPOGLYCEMIA NEEDED

The landmark study by Van den Berghe et al of intensive insulin therapy in surgical ICU patients demonstrated significant reductions in morbidity and mortality when glucose levels were controlled aggressively (80 to 110 mg/dL; average, 103 mg/dL) compared with conventional control (180 to 200 mg/dL).⁹ The benefit of intensive glycemic control was evident on outcomes such as the occurrence of sepsis, need for dialysis, need for blood transfusion, and development of acute polyneuropathy. Intensive insulin therapy was also associated with cost savings compared with conventional insulin therapy in mechanically ventilated patients.¹⁰

However, a number of subsequent studies have clearly shown that as blood glucose levels approach normoglycemia, the risks of hypoglycemia, especially severe hypoglycemia, can offset the benefits of tight blood glucose control.

A follow-up study by Ven den Berghe et al in a medical ICU failed to show a mortality benefit from tight glycemic control, though patients in the intensive control arm experienced less renal injury, faster weaning from ventilation, and earlier discharge from the ICU and hospital.¹¹

The recent NICE-SUGAR study of aggressive glucose control in the ICU randomized patients to a target blood glucose of 81 to 108 mg/dL (intensive group) or 180 mg/dL or less (control group).¹² At study’s end, the groups’ mean blood glucose levels were 115 mg/dL and 144 mg/dL, respectively, while rates of severe hypoglycemia (blood glucose < 40 mg/dL) were 6.8% and 0.5%, respectively. Mortality rates were higher in the intensive therapy group (27.5%) than in the control group (24.9%), driven by severe hypoglycemic events. Notably, blood glucose monitoring in this and other studies was conducted at a frequency of anywhere between 1 and 4 hours.

The conclusions of the available data would support, for the time being, a modified glycemic target in critically ill patients, with strict avoidance of severe hypoglycemia. The recent consensus statement from the American Association of Clinical Endocrinologists and the American Diabetes Association recommends using insulin therapy if blood glucose levels exceed 180 mg/dL, with target glucose levels less than 180 mg/dL in critically ill patients and less than 140 mg/dL in non–critically ill patients.¹³ Development and implementation of safer insulin infusion algorithms and more frequent and accurate blood glucose monitoring in this setting should enable us to achieve better glycemic targets with lower risk.

 

 

ELEMENTS OF PHYSIOLOGIC INSULIN REPLACEMENT

In hospitalized patients with hyperglycemia, three different components of insulin replacement require management¹:

Basal insulin replacement consists of a long-acting insulin preparation administered regardless of the patient’s oral intake status, with the premise of matching hepatic (endogenous) glucose production

Prandial insulin replacement requires a rapid-acting insulin preparation given to cover nutritional needs

Supplemental (or correction) insulin replacement requires a rapid-acting preparation (usually the same insulin type as for prandial coverage) to correct blood glucose values that exceed predetermined glycemic targets.

For most patients, basal insulin replacement might be appropriate preoperatively to control fasting glucose, whereas during surgery, especially if prolonged or high risk, an intravenous (IV) insulin drip is the most effective means of glucose control. The postoperative transition from the IV insulin drip usually involves basal insulin replacement plus supplemental rapid-acting insulin. Prandial or nutritional insulin should be started once the patient begins to receive nutrition (oral, enteral, or hyperalimentation).

GOALS OF PERIOPERATIVE GLYCEMIC CONTROL

Perioperative glycemic management has several key objectives:

• Avoidance of clinically significant hyper- or hypoglycemia
• Maintenance of electrolyte and fluid balance
• Prevention of ketoacidosis, which is imperative in patients with type 1 diabetes, who require insulin at all times
• Achievement of specific glycemic targets, as discussed above—ie, less than 180 mg/dL in critically ill patients and less than 140 mg/dL in stable patients.¹³

Strategies differ across the perioperative timeline

Strategies for perioperative glycemic control differ before, during, and after surgery, as summarized immediately below and detailed in the following sections.

Preoperatively, glycemia should be stabilized, typically with subcutaneous insulin, if there is enough time to do so. For patients who have not previously been on insulin, placing them on an insulin supplemental scale to correct glycemia to desired targets might be a first step. In the setting of hyperglycemia, these patients may also be started on a low dose of basal insulin, with preference given to basal insulin analogs, given their consistent and relatively peakless action profile and lower risk of hypoglycemia. A starting dose of 0.2 to 0.4 U/kg is appropriate and carries a low risk of hypoglycemia. For patients already using insulin on an outpatient basis, continuing their basal insulin dose, possibly at a reduced dosage (25% less), together with supplemental-scale insulin coverage, should stabilize blood glucose levels. For patients on combination insulin or premixed insulin types, the basal insulin dose for preoperative management can be estimated by taking the patient’s usual total daily dose and delivering 40% to 50% of that dose as a basal insulin analog injection. Clearly, a supplemental scale should be implemented along with basal insulin replacement.

Intraoperatively, switching to IV insulin may be appropriate for stabilizing glycemia, depending on the type of surgery. A number of IV insulin protocols have been proposed, although no consistent comparisons of efficacy or safety among these protocols have been published.

Postoperatively, patients eventually should be transitioned from IV to subcutaneous insulin when glycemic control stabilizes. This transition may be complicated for many reasons. Oral intake may be inconsistent. The surgery and surrounding environment can induce stressors, promote susceptibility to infection, and increase insulin resistance. Additionally, some patients may be on hyperalimentation. Specific instructions for the transition from IV to subcutaneous insulin are covered later in this article.

PREOPERATIVE GLYCEMIC MANAGEMENT

In patients with type 2 diabetes, oral agents pose certain safety risks and should be discontinued prior to surgery.

Sulfonylureas may induce hypoglycemia in patients who are placed on NPO (“nothing by mouth”) orders and should be held in patients who are fasting.

Metformin can induce lactic acidosis if kidney function declines and should be withheld 1 to 2 days before planned surgery if a need for IV contrast is anticipated or the procedure could potentially lead to hemodynamic instability and reduced renal perfusion.

Thiazolidinediones may cause fluid retention that can complicate the postoperative period; they can be discontinued several days prior to a planned surgery.

GLP-1 agonists, such as exenatide, can slow gastric motility and potentially delay gastrointestinal recovery after major surgery; they should be held the day of surgery.

DPP-4 inhibitors (incretin enhancers), such as sitagliptin, do not have significant side effects and, if need be, can be continued. Because incretin therapies act via a glucose-dependent mechanism, they are unlikely to cause hypoglycemia, even in a patient whose oral intake is held or delayed. On the other hand, since their effect is mostly in reducing postprandial glycemia, there may be little need to use them in a patient who is NPO.

Patients with type 1 diabetes must continue basal insulin replacement preoperatively (0.2 to 0.3 U/kg/day of a long-acting insulin). Patients with type 2 diabetes may benefit from basal insulin replacement, as previously noted.

Supplemental insulin scales are used to correct hyper­glycemia regardless of a patient’s oral intake status. They can be individualized based on the estimated total daily insulin dose and require glycemic targets to be established. Fingerstick glucose monitoring should be done every 4 to 6 hours in a patient who is NPO, and supplemental-scale insulin should be used to correct glucose values that exceed target. For supplemental-scale coverage, rapid-acting insulin analogs have a shorter duration of action than human regular insulin and may be given subcutaneously every 4 to 6 hours, whereas regular insulin should not be given more often than every 6 hours to correct hyperglycemia. These differences in action duration should be kept in mind to minimize the potential for insulin stacking.

INTRAOPERATIVE GLYCEMIC MANAGEMENT

Procedure length is an important determinant

Strategies for intraoperative glucose management vary according to the length of the procedure.

For minor, short procedures, the preoperative glucose management orders may be continued.

For longer, more complex procedures, a switch to an IV insulin drip is safe and allows rapid adjustments in dosing and plasma glucose levels. Ideally, IV insulin is started prior to the procedure so that the glucose level is stable once the patient arrives in the operating room. Given the logistics of IV insulin management, including the need for frequent monitoring (hourly) and dose adjustments, this type of treatment should be reserved for environments with adequate numbers of trained staff.

IV regular insulin is therapy of choice

Adapted, with permission, from Diabetes Care (Goldberg PA, et al. Diabetes Care 2004; 27:461–467), Copyright © 2004 by the American Diabetes Association.

Regular insulin delivered IV has a serum half-life of 7 minutes with a duration of effect of approximately 1 hour. These properties make IV regular insulin an effective tool for adjusting insulin therapy and addressing rapid changes in blood glucose values in critically ill patients. For this reason, IV regular insulin has become the preferred insulin for perioperative and critical care management. Although rapid-acting analogs can also be used IV, they confer no benefit over IV regular insulin and are more expensive.

Several different algorithms for IV regular insulin therapy are in use. Some are static, such as those of Markovitz et al¹⁴ and Stockton et al,¹⁵ while others are dynamic (ie, doses are self-adjusted based on changes in blood glucose level), such as the “Yale protocol” of Goldberg et al (Figure 1).¹⁶

 

 

POSTOPERATIVE GLYCEMIC MANAGEMENT

Start subcutaneous transition before stopping IV drip

Transitioning from IV to subcutaneous insulin is often complicated. Nonoral nutrition options (ie, parenteral nutrition or enteral supplementation) must be considered. As noted, insulin must be replaced according to physiologic needs, which requires that a long-acting basal insulin be used regardless of oral intake status, a rapid-acting insulin be given to cover prandial or nutritional needs, and supplemental rapid-acting insulin be used to correct hyperglycemia.

In the transition from IV insulin, basal insulin replacement can begin at any time. I recommend starting the transition from IV to subcutaneous insulin about 12 to 24 hours before discontinuing the insulin drip. In type 1 diabetes, this transition ensures basal insulin coverage and minimizes the risk of developing ketones and ketoacidosis. In type 2 diabetes, it can ensure a more stable transition and better glycemic control.

Determining the basal insulin dose

The starting dose of basal insulin should be 50% to 80% of the prior IV insulin total daily dose, if stable glycemic control had been achieved with IV insulin. Alternatively, a calculation called the “Miami 4/12 rule” can be used, whereby the basal insulin replacement dose is equal to the patient’s weight in kilograms divided by 4 (Figure 2). I recommend that basal insulin replacement be given either once daily or divided twice daily as a long-acting insulin analog (eg, insulin glargine or insulin detemir).

Switching to subcutaneous supplemental insulin

Instructions must be given for switching to subcutaneous supplemental doses of insulin. Glycemic targets, generally from less than 130 to 150 mg/dL, must be established, as must the frequency of fingerstick testing:

• If the patient is being fed enterally or parenterally, fingerstick testing is recommended every 4 to 6 hours if a rapid-acting insulin analog is used and every 6 hours if regular insulin is used.
• If the patient is eating, fingerstick testing should be performed before meals and at bedtime.

The increment in supplemental insulin to correct hyperglycemia can be individualized based on a patient’s perceived sensitivity to insulin, as detailed in Table 1.¹⁷ Adjustments to supplemental doses are needed to maintain glycemic targets.

Covering nutritional requirements

Nutrition-related insulin needs depend on the type of caloric intake prescribed:

In patients receiving total parenteral nutrition (TPN), start 1 U of regular insulin (placed in the bag) for every 10 to 15 g of dextrose in the TPN mixture.

In patients receiving enteral nutrition, use regular insulin every 6 hours or a rapid-acting insulin analog every 4 hours. Start 1 U of insulin subcutaneously for every 10 to 15 g of delivered carbohydrates. For example, if a patient is receiving 10 g of carbohydrates per hour, a rapid-acting analog given at a dose of 4 U every 4 hours (1 U per 10 g of carbohydrates) should adequately cover enteral feedings. For any bolus feedings, give the injection as a full bolus 15 to 20 minutes in advance, based on the carbohydrate content of the feeding.

In patients who are eating, use regular insulin or a rapid-acting insulin analog before meals. Again, start 1 U of insulin subcutaneously for every 10 to 15 g of carbohydrates, or use the prandial portion of the Miami 4/12 rule (Figure 2). For example, in a 60-kg patient one would start with 5 U (60 ÷ 12) of a rapid-acting insulin before each meal.

Basal/bolus replacement outperforms supplemental-scale regular insulin

Use of a basal/bolus insulin regimen appears to be more beneficial than supplemental-scale regular insulin in hospitalized patients with type 2 diabetes, according to a recent randomized trial comparing the two approaches in 130 such patients with blood glucose levels greater than 140 mg/dL.¹⁷ In the group randomized to basal/bolus insulin, the starting total daily dose was 0.4 to 0.5 U/kg/day, with half the dose given as basal insulin (insulin glargine) once daily and half given as a rapid-acting insulin analog (glulisine) in fixed doses before every meal. A rapid-acting analog was used for supplemental insulin in the basal/bolus regimen. By study’s end, patients in the basal/bolus group were receiving a higher total daily insulin dose than those in the supplemental-scale group (mean of 42 U/day vs 13 U/day).

Mean daily blood glucose levels were 27 mg/dL lower, on average, in patients who received basal/bolus therapy compared with the supplemental-scale group, yet there was no difference between groups in the risk of hypoglycemia. More patients randomized to basal/bolus therapy achieved the glycemic goal of less than 140 mg/dL (66% vs 38%). Fourteen percent of patients assigned to supplemental-scale insulin had values persistently greater than 240 mg/dL and had to be switched to the basal/bolus regimen.¹⁷

SUMMARY

Perioperative glycemic control can reduce morbidity, particularly the incidence of infectious complications, in surgical patients, even in those without diagnosed diabetes. Optimal management of glycemia in the perioperative period involves applying principles of physiologic insulin replacement. Postoperatively, the transition from IV to subcutaneous insulin can be achieved through the use of basal insulin for coverage of fasting insulin needs, regardless of the patient’s feeding status, and the use of rapid-acting insulin to cover hyperglycemia and nutritional needs. Management of hospitalized patients exclusively with supplemental-scale regular insulin should be abandoned.

 

 

DISCUSSION

Question from the audience: As an attending physician in a preoperative clinic I’m never sure what to do with NPH insulin the morning of surgery. What guidance can you give?

Dr. Meneghini: NPH is a peaking basal insulin, and the peak can induce hypoglycemia in a patient who is NPO. If we have the opportunity, we try to switch patients previously receiving insulin therapy to a long-acting basal insulin analog, which has a much flatter action profile and is safer in the fasting state. If there is no opportunity for switching, we instruct the patient to take two-thirds of his or her usual morning dose of insulin and we initiate a D5 drip when the patient arrives at the hospital.

Question from the audience: How do you handle perioperative insulin in patients on insulin pumps?

Dr. Meneghini: The pumps provide a subcutaneous basal insulin infusion, which should, if set correctly, maintain stable blood glucose levels when the patient is NPO. Supplemental doses of insulin to correct hyperglycemia can be delivered via the usual subcutaneous practice with a syringe or insulin pen. If you are uncomfortable with pump function, or if the pump insertion site interferes with the surgery site, simply replace the 24-hour basal amount delivered via pump with an injection of glargine or detemir divided into twice-daily injections. Correct hyperglycemia with supplemental-scale insulin as per usual protocol.

Question from the audience: The manufacturer of insulin glargine makes no recommendations for its use the night before or morning of surgery. What do you recommend?

Dr. Meneghini: It depends on whether the glargine is dosed appropriately. Most patients with type 2 diabetes require 0.4 to 0.6 U/kg/day of a long-acting insulin. If they’re on much more, they may be overdosed, and I would cut the basal dose by about half. Otherwise, 75% to 100% of the usual basal amount is appropriate. In type 1 diabetes, the usual replacement dose of basal insulin is 0.2 to 0.3 U/kg/day. If a patient is in this range, the basal insulin can be continued. Patients who experience hypoglycemia, or a substantial fall in blood glucose if meals are skipped or delayed, may be getting too much basal insulin and might benefit from a dose reduction when placed on NPO status.

Question from the audience: Metformin has a black-box warning advising that it be stopped at least 48 hours before surgery, but patients often come to surgery having taken metformin within the prior 12 to 24 hours. How should we manage such patients coming for elective surgery?

Dr. Meneghini: Metformin is cleared exclusively by the kidneys; its accumulation as a result of impaired kidney function (eg, due to hemodynamic instability or radiology studies using IV iodine) can result in increased lactic acid production by the liver and lactic acidosis. A patient who has taken metformin within the prior 48 hours but doesn’t have a risk of hemodynamic dysfunction is at low risk of lactic acidosis if hydrated appropriately. There’s not much choice if a patient needs urgent surgery and has recently taken metformin; in that case, just ensure maintenance of adequate glomerular filtration via fluid repletion to clear the drug.

Question from the audience: What’s the evidence for tight glycemic control or any type of glycemic control in patients undergoing outpatient surgery or “same-day” patients who will be admitted to a regular surgical floor? Also, what would you consider maximal glucose values for a patient going into elective surgery?

Dr. Meneghini: I haven’t seen any guidelines for glycemic control in patients undergoing outpatient surgery. If a patient has poor glycemic control coming into surgery, even for a minor procedure, the risk of an infectious complication may be increased. Keeping blood glucose below 180 mg/dL and avoiding electrolyte imbalances is likely sufficient in such patients. On the second question, if it’s an elective procedure and can be delayed a few hours, you can certainly institute IV insulin therapy to correct hyperglycemia rapidly—just ensure adequate replacement of fluids since the patient may have had volume depletion or dehydration as a result of the preceding osmotic diuresis. Once glycemic control is improved (blood glucose < 180–200 mg/dL), the patient can proceed to surgery.

Question from the audience: What are your recommendations for resuming oral diabetes medications after surgery?

Dr. Meneghini: Once patients are tolerating their meals and being considered for discharge, you may want to resume their oral medications, assuming their admission hemoglobin A_1c levels were near goal. If glycemic control was inadequate preoperatively, this may be a good opportunity to adjust their prior regimen to more appropriate therapy. In some cases, this might include some form of insulin, either basal therapy or basal and supplemental insulin.

Diabetes confers an increased risk of perioperative morbidity and mortality, mostly from infection and cardiovascular events. It is not unusual for surgical patients with diabetes to have a number of comorbidities or underlying chronic vascular complications that put them at risk for cardiovascular events or an infectious complication. Silent ischemia, coronary artery disease, and autonomic neuropathy are common among patients with diabetes, and each can contribute to perioperative morbidity and mortality. These are important considerations since nearly one-fifth of surgical patients have diabetes and since a person with diabetes has a 50% risk of undergoing surgery at some point in his or her lifetime.¹

This article reviews the preoperative evaluation of patients with diabetes, discusses the relation between glycemic control and perioperative outcomes, and examines targets and strategies for glycemic control in patients with type 1 and type 2 diabetes throughout the perioperative period.

PREOPERATIVE EVALUATION

The preoperative evaluation must consider first and foremost the status of the patient’s diabetes and his or her surgical risk factors. Also important are the characteristics of the procedure to be performed, the method of anesthesia to be used, and select laboratory values.

Diabetes status

The type of diabetes and its treatment must be considered. Type 1 diabetes requires continuous insulin therapy to prevent ketoacidosis; patients with type 2 diabetes are usually treated with oral medications with or without insulin. Baseline control of blood glucose is a predictor of morbidity following surgery. Hypoglycemia is associated with increased morbidity in the inpatient setting, so a history of severe hypoglycemic events or of difficulty recognizing hypoglycemia (hypoglycemia unawareness) should be elicited in the preoperative evaluation. Complications of diabetes and other comorbidities also must be evaluated, along with their treatments.

Surgical risk factors

Patients with diabetes have surgical risk factors specific to their health—namely, cardiovascular risk factors that may or may not have been previously diagnosed. Patients with diabetes may have silent ischemia, atypical manifestations of coronary ischemia, or underlying cardiomyopathy. Many patients with type 2 diabetes have hypertension, which may complicate perioperative management. Other common surgical risk factors in this population include obesity, chronic kidney disease, and undiagnosed autonomic dysfunction, which may compromise hemodynamic stability in the perioperative period. Additionally, patients with long-standing diabetes experience reductions in pulmonary function (eg, forced expiratory volume, peak expiratory flow, and diffusion capacity for carbon monoxide) related to disease duration and vascular injury,² which may complicate weaning from ventilatory support.

Characteristics of the procedure and anesthetic

Both surgery and anesthesia may induce an increase in levels of stress hormones (epinephrine, cortisol, growth hormone) and inflammatory cytokines (interleukin-6 and tumor necrosis factor–alpha), resulting in insulin resistance and impaired insulin secretion (even among patients who present with adequate insulin secretion). These in turn contribute to lipolysis and protein catabolism, leading to hyperglycemia and, if a patient is severely insulin deficient, ketoacidosis. Other factors that particularly affect insulin resistance and secretion include cardiovascular bypass surgery, sepsis, the need for total parenteral nutrition, and steroid therapy.

The characteristics of the surgical procedure, including the type of surgery as well as its urgency, duration, and timing (morning vs later in the day), are important in planning for perioperative glycemic management. For example, a short, minor procedure may require only observation, whereas more extensive procedures warrant periodic monitoring and active glycemic management with insulin infusions.

The type of anesthesia should also be considered. Compared with epidural anesthesia, general anesthesia is associated with greater stimulation of the sympathetic nervous system and increased catecholamine levels, resulting in more pronounced hyperglycemia.³

Preoperative tests

Preoperative testing and laboratory evaluation should include, at minimum, an electrocardiogram, a basic metabolic panel to assess renal function, electrolyte levels, and hemoglobin A_1c measurement. For low-risk procedures in patients with adequate exercise tolerance, no diagnostic tests might be needed. In any case, knowledge of the hemoglobin A_1c level may help not only to classify perioperative risk but also to determine postoperative care, including the choice of antiglycemic medications at discharge.

IMPORTANCE OF GLYCEMIC CONTROL

Preoperative glycemic control has a significant impact on the risk of infectious complications—including pneumonia, wound infection, urinary tract infection, and sepsis—in patients with diabetes across a variety of surgical procedures.⁴ Similarly, postoperative glycemic control—to a mean blood glucose level less than 200 mg/dL in the immediate postoperative period—significantly reduces the incidence of deep sternal wound infection after open heart surgery.⁵

Among patients undergoing cardiothoracic surgery, both cardiac-related and overall mortality are greater with increasing postoperative blood glucose levels, although a cause-and-effect relationship has not been established.⁶

Glycemic control matters regardless of diabetes status

Hyperglycemia affects mortality regardless of diabetes status. In a study of 779 consecutive patients admitted for acute myocardial infarction, mortality at 180 days was highly associated with hyperglycemia on admission independent of a history of diabetes; the highest mortality was among hyperglycemic patients without previously known diabetes.⁷ Similarly, a large study of glycemic control in intensive care unit (ICU) patients receiving insulin found that mortality in nondiabetic patients increased with median glucose level and was higher than mortality in diabetic patients.⁸ These findings suggest a need for vigilance in the perioperative and critical care management of all patients with hyperglycemia, regardless of preadmission diabetes diagnosis, as they carry significant morbidity and mortality risk.

GLYCEMIC CONTROL IN THE CRITICALLY ILL: SOME SUPPORT FOR A MODIFIED TARGET, BUT VIGILANCE FOR HYPOGLYCEMIA NEEDED

The landmark study by Van den Berghe et al of intensive insulin therapy in surgical ICU patients demonstrated significant reductions in morbidity and mortality when glucose levels were controlled aggressively (80 to 110 mg/dL; average, 103 mg/dL) compared with conventional control (180 to 200 mg/dL).⁹ The benefit of intensive glycemic control was evident on outcomes such as the occurrence of sepsis, need for dialysis, need for blood transfusion, and development of acute polyneuropathy. Intensive insulin therapy was also associated with cost savings compared with conventional insulin therapy in mechanically ventilated patients.¹⁰

However, a number of subsequent studies have clearly shown that as blood glucose levels approach normoglycemia, the risks of hypoglycemia, especially severe hypoglycemia, can offset the benefits of tight blood glucose control.

A follow-up study by Ven den Berghe et al in a medical ICU failed to show a mortality benefit from tight glycemic control, though patients in the intensive control arm experienced less renal injury, faster weaning from ventilation, and earlier discharge from the ICU and hospital.¹¹

The recent NICE-SUGAR study of aggressive glucose control in the ICU randomized patients to a target blood glucose of 81 to 108 mg/dL (intensive group) or 180 mg/dL or less (control group).¹² At study’s end, the groups’ mean blood glucose levels were 115 mg/dL and 144 mg/dL, respectively, while rates of severe hypoglycemia (blood glucose < 40 mg/dL) were 6.8% and 0.5%, respectively. Mortality rates were higher in the intensive therapy group (27.5%) than in the control group (24.9%), driven by severe hypoglycemic events. Notably, blood glucose monitoring in this and other studies was conducted at a frequency of anywhere between 1 and 4 hours.

The conclusions of the available data would support, for the time being, a modified glycemic target in critically ill patients, with strict avoidance of severe hypoglycemia. The recent consensus statement from the American Association of Clinical Endocrinologists and the American Diabetes Association recommends using insulin therapy if blood glucose levels exceed 180 mg/dL, with target glucose levels less than 180 mg/dL in critically ill patients and less than 140 mg/dL in non–critically ill patients.¹³ Development and implementation of safer insulin infusion algorithms and more frequent and accurate blood glucose monitoring in this setting should enable us to achieve better glycemic targets with lower risk.

 

 

ELEMENTS OF PHYSIOLOGIC INSULIN REPLACEMENT

In hospitalized patients with hyperglycemia, three different components of insulin replacement require management¹:

Basal insulin replacement consists of a long-acting insulin preparation administered regardless of the patient’s oral intake status, with the premise of matching hepatic (endogenous) glucose production

Prandial insulin replacement requires a rapid-acting insulin preparation given to cover nutritional needs

Supplemental (or correction) insulin replacement requires a rapid-acting preparation (usually the same insulin type as for prandial coverage) to correct blood glucose values that exceed predetermined glycemic targets.

For most patients, basal insulin replacement might be appropriate preoperatively to control fasting glucose, whereas during surgery, especially if prolonged or high risk, an intravenous (IV) insulin drip is the most effective means of glucose control. The postoperative transition from the IV insulin drip usually involves basal insulin replacement plus supplemental rapid-acting insulin. Prandial or nutritional insulin should be started once the patient begins to receive nutrition (oral, enteral, or hyperalimentation).

GOALS OF PERIOPERATIVE GLYCEMIC CONTROL

Perioperative glycemic management has several key objectives:

• Avoidance of clinically significant hyper- or hypoglycemia
• Maintenance of electrolyte and fluid balance
• Prevention of ketoacidosis, which is imperative in patients with type 1 diabetes, who require insulin at all times
• Achievement of specific glycemic targets, as discussed above—ie, less than 180 mg/dL in critically ill patients and less than 140 mg/dL in stable patients.¹³

Strategies differ across the perioperative timeline

Strategies for perioperative glycemic control differ before, during, and after surgery, as summarized immediately below and detailed in the following sections.

Preoperatively, glycemia should be stabilized, typically with subcutaneous insulin, if there is enough time to do so. For patients who have not previously been on insulin, placing them on an insulin supplemental scale to correct glycemia to desired targets might be a first step. In the setting of hyperglycemia, these patients may also be started on a low dose of basal insulin, with preference given to basal insulin analogs, given their consistent and relatively peakless action profile and lower risk of hypoglycemia. A starting dose of 0.2 to 0.4 U/kg is appropriate and carries a low risk of hypoglycemia. For patients already using insulin on an outpatient basis, continuing their basal insulin dose, possibly at a reduced dosage (25% less), together with supplemental-scale insulin coverage, should stabilize blood glucose levels. For patients on combination insulin or premixed insulin types, the basal insulin dose for preoperative management can be estimated by taking the patient’s usual total daily dose and delivering 40% to 50% of that dose as a basal insulin analog injection. Clearly, a supplemental scale should be implemented along with basal insulin replacement.

Intraoperatively, switching to IV insulin may be appropriate for stabilizing glycemia, depending on the type of surgery. A number of IV insulin protocols have been proposed, although no consistent comparisons of efficacy or safety among these protocols have been published.

Postoperatively, patients eventually should be transitioned from IV to subcutaneous insulin when glycemic control stabilizes. This transition may be complicated for many reasons. Oral intake may be inconsistent. The surgery and surrounding environment can induce stressors, promote susceptibility to infection, and increase insulin resistance. Additionally, some patients may be on hyperalimentation. Specific instructions for the transition from IV to subcutaneous insulin are covered later in this article.

PREOPERATIVE GLYCEMIC MANAGEMENT

In patients with type 2 diabetes, oral agents pose certain safety risks and should be discontinued prior to surgery.

Sulfonylureas may induce hypoglycemia in patients who are placed on NPO (“nothing by mouth”) orders and should be held in patients who are fasting.

Metformin can induce lactic acidosis if kidney function declines and should be withheld 1 to 2 days before planned surgery if a need for IV contrast is anticipated or the procedure could potentially lead to hemodynamic instability and reduced renal perfusion.

Thiazolidinediones may cause fluid retention that can complicate the postoperative period; they can be discontinued several days prior to a planned surgery.

GLP-1 agonists, such as exenatide, can slow gastric motility and potentially delay gastrointestinal recovery after major surgery; they should be held the day of surgery.

DPP-4 inhibitors (incretin enhancers), such as sitagliptin, do not have significant side effects and, if need be, can be continued. Because incretin therapies act via a glucose-dependent mechanism, they are unlikely to cause hypoglycemia, even in a patient whose oral intake is held or delayed. On the other hand, since their effect is mostly in reducing postprandial glycemia, there may be little need to use them in a patient who is NPO.

Patients with type 1 diabetes must continue basal insulin replacement preoperatively (0.2 to 0.3 U/kg/day of a long-acting insulin). Patients with type 2 diabetes may benefit from basal insulin replacement, as previously noted.

Supplemental insulin scales are used to correct hyper­glycemia regardless of a patient’s oral intake status. They can be individualized based on the estimated total daily insulin dose and require glycemic targets to be established. Fingerstick glucose monitoring should be done every 4 to 6 hours in a patient who is NPO, and supplemental-scale insulin should be used to correct glucose values that exceed target. For supplemental-scale coverage, rapid-acting insulin analogs have a shorter duration of action than human regular insulin and may be given subcutaneously every 4 to 6 hours, whereas regular insulin should not be given more often than every 6 hours to correct hyperglycemia. These differences in action duration should be kept in mind to minimize the potential for insulin stacking.

INTRAOPERATIVE GLYCEMIC MANAGEMENT

Procedure length is an important determinant

Strategies for intraoperative glucose management vary according to the length of the procedure.

For minor, short procedures, the preoperative glucose management orders may be continued.

For longer, more complex procedures, a switch to an IV insulin drip is safe and allows rapid adjustments in dosing and plasma glucose levels. Ideally, IV insulin is started prior to the procedure so that the glucose level is stable once the patient arrives in the operating room. Given the logistics of IV insulin management, including the need for frequent monitoring (hourly) and dose adjustments, this type of treatment should be reserved for environments with adequate numbers of trained staff.

IV regular insulin is therapy of choice

Adapted, with permission, from Diabetes Care (Goldberg PA, et al. Diabetes Care 2004; 27:461–467), Copyright © 2004 by the American Diabetes Association.

Regular insulin delivered IV has a serum half-life of 7 minutes with a duration of effect of approximately 1 hour. These properties make IV regular insulin an effective tool for adjusting insulin therapy and addressing rapid changes in blood glucose values in critically ill patients. For this reason, IV regular insulin has become the preferred insulin for perioperative and critical care management. Although rapid-acting analogs can also be used IV, they confer no benefit over IV regular insulin and are more expensive.

Several different algorithms for IV regular insulin therapy are in use. Some are static, such as those of Markovitz et al¹⁴ and Stockton et al,¹⁵ while others are dynamic (ie, doses are self-adjusted based on changes in blood glucose level), such as the “Yale protocol” of Goldberg et al (Figure 1).¹⁶

 

 

POSTOPERATIVE GLYCEMIC MANAGEMENT

Start subcutaneous transition before stopping IV drip

Transitioning from IV to subcutaneous insulin is often complicated. Nonoral nutrition options (ie, parenteral nutrition or enteral supplementation) must be considered. As noted, insulin must be replaced according to physiologic needs, which requires that a long-acting basal insulin be used regardless of oral intake status, a rapid-acting insulin be given to cover prandial or nutritional needs, and supplemental rapid-acting insulin be used to correct hyperglycemia.

In the transition from IV insulin, basal insulin replacement can begin at any time. I recommend starting the transition from IV to subcutaneous insulin about 12 to 24 hours before discontinuing the insulin drip. In type 1 diabetes, this transition ensures basal insulin coverage and minimizes the risk of developing ketones and ketoacidosis. In type 2 diabetes, it can ensure a more stable transition and better glycemic control.

Determining the basal insulin dose

The starting dose of basal insulin should be 50% to 80% of the prior IV insulin total daily dose, if stable glycemic control had been achieved with IV insulin. Alternatively, a calculation called the “Miami 4/12 rule” can be used, whereby the basal insulin replacement dose is equal to the patient’s weight in kilograms divided by 4 (Figure 2). I recommend that basal insulin replacement be given either once daily or divided twice daily as a long-acting insulin analog (eg, insulin glargine or insulin detemir).

Switching to subcutaneous supplemental insulin

Instructions must be given for switching to subcutaneous supplemental doses of insulin. Glycemic targets, generally from less than 130 to 150 mg/dL, must be established, as must the frequency of fingerstick testing:

• If the patient is being fed enterally or parenterally, fingerstick testing is recommended every 4 to 6 hours if a rapid-acting insulin analog is used and every 6 hours if regular insulin is used.
• If the patient is eating, fingerstick testing should be performed before meals and at bedtime.

The increment in supplemental insulin to correct hyperglycemia can be individualized based on a patient’s perceived sensitivity to insulin, as detailed in Table 1.¹⁷ Adjustments to supplemental doses are needed to maintain glycemic targets.

Covering nutritional requirements

Nutrition-related insulin needs depend on the type of caloric intake prescribed:

In patients receiving total parenteral nutrition (TPN), start 1 U of regular insulin (placed in the bag) for every 10 to 15 g of dextrose in the TPN mixture.

In patients receiving enteral nutrition, use regular insulin every 6 hours or a rapid-acting insulin analog every 4 hours. Start 1 U of insulin subcutaneously for every 10 to 15 g of delivered carbohydrates. For example, if a patient is receiving 10 g of carbohydrates per hour, a rapid-acting analog given at a dose of 4 U every 4 hours (1 U per 10 g of carbohydrates) should adequately cover enteral feedings. For any bolus feedings, give the injection as a full bolus 15 to 20 minutes in advance, based on the carbohydrate content of the feeding.

In patients who are eating, use regular insulin or a rapid-acting insulin analog before meals. Again, start 1 U of insulin subcutaneously for every 10 to 15 g of carbohydrates, or use the prandial portion of the Miami 4/12 rule (Figure 2). For example, in a 60-kg patient one would start with 5 U (60 ÷ 12) of a rapid-acting insulin before each meal.

Basal/bolus replacement outperforms supplemental-scale regular insulin

Use of a basal/bolus insulin regimen appears to be more beneficial than supplemental-scale regular insulin in hospitalized patients with type 2 diabetes, according to a recent randomized trial comparing the two approaches in 130 such patients with blood glucose levels greater than 140 mg/dL.¹⁷ In the group randomized to basal/bolus insulin, the starting total daily dose was 0.4 to 0.5 U/kg/day, with half the dose given as basal insulin (insulin glargine) once daily and half given as a rapid-acting insulin analog (glulisine) in fixed doses before every meal. A rapid-acting analog was used for supplemental insulin in the basal/bolus regimen. By study’s end, patients in the basal/bolus group were receiving a higher total daily insulin dose than those in the supplemental-scale group (mean of 42 U/day vs 13 U/day).

Mean daily blood glucose levels were 27 mg/dL lower, on average, in patients who received basal/bolus therapy compared with the supplemental-scale group, yet there was no difference between groups in the risk of hypoglycemia. More patients randomized to basal/bolus therapy achieved the glycemic goal of less than 140 mg/dL (66% vs 38%). Fourteen percent of patients assigned to supplemental-scale insulin had values persistently greater than 240 mg/dL and had to be switched to the basal/bolus regimen.¹⁷

SUMMARY

Perioperative glycemic control can reduce morbidity, particularly the incidence of infectious complications, in surgical patients, even in those without diagnosed diabetes. Optimal management of glycemia in the perioperative period involves applying principles of physiologic insulin replacement. Postoperatively, the transition from IV to subcutaneous insulin can be achieved through the use of basal insulin for coverage of fasting insulin needs, regardless of the patient’s feeding status, and the use of rapid-acting insulin to cover hyperglycemia and nutritional needs. Management of hospitalized patients exclusively with supplemental-scale regular insulin should be abandoned.

 

 

DISCUSSION

Question from the audience: As an attending physician in a preoperative clinic I’m never sure what to do with NPH insulin the morning of surgery. What guidance can you give?

Dr. Meneghini: NPH is a peaking basal insulin, and the peak can induce hypoglycemia in a patient who is NPO. If we have the opportunity, we try to switch patients previously receiving insulin therapy to a long-acting basal insulin analog, which has a much flatter action profile and is safer in the fasting state. If there is no opportunity for switching, we instruct the patient to take two-thirds of his or her usual morning dose of insulin and we initiate a D5 drip when the patient arrives at the hospital.

Question from the audience: How do you handle perioperative insulin in patients on insulin pumps?

Dr. Meneghini: The pumps provide a subcutaneous basal insulin infusion, which should, if set correctly, maintain stable blood glucose levels when the patient is NPO. Supplemental doses of insulin to correct hyperglycemia can be delivered via the usual subcutaneous practice with a syringe or insulin pen. If you are uncomfortable with pump function, or if the pump insertion site interferes with the surgery site, simply replace the 24-hour basal amount delivered via pump with an injection of glargine or detemir divided into twice-daily injections. Correct hyperglycemia with supplemental-scale insulin as per usual protocol.

Question from the audience: The manufacturer of insulin glargine makes no recommendations for its use the night before or morning of surgery. What do you recommend?

Dr. Meneghini: It depends on whether the glargine is dosed appropriately. Most patients with type 2 diabetes require 0.4 to 0.6 U/kg/day of a long-acting insulin. If they’re on much more, they may be overdosed, and I would cut the basal dose by about half. Otherwise, 75% to 100% of the usual basal amount is appropriate. In type 1 diabetes, the usual replacement dose of basal insulin is 0.2 to 0.3 U/kg/day. If a patient is in this range, the basal insulin can be continued. Patients who experience hypoglycemia, or a substantial fall in blood glucose if meals are skipped or delayed, may be getting too much basal insulin and might benefit from a dose reduction when placed on NPO status.

Question from the audience: Metformin has a black-box warning advising that it be stopped at least 48 hours before surgery, but patients often come to surgery having taken metformin within the prior 12 to 24 hours. How should we manage such patients coming for elective surgery?

Dr. Meneghini: Metformin is cleared exclusively by the kidneys; its accumulation as a result of impaired kidney function (eg, due to hemodynamic instability or radiology studies using IV iodine) can result in increased lactic acid production by the liver and lactic acidosis. A patient who has taken metformin within the prior 48 hours but doesn’t have a risk of hemodynamic dysfunction is at low risk of lactic acidosis if hydrated appropriately. There’s not much choice if a patient needs urgent surgery and has recently taken metformin; in that case, just ensure maintenance of adequate glomerular filtration via fluid repletion to clear the drug.

Question from the audience: What’s the evidence for tight glycemic control or any type of glycemic control in patients undergoing outpatient surgery or “same-day” patients who will be admitted to a regular surgical floor? Also, what would you consider maximal glucose values for a patient going into elective surgery?

Dr. Meneghini: I haven’t seen any guidelines for glycemic control in patients undergoing outpatient surgery. If a patient has poor glycemic control coming into surgery, even for a minor procedure, the risk of an infectious complication may be increased. Keeping blood glucose below 180 mg/dL and avoiding electrolyte imbalances is likely sufficient in such patients. On the second question, if it’s an elective procedure and can be delayed a few hours, you can certainly institute IV insulin therapy to correct hyperglycemia rapidly—just ensure adequate replacement of fluids since the patient may have had volume depletion or dehydration as a result of the preceding osmotic diuresis. Once glycemic control is improved (blood glucose < 180–200 mg/dL), the patient can proceed to surgery.

Question from the audience: What are your recommendations for resuming oral diabetes medications after surgery?

Dr. Meneghini: Once patients are tolerating their meals and being considered for discharge, you may want to resume their oral medications, assuming their admission hemoglobin A_1c levels were near goal. If glycemic control was inadequate preoperatively, this may be a good opportunity to adjust their prior regimen to more appropriate therapy. In some cases, this might include some form of insulin, either basal therapy or basal and supplemental insulin.

Diabetes confers an increased risk of perioperative morbidity and mortality, mostly from infection and cardiovascular events. It is not unusual for surgical patients with diabetes to have a number of comorbidities or underlying chronic vascular complications that put them at risk for cardiovascular events or an infectious complication. Silent ischemia, coronary artery disease, and autonomic neuropathy are common among patients with diabetes, and each can contribute to perioperative morbidity and mortality. These are important considerations since nearly one-fifth of surgical patients have diabetes and since a person with diabetes has a 50% risk of undergoing surgery at some point in his or her lifetime.¹

This article reviews the preoperative evaluation of patients with diabetes, discusses the relation between glycemic control and perioperative outcomes, and examines targets and strategies for glycemic control in patients with type 1 and type 2 diabetes throughout the perioperative period.

PREOPERATIVE EVALUATION

The preoperative evaluation must consider first and foremost the status of the patient’s diabetes and his or her surgical risk factors. Also important are the characteristics of the procedure to be performed, the method of anesthesia to be used, and select laboratory values.

Diabetes status

The type of diabetes and its treatment must be considered. Type 1 diabetes requires continuous insulin therapy to prevent ketoacidosis; patients with type 2 diabetes are usually treated with oral medications with or without insulin. Baseline control of blood glucose is a predictor of morbidity following surgery. Hypoglycemia is associated with increased morbidity in the inpatient setting, so a history of severe hypoglycemic events or of difficulty recognizing hypoglycemia (hypoglycemia unawareness) should be elicited in the preoperative evaluation. Complications of diabetes and other comorbidities also must be evaluated, along with their treatments.

Surgical risk factors

Patients with diabetes have surgical risk factors specific to their health—namely, cardiovascular risk factors that may or may not have been previously diagnosed. Patients with diabetes may have silent ischemia, atypical manifestations of coronary ischemia, or underlying cardiomyopathy. Many patients with type 2 diabetes have hypertension, which may complicate perioperative management. Other common surgical risk factors in this population include obesity, chronic kidney disease, and undiagnosed autonomic dysfunction, which may compromise hemodynamic stability in the perioperative period. Additionally, patients with long-standing diabetes experience reductions in pulmonary function (eg, forced expiratory volume, peak expiratory flow, and diffusion capacity for carbon monoxide) related to disease duration and vascular injury,² which may complicate weaning from ventilatory support.

Characteristics of the procedure and anesthetic

Both surgery and anesthesia may induce an increase in levels of stress hormones (epinephrine, cortisol, growth hormone) and inflammatory cytokines (interleukin-6 and tumor necrosis factor–alpha), resulting in insulin resistance and impaired insulin secretion (even among patients who present with adequate insulin secretion). These in turn contribute to lipolysis and protein catabolism, leading to hyperglycemia and, if a patient is severely insulin deficient, ketoacidosis. Other factors that particularly affect insulin resistance and secretion include cardiovascular bypass surgery, sepsis, the need for total parenteral nutrition, and steroid therapy.

The characteristics of the surgical procedure, including the type of surgery as well as its urgency, duration, and timing (morning vs later in the day), are important in planning for perioperative glycemic management. For example, a short, minor procedure may require only observation, whereas more extensive procedures warrant periodic monitoring and active glycemic management with insulin infusions.

The type of anesthesia should also be considered. Compared with epidural anesthesia, general anesthesia is associated with greater stimulation of the sympathetic nervous system and increased catecholamine levels, resulting in more pronounced hyperglycemia.³

Preoperative tests

Preoperative testing and laboratory evaluation should include, at minimum, an electrocardiogram, a basic metabolic panel to assess renal function, electrolyte levels, and hemoglobin A_1c measurement. For low-risk procedures in patients with adequate exercise tolerance, no diagnostic tests might be needed. In any case, knowledge of the hemoglobin A_1c level may help not only to classify perioperative risk but also to determine postoperative care, including the choice of antiglycemic medications at discharge.

IMPORTANCE OF GLYCEMIC CONTROL

Preoperative glycemic control has a significant impact on the risk of infectious complications—including pneumonia, wound infection, urinary tract infection, and sepsis—in patients with diabetes across a variety of surgical procedures.⁴ Similarly, postoperative glycemic control—to a mean blood glucose level less than 200 mg/dL in the immediate postoperative period—significantly reduces the incidence of deep sternal wound infection after open heart surgery.⁵

Among patients undergoing cardiothoracic surgery, both cardiac-related and overall mortality are greater with increasing postoperative blood glucose levels, although a cause-and-effect relationship has not been established.⁶

Glycemic control matters regardless of diabetes status

Hyperglycemia affects mortality regardless of diabetes status. In a study of 779 consecutive patients admitted for acute myocardial infarction, mortality at 180 days was highly associated with hyperglycemia on admission independent of a history of diabetes; the highest mortality was among hyperglycemic patients without previously known diabetes.⁷ Similarly, a large study of glycemic control in intensive care unit (ICU) patients receiving insulin found that mortality in nondiabetic patients increased with median glucose level and was higher than mortality in diabetic patients.⁸ These findings suggest a need for vigilance in the perioperative and critical care management of all patients with hyperglycemia, regardless of preadmission diabetes diagnosis, as they carry significant morbidity and mortality risk.

GLYCEMIC CONTROL IN THE CRITICALLY ILL: SOME SUPPORT FOR A MODIFIED TARGET, BUT VIGILANCE FOR HYPOGLYCEMIA NEEDED

The landmark study by Van den Berghe et al of intensive insulin therapy in surgical ICU patients demonstrated significant reductions in morbidity and mortality when glucose levels were controlled aggressively (80 to 110 mg/dL; average, 103 mg/dL) compared with conventional control (180 to 200 mg/dL).⁹ The benefit of intensive glycemic control was evident on outcomes such as the occurrence of sepsis, need for dialysis, need for blood transfusion, and development of acute polyneuropathy. Intensive insulin therapy was also associated with cost savings compared with conventional insulin therapy in mechanically ventilated patients.¹⁰

However, a number of subsequent studies have clearly shown that as blood glucose levels approach normoglycemia, the risks of hypoglycemia, especially severe hypoglycemia, can offset the benefits of tight blood glucose control.

A follow-up study by Ven den Berghe et al in a medical ICU failed to show a mortality benefit from tight glycemic control, though patients in the intensive control arm experienced less renal injury, faster weaning from ventilation, and earlier discharge from the ICU and hospital.¹¹

The recent NICE-SUGAR study of aggressive glucose control in the ICU randomized patients to a target blood glucose of 81 to 108 mg/dL (intensive group) or 180 mg/dL or less (control group).¹² At study’s end, the groups’ mean blood glucose levels were 115 mg/dL and 144 mg/dL, respectively, while rates of severe hypoglycemia (blood glucose < 40 mg/dL) were 6.8% and 0.5%, respectively. Mortality rates were higher in the intensive therapy group (27.5%) than in the control group (24.9%), driven by severe hypoglycemic events. Notably, blood glucose monitoring in this and other studies was conducted at a frequency of anywhere between 1 and 4 hours.

The conclusions of the available data would support, for the time being, a modified glycemic target in critically ill patients, with strict avoidance of severe hypoglycemia. The recent consensus statement from the American Association of Clinical Endocrinologists and the American Diabetes Association recommends using insulin therapy if blood glucose levels exceed 180 mg/dL, with target glucose levels less than 180 mg/dL in critically ill patients and less than 140 mg/dL in non–critically ill patients.¹³ Development and implementation of safer insulin infusion algorithms and more frequent and accurate blood glucose monitoring in this setting should enable us to achieve better glycemic targets with lower risk.

 

 

ELEMENTS OF PHYSIOLOGIC INSULIN REPLACEMENT

In hospitalized patients with hyperglycemia, three different components of insulin replacement require management¹:

Basal insulin replacement consists of a long-acting insulin preparation administered regardless of the patient’s oral intake status, with the premise of matching hepatic (endogenous) glucose production

Prandial insulin replacement requires a rapid-acting insulin preparation given to cover nutritional needs

Supplemental (or correction) insulin replacement requires a rapid-acting preparation (usually the same insulin type as for prandial coverage) to correct blood glucose values that exceed predetermined glycemic targets.

For most patients, basal insulin replacement might be appropriate preoperatively to control fasting glucose, whereas during surgery, especially if prolonged or high risk, an intravenous (IV) insulin drip is the most effective means of glucose control. The postoperative transition from the IV insulin drip usually involves basal insulin replacement plus supplemental rapid-acting insulin. Prandial or nutritional insulin should be started once the patient begins to receive nutrition (oral, enteral, or hyperalimentation).

GOALS OF PERIOPERATIVE GLYCEMIC CONTROL

Perioperative glycemic management has several key objectives:

• Avoidance of clinically significant hyper- or hypoglycemia
• Maintenance of electrolyte and fluid balance
• Prevention of ketoacidosis, which is imperative in patients with type 1 diabetes, who require insulin at all times
• Achievement of specific glycemic targets, as discussed above—ie, less than 180 mg/dL in critically ill patients and less than 140 mg/dL in stable patients.¹³

Strategies differ across the perioperative timeline

Strategies for perioperative glycemic control differ before, during, and after surgery, as summarized immediately below and detailed in the following sections.

Preoperatively, glycemia should be stabilized, typically with subcutaneous insulin, if there is enough time to do so. For patients who have not previously been on insulin, placing them on an insulin supplemental scale to correct glycemia to desired targets might be a first step. In the setting of hyperglycemia, these patients may also be started on a low dose of basal insulin, with preference given to basal insulin analogs, given their consistent and relatively peakless action profile and lower risk of hypoglycemia. A starting dose of 0.2 to 0.4 U/kg is appropriate and carries a low risk of hypoglycemia. For patients already using insulin on an outpatient basis, continuing their basal insulin dose, possibly at a reduced dosage (25% less), together with supplemental-scale insulin coverage, should stabilize blood glucose levels. For patients on combination insulin or premixed insulin types, the basal insulin dose for preoperative management can be estimated by taking the patient’s usual total daily dose and delivering 40% to 50% of that dose as a basal insulin analog injection. Clearly, a supplemental scale should be implemented along with basal insulin replacement.

Intraoperatively, switching to IV insulin may be appropriate for stabilizing glycemia, depending on the type of surgery. A number of IV insulin protocols have been proposed, although no consistent comparisons of efficacy or safety among these protocols have been published.

Postoperatively, patients eventually should be transitioned from IV to subcutaneous insulin when glycemic control stabilizes. This transition may be complicated for many reasons. Oral intake may be inconsistent. The surgery and surrounding environment can induce stressors, promote susceptibility to infection, and increase insulin resistance. Additionally, some patients may be on hyperalimentation. Specific instructions for the transition from IV to subcutaneous insulin are covered later in this article.

PREOPERATIVE GLYCEMIC MANAGEMENT

In patients with type 2 diabetes, oral agents pose certain safety risks and should be discontinued prior to surgery.

Sulfonylureas may induce hypoglycemia in patients who are placed on NPO (“nothing by mouth”) orders and should be held in patients who are fasting.

Metformin can induce lactic acidosis if kidney function declines and should be withheld 1 to 2 days before planned surgery if a need for IV contrast is anticipated or the procedure could potentially lead to hemodynamic instability and reduced renal perfusion.

Thiazolidinediones may cause fluid retention that can complicate the postoperative period; they can be discontinued several days prior to a planned surgery.

GLP-1 agonists, such as exenatide, can slow gastric motility and potentially delay gastrointestinal recovery after major surgery; they should be held the day of surgery.

DPP-4 inhibitors (incretin enhancers), such as sitagliptin, do not have significant side effects and, if need be, can be continued. Because incretin therapies act via a glucose-dependent mechanism, they are unlikely to cause hypoglycemia, even in a patient whose oral intake is held or delayed. On the other hand, since their effect is mostly in reducing postprandial glycemia, there may be little need to use them in a patient who is NPO.

Patients with type 1 diabetes must continue basal insulin replacement preoperatively (0.2 to 0.3 U/kg/day of a long-acting insulin). Patients with type 2 diabetes may benefit from basal insulin replacement, as previously noted.

Supplemental insulin scales are used to correct hyper­glycemia regardless of a patient’s oral intake status. They can be individualized based on the estimated total daily insulin dose and require glycemic targets to be established. Fingerstick glucose monitoring should be done every 4 to 6 hours in a patient who is NPO, and supplemental-scale insulin should be used to correct glucose values that exceed target. For supplemental-scale coverage, rapid-acting insulin analogs have a shorter duration of action than human regular insulin and may be given subcutaneously every 4 to 6 hours, whereas regular insulin should not be given more often than every 6 hours to correct hyperglycemia. These differences in action duration should be kept in mind to minimize the potential for insulin stacking.

INTRAOPERATIVE GLYCEMIC MANAGEMENT

Procedure length is an important determinant

Strategies for intraoperative glucose management vary according to the length of the procedure.

For minor, short procedures, the preoperative glucose management orders may be continued.

For longer, more complex procedures, a switch to an IV insulin drip is safe and allows rapid adjustments in dosing and plasma glucose levels. Ideally, IV insulin is started prior to the procedure so that the glucose level is stable once the patient arrives in the operating room. Given the logistics of IV insulin management, including the need for frequent monitoring (hourly) and dose adjustments, this type of treatment should be reserved for environments with adequate numbers of trained staff.

IV regular insulin is therapy of choice

Adapted, with permission, from Diabetes Care (Goldberg PA, et al. Diabetes Care 2004; 27:461–467), Copyright © 2004 by the American Diabetes Association.

Regular insulin delivered IV has a serum half-life of 7 minutes with a duration of effect of approximately 1 hour. These properties make IV regular insulin an effective tool for adjusting insulin therapy and addressing rapid changes in blood glucose values in critically ill patients. For this reason, IV regular insulin has become the preferred insulin for perioperative and critical care management. Although rapid-acting analogs can also be used IV, they confer no benefit over IV regular insulin and are more expensive.

Several different algorithms for IV regular insulin therapy are in use. Some are static, such as those of Markovitz et al¹⁴ and Stockton et al,¹⁵ while others are dynamic (ie, doses are self-adjusted based on changes in blood glucose level), such as the “Yale protocol” of Goldberg et al (Figure 1).¹⁶

 

 

POSTOPERATIVE GLYCEMIC MANAGEMENT

Start subcutaneous transition before stopping IV drip

Transitioning from IV to subcutaneous insulin is often complicated. Nonoral nutrition options (ie, parenteral nutrition or enteral supplementation) must be considered. As noted, insulin must be replaced according to physiologic needs, which requires that a long-acting basal insulin be used regardless of oral intake status, a rapid-acting insulin be given to cover prandial or nutritional needs, and supplemental rapid-acting insulin be used to correct hyperglycemia.

In the transition from IV insulin, basal insulin replacement can begin at any time. I recommend starting the transition from IV to subcutaneous insulin about 12 to 24 hours before discontinuing the insulin drip. In type 1 diabetes, this transition ensures basal insulin coverage and minimizes the risk of developing ketones and ketoacidosis. In type 2 diabetes, it can ensure a more stable transition and better glycemic control.

Determining the basal insulin dose

The starting dose of basal insulin should be 50% to 80% of the prior IV insulin total daily dose, if stable glycemic control had been achieved with IV insulin. Alternatively, a calculation called the “Miami 4/12 rule” can be used, whereby the basal insulin replacement dose is equal to the patient’s weight in kilograms divided by 4 (Figure 2). I recommend that basal insulin replacement be given either once daily or divided twice daily as a long-acting insulin analog (eg, insulin glargine or insulin detemir).

Switching to subcutaneous supplemental insulin

Instructions must be given for switching to subcutaneous supplemental doses of insulin. Glycemic targets, generally from less than 130 to 150 mg/dL, must be established, as must the frequency of fingerstick testing:

• If the patient is being fed enterally or parenterally, fingerstick testing is recommended every 4 to 6 hours if a rapid-acting insulin analog is used and every 6 hours if regular insulin is used.
• If the patient is eating, fingerstick testing should be performed before meals and at bedtime.

The increment in supplemental insulin to correct hyperglycemia can be individualized based on a patient’s perceived sensitivity to insulin, as detailed in Table 1.¹⁷ Adjustments to supplemental doses are needed to maintain glycemic targets.

Covering nutritional requirements

Nutrition-related insulin needs depend on the type of caloric intake prescribed:

In patients receiving total parenteral nutrition (TPN), start 1 U of regular insulin (placed in the bag) for every 10 to 15 g of dextrose in the TPN mixture.

In patients receiving enteral nutrition, use regular insulin every 6 hours or a rapid-acting insulin analog every 4 hours. Start 1 U of insulin subcutaneously for every 10 to 15 g of delivered carbohydrates. For example, if a patient is receiving 10 g of carbohydrates per hour, a rapid-acting analog given at a dose of 4 U every 4 hours (1 U per 10 g of carbohydrates) should adequately cover enteral feedings. For any bolus feedings, give the injection as a full bolus 15 to 20 minutes in advance, based on the carbohydrate content of the feeding.

In patients who are eating, use regular insulin or a rapid-acting insulin analog before meals. Again, start 1 U of insulin subcutaneously for every 10 to 15 g of carbohydrates, or use the prandial portion of the Miami 4/12 rule (Figure 2). For example, in a 60-kg patient one would start with 5 U (60 ÷ 12) of a rapid-acting insulin before each meal.

Basal/bolus replacement outperforms supplemental-scale regular insulin

Use of a basal/bolus insulin regimen appears to be more beneficial than supplemental-scale regular insulin in hospitalized patients with type 2 diabetes, according to a recent randomized trial comparing the two approaches in 130 such patients with blood glucose levels greater than 140 mg/dL.¹⁷ In the group randomized to basal/bolus insulin, the starting total daily dose was 0.4 to 0.5 U/kg/day, with half the dose given as basal insulin (insulin glargine) once daily and half given as a rapid-acting insulin analog (glulisine) in fixed doses before every meal. A rapid-acting analog was used for supplemental insulin in the basal/bolus regimen. By study’s end, patients in the basal/bolus group were receiving a higher total daily insulin dose than those in the supplemental-scale group (mean of 42 U/day vs 13 U/day).

Mean daily blood glucose levels were 27 mg/dL lower, on average, in patients who received basal/bolus therapy compared with the supplemental-scale group, yet there was no difference between groups in the risk of hypoglycemia. More patients randomized to basal/bolus therapy achieved the glycemic goal of less than 140 mg/dL (66% vs 38%). Fourteen percent of patients assigned to supplemental-scale insulin had values persistently greater than 240 mg/dL and had to be switched to the basal/bolus regimen.¹⁷

SUMMARY

Perioperative glycemic control can reduce morbidity, particularly the incidence of infectious complications, in surgical patients, even in those without diagnosed diabetes. Optimal management of glycemia in the perioperative period involves applying principles of physiologic insulin replacement. Postoperatively, the transition from IV to subcutaneous insulin can be achieved through the use of basal insulin for coverage of fasting insulin needs, regardless of the patient’s feeding status, and the use of rapid-acting insulin to cover hyperglycemia and nutritional needs. Management of hospitalized patients exclusively with supplemental-scale regular insulin should be abandoned.

 

 

DISCUSSION

Question from the audience: As an attending physician in a preoperative clinic I’m never sure what to do with NPH insulin the morning of surgery. What guidance can you give?

Dr. Meneghini: NPH is a peaking basal insulin, and the peak can induce hypoglycemia in a patient who is NPO. If we have the opportunity, we try to switch patients previously receiving insulin therapy to a long-acting basal insulin analog, which has a much flatter action profile and is safer in the fasting state. If there is no opportunity for switching, we instruct the patient to take two-thirds of his or her usual morning dose of insulin and we initiate a D5 drip when the patient arrives at the hospital.

Question from the audience: How do you handle perioperative insulin in patients on insulin pumps?

Dr. Meneghini: The pumps provide a subcutaneous basal insulin infusion, which should, if set correctly, maintain stable blood glucose levels when the patient is NPO. Supplemental doses of insulin to correct hyperglycemia can be delivered via the usual subcutaneous practice with a syringe or insulin pen. If you are uncomfortable with pump function, or if the pump insertion site interferes with the surgery site, simply replace the 24-hour basal amount delivered via pump with an injection of glargine or detemir divided into twice-daily injections. Correct hyperglycemia with supplemental-scale insulin as per usual protocol.

Question from the audience: The manufacturer of insulin glargine makes no recommendations for its use the night before or morning of surgery. What do you recommend?

Dr. Meneghini: It depends on whether the glargine is dosed appropriately. Most patients with type 2 diabetes require 0.4 to 0.6 U/kg/day of a long-acting insulin. If they’re on much more, they may be overdosed, and I would cut the basal dose by about half. Otherwise, 75% to 100% of the usual basal amount is appropriate. In type 1 diabetes, the usual replacement dose of basal insulin is 0.2 to 0.3 U/kg/day. If a patient is in this range, the basal insulin can be continued. Patients who experience hypoglycemia, or a substantial fall in blood glucose if meals are skipped or delayed, may be getting too much basal insulin and might benefit from a dose reduction when placed on NPO status.

Question from the audience: Metformin has a black-box warning advising that it be stopped at least 48 hours before surgery, but patients often come to surgery having taken metformin within the prior 12 to 24 hours. How should we manage such patients coming for elective surgery?

Dr. Meneghini: Metformin is cleared exclusively by the kidneys; its accumulation as a result of impaired kidney function (eg, due to hemodynamic instability or radiology studies using IV iodine) can result in increased lactic acid production by the liver and lactic acidosis. A patient who has taken metformin within the prior 48 hours but doesn’t have a risk of hemodynamic dysfunction is at low risk of lactic acidosis if hydrated appropriately. There’s not much choice if a patient needs urgent surgery and has recently taken metformin; in that case, just ensure maintenance of adequate glomerular filtration via fluid repletion to clear the drug.

Question from the audience: What’s the evidence for tight glycemic control or any type of glycemic control in patients undergoing outpatient surgery or “same-day” patients who will be admitted to a regular surgical floor? Also, what would you consider maximal glucose values for a patient going into elective surgery?

Dr. Meneghini: I haven’t seen any guidelines for glycemic control in patients undergoing outpatient surgery. If a patient has poor glycemic control coming into surgery, even for a minor procedure, the risk of an infectious complication may be increased. Keeping blood glucose below 180 mg/dL and avoiding electrolyte imbalances is likely sufficient in such patients. On the second question, if it’s an elective procedure and can be delayed a few hours, you can certainly institute IV insulin therapy to correct hyperglycemia rapidly—just ensure adequate replacement of fluids since the patient may have had volume depletion or dehydration as a result of the preceding osmotic diuresis. Once glycemic control is improved (blood glucose < 180–200 mg/dL), the patient can proceed to surgery.

Question from the audience: What are your recommendations for resuming oral diabetes medications after surgery?

Dr. Meneghini: Once patients are tolerating their meals and being considered for discharge, you may want to resume their oral medications, assuming their admission hemoglobin A_1c levels were near goal. If glycemic control was inadequate preoperatively, this may be a good opportunity to adjust their prior regimen to more appropriate therapy. In some cases, this might include some form of insulin, either basal therapy or basal and supplemental insulin.

Although pulmonary complications are not as well studied as cardiac complications in the postoperative setting, they are just as common following noncardiac surgery and are even more costly. It is worthwhile to identify surgical patients most at risk of postoperative pulmonary complications and take measures known to mitigate risk. This paper discusses important risk factors to identify during a preoperative pulmonary evaluation and then focuses on recent advances in strategies for reducing postoperative pulmonary complications. Teaching questions are included throughout, along with the rationale behind their answers.

POSTOPERATIVE PULMONARY COMPLICATIONS: WHAT ARE WE TRYING TO PREVENT AND WHY?

The definition of postoperative pulmonary complications is more variable and less intuitive than that of cardiac complications. Cardiac complications—postoperative myocardial infarction, cardiac death, and pulmonary edema—are more consistently defined and measured in clinical trials. Studies of postoperative pulmonary complications often group together pneumonia, respiratory failure, atelectasis, bronchospasm, and exacerbation of chronic obstructive pulmonary disease (COPD), making it more difficult to individually evaluate risk factors for different outcomes.

There are several reasons why it is important to consider pulmonary risk when evaluating patients preoperatively:

Pulmonary complications are as common as cardiac complications following noncardiac surgery. For example, in a secondary analysis of the cohort of noncardiac surgical patients used to validate the Revised Cardiac Risk Index,¹ Fleischmann et al found that the incidence of pulmonary complications (2.7%) was highly comparable to that of cardiac complications (2.5%).²

Respiratory failure is a marker of ill health and predicts further complications. Postoperative respiratory failure (often defined as the need for ventilation for more than 48 hours after surgery) is an extremely morbid event. Johnson et al compared the outcomes of patients with and without respiratory failure as a complication of surgery.³ Among patients with respiratory failure, 26% died within 30 days, 6% had a myocardial infarction, 35% developed pneumonia, 10% developed acute renal failure, and 3% developed a deep vein thrombosis or pulmonary embolism; in contrast, rates of each of these events were lower than 2% among patients without respiratory failure.

Pulmonary complications are expensive and require lengthy hospitalization. The National Surgical Quality Improvement Program (NSQIP) compared hospitalization costs and length of stay among patients with various postoperative complications.⁴ Among infectious, cardiovascular, venous thromboembolic, and pulmonary complications, pulmonary complications were by far the most costly and, along with venous thromboembolic complications, required the longest mean hospital stay.

For these reasons, identifying patients at risk for pulmonary complications and developing a strategy to reduce the risk is clearly worthwhile.

IDENTIFYING RISK FOR PULMONARY COMPLICATIONS

Question: Which of the following is the most important risk factor for postoperative pulmonary complications?

A. High-risk surgical site

B. General anesthesia

C. COPD

D. Obesity

The correct answer is A. Pulmonary complications differ from cardiac complications in an important way: procedure-related factors are more predictive of pulmonary complications than are patient-related factors. Even healthy patients undergoing high-risk surgery are at risk for pulmonary complications. As for the other answer choices, general anesthesia and COPD are risk factors but are not as important as surgical site, and obesity has not been shown to be a risk factor at all.

Take-home points from the 2006 ACP guideline

Along with my colleagues Valerie Lawrence and John Cornell, I co-authored the systematic reviews that supported the 2006 American College of Physicians (ACP) guideline on risk assessment for and strategies to reduce perioperative pulmonary complications in patients undergoing noncardiothoracic surgery.^5–7 We reviewed the literature since 1980 that used multivariate analysis to adjust for potential confounders, and we performed a meta-analysis to estimate odds ratios for various risk factors. We then assigned letter grades to the risk factors based on the strength of evidence, as summarized in Table 1.⁶

Patient-related risk factors. As noted in Table 1, the most important patient-related risk factors identified in the ACP guideline are increasing age and increasing American Society of Anesthesiologists (ASA) classification of comorbidity.

The effect of advanced age becomes particularly notable around age 60 years and escalates from there. This effect of age differs from that for cardiac complications, for which age drops out as a risk factor after adjustment for other diseases and risk factors. For pulmonary complications, in contrast, even older patients who are healthy are at increased risk.

The ASA classification is a general index of overall morbidity that ranges from class 1 (normal healthy patient) to class 5 (moribund patient who is not expected to survive without the operation).

Notably, COPD and smoking were only minor risk factors in the ACP analysis.

Procedure-related risk factors. Surgical site was found to be the most important of any of the patient- or procedure-related risk factors. The closer the incision is to the diaphragm, the greater the risk for pulmonary complications. Aortic, thoracic, and abdominal procedures carry the highest risk (Table 1), and among abdominal procedures, upper abdominal surgery (eg, cholecystectomy) is riskier than lower abdominal surgery (eg, gynecologic).

Other procedure-related risk factors identified were emergency surgery, surgery lasting more than 3 hours, use of general anesthesia, and multiple transfusions (Table 1).

 

 

Newly identified risk factors

Question: Which of the following has recently been identified as a risk factor for postoperative pulmonary complications?

A. Epidural anesthesia

B. Insulin-treated diabetes

C. Obstructive sleep apnea

D. Immobility

The correct answer is C. There is no evidence that epidural anesthesia or insulin-treated diabetes are risk factors. Immobility seems intuitively correct but has not emerged as a risk factor among high-quality studies in the literature.

Obstructive sleep apnea. The role of obstructive sleep apnea was unclear prior to publication of new data in the last couple of years. Hwang et al enrolled 172 patients who were soon to have elective surgery and had at least two of four clinical features of obstructive sleep apnea (snoring, daytime somnolence, witnessed apnea event, or crowded oropharynx).⁸ Patients underwent nocturnal oximetry before surgery and were divided into two groups based on number of desaturation episodes per hour. Patients with five or more desaturations had markedly higher rates of postoperative respiratory complications (8 complications among 98 patients) than did patients with fewer than five desaturations (1 complication among 74 patients). The presence of five or more desaturations was also associated with higher rates of cardiac, gastrointestinal, and bleeding complications. Though this was a small study, its results suggest a significant association between obstructive sleep apnea and pulmonary complications.

The issue of whether to screen patients for obstructive sleep apnea before major noncardiac surgery is still unresolved.

Pulmonary hypertension has also been identified as a risk factor in recent years with the publication of two studies that estimated its impact on morbidity and mortality after major noncardiac surgery.^9,10 One of the studies, a retrospective database review, found a 28% incidence of respiratory failure among 145 surgical patients with pulmonary hypertension.⁹ In the other study, a prospective case-control trial, respiratory failure occurred in 21% of patients with pulmonary hypertension compared with only 3% of matched controls.¹⁰ In the case-control study, pulmonary hypertension was also associated with significantly elevated rates of heart failure and in-hospital death.

The results of these studies do not support preoperative screening for undiagnosed pulmonary hypertension, but they do underscore the need to recognize established pulmonary hypertension as an important risk factor for postoperative complications.

AN UPDATED INDEX FOR RESPIRATORY FAILURE

Several years ago, investigators from the Veterans Affairs Medical Centers developed a respiratory failure index using a design similar to those of well-established indices for cardiac risk.¹¹ The same group also developed a separate risk index for pneumonia.¹²

This respiratory failure index was recently updated³ to reflect experience from private and academic hospitals, making the results more generally applicable. The researchers evaluated data from 180,000 patients undergoing major general or vascular surgery (defined according to the NSQIP) over a 3-year period. Respiratory failure was defined as requiring at least 48 hours of ventilation or unplanned reintubation.

Of the 45 potential risk factors evaluated, 28 were identified as independent risk factors for respiratory failure on the basis of a multivariate analysis. Each factor was weighted according to risk and combined into a point-based index, which performed very well in predicting postoperative respiratory failure: the highest of the three broad point-based risk groups had a 6.8% risk of respiratory failure, while the lowest-risk group had a 0.1% risk. Important observations are listed in Table 2.³

Comparison and contrast with the ACP guideline

Question: How does the updated respiratory failure index differ most significantly from the 2006 ACP guideline?

A. New index places greater emphasis on ASA class

B. New index offers a simplified weighted point scheme

C. New index ranks low albumin as a less important risk factor

D. New index attributes low risk to cigarette use

The correct answer is C: low albumin is a minor risk factor in the respiratory failure index, whereas it was one of the single most important predictors in the ACP guideline. As for the other answer choices, the new index places about the same emphasis on ASA class and cigarette use as does the ACP guideline, and it does not offer a simplified approach, as it incorporates 28 different factors.

Overall, most risk factors were similar in the updated respiratory failure index and the ACP guideline, but the index differs in several important ways:

• The index assigns less risk to low albumin, functional dependence, and congestive heart failure
• The index assigns greater risk to orofacial surgery
• The index identifies several new risk factors—high-complexity surgery, preoperative sepsis, ascites, and hypernatremia (serum sodium > 145 mmol/L).

 

 

STRATEGIES FOR RISK REDUCTION

The 2006 ACP guideline assigned evidence grades to various strategies to reduce risk for postoperative pulmonary complications based on a systematic review of the literature (Table 3).⁷ The only strategy that was supported by good evidence was postoperative lung expansion modalities, which comprise incentive spirometry, deep breathing exercises, intermittent positive-pressure breathing, and continuous positive airway pressure. Fair evidence supported selective postoperative use of nasogastric tubes and use of short-acting neuromuscular blockade.

Postoperative CPAP: Good option when exercise ability is limited

Among the postoperative lung expansion modalities, continuous positive airway pressure (CPAP) is particularly useful for patients who are unable to perform deep breathing or incentive spirometry exercises. A recent systematic literature review identified nine randomized controlled trials of CPAP vs standard therapy in a total of 654 patients undergoing abdominal surgery.¹³ Meta-analysis of these studies showed that CPAP was associated with significant reductions in the risk of overall postoperative pulmonary complications (odds ratio [OR] = 0.66; 95% CI, 0.52–0.85), atelectasis (OR = 0.75; 95% CI, 0.58–0.97), and pneumonia (OR = 0.33; 95% CI, 0.14–0.75) relative to standard therapy.

Use nasogastric tubes selectively

Nasogastric tubes can be used either routinely following abdominal surgery or only in select patients—eg, those who have symptomatic abdominal distention or nausea. The difference is important since nasogastric tubes may potentially increase the risk of aspiration and thus lead to a pulmonary complication. Nelson et al conducted a meta-analysis of 24 studies that compared routine nasogastric tube use in abdominal surgery with selective use based on symptoms or abdominal distention.¹⁴ They found that routine use was associated with a significant increase in postoperative pulmonary complications (OR = 1.45; 95% CI, 1.08–1.93) relative to selective use, without achieving any of its intended goals.

Laparoscopic vs open surgery: Evidence begins to follow intuition

Intuitively, it seems that laparoscopic procedures should reduce risk for postoperative pulmonary complications compared with open surgical procedures, as they are associated with less postoperative pain, which should facilitate deep breathing and improve postoperative lung volumes. Nevertheless, evidence for whether laparoscopic surgery reduces the risk of pulmonary complications has been mixed until recently.

In 2008, however, Weller and Rosati published an analysis of a nationally representative database of 19,156 patients who underwent bariatric surgery in 2005.¹⁵ After adjusting for comorbidities, they found that the rate of postoperative pulmonary complications was nearly double if patients underwent open surgery as opposed to laparoscopic surgery (OR = 1.92; 95% CI, 1.54–2.38). Open surgery was also associated with significantly higher rates of sepsis, cardiovascular events, and reoperation compared with laparoscopic procedures. This study suggests that choosing laparoscopic procedures is another strategy that may reduce pulmonary complication rates, at least in the setting of bariatric surgery.

Postoperative thoracic epidural analgesia

Question: Thoracic epidural analgesia reduces rates of which of the following?

A. Pneumonia following abdominal aortic aneurysm repair

B. Pulmonary complications following coronary bypass surgery

C. Respiratory failure following abdominal surgery

D. All of the above

The correct answer is D. Thoracic epidural analgesia is another important strategy for reducing postoperative pulmonary complications, as demonstrated by a 2007 systematic literature review by Liu and Wu.¹⁶ Their analysis showed that rates of pneumonia, respiratory failure, and pulmonary complications overall were reduced by approximately one-third to more than one-half with the use of postoperative thoracic epidural analgesia in patients undergoing aortic aneurysm repair, coronary bypass surgery, and abdominal surgery.

Smoking cessation: The jury is still out

Whether preoperative cigarette cessation reduces pulmonary complication rates has been controversial over the past decade. Early reports showed that among patients who smoke, those who quit shortly before surgery actually had higher complication rates than patients who continued to smoke. The most reasonable explanation seems to be that many patients who stop smoking report increased coughing and sputum production for the first month or two. Selection bias also may have played a role in these findings.

More recently, two randomized trials studied the impact of perioperative smoking intervention programs involving counseling and nicotine replacement.^17,18 Unfortunately, both studies primarily studied patients undergoing low-risk procedures and were insufficiently powered to show a difference in  pulmonary complication rates. The question of whether smoking cessation is an effective strategy to reduce postoperative pulmonary risk remains unanswered.

Preoperative intensive lung expansion: A promising new intervention

While the effectiveness of postoperative lung expansion techniques is undisputed,⁷preoperative lung expansion—also known as inspiratory muscle training—has only recently been investigated. Hulzebos et al randomized 279 patients undergoing coronary artery bypass graft surgery who were at high risk for developing pulmonary complications to either usual care or inspiratory muscle training.¹⁹ The latter intervention involved 20 minutes per day of incentive spirometry, active breathing, and forced expiration techniques for at least 2 weeks prior to surgery. Rates of high-grade postoperative pulmonary complications were cut in half (OR = 0.52; 95% CI, 0.30–0.92) and rates of pneumonia were reduced by 60% (OR = 0.40; 95% CI, 0.19–0.84) in patients who received inspiratory muscle training relative to the usual-care group.

In clinical practice, preoperative inspiratory muscle training can be done in a chest physical therapy outpatient setting or a pulmonary rehabilitation clinic in the hospital.

 

 

SUMMARY

There have been a number of significant recent developments in the perioperative management of pulmonary complications:

• Obstructive sleep apnea has been confirmed as a risk factor, and pulmonary hypertension has emerged as a novel risk factor.
• An updated respiratory failure index has emerged as a useful research tool to identify high-risk patients and to ensure uniform risk stratification in future research.
• Evidence has mounted for the effectiveness of several risk-reduction strategies, including the use of laparoscopic procedures for bariatric surgery; selective use of nasogastric tubes; postoperative thoracic epidural analgesia; and intensive preoperative inspiratory muscle training.

DISCUSSION

Question from the audience: I do preoperative evaluations in an orthopedic ambulatory surgery center. Our surgeons often tell me, “Just order preoperative pulmonary function tests,” or, “Get a blood gas.” How should I respond?

Dr. Smetana: This is an area of some controversy, but in general, spirometry does not add much to a preoperative risk assessment that is based on a history and physical exam. Usually if the spirometry is abnormal, it will not be a surprise after careful clinical assessment. Arterial blood gases have no role in routine preoperative assessment.

Question from the audience: A chest x-ray is often requested preoperatively, but is it a necessary study?

Dr. Smetana: The data for preoperative chest x-rays are fairly poor and don’t allow us to assess whether they accurately predict complication rates. Most studies on chest x-rays have looked at how they affect preoperative management—eg, whether they change the anesthesia or even the surgery—and have shown that preoperative management changes in only about 1% to 2% of cases. So the chest x-ray is a fairly low-yield test in this setting.

One could argue that a preoperative chest x-ray might provide a baseline for postoperative comparison, but actually it is not usually helpful in this regard. Having a baseline does not make it easier to correctly diagnose pneumonia postoperatively, for example. Abnormal chest x-rays correlate with higher risk, but most patients with abnormal films would be suspected of being at higher risk anyway based on findings from the clinical assessment.

Question from the audience: Many primary care doctors in my hospital screen patients for pulmonary hypertension, but this raises the question of what to do with any information gained. What do you tell patients? Anesthesiologists?

Dr. Smetana: I don’t recommend preoperative screening for pulmonary hypertension unless there is some specific clinical reason to look for it. We don’t know if the perioperative risks that I described for patients with diagnosed or symptomatic pulmonary hypertension would also apply to patients with unrecognized, asymptomatic pulmonary hypertension that happened to be identified by screening.

Patients with pulmonary hypertension are at very high risk, especially for respiratory failure. But we don’t have any risk-reduction strategies specific to these patients, although I would recommend applying the general risk-reduction strategies that I discussed.

Question from the audience: I saw a man at my high-risk preoperative clinic who scored normally on a 6-minute walk test but then was found sound asleep when I was ready to see him a little while later. I suspected he had undiagnosed sleep apnea, and therefore had an increased risk of postoperative pulmonary complications, but what evidence would I have to delay his surgery to diagnose the sleep apnea and stabilize him on CPAP?

Dr. Smetana: For a patient with clinically suspected but undiagnosed sleep apnea, we have some evidence that the diagnosis should be pursued before surgery is performed.⁸ If the surgery were elective, it would be appropriate to have the patient evaluated and, if obstructive sleep apnea were diagnosed, treated in the customary way with CPAP. For patients who are hospitalized after surgery, CPAP can be continued as soon as possible in the hospital.

I would not have made this recommendation a few years ago, but now the evidence is more compelling. However, at this point I would not recommend routine preoperative screening of all patients for sleep apnea. Ongoing research is looking at this question.

Follow-up question: How long should surgery be delayed to optimize the patient on CPAP?

Dr. Smetana: Risk for postoperative respiratory failure is reduced very quickly after initiating CPAP therapy. A week would probably be sufficient, but there are no good data to specifically address that question.

Question from the audience: What about patients with asthma who are undergoing surgery—which ones benefit from stress-level steroids and preoperative nebulizer therapy?

Dr. Smetana: Surprisingly, asthma—if well controlled—is not a risk factor for postoperative pulmonary complications. Patients within 80% of their predicted or personal best peak flow appear to have a risk similar to that of patients without asthma. For patients with uncontrolled or poorly controlled asthma, the general rule is the same as for patients with COPD: treat them the same as if they weren’t having surgery. If a patient with asthma has a clinical indication for cortico­steroids based on his or her condition, give cortico­steroids whether or not surgery is planned. Corticosteroids are safe and do not raise the risk of postoperative wound complications. But we have no evidence to support routine use of steroids for all patients with asthma simply because elective surgery is planned.

Follow-up question: Do you optimize poorly controlled patients with oral prednisone for several days preoperatively, or do you use a stress protocol?

Dr. Smetana: For a patient whom you would normally treat with an outpatient course of prednisone, you should do just that. For a patient with an exacerbation severe enough to require admission for intravenous steroids and inhaled nebulizer therapy, then you should use that strategy. If the surgery is elective, it should be delayed until the patient is at his or her personal best.

Although pulmonary complications are not as well studied as cardiac complications in the postoperative setting, they are just as common following noncardiac surgery and are even more costly. It is worthwhile to identify surgical patients most at risk of postoperative pulmonary complications and take measures known to mitigate risk. This paper discusses important risk factors to identify during a preoperative pulmonary evaluation and then focuses on recent advances in strategies for reducing postoperative pulmonary complications. Teaching questions are included throughout, along with the rationale behind their answers.

POSTOPERATIVE PULMONARY COMPLICATIONS: WHAT ARE WE TRYING TO PREVENT AND WHY?

The definition of postoperative pulmonary complications is more variable and less intuitive than that of cardiac complications. Cardiac complications—postoperative myocardial infarction, cardiac death, and pulmonary edema—are more consistently defined and measured in clinical trials. Studies of postoperative pulmonary complications often group together pneumonia, respiratory failure, atelectasis, bronchospasm, and exacerbation of chronic obstructive pulmonary disease (COPD), making it more difficult to individually evaluate risk factors for different outcomes.

There are several reasons why it is important to consider pulmonary risk when evaluating patients preoperatively:

Pulmonary complications are as common as cardiac complications following noncardiac surgery. For example, in a secondary analysis of the cohort of noncardiac surgical patients used to validate the Revised Cardiac Risk Index,¹ Fleischmann et al found that the incidence of pulmonary complications (2.7%) was highly comparable to that of cardiac complications (2.5%).²

Respiratory failure is a marker of ill health and predicts further complications. Postoperative respiratory failure (often defined as the need for ventilation for more than 48 hours after surgery) is an extremely morbid event. Johnson et al compared the outcomes of patients with and without respiratory failure as a complication of surgery.³ Among patients with respiratory failure, 26% died within 30 days, 6% had a myocardial infarction, 35% developed pneumonia, 10% developed acute renal failure, and 3% developed a deep vein thrombosis or pulmonary embolism; in contrast, rates of each of these events were lower than 2% among patients without respiratory failure.

Pulmonary complications are expensive and require lengthy hospitalization. The National Surgical Quality Improvement Program (NSQIP) compared hospitalization costs and length of stay among patients with various postoperative complications.⁴ Among infectious, cardiovascular, venous thromboembolic, and pulmonary complications, pulmonary complications were by far the most costly and, along with venous thromboembolic complications, required the longest mean hospital stay.

For these reasons, identifying patients at risk for pulmonary complications and developing a strategy to reduce the risk is clearly worthwhile.

IDENTIFYING RISK FOR PULMONARY COMPLICATIONS

Question: Which of the following is the most important risk factor for postoperative pulmonary complications?

A. High-risk surgical site

B. General anesthesia

C. COPD

D. Obesity

The correct answer is A. Pulmonary complications differ from cardiac complications in an important way: procedure-related factors are more predictive of pulmonary complications than are patient-related factors. Even healthy patients undergoing high-risk surgery are at risk for pulmonary complications. As for the other answer choices, general anesthesia and COPD are risk factors but are not as important as surgical site, and obesity has not been shown to be a risk factor at all.

Take-home points from the 2006 ACP guideline

Along with my colleagues Valerie Lawrence and John Cornell, I co-authored the systematic reviews that supported the 2006 American College of Physicians (ACP) guideline on risk assessment for and strategies to reduce perioperative pulmonary complications in patients undergoing noncardiothoracic surgery.^5–7 We reviewed the literature since 1980 that used multivariate analysis to adjust for potential confounders, and we performed a meta-analysis to estimate odds ratios for various risk factors. We then assigned letter grades to the risk factors based on the strength of evidence, as summarized in Table 1.⁶

Patient-related risk factors. As noted in Table 1, the most important patient-related risk factors identified in the ACP guideline are increasing age and increasing American Society of Anesthesiologists (ASA) classification of comorbidity.

The effect of advanced age becomes particularly notable around age 60 years and escalates from there. This effect of age differs from that for cardiac complications, for which age drops out as a risk factor after adjustment for other diseases and risk factors. For pulmonary complications, in contrast, even older patients who are healthy are at increased risk.

The ASA classification is a general index of overall morbidity that ranges from class 1 (normal healthy patient) to class 5 (moribund patient who is not expected to survive without the operation).

Notably, COPD and smoking were only minor risk factors in the ACP analysis.

Procedure-related risk factors. Surgical site was found to be the most important of any of the patient- or procedure-related risk factors. The closer the incision is to the diaphragm, the greater the risk for pulmonary complications. Aortic, thoracic, and abdominal procedures carry the highest risk (Table 1), and among abdominal procedures, upper abdominal surgery (eg, cholecystectomy) is riskier than lower abdominal surgery (eg, gynecologic).

Other procedure-related risk factors identified were emergency surgery, surgery lasting more than 3 hours, use of general anesthesia, and multiple transfusions (Table 1).

 

 

Newly identified risk factors

Question: Which of the following has recently been identified as a risk factor for postoperative pulmonary complications?

A. Epidural anesthesia

B. Insulin-treated diabetes

C. Obstructive sleep apnea

D. Immobility

The correct answer is C. There is no evidence that epidural anesthesia or insulin-treated diabetes are risk factors. Immobility seems intuitively correct but has not emerged as a risk factor among high-quality studies in the literature.

Obstructive sleep apnea. The role of obstructive sleep apnea was unclear prior to publication of new data in the last couple of years. Hwang et al enrolled 172 patients who were soon to have elective surgery and had at least two of four clinical features of obstructive sleep apnea (snoring, daytime somnolence, witnessed apnea event, or crowded oropharynx).⁸ Patients underwent nocturnal oximetry before surgery and were divided into two groups based on number of desaturation episodes per hour. Patients with five or more desaturations had markedly higher rates of postoperative respiratory complications (8 complications among 98 patients) than did patients with fewer than five desaturations (1 complication among 74 patients). The presence of five or more desaturations was also associated with higher rates of cardiac, gastrointestinal, and bleeding complications. Though this was a small study, its results suggest a significant association between obstructive sleep apnea and pulmonary complications.

The issue of whether to screen patients for obstructive sleep apnea before major noncardiac surgery is still unresolved.

Pulmonary hypertension has also been identified as a risk factor in recent years with the publication of two studies that estimated its impact on morbidity and mortality after major noncardiac surgery.^9,10 One of the studies, a retrospective database review, found a 28% incidence of respiratory failure among 145 surgical patients with pulmonary hypertension.⁹ In the other study, a prospective case-control trial, respiratory failure occurred in 21% of patients with pulmonary hypertension compared with only 3% of matched controls.¹⁰ In the case-control study, pulmonary hypertension was also associated with significantly elevated rates of heart failure and in-hospital death.

The results of these studies do not support preoperative screening for undiagnosed pulmonary hypertension, but they do underscore the need to recognize established pulmonary hypertension as an important risk factor for postoperative complications.

AN UPDATED INDEX FOR RESPIRATORY FAILURE

Several years ago, investigators from the Veterans Affairs Medical Centers developed a respiratory failure index using a design similar to those of well-established indices for cardiac risk.¹¹ The same group also developed a separate risk index for pneumonia.¹²

This respiratory failure index was recently updated³ to reflect experience from private and academic hospitals, making the results more generally applicable. The researchers evaluated data from 180,000 patients undergoing major general or vascular surgery (defined according to the NSQIP) over a 3-year period. Respiratory failure was defined as requiring at least 48 hours of ventilation or unplanned reintubation.

Of the 45 potential risk factors evaluated, 28 were identified as independent risk factors for respiratory failure on the basis of a multivariate analysis. Each factor was weighted according to risk and combined into a point-based index, which performed very well in predicting postoperative respiratory failure: the highest of the three broad point-based risk groups had a 6.8% risk of respiratory failure, while the lowest-risk group had a 0.1% risk. Important observations are listed in Table 2.³

Comparison and contrast with the ACP guideline

Question: How does the updated respiratory failure index differ most significantly from the 2006 ACP guideline?

A. New index places greater emphasis on ASA class

B. New index offers a simplified weighted point scheme

C. New index ranks low albumin as a less important risk factor

D. New index attributes low risk to cigarette use

The correct answer is C: low albumin is a minor risk factor in the respiratory failure index, whereas it was one of the single most important predictors in the ACP guideline. As for the other answer choices, the new index places about the same emphasis on ASA class and cigarette use as does the ACP guideline, and it does not offer a simplified approach, as it incorporates 28 different factors.

Overall, most risk factors were similar in the updated respiratory failure index and the ACP guideline, but the index differs in several important ways:

• The index assigns less risk to low albumin, functional dependence, and congestive heart failure
• The index assigns greater risk to orofacial surgery
• The index identifies several new risk factors—high-complexity surgery, preoperative sepsis, ascites, and hypernatremia (serum sodium > 145 mmol/L).

 

 

STRATEGIES FOR RISK REDUCTION

The 2006 ACP guideline assigned evidence grades to various strategies to reduce risk for postoperative pulmonary complications based on a systematic review of the literature (Table 3).⁷ The only strategy that was supported by good evidence was postoperative lung expansion modalities, which comprise incentive spirometry, deep breathing exercises, intermittent positive-pressure breathing, and continuous positive airway pressure. Fair evidence supported selective postoperative use of nasogastric tubes and use of short-acting neuromuscular blockade.

Postoperative CPAP: Good option when exercise ability is limited

Among the postoperative lung expansion modalities, continuous positive airway pressure (CPAP) is particularly useful for patients who are unable to perform deep breathing or incentive spirometry exercises. A recent systematic literature review identified nine randomized controlled trials of CPAP vs standard therapy in a total of 654 patients undergoing abdominal surgery.¹³ Meta-analysis of these studies showed that CPAP was associated with significant reductions in the risk of overall postoperative pulmonary complications (odds ratio [OR] = 0.66; 95% CI, 0.52–0.85), atelectasis (OR = 0.75; 95% CI, 0.58–0.97), and pneumonia (OR = 0.33; 95% CI, 0.14–0.75) relative to standard therapy.

Use nasogastric tubes selectively

Nasogastric tubes can be used either routinely following abdominal surgery or only in select patients—eg, those who have symptomatic abdominal distention or nausea. The difference is important since nasogastric tubes may potentially increase the risk of aspiration and thus lead to a pulmonary complication. Nelson et al conducted a meta-analysis of 24 studies that compared routine nasogastric tube use in abdominal surgery with selective use based on symptoms or abdominal distention.¹⁴ They found that routine use was associated with a significant increase in postoperative pulmonary complications (OR = 1.45; 95% CI, 1.08–1.93) relative to selective use, without achieving any of its intended goals.

Laparoscopic vs open surgery: Evidence begins to follow intuition

Intuitively, it seems that laparoscopic procedures should reduce risk for postoperative pulmonary complications compared with open surgical procedures, as they are associated with less postoperative pain, which should facilitate deep breathing and improve postoperative lung volumes. Nevertheless, evidence for whether laparoscopic surgery reduces the risk of pulmonary complications has been mixed until recently.

In 2008, however, Weller and Rosati published an analysis of a nationally representative database of 19,156 patients who underwent bariatric surgery in 2005.¹⁵ After adjusting for comorbidities, they found that the rate of postoperative pulmonary complications was nearly double if patients underwent open surgery as opposed to laparoscopic surgery (OR = 1.92; 95% CI, 1.54–2.38). Open surgery was also associated with significantly higher rates of sepsis, cardiovascular events, and reoperation compared with laparoscopic procedures. This study suggests that choosing laparoscopic procedures is another strategy that may reduce pulmonary complication rates, at least in the setting of bariatric surgery.

Postoperative thoracic epidural analgesia

Question: Thoracic epidural analgesia reduces rates of which of the following?

A. Pneumonia following abdominal aortic aneurysm repair

B. Pulmonary complications following coronary bypass surgery

C. Respiratory failure following abdominal surgery

D. All of the above

The correct answer is D. Thoracic epidural analgesia is another important strategy for reducing postoperative pulmonary complications, as demonstrated by a 2007 systematic literature review by Liu and Wu.¹⁶ Their analysis showed that rates of pneumonia, respiratory failure, and pulmonary complications overall were reduced by approximately one-third to more than one-half with the use of postoperative thoracic epidural analgesia in patients undergoing aortic aneurysm repair, coronary bypass surgery, and abdominal surgery.

Smoking cessation: The jury is still out

Whether preoperative cigarette cessation reduces pulmonary complication rates has been controversial over the past decade. Early reports showed that among patients who smoke, those who quit shortly before surgery actually had higher complication rates than patients who continued to smoke. The most reasonable explanation seems to be that many patients who stop smoking report increased coughing and sputum production for the first month or two. Selection bias also may have played a role in these findings.

More recently, two randomized trials studied the impact of perioperative smoking intervention programs involving counseling and nicotine replacement.^17,18 Unfortunately, both studies primarily studied patients undergoing low-risk procedures and were insufficiently powered to show a difference in  pulmonary complication rates. The question of whether smoking cessation is an effective strategy to reduce postoperative pulmonary risk remains unanswered.

Preoperative intensive lung expansion: A promising new intervention

While the effectiveness of postoperative lung expansion techniques is undisputed,⁷preoperative lung expansion—also known as inspiratory muscle training—has only recently been investigated. Hulzebos et al randomized 279 patients undergoing coronary artery bypass graft surgery who were at high risk for developing pulmonary complications to either usual care or inspiratory muscle training.¹⁹ The latter intervention involved 20 minutes per day of incentive spirometry, active breathing, and forced expiration techniques for at least 2 weeks prior to surgery. Rates of high-grade postoperative pulmonary complications were cut in half (OR = 0.52; 95% CI, 0.30–0.92) and rates of pneumonia were reduced by 60% (OR = 0.40; 95% CI, 0.19–0.84) in patients who received inspiratory muscle training relative to the usual-care group.

In clinical practice, preoperative inspiratory muscle training can be done in a chest physical therapy outpatient setting or a pulmonary rehabilitation clinic in the hospital.

 

 

SUMMARY

There have been a number of significant recent developments in the perioperative management of pulmonary complications:

• Obstructive sleep apnea has been confirmed as a risk factor, and pulmonary hypertension has emerged as a novel risk factor.
• An updated respiratory failure index has emerged as a useful research tool to identify high-risk patients and to ensure uniform risk stratification in future research.
• Evidence has mounted for the effectiveness of several risk-reduction strategies, including the use of laparoscopic procedures for bariatric surgery; selective use of nasogastric tubes; postoperative thoracic epidural analgesia; and intensive preoperative inspiratory muscle training.

DISCUSSION

Question from the audience: I do preoperative evaluations in an orthopedic ambulatory surgery center. Our surgeons often tell me, “Just order preoperative pulmonary function tests,” or, “Get a blood gas.” How should I respond?

Dr. Smetana: This is an area of some controversy, but in general, spirometry does not add much to a preoperative risk assessment that is based on a history and physical exam. Usually if the spirometry is abnormal, it will not be a surprise after careful clinical assessment. Arterial blood gases have no role in routine preoperative assessment.

Question from the audience: A chest x-ray is often requested preoperatively, but is it a necessary study?

Dr. Smetana: The data for preoperative chest x-rays are fairly poor and don’t allow us to assess whether they accurately predict complication rates. Most studies on chest x-rays have looked at how they affect preoperative management—eg, whether they change the anesthesia or even the surgery—and have shown that preoperative management changes in only about 1% to 2% of cases. So the chest x-ray is a fairly low-yield test in this setting.

One could argue that a preoperative chest x-ray might provide a baseline for postoperative comparison, but actually it is not usually helpful in this regard. Having a baseline does not make it easier to correctly diagnose pneumonia postoperatively, for example. Abnormal chest x-rays correlate with higher risk, but most patients with abnormal films would be suspected of being at higher risk anyway based on findings from the clinical assessment.

Question from the audience: Many primary care doctors in my hospital screen patients for pulmonary hypertension, but this raises the question of what to do with any information gained. What do you tell patients? Anesthesiologists?

Dr. Smetana: I don’t recommend preoperative screening for pulmonary hypertension unless there is some specific clinical reason to look for it. We don’t know if the perioperative risks that I described for patients with diagnosed or symptomatic pulmonary hypertension would also apply to patients with unrecognized, asymptomatic pulmonary hypertension that happened to be identified by screening.

Patients with pulmonary hypertension are at very high risk, especially for respiratory failure. But we don’t have any risk-reduction strategies specific to these patients, although I would recommend applying the general risk-reduction strategies that I discussed.

Question from the audience: I saw a man at my high-risk preoperative clinic who scored normally on a 6-minute walk test but then was found sound asleep when I was ready to see him a little while later. I suspected he had undiagnosed sleep apnea, and therefore had an increased risk of postoperative pulmonary complications, but what evidence would I have to delay his surgery to diagnose the sleep apnea and stabilize him on CPAP?

Dr. Smetana: For a patient with clinically suspected but undiagnosed sleep apnea, we have some evidence that the diagnosis should be pursued before surgery is performed.⁸ If the surgery were elective, it would be appropriate to have the patient evaluated and, if obstructive sleep apnea were diagnosed, treated in the customary way with CPAP. For patients who are hospitalized after surgery, CPAP can be continued as soon as possible in the hospital.

I would not have made this recommendation a few years ago, but now the evidence is more compelling. However, at this point I would not recommend routine preoperative screening of all patients for sleep apnea. Ongoing research is looking at this question.

Follow-up question: How long should surgery be delayed to optimize the patient on CPAP?

Dr. Smetana: Risk for postoperative respiratory failure is reduced very quickly after initiating CPAP therapy. A week would probably be sufficient, but there are no good data to specifically address that question.

Question from the audience: What about patients with asthma who are undergoing surgery—which ones benefit from stress-level steroids and preoperative nebulizer therapy?

Dr. Smetana: Surprisingly, asthma—if well controlled—is not a risk factor for postoperative pulmonary complications. Patients within 80% of their predicted or personal best peak flow appear to have a risk similar to that of patients without asthma. For patients with uncontrolled or poorly controlled asthma, the general rule is the same as for patients with COPD: treat them the same as if they weren’t having surgery. If a patient with asthma has a clinical indication for cortico­steroids based on his or her condition, give cortico­steroids whether or not surgery is planned. Corticosteroids are safe and do not raise the risk of postoperative wound complications. But we have no evidence to support routine use of steroids for all patients with asthma simply because elective surgery is planned.

Follow-up question: Do you optimize poorly controlled patients with oral prednisone for several days preoperatively, or do you use a stress protocol?

Dr. Smetana: For a patient whom you would normally treat with an outpatient course of prednisone, you should do just that. For a patient with an exacerbation severe enough to require admission for intravenous steroids and inhaled nebulizer therapy, then you should use that strategy. If the surgery is elective, it should be delayed until the patient is at his or her personal best.

Although pulmonary complications are not as well studied as cardiac complications in the postoperative setting, they are just as common following noncardiac surgery and are even more costly. It is worthwhile to identify surgical patients most at risk of postoperative pulmonary complications and take measures known to mitigate risk. This paper discusses important risk factors to identify during a preoperative pulmonary evaluation and then focuses on recent advances in strategies for reducing postoperative pulmonary complications. Teaching questions are included throughout, along with the rationale behind their answers.

POSTOPERATIVE PULMONARY COMPLICATIONS: WHAT ARE WE TRYING TO PREVENT AND WHY?

The definition of postoperative pulmonary complications is more variable and less intuitive than that of cardiac complications. Cardiac complications—postoperative myocardial infarction, cardiac death, and pulmonary edema—are more consistently defined and measured in clinical trials. Studies of postoperative pulmonary complications often group together pneumonia, respiratory failure, atelectasis, bronchospasm, and exacerbation of chronic obstructive pulmonary disease (COPD), making it more difficult to individually evaluate risk factors for different outcomes.

There are several reasons why it is important to consider pulmonary risk when evaluating patients preoperatively:

Pulmonary complications are as common as cardiac complications following noncardiac surgery. For example, in a secondary analysis of the cohort of noncardiac surgical patients used to validate the Revised Cardiac Risk Index,¹ Fleischmann et al found that the incidence of pulmonary complications (2.7%) was highly comparable to that of cardiac complications (2.5%).²

Respiratory failure is a marker of ill health and predicts further complications. Postoperative respiratory failure (often defined as the need for ventilation for more than 48 hours after surgery) is an extremely morbid event. Johnson et al compared the outcomes of patients with and without respiratory failure as a complication of surgery.³ Among patients with respiratory failure, 26% died within 30 days, 6% had a myocardial infarction, 35% developed pneumonia, 10% developed acute renal failure, and 3% developed a deep vein thrombosis or pulmonary embolism; in contrast, rates of each of these events were lower than 2% among patients without respiratory failure.

Pulmonary complications are expensive and require lengthy hospitalization. The National Surgical Quality Improvement Program (NSQIP) compared hospitalization costs and length of stay among patients with various postoperative complications.⁴ Among infectious, cardiovascular, venous thromboembolic, and pulmonary complications, pulmonary complications were by far the most costly and, along with venous thromboembolic complications, required the longest mean hospital stay.

For these reasons, identifying patients at risk for pulmonary complications and developing a strategy to reduce the risk is clearly worthwhile.

IDENTIFYING RISK FOR PULMONARY COMPLICATIONS

Question: Which of the following is the most important risk factor for postoperative pulmonary complications?

A. High-risk surgical site

B. General anesthesia

C. COPD

D. Obesity

The correct answer is A. Pulmonary complications differ from cardiac complications in an important way: procedure-related factors are more predictive of pulmonary complications than are patient-related factors. Even healthy patients undergoing high-risk surgery are at risk for pulmonary complications. As for the other answer choices, general anesthesia and COPD are risk factors but are not as important as surgical site, and obesity has not been shown to be a risk factor at all.

Take-home points from the 2006 ACP guideline

Along with my colleagues Valerie Lawrence and John Cornell, I co-authored the systematic reviews that supported the 2006 American College of Physicians (ACP) guideline on risk assessment for and strategies to reduce perioperative pulmonary complications in patients undergoing noncardiothoracic surgery.^5–7 We reviewed the literature since 1980 that used multivariate analysis to adjust for potential confounders, and we performed a meta-analysis to estimate odds ratios for various risk factors. We then assigned letter grades to the risk factors based on the strength of evidence, as summarized in Table 1.⁶

Patient-related risk factors. As noted in Table 1, the most important patient-related risk factors identified in the ACP guideline are increasing age and increasing American Society of Anesthesiologists (ASA) classification of comorbidity.

The effect of advanced age becomes particularly notable around age 60 years and escalates from there. This effect of age differs from that for cardiac complications, for which age drops out as a risk factor after adjustment for other diseases and risk factors. For pulmonary complications, in contrast, even older patients who are healthy are at increased risk.

The ASA classification is a general index of overall morbidity that ranges from class 1 (normal healthy patient) to class 5 (moribund patient who is not expected to survive without the operation).

Notably, COPD and smoking were only minor risk factors in the ACP analysis.

Procedure-related risk factors. Surgical site was found to be the most important of any of the patient- or procedure-related risk factors. The closer the incision is to the diaphragm, the greater the risk for pulmonary complications. Aortic, thoracic, and abdominal procedures carry the highest risk (Table 1), and among abdominal procedures, upper abdominal surgery (eg, cholecystectomy) is riskier than lower abdominal surgery (eg, gynecologic).

Other procedure-related risk factors identified were emergency surgery, surgery lasting more than 3 hours, use of general anesthesia, and multiple transfusions (Table 1).

 

 

Newly identified risk factors

Question: Which of the following has recently been identified as a risk factor for postoperative pulmonary complications?

A. Epidural anesthesia

B. Insulin-treated diabetes

C. Obstructive sleep apnea

D. Immobility

The correct answer is C. There is no evidence that epidural anesthesia or insulin-treated diabetes are risk factors. Immobility seems intuitively correct but has not emerged as a risk factor among high-quality studies in the literature.

Obstructive sleep apnea. The role of obstructive sleep apnea was unclear prior to publication of new data in the last couple of years. Hwang et al enrolled 172 patients who were soon to have elective surgery and had at least two of four clinical features of obstructive sleep apnea (snoring, daytime somnolence, witnessed apnea event, or crowded oropharynx).⁸ Patients underwent nocturnal oximetry before surgery and were divided into two groups based on number of desaturation episodes per hour. Patients with five or more desaturations had markedly higher rates of postoperative respiratory complications (8 complications among 98 patients) than did patients with fewer than five desaturations (1 complication among 74 patients). The presence of five or more desaturations was also associated with higher rates of cardiac, gastrointestinal, and bleeding complications. Though this was a small study, its results suggest a significant association between obstructive sleep apnea and pulmonary complications.

The issue of whether to screen patients for obstructive sleep apnea before major noncardiac surgery is still unresolved.

Pulmonary hypertension has also been identified as a risk factor in recent years with the publication of two studies that estimated its impact on morbidity and mortality after major noncardiac surgery.^9,10 One of the studies, a retrospective database review, found a 28% incidence of respiratory failure among 145 surgical patients with pulmonary hypertension.⁹ In the other study, a prospective case-control trial, respiratory failure occurred in 21% of patients with pulmonary hypertension compared with only 3% of matched controls.¹⁰ In the case-control study, pulmonary hypertension was also associated with significantly elevated rates of heart failure and in-hospital death.

The results of these studies do not support preoperative screening for undiagnosed pulmonary hypertension, but they do underscore the need to recognize established pulmonary hypertension as an important risk factor for postoperative complications.

AN UPDATED INDEX FOR RESPIRATORY FAILURE

Several years ago, investigators from the Veterans Affairs Medical Centers developed a respiratory failure index using a design similar to those of well-established indices for cardiac risk.¹¹ The same group also developed a separate risk index for pneumonia.¹²

This respiratory failure index was recently updated³ to reflect experience from private and academic hospitals, making the results more generally applicable. The researchers evaluated data from 180,000 patients undergoing major general or vascular surgery (defined according to the NSQIP) over a 3-year period. Respiratory failure was defined as requiring at least 48 hours of ventilation or unplanned reintubation.

Of the 45 potential risk factors evaluated, 28 were identified as independent risk factors for respiratory failure on the basis of a multivariate analysis. Each factor was weighted according to risk and combined into a point-based index, which performed very well in predicting postoperative respiratory failure: the highest of the three broad point-based risk groups had a 6.8% risk of respiratory failure, while the lowest-risk group had a 0.1% risk. Important observations are listed in Table 2.³

Comparison and contrast with the ACP guideline

Question: How does the updated respiratory failure index differ most significantly from the 2006 ACP guideline?

A. New index places greater emphasis on ASA class

B. New index offers a simplified weighted point scheme

C. New index ranks low albumin as a less important risk factor

D. New index attributes low risk to cigarette use

The correct answer is C: low albumin is a minor risk factor in the respiratory failure index, whereas it was one of the single most important predictors in the ACP guideline. As for the other answer choices, the new index places about the same emphasis on ASA class and cigarette use as does the ACP guideline, and it does not offer a simplified approach, as it incorporates 28 different factors.

Overall, most risk factors were similar in the updated respiratory failure index and the ACP guideline, but the index differs in several important ways:

• The index assigns less risk to low albumin, functional dependence, and congestive heart failure
• The index assigns greater risk to orofacial surgery
• The index identifies several new risk factors—high-complexity surgery, preoperative sepsis, ascites, and hypernatremia (serum sodium > 145 mmol/L).

 

 

STRATEGIES FOR RISK REDUCTION

The 2006 ACP guideline assigned evidence grades to various strategies to reduce risk for postoperative pulmonary complications based on a systematic review of the literature (Table 3).⁷ The only strategy that was supported by good evidence was postoperative lung expansion modalities, which comprise incentive spirometry, deep breathing exercises, intermittent positive-pressure breathing, and continuous positive airway pressure. Fair evidence supported selective postoperative use of nasogastric tubes and use of short-acting neuromuscular blockade.

Postoperative CPAP: Good option when exercise ability is limited

Among the postoperative lung expansion modalities, continuous positive airway pressure (CPAP) is particularly useful for patients who are unable to perform deep breathing or incentive spirometry exercises. A recent systematic literature review identified nine randomized controlled trials of CPAP vs standard therapy in a total of 654 patients undergoing abdominal surgery.¹³ Meta-analysis of these studies showed that CPAP was associated with significant reductions in the risk of overall postoperative pulmonary complications (odds ratio [OR] = 0.66; 95% CI, 0.52–0.85), atelectasis (OR = 0.75; 95% CI, 0.58–0.97), and pneumonia (OR = 0.33; 95% CI, 0.14–0.75) relative to standard therapy.

Use nasogastric tubes selectively

Nasogastric tubes can be used either routinely following abdominal surgery or only in select patients—eg, those who have symptomatic abdominal distention or nausea. The difference is important since nasogastric tubes may potentially increase the risk of aspiration and thus lead to a pulmonary complication. Nelson et al conducted a meta-analysis of 24 studies that compared routine nasogastric tube use in abdominal surgery with selective use based on symptoms or abdominal distention.¹⁴ They found that routine use was associated with a significant increase in postoperative pulmonary complications (OR = 1.45; 95% CI, 1.08–1.93) relative to selective use, without achieving any of its intended goals.

Laparoscopic vs open surgery: Evidence begins to follow intuition

Intuitively, it seems that laparoscopic procedures should reduce risk for postoperative pulmonary complications compared with open surgical procedures, as they are associated with less postoperative pain, which should facilitate deep breathing and improve postoperative lung volumes. Nevertheless, evidence for whether laparoscopic surgery reduces the risk of pulmonary complications has been mixed until recently.

In 2008, however, Weller and Rosati published an analysis of a nationally representative database of 19,156 patients who underwent bariatric surgery in 2005.¹⁵ After adjusting for comorbidities, they found that the rate of postoperative pulmonary complications was nearly double if patients underwent open surgery as opposed to laparoscopic surgery (OR = 1.92; 95% CI, 1.54–2.38). Open surgery was also associated with significantly higher rates of sepsis, cardiovascular events, and reoperation compared with laparoscopic procedures. This study suggests that choosing laparoscopic procedures is another strategy that may reduce pulmonary complication rates, at least in the setting of bariatric surgery.

Postoperative thoracic epidural analgesia

Question: Thoracic epidural analgesia reduces rates of which of the following?

A. Pneumonia following abdominal aortic aneurysm repair

B. Pulmonary complications following coronary bypass surgery

C. Respiratory failure following abdominal surgery

D. All of the above

The correct answer is D. Thoracic epidural analgesia is another important strategy for reducing postoperative pulmonary complications, as demonstrated by a 2007 systematic literature review by Liu and Wu.¹⁶ Their analysis showed that rates of pneumonia, respiratory failure, and pulmonary complications overall were reduced by approximately one-third to more than one-half with the use of postoperative thoracic epidural analgesia in patients undergoing aortic aneurysm repair, coronary bypass surgery, and abdominal surgery.

Smoking cessation: The jury is still out

Whether preoperative cigarette cessation reduces pulmonary complication rates has been controversial over the past decade. Early reports showed that among patients who smoke, those who quit shortly before surgery actually had higher complication rates than patients who continued to smoke. The most reasonable explanation seems to be that many patients who stop smoking report increased coughing and sputum production for the first month or two. Selection bias also may have played a role in these findings.

More recently, two randomized trials studied the impact of perioperative smoking intervention programs involving counseling and nicotine replacement.^17,18 Unfortunately, both studies primarily studied patients undergoing low-risk procedures and were insufficiently powered to show a difference in  pulmonary complication rates. The question of whether smoking cessation is an effective strategy to reduce postoperative pulmonary risk remains unanswered.

Preoperative intensive lung expansion: A promising new intervention

While the effectiveness of postoperative lung expansion techniques is undisputed,⁷preoperative lung expansion—also known as inspiratory muscle training—has only recently been investigated. Hulzebos et al randomized 279 patients undergoing coronary artery bypass graft surgery who were at high risk for developing pulmonary complications to either usual care or inspiratory muscle training.¹⁹ The latter intervention involved 20 minutes per day of incentive spirometry, active breathing, and forced expiration techniques for at least 2 weeks prior to surgery. Rates of high-grade postoperative pulmonary complications were cut in half (OR = 0.52; 95% CI, 0.30–0.92) and rates of pneumonia were reduced by 60% (OR = 0.40; 95% CI, 0.19–0.84) in patients who received inspiratory muscle training relative to the usual-care group.

In clinical practice, preoperative inspiratory muscle training can be done in a chest physical therapy outpatient setting or a pulmonary rehabilitation clinic in the hospital.

 

 

SUMMARY

There have been a number of significant recent developments in the perioperative management of pulmonary complications:

• Obstructive sleep apnea has been confirmed as a risk factor, and pulmonary hypertension has emerged as a novel risk factor.
• An updated respiratory failure index has emerged as a useful research tool to identify high-risk patients and to ensure uniform risk stratification in future research.
• Evidence has mounted for the effectiveness of several risk-reduction strategies, including the use of laparoscopic procedures for bariatric surgery; selective use of nasogastric tubes; postoperative thoracic epidural analgesia; and intensive preoperative inspiratory muscle training.

DISCUSSION

Question from the audience: I do preoperative evaluations in an orthopedic ambulatory surgery center. Our surgeons often tell me, “Just order preoperative pulmonary function tests,” or, “Get a blood gas.” How should I respond?

Dr. Smetana: This is an area of some controversy, but in general, spirometry does not add much to a preoperative risk assessment that is based on a history and physical exam. Usually if the spirometry is abnormal, it will not be a surprise after careful clinical assessment. Arterial blood gases have no role in routine preoperative assessment.

Question from the audience: A chest x-ray is often requested preoperatively, but is it a necessary study?

Dr. Smetana: The data for preoperative chest x-rays are fairly poor and don’t allow us to assess whether they accurately predict complication rates. Most studies on chest x-rays have looked at how they affect preoperative management—eg, whether they change the anesthesia or even the surgery—and have shown that preoperative management changes in only about 1% to 2% of cases. So the chest x-ray is a fairly low-yield test in this setting.

One could argue that a preoperative chest x-ray might provide a baseline for postoperative comparison, but actually it is not usually helpful in this regard. Having a baseline does not make it easier to correctly diagnose pneumonia postoperatively, for example. Abnormal chest x-rays correlate with higher risk, but most patients with abnormal films would be suspected of being at higher risk anyway based on findings from the clinical assessment.

Question from the audience: Many primary care doctors in my hospital screen patients for pulmonary hypertension, but this raises the question of what to do with any information gained. What do you tell patients? Anesthesiologists?

Dr. Smetana: I don’t recommend preoperative screening for pulmonary hypertension unless there is some specific clinical reason to look for it. We don’t know if the perioperative risks that I described for patients with diagnosed or symptomatic pulmonary hypertension would also apply to patients with unrecognized, asymptomatic pulmonary hypertension that happened to be identified by screening.

Patients with pulmonary hypertension are at very high risk, especially for respiratory failure. But we don’t have any risk-reduction strategies specific to these patients, although I would recommend applying the general risk-reduction strategies that I discussed.

Question from the audience: I saw a man at my high-risk preoperative clinic who scored normally on a 6-minute walk test but then was found sound asleep when I was ready to see him a little while later. I suspected he had undiagnosed sleep apnea, and therefore had an increased risk of postoperative pulmonary complications, but what evidence would I have to delay his surgery to diagnose the sleep apnea and stabilize him on CPAP?

Dr. Smetana: For a patient with clinically suspected but undiagnosed sleep apnea, we have some evidence that the diagnosis should be pursued before surgery is performed.⁸ If the surgery were elective, it would be appropriate to have the patient evaluated and, if obstructive sleep apnea were diagnosed, treated in the customary way with CPAP. For patients who are hospitalized after surgery, CPAP can be continued as soon as possible in the hospital.

I would not have made this recommendation a few years ago, but now the evidence is more compelling. However, at this point I would not recommend routine preoperative screening of all patients for sleep apnea. Ongoing research is looking at this question.

Follow-up question: How long should surgery be delayed to optimize the patient on CPAP?

Dr. Smetana: Risk for postoperative respiratory failure is reduced very quickly after initiating CPAP therapy. A week would probably be sufficient, but there are no good data to specifically address that question.

Question from the audience: What about patients with asthma who are undergoing surgery—which ones benefit from stress-level steroids and preoperative nebulizer therapy?

Dr. Smetana: Surprisingly, asthma—if well controlled—is not a risk factor for postoperative pulmonary complications. Patients within 80% of their predicted or personal best peak flow appear to have a risk similar to that of patients without asthma. For patients with uncontrolled or poorly controlled asthma, the general rule is the same as for patients with COPD: treat them the same as if they weren’t having surgery. If a patient with asthma has a clinical indication for cortico­steroids based on his or her condition, give cortico­steroids whether or not surgery is planned. Corticosteroids are safe and do not raise the risk of postoperative wound complications. But we have no evidence to support routine use of steroids for all patients with asthma simply because elective surgery is planned.

Follow-up question: Do you optimize poorly controlled patients with oral prednisone for several days preoperatively, or do you use a stress protocol?

Dr. Smetana: For a patient whom you would normally treat with an outpatient course of prednisone, you should do just that. For a patient with an exacerbation severe enough to require admission for intravenous steroids and inhaled nebulizer therapy, then you should use that strategy. If the surgery is elective, it should be delayed until the patient is at his or her personal best.

Tolerance of an enteral diet is one of the fundamental components of postoperative wellness, along with the ability to mobilize freely without supplemental oxygen and a readiness to be discharged home as soon as possible. Accordingly, post­operative gastrointestinal (GI) tract dysfunction is best defined as intolerance of an enteral diet after having been tolerant of one preoperatively. I prefer the term postoperative GI tract dysfunction over postoperative ileus, as ileus is ill defined, covering a wide spectrum of clinical signs and having a range of published incidences so broad (5%–100%) that it defies useful discussion.

Table 1 presents a schema for classifying postoperative GI tract dysfunction.¹ This review focuses on the causes and management of early-onset GI dysfunction—ie, developing within 6 to 48 hours of surgery—which can develop into persistent dysfunction (> 72 hours) and thereby prolong the hospital stay and potentially manifest systemically. This review will not address immediate and transient postoperative nausea and vomiting, which is distinct from intolerance of an enteral diet and has been reviewed extensively elsewhere.²

GI DYSFUNCTION: A COMMON POSTOPERATIVE MORBIDITY

Postoperative GI tract dysfunction is common, as illustrated by a large prospective cohort study at Duke University Medical Center³ that used the Postoperative Morbidity Survey (which has since been validated⁴) to document complications following major noncardiac surgery (ie, anticipated duration > 2 hours and anticipated blood loss > 500 mL). Hospital discharge was delayed in 27% of the study’s 438 patients as a result of a postoperative complication, and GI dysfunction was the most common type of complication overall and on postoperative days 5, 8, and 15. Episodes of GI dysfunction ranged from intolerance of an enteral diet to ischemic gut resulting in multiple organ failure.³

Adapted from a PowerPoint slide developed by Dr. M.P.W. Grocott.

A similar prospective cohort study conducted in the United Kingdom yielded comparable findings, with GI dysfunction being the most common type of postoperative complication reported.⁴ This study served to validate the Postoperative Morbidity Survey, which is now used worldwide to describe morbidity after major surgery. Figure 1 presents rates of postoperative GI dysfunction relative to other common types of postoperative complications in both the Duke study and the UK study.^3,4

A MULTIFACTORIAL PATHOGENESIS

The pathophysiology of postoperative GI tract dysfunction can be ischemic, metabolic, toxic, neurogenic, myogenic, pharmacologic, or mechanical.

It is important to recognize that in many cases no single factor explains the whole story behind postsurgical GI tract dysfunction, and none of these factors is an ipso facto cause of such dysfunction. For instance, a “mechanical” pathogenesis refers to any manipulation of the gut that causes an inflammatory response in the gut’s various layers, resulting in injury.^5,6 However, GI tract dysfunction commonly occurs after operations (including laparoscopic procedures) in which the gut was not handled at all. Similarly, in terms of a pharmacologic pathophysiology, while opioids can affect GI propulsion and cause constipation,^7,8 avoidance of opioid use does not ensure prevention of GI tract dysfunction. Moreover, opioid abusers do not generally exhibit intolerance of enteral nutrition.

A common mechanism that is often ignored is peri­operative gut ischemia resulting in low-grade injury. Low-grade hypovolemia can cause loss of perfusion to the tip of the microvillus, triggering apoptosis and potentially necrosis, which typically requires about 3 days for recovery. An experiment among 6 healthy volunteers who underwent elective hemorrhage (25% of blood volume removed) over 1 hour demonstrated that gastric tonometry was an earlier indicator of hypovolemia than were commonly measured hemodynamic variables such as invasive blood pressure, stroke volume, heart rate, and lactate and arterial blood gas measurements.⁹

FLUID LOADING AIDS GI RECOVERY

A targeted increase of intravascular volume and global blood flow perioperatively has been shown repeatedly to improve surgical outcome.^10–24 In clinical trials, the most common intervention to achieve the predetermined hemo­dynamic goal has been fluid loading. Overall, targeted increases in perioperative global blood flow have been associated with reduced mortality,²⁵ with the presumed mechanism being maintenance of end-organ perfusion.

The role of end-organ perfusion maintenance was confirmed in a controlled study of 60 patients under­going cardiac surgery in which perioperative fluid loading (with colloid) maintained gut perfusion as measured by gastric tonometry, whereas a control group had a reproducible reduction in gut perfusion.¹⁵ Fluid loading was associated with a significant reduction in the incidence of gut mucosal hypoperfusion—from 56% to 7%—and significant reductions in the incidence of minor and major complications, mean days in the hospital, and mean days in the intensive care unit.

Fluid type matters

The type of intraoperative fluid loading is a factor in postoperative recovery.

Colloid vs crystalloid. Moretti et al found that colloid (6% hetastarch in saline or 6% hetastarch in balanced salt) was superior to crystalloid (lactated Ringer’s solution) in preventing nausea, severe pain, vomiting, periorbital edema, and double vision postoperatively (P < .05 for all) despite comparable hemodynamic profiles.²⁶

Ringer’s vs normal saline. Williams et al compared intravenous lactated Ringer’s solution with normal saline (0.9% sodium chloride) in a randomized study of healthy volunteers.²⁷ The group that received normal saline demonstrated central nervous system changes and a much higher incidence of abdominal discomfort, a finding consistent with the toxic properties of chlorine to the gut.

Balanced electrolyte solutions vs saline-based fluids. Wilkes et al compared crystalloid and colloid solutions with physiologically balanced electrolyte formulations (Hextend) against saline-based fluids (Hespan) in elderly surgical patients.²⁸ They found that balanced electrolyte solutions were superior in improving gastric mucosal perfusion and preventing hyperchloremic metabolic acidosis. As a result of a reduction in GI tract perfusion, postoperative vomiting was more frequent in the group receiving saline-based fluids.

Evidence for Doppler-guided fluid management

Use of esophageal Doppler ultrasonography to guide fluid administration intraoperatively is fairly common in the United Kingdom and is based on randomized controlled trials showing that Doppler-guided colloid administration to maximize stroke volume reduces morbidity and length of hospital stay in surgical patients. In one government-supported study of 128 colorectal resection patients, Doppler-guided small boluses of colloid increased stroke volume, cardiac output, and oxygen delivery compared with conventional (central venous pressure–based) fluid management.²⁹ Gut function improved significantly faster with Doppler-guided fluid management as evidenced by a more rapid return of flatus, opening of bowels, and achievement of a full diet, and by faster discharge from the hospital. The incidence of GI complications was reduced from 45.3% in the conventional management group to 14.1% in the Doppler group. The relative risk of GI tract dysfunction was 5.3 times higher with conventional management.

 

 

OTHER STRATEGIES TO REDUCE POSTOPERATIVE GI DYSFUNCTION

In addition to fluid loading, a number of other methods have been studied in an attempt to reduce the incidence of postoperative GI tract dysfunction.

Epidural neostigmine: Improvement in some measures

Epidural neostigmine was compared with saline control in a randomized study of 45 patients scheduled for abdominal aortic surgery.³⁰ Time to first bowel sounds and time to first flatus were significantly shorter in the neostigmine group, but time to first defecation and the incidence of post­operative complications were similar between the groups.

Laxatives speed return of GI function

In a study of 53 women undergoing fast-track hysterectomy, recovery of GI tract function was faster in those randomized to receive laxatives (magnesium oxide and disodium phosphate) starting 6 hours postoperatively compared with those receiving placebo.³¹ Median time to first defecation was reduced from 69 hours in the placebo group to 45 hours in the laxative group (P < .0001), and postoperative hospitalization was shortened by a median of 1 day in the laxative group. There were no significant between-group differences in pain scores, postoperative nausea and vomiting, or the use of morphine or antiemetics.

Fentanyl reduces gastric myoelectrical activity

Intravenous administration of the opioid fentanyl significantly reduced gastric myoelectrical activity in an uncontrolled study of 20 patients undergoing elective surgery, but wide variation in effect was observed among patients.³² There was no correlation between the myoelectrical outcome and the presence of polymorphisms of the mu-opioid receptor gene.

Systemic lidocaine accelerates return of bowel function

Perioperative administration of systemic lidocaine, given as a 1.5-mg/kg bolus followed by continuous infusion at 2 mg/min, accelerated the return of bowel function and shortened the length of hospital stay compared with placebo in a randomized study of 60 colorectal surgery patients.³³

Early oral feeding cuts length of stay

A recent meta-analysis of randomized trials found that early oral intake of fluids and food after major abdominal gynecologic surgery was associated with an increased risk of nausea but a reduced length of hospital stay.³⁴ The authors recommended an individualized approach to early feeding, and called for cost-effectiveness and patient satisfaction studies.

Mosapride improves gastric emptying

Mosapride is a 5-HT₄ agonist that has been shown to improve gastric emptying in a randomized controlled study of 40 patients undergoing laparoscopic colectomy.³⁵ Time to first postoperative bowel movement, time to maximal gastric emptying rate, and postoperative hospital stay were all significantly shorter in patients receiving mosapride versus control. Mosapride is not currently approved for marketing in the United States.

Mu-opioid antagonists: Some show promise, others don’t

Mu-opioid receptor antagonists have been developed primarily to reverse opioid-induced bowel dysfunction. Commercially available drugs in this class include alvimopan, methylnaltrexone, nalbuphine, and naloxone. A recent meta-analysis of 23 randomized controlled studies of these agents for opioid-induced bowel dysfunction concluded that alvimopan and methylnaltrexone were superior to placebo but that evidence was insufficient for the safety or efficacy of naloxone and nalbuphine.³⁶

Nasogastric decompression: Usually more harm than benefit

Prophylactic nasogastric decompression is an intervention devoid of evidence. A meta-analysis of 33 studies encompassing 5,240 patients randomized to routine nasogastric tube placement, selective nasogastric tube use, or no nasogastric tube placement after abdominal surgery found no advantage to routine nasogastric tube use.³⁷ In fact, patients not receiving routine tube placement had a significantly earlier return of bowel function and a significant decrease in pulmonary complications. The incidence of anastomotic leak was not different among the groups. Routine tube use was associated with a lower incidence of vomiting but more patient discomfort. The clear conclusion is that, in most situations, elective placement of a nasogastric tube only causes harm.

Chewing gum: A simple intervention that works

In a recent meta-analysis of five randomized controlled trials, the simple intervention of gum chewing after colorectal surgery significantly accelerated the time to flatus and time to defecation, and was associated with a nonsignificant trend toward a shorter postoperative hospital stay.³⁸

CONCLUSIONS ON MANAGEMENT

Traditional measures intended to reduce the incidence of postoperative GI tract dysfunction—administration of prokinetic drugs, placement of nasogastric tubes, avoidance of food and fluids—are not beneficial and are often harmful. Administration of targeted amounts of fluid to optimize ventricular filling and end-organ perfusion has repeatedly been demonstrated to improve outcomes, particularly those related to GI tract perfusion and function. Administration of larger volumes of colloid, to achieve predetermined increases in stroke volume, improves gut perfusion and reduces the incidence of GI tract dysfunction.

Many simple, inexpensive, and readily available strategies for preventing or reversing postoperative GI tract dysfunction have some degree of evidence-based support and should be considered. I would recommend a multimodal approach that includes a limited surgical incision, regional local anesthesia without use of opioids, immediate postoperative mobilization, early enteral feeding, and postoperative gum chewing.¹ Such an approach promises to reduce GI tract dysfunction and other postoperative complications as well as to shorten hospital stay.

 

 

DISCUSSION

Question from the audience: You mentioned the selective use of nasogastric tubes. In which patients would you use them?

Dr. Mythen: For upper GI surgeries—esophagectomy, for example—a nasogastric tube is inevitable. Beyond that, the specific indications for tube placement are very limited. At our institution, we no longer place nasogastric tubes following the vast majority of GI tract operations, with esophagectomy being the exception.

Question from the audience: Would you comment on the selective contribution of thoracic epidural analgesia with respect to early feeding after abdominal or colon surgery?

Dr. Mythen: If you’re an enthusiast for thoracic epidurals, you can present the literature in a way that definitively demonstrates a huge advantage to thoracic epidurals. When they work well for the individual, they are fantastic, but you must have a very effective team and system to deliver success to the whole patient population. At our institution the failure rate 20 to 24 hours postoperatively is about 50%.

Question from the audience: I’m an internist and I’ve never heard of the esophageal Doppler-directed fluid bolus protocol—or of anyone using colloids at all. Is that something that is generally practiced in the United States?

Dr. Mythen: Some institutions are practicing goal-directed fluid management now. If you measure stroke volume and give small boluses of colloid, you need a lot less fluid to achieve a higher intravascular volume and goal. At our institution, we’ve repackaged it as “goal-directed fluid restriction” to gain acceptance among surgeons. Uptake has been slower in the United States, though studies here have reinforced the message and been supported by editorials. Guessing about fluids, which we’ve done historically, is not very smart. One thing that differentiates an anesthesiologist from an anesthetic technician is the ability to give goal-directed fluid therapy. The ability to act in a targeted fashion makes it possible to achieve an appropriate physiological goal, but it is more difficult.

Question from the audience: In terms of maintenance fluids and chloride toxicity, is there an alternative to D5 half-normal saline for maintenance fluid?

Dr. Mythen: We don’t have a very good postoperative maintenance fluid; D5 half-normal with some potassium is probably as good as it gets at present. I emphasize getting patients to drink as quickly as possible. If they’re not drinking (not using the GI tract), they need a very high level of physician input because fluid balance is rocket science. The GI tract is very clever. Once patients are drinking and eating, they’re fine, but if they still have an intravenous line in, close attention is required.

Question from the audience: Would you use lactated Ringer’s solution in a patient who is just not eating or drinking?

Dr. Mythen: I do, actually. I tend to mix it in with some D5 half-normal saline because lactated Ringer’s is a great solution. The body can use the lactate to make sugar if necessary. The brain is one of the few organs that will metabolize lactate.

Follow-up question: Would you use it at a lower rate to prevent volume overload?

Dr. Mythen: Yes, at 60 mL/hr. The important thing is that if intravenous fluids are still required, the patient needs to be in a fairly supervised, high-dependency environment. You must address the real issue: Why aren’t they drinking? If the patient is not drinking postoperatively, someone’s done a bad job or there is something that needs fixing.

Question from audience: In the operating room, do you have a preference between albumin and a high-molecular-weight hetastarch like Hextend?

Dr. Mythen: Europe is slightly different in its choice of colloids. We’ve pretty much abandoned the high-molecular-weight starches. We do not use albumin at our institution for cost reasons, and we can’t find any evidence to support its use. We would have to close one intensive care unit bed to be able to afford using albumin. We use low-molecular-weight hydroxyethyl starches, which I believe are now coming into the United States. They have no major coagulation effect.

Tolerance of an enteral diet is one of the fundamental components of postoperative wellness, along with the ability to mobilize freely without supplemental oxygen and a readiness to be discharged home as soon as possible. Accordingly, post­operative gastrointestinal (GI) tract dysfunction is best defined as intolerance of an enteral diet after having been tolerant of one preoperatively. I prefer the term postoperative GI tract dysfunction over postoperative ileus, as ileus is ill defined, covering a wide spectrum of clinical signs and having a range of published incidences so broad (5%–100%) that it defies useful discussion.

Table 1 presents a schema for classifying postoperative GI tract dysfunction.¹ This review focuses on the causes and management of early-onset GI dysfunction—ie, developing within 6 to 48 hours of surgery—which can develop into persistent dysfunction (> 72 hours) and thereby prolong the hospital stay and potentially manifest systemically. This review will not address immediate and transient postoperative nausea and vomiting, which is distinct from intolerance of an enteral diet and has been reviewed extensively elsewhere.²

GI DYSFUNCTION: A COMMON POSTOPERATIVE MORBIDITY

Postoperative GI tract dysfunction is common, as illustrated by a large prospective cohort study at Duke University Medical Center³ that used the Postoperative Morbidity Survey (which has since been validated⁴) to document complications following major noncardiac surgery (ie, anticipated duration > 2 hours and anticipated blood loss > 500 mL). Hospital discharge was delayed in 27% of the study’s 438 patients as a result of a postoperative complication, and GI dysfunction was the most common type of complication overall and on postoperative days 5, 8, and 15. Episodes of GI dysfunction ranged from intolerance of an enteral diet to ischemic gut resulting in multiple organ failure.³

Adapted from a PowerPoint slide developed by Dr. M.P.W. Grocott.

A similar prospective cohort study conducted in the United Kingdom yielded comparable findings, with GI dysfunction being the most common type of postoperative complication reported.⁴ This study served to validate the Postoperative Morbidity Survey, which is now used worldwide to describe morbidity after major surgery. Figure 1 presents rates of postoperative GI dysfunction relative to other common types of postoperative complications in both the Duke study and the UK study.^3,4

A MULTIFACTORIAL PATHOGENESIS

The pathophysiology of postoperative GI tract dysfunction can be ischemic, metabolic, toxic, neurogenic, myogenic, pharmacologic, or mechanical.

It is important to recognize that in many cases no single factor explains the whole story behind postsurgical GI tract dysfunction, and none of these factors is an ipso facto cause of such dysfunction. For instance, a “mechanical” pathogenesis refers to any manipulation of the gut that causes an inflammatory response in the gut’s various layers, resulting in injury.^5,6 However, GI tract dysfunction commonly occurs after operations (including laparoscopic procedures) in which the gut was not handled at all. Similarly, in terms of a pharmacologic pathophysiology, while opioids can affect GI propulsion and cause constipation,^7,8 avoidance of opioid use does not ensure prevention of GI tract dysfunction. Moreover, opioid abusers do not generally exhibit intolerance of enteral nutrition.

A common mechanism that is often ignored is peri­operative gut ischemia resulting in low-grade injury. Low-grade hypovolemia can cause loss of perfusion to the tip of the microvillus, triggering apoptosis and potentially necrosis, which typically requires about 3 days for recovery. An experiment among 6 healthy volunteers who underwent elective hemorrhage (25% of blood volume removed) over 1 hour demonstrated that gastric tonometry was an earlier indicator of hypovolemia than were commonly measured hemodynamic variables such as invasive blood pressure, stroke volume, heart rate, and lactate and arterial blood gas measurements.⁹

FLUID LOADING AIDS GI RECOVERY

A targeted increase of intravascular volume and global blood flow perioperatively has been shown repeatedly to improve surgical outcome.^10–24 In clinical trials, the most common intervention to achieve the predetermined hemo­dynamic goal has been fluid loading. Overall, targeted increases in perioperative global blood flow have been associated with reduced mortality,²⁵ with the presumed mechanism being maintenance of end-organ perfusion.

The role of end-organ perfusion maintenance was confirmed in a controlled study of 60 patients under­going cardiac surgery in which perioperative fluid loading (with colloid) maintained gut perfusion as measured by gastric tonometry, whereas a control group had a reproducible reduction in gut perfusion.¹⁵ Fluid loading was associated with a significant reduction in the incidence of gut mucosal hypoperfusion—from 56% to 7%—and significant reductions in the incidence of minor and major complications, mean days in the hospital, and mean days in the intensive care unit.

Fluid type matters

The type of intraoperative fluid loading is a factor in postoperative recovery.

Colloid vs crystalloid. Moretti et al found that colloid (6% hetastarch in saline or 6% hetastarch in balanced salt) was superior to crystalloid (lactated Ringer’s solution) in preventing nausea, severe pain, vomiting, periorbital edema, and double vision postoperatively (P < .05 for all) despite comparable hemodynamic profiles.²⁶

Ringer’s vs normal saline. Williams et al compared intravenous lactated Ringer’s solution with normal saline (0.9% sodium chloride) in a randomized study of healthy volunteers.²⁷ The group that received normal saline demonstrated central nervous system changes and a much higher incidence of abdominal discomfort, a finding consistent with the toxic properties of chlorine to the gut.

Balanced electrolyte solutions vs saline-based fluids. Wilkes et al compared crystalloid and colloid solutions with physiologically balanced electrolyte formulations (Hextend) against saline-based fluids (Hespan) in elderly surgical patients.²⁸ They found that balanced electrolyte solutions were superior in improving gastric mucosal perfusion and preventing hyperchloremic metabolic acidosis. As a result of a reduction in GI tract perfusion, postoperative vomiting was more frequent in the group receiving saline-based fluids.

Evidence for Doppler-guided fluid management

Use of esophageal Doppler ultrasonography to guide fluid administration intraoperatively is fairly common in the United Kingdom and is based on randomized controlled trials showing that Doppler-guided colloid administration to maximize stroke volume reduces morbidity and length of hospital stay in surgical patients. In one government-supported study of 128 colorectal resection patients, Doppler-guided small boluses of colloid increased stroke volume, cardiac output, and oxygen delivery compared with conventional (central venous pressure–based) fluid management.²⁹ Gut function improved significantly faster with Doppler-guided fluid management as evidenced by a more rapid return of flatus, opening of bowels, and achievement of a full diet, and by faster discharge from the hospital. The incidence of GI complications was reduced from 45.3% in the conventional management group to 14.1% in the Doppler group. The relative risk of GI tract dysfunction was 5.3 times higher with conventional management.

 

 

OTHER STRATEGIES TO REDUCE POSTOPERATIVE GI DYSFUNCTION

In addition to fluid loading, a number of other methods have been studied in an attempt to reduce the incidence of postoperative GI tract dysfunction.

Epidural neostigmine: Improvement in some measures

Epidural neostigmine was compared with saline control in a randomized study of 45 patients scheduled for abdominal aortic surgery.³⁰ Time to first bowel sounds and time to first flatus were significantly shorter in the neostigmine group, but time to first defecation and the incidence of post­operative complications were similar between the groups.

Laxatives speed return of GI function

In a study of 53 women undergoing fast-track hysterectomy, recovery of GI tract function was faster in those randomized to receive laxatives (magnesium oxide and disodium phosphate) starting 6 hours postoperatively compared with those receiving placebo.³¹ Median time to first defecation was reduced from 69 hours in the placebo group to 45 hours in the laxative group (P < .0001), and postoperative hospitalization was shortened by a median of 1 day in the laxative group. There were no significant between-group differences in pain scores, postoperative nausea and vomiting, or the use of morphine or antiemetics.

Fentanyl reduces gastric myoelectrical activity

Intravenous administration of the opioid fentanyl significantly reduced gastric myoelectrical activity in an uncontrolled study of 20 patients undergoing elective surgery, but wide variation in effect was observed among patients.³² There was no correlation between the myoelectrical outcome and the presence of polymorphisms of the mu-opioid receptor gene.

Systemic lidocaine accelerates return of bowel function

Perioperative administration of systemic lidocaine, given as a 1.5-mg/kg bolus followed by continuous infusion at 2 mg/min, accelerated the return of bowel function and shortened the length of hospital stay compared with placebo in a randomized study of 60 colorectal surgery patients.³³

Early oral feeding cuts length of stay

A recent meta-analysis of randomized trials found that early oral intake of fluids and food after major abdominal gynecologic surgery was associated with an increased risk of nausea but a reduced length of hospital stay.³⁴ The authors recommended an individualized approach to early feeding, and called for cost-effectiveness and patient satisfaction studies.

Mosapride improves gastric emptying

Mosapride is a 5-HT₄ agonist that has been shown to improve gastric emptying in a randomized controlled study of 40 patients undergoing laparoscopic colectomy.³⁵ Time to first postoperative bowel movement, time to maximal gastric emptying rate, and postoperative hospital stay were all significantly shorter in patients receiving mosapride versus control. Mosapride is not currently approved for marketing in the United States.

Mu-opioid antagonists: Some show promise, others don’t

Mu-opioid receptor antagonists have been developed primarily to reverse opioid-induced bowel dysfunction. Commercially available drugs in this class include alvimopan, methylnaltrexone, nalbuphine, and naloxone. A recent meta-analysis of 23 randomized controlled studies of these agents for opioid-induced bowel dysfunction concluded that alvimopan and methylnaltrexone were superior to placebo but that evidence was insufficient for the safety or efficacy of naloxone and nalbuphine.³⁶

Nasogastric decompression: Usually more harm than benefit

Prophylactic nasogastric decompression is an intervention devoid of evidence. A meta-analysis of 33 studies encompassing 5,240 patients randomized to routine nasogastric tube placement, selective nasogastric tube use, or no nasogastric tube placement after abdominal surgery found no advantage to routine nasogastric tube use.³⁷ In fact, patients not receiving routine tube placement had a significantly earlier return of bowel function and a significant decrease in pulmonary complications. The incidence of anastomotic leak was not different among the groups. Routine tube use was associated with a lower incidence of vomiting but more patient discomfort. The clear conclusion is that, in most situations, elective placement of a nasogastric tube only causes harm.

Chewing gum: A simple intervention that works

In a recent meta-analysis of five randomized controlled trials, the simple intervention of gum chewing after colorectal surgery significantly accelerated the time to flatus and time to defecation, and was associated with a nonsignificant trend toward a shorter postoperative hospital stay.³⁸

CONCLUSIONS ON MANAGEMENT

Traditional measures intended to reduce the incidence of postoperative GI tract dysfunction—administration of prokinetic drugs, placement of nasogastric tubes, avoidance of food and fluids—are not beneficial and are often harmful. Administration of targeted amounts of fluid to optimize ventricular filling and end-organ perfusion has repeatedly been demonstrated to improve outcomes, particularly those related to GI tract perfusion and function. Administration of larger volumes of colloid, to achieve predetermined increases in stroke volume, improves gut perfusion and reduces the incidence of GI tract dysfunction.

Many simple, inexpensive, and readily available strategies for preventing or reversing postoperative GI tract dysfunction have some degree of evidence-based support and should be considered. I would recommend a multimodal approach that includes a limited surgical incision, regional local anesthesia without use of opioids, immediate postoperative mobilization, early enteral feeding, and postoperative gum chewing.¹ Such an approach promises to reduce GI tract dysfunction and other postoperative complications as well as to shorten hospital stay.

 

 

DISCUSSION

Question from the audience: You mentioned the selective use of nasogastric tubes. In which patients would you use them?

Dr. Mythen: For upper GI surgeries—esophagectomy, for example—a nasogastric tube is inevitable. Beyond that, the specific indications for tube placement are very limited. At our institution, we no longer place nasogastric tubes following the vast majority of GI tract operations, with esophagectomy being the exception.

Question from the audience: Would you comment on the selective contribution of thoracic epidural analgesia with respect to early feeding after abdominal or colon surgery?

Dr. Mythen: If you’re an enthusiast for thoracic epidurals, you can present the literature in a way that definitively demonstrates a huge advantage to thoracic epidurals. When they work well for the individual, they are fantastic, but you must have a very effective team and system to deliver success to the whole patient population. At our institution the failure rate 20 to 24 hours postoperatively is about 50%.

Question from the audience: I’m an internist and I’ve never heard of the esophageal Doppler-directed fluid bolus protocol—or of anyone using colloids at all. Is that something that is generally practiced in the United States?

Dr. Mythen: Some institutions are practicing goal-directed fluid management now. If you measure stroke volume and give small boluses of colloid, you need a lot less fluid to achieve a higher intravascular volume and goal. At our institution, we’ve repackaged it as “goal-directed fluid restriction” to gain acceptance among surgeons. Uptake has been slower in the United States, though studies here have reinforced the message and been supported by editorials. Guessing about fluids, which we’ve done historically, is not very smart. One thing that differentiates an anesthesiologist from an anesthetic technician is the ability to give goal-directed fluid therapy. The ability to act in a targeted fashion makes it possible to achieve an appropriate physiological goal, but it is more difficult.

Question from the audience: In terms of maintenance fluids and chloride toxicity, is there an alternative to D5 half-normal saline for maintenance fluid?

Dr. Mythen: We don’t have a very good postoperative maintenance fluid; D5 half-normal with some potassium is probably as good as it gets at present. I emphasize getting patients to drink as quickly as possible. If they’re not drinking (not using the GI tract), they need a very high level of physician input because fluid balance is rocket science. The GI tract is very clever. Once patients are drinking and eating, they’re fine, but if they still have an intravenous line in, close attention is required.

Question from the audience: Would you use lactated Ringer’s solution in a patient who is just not eating or drinking?

Dr. Mythen: I do, actually. I tend to mix it in with some D5 half-normal saline because lactated Ringer’s is a great solution. The body can use the lactate to make sugar if necessary. The brain is one of the few organs that will metabolize lactate.

Follow-up question: Would you use it at a lower rate to prevent volume overload?

Dr. Mythen: Yes, at 60 mL/hr. The important thing is that if intravenous fluids are still required, the patient needs to be in a fairly supervised, high-dependency environment. You must address the real issue: Why aren’t they drinking? If the patient is not drinking postoperatively, someone’s done a bad job or there is something that needs fixing.

Question from audience: In the operating room, do you have a preference between albumin and a high-molecular-weight hetastarch like Hextend?

Dr. Mythen: Europe is slightly different in its choice of colloids. We’ve pretty much abandoned the high-molecular-weight starches. We do not use albumin at our institution for cost reasons, and we can’t find any evidence to support its use. We would have to close one intensive care unit bed to be able to afford using albumin. We use low-molecular-weight hydroxyethyl starches, which I believe are now coming into the United States. They have no major coagulation effect.

Tolerance of an enteral diet is one of the fundamental components of postoperative wellness, along with the ability to mobilize freely without supplemental oxygen and a readiness to be discharged home as soon as possible. Accordingly, post­operative gastrointestinal (GI) tract dysfunction is best defined as intolerance of an enteral diet after having been tolerant of one preoperatively. I prefer the term postoperative GI tract dysfunction over postoperative ileus, as ileus is ill defined, covering a wide spectrum of clinical signs and having a range of published incidences so broad (5%–100%) that it defies useful discussion.

Table 1 presents a schema for classifying postoperative GI tract dysfunction.¹ This review focuses on the causes and management of early-onset GI dysfunction—ie, developing within 6 to 48 hours of surgery—which can develop into persistent dysfunction (> 72 hours) and thereby prolong the hospital stay and potentially manifest systemically. This review will not address immediate and transient postoperative nausea and vomiting, which is distinct from intolerance of an enteral diet and has been reviewed extensively elsewhere.²

GI DYSFUNCTION: A COMMON POSTOPERATIVE MORBIDITY

Postoperative GI tract dysfunction is common, as illustrated by a large prospective cohort study at Duke University Medical Center³ that used the Postoperative Morbidity Survey (which has since been validated⁴) to document complications following major noncardiac surgery (ie, anticipated duration > 2 hours and anticipated blood loss > 500 mL). Hospital discharge was delayed in 27% of the study’s 438 patients as a result of a postoperative complication, and GI dysfunction was the most common type of complication overall and on postoperative days 5, 8, and 15. Episodes of GI dysfunction ranged from intolerance of an enteral diet to ischemic gut resulting in multiple organ failure.³

Adapted from a PowerPoint slide developed by Dr. M.P.W. Grocott.

A similar prospective cohort study conducted in the United Kingdom yielded comparable findings, with GI dysfunction being the most common type of postoperative complication reported.⁴ This study served to validate the Postoperative Morbidity Survey, which is now used worldwide to describe morbidity after major surgery. Figure 1 presents rates of postoperative GI dysfunction relative to other common types of postoperative complications in both the Duke study and the UK study.^3,4

A MULTIFACTORIAL PATHOGENESIS

The pathophysiology of postoperative GI tract dysfunction can be ischemic, metabolic, toxic, neurogenic, myogenic, pharmacologic, or mechanical.

It is important to recognize that in many cases no single factor explains the whole story behind postsurgical GI tract dysfunction, and none of these factors is an ipso facto cause of such dysfunction. For instance, a “mechanical” pathogenesis refers to any manipulation of the gut that causes an inflammatory response in the gut’s various layers, resulting in injury.^5,6 However, GI tract dysfunction commonly occurs after operations (including laparoscopic procedures) in which the gut was not handled at all. Similarly, in terms of a pharmacologic pathophysiology, while opioids can affect GI propulsion and cause constipation,^7,8 avoidance of opioid use does not ensure prevention of GI tract dysfunction. Moreover, opioid abusers do not generally exhibit intolerance of enteral nutrition.

A common mechanism that is often ignored is peri­operative gut ischemia resulting in low-grade injury. Low-grade hypovolemia can cause loss of perfusion to the tip of the microvillus, triggering apoptosis and potentially necrosis, which typically requires about 3 days for recovery. An experiment among 6 healthy volunteers who underwent elective hemorrhage (25% of blood volume removed) over 1 hour demonstrated that gastric tonometry was an earlier indicator of hypovolemia than were commonly measured hemodynamic variables such as invasive blood pressure, stroke volume, heart rate, and lactate and arterial blood gas measurements.⁹

FLUID LOADING AIDS GI RECOVERY

A targeted increase of intravascular volume and global blood flow perioperatively has been shown repeatedly to improve surgical outcome.^10–24 In clinical trials, the most common intervention to achieve the predetermined hemo­dynamic goal has been fluid loading. Overall, targeted increases in perioperative global blood flow have been associated with reduced mortality,²⁵ with the presumed mechanism being maintenance of end-organ perfusion.

The role of end-organ perfusion maintenance was confirmed in a controlled study of 60 patients under­going cardiac surgery in which perioperative fluid loading (with colloid) maintained gut perfusion as measured by gastric tonometry, whereas a control group had a reproducible reduction in gut perfusion.¹⁵ Fluid loading was associated with a significant reduction in the incidence of gut mucosal hypoperfusion—from 56% to 7%—and significant reductions in the incidence of minor and major complications, mean days in the hospital, and mean days in the intensive care unit.

Fluid type matters

The type of intraoperative fluid loading is a factor in postoperative recovery.

Colloid vs crystalloid. Moretti et al found that colloid (6% hetastarch in saline or 6% hetastarch in balanced salt) was superior to crystalloid (lactated Ringer’s solution) in preventing nausea, severe pain, vomiting, periorbital edema, and double vision postoperatively (P < .05 for all) despite comparable hemodynamic profiles.²⁶

Ringer’s vs normal saline. Williams et al compared intravenous lactated Ringer’s solution with normal saline (0.9% sodium chloride) in a randomized study of healthy volunteers.²⁷ The group that received normal saline demonstrated central nervous system changes and a much higher incidence of abdominal discomfort, a finding consistent with the toxic properties of chlorine to the gut.

Balanced electrolyte solutions vs saline-based fluids. Wilkes et al compared crystalloid and colloid solutions with physiologically balanced electrolyte formulations (Hextend) against saline-based fluids (Hespan) in elderly surgical patients.²⁸ They found that balanced electrolyte solutions were superior in improving gastric mucosal perfusion and preventing hyperchloremic metabolic acidosis. As a result of a reduction in GI tract perfusion, postoperative vomiting was more frequent in the group receiving saline-based fluids.

Evidence for Doppler-guided fluid management

Use of esophageal Doppler ultrasonography to guide fluid administration intraoperatively is fairly common in the United Kingdom and is based on randomized controlled trials showing that Doppler-guided colloid administration to maximize stroke volume reduces morbidity and length of hospital stay in surgical patients. In one government-supported study of 128 colorectal resection patients, Doppler-guided small boluses of colloid increased stroke volume, cardiac output, and oxygen delivery compared with conventional (central venous pressure–based) fluid management.²⁹ Gut function improved significantly faster with Doppler-guided fluid management as evidenced by a more rapid return of flatus, opening of bowels, and achievement of a full diet, and by faster discharge from the hospital. The incidence of GI complications was reduced from 45.3% in the conventional management group to 14.1% in the Doppler group. The relative risk of GI tract dysfunction was 5.3 times higher with conventional management.

 

 

OTHER STRATEGIES TO REDUCE POSTOPERATIVE GI DYSFUNCTION

In addition to fluid loading, a number of other methods have been studied in an attempt to reduce the incidence of postoperative GI tract dysfunction.

Epidural neostigmine: Improvement in some measures

Epidural neostigmine was compared with saline control in a randomized study of 45 patients scheduled for abdominal aortic surgery.³⁰ Time to first bowel sounds and time to first flatus were significantly shorter in the neostigmine group, but time to first defecation and the incidence of post­operative complications were similar between the groups.

Laxatives speed return of GI function

In a study of 53 women undergoing fast-track hysterectomy, recovery of GI tract function was faster in those randomized to receive laxatives (magnesium oxide and disodium phosphate) starting 6 hours postoperatively compared with those receiving placebo.³¹ Median time to first defecation was reduced from 69 hours in the placebo group to 45 hours in the laxative group (P < .0001), and postoperative hospitalization was shortened by a median of 1 day in the laxative group. There were no significant between-group differences in pain scores, postoperative nausea and vomiting, or the use of morphine or antiemetics.

Fentanyl reduces gastric myoelectrical activity

Intravenous administration of the opioid fentanyl significantly reduced gastric myoelectrical activity in an uncontrolled study of 20 patients undergoing elective surgery, but wide variation in effect was observed among patients.³² There was no correlation between the myoelectrical outcome and the presence of polymorphisms of the mu-opioid receptor gene.

Systemic lidocaine accelerates return of bowel function

Perioperative administration of systemic lidocaine, given as a 1.5-mg/kg bolus followed by continuous infusion at 2 mg/min, accelerated the return of bowel function and shortened the length of hospital stay compared with placebo in a randomized study of 60 colorectal surgery patients.³³

Early oral feeding cuts length of stay

A recent meta-analysis of randomized trials found that early oral intake of fluids and food after major abdominal gynecologic surgery was associated with an increased risk of nausea but a reduced length of hospital stay.³⁴ The authors recommended an individualized approach to early feeding, and called for cost-effectiveness and patient satisfaction studies.

Mosapride improves gastric emptying

Mosapride is a 5-HT₄ agonist that has been shown to improve gastric emptying in a randomized controlled study of 40 patients undergoing laparoscopic colectomy.³⁵ Time to first postoperative bowel movement, time to maximal gastric emptying rate, and postoperative hospital stay were all significantly shorter in patients receiving mosapride versus control. Mosapride is not currently approved for marketing in the United States.

Mu-opioid antagonists: Some show promise, others don’t

Mu-opioid receptor antagonists have been developed primarily to reverse opioid-induced bowel dysfunction. Commercially available drugs in this class include alvimopan, methylnaltrexone, nalbuphine, and naloxone. A recent meta-analysis of 23 randomized controlled studies of these agents for opioid-induced bowel dysfunction concluded that alvimopan and methylnaltrexone were superior to placebo but that evidence was insufficient for the safety or efficacy of naloxone and nalbuphine.³⁶

Nasogastric decompression: Usually more harm than benefit

Prophylactic nasogastric decompression is an intervention devoid of evidence. A meta-analysis of 33 studies encompassing 5,240 patients randomized to routine nasogastric tube placement, selective nasogastric tube use, or no nasogastric tube placement after abdominal surgery found no advantage to routine nasogastric tube use.³⁷ In fact, patients not receiving routine tube placement had a significantly earlier return of bowel function and a significant decrease in pulmonary complications. The incidence of anastomotic leak was not different among the groups. Routine tube use was associated with a lower incidence of vomiting but more patient discomfort. The clear conclusion is that, in most situations, elective placement of a nasogastric tube only causes harm.

Chewing gum: A simple intervention that works

In a recent meta-analysis of five randomized controlled trials, the simple intervention of gum chewing after colorectal surgery significantly accelerated the time to flatus and time to defecation, and was associated with a nonsignificant trend toward a shorter postoperative hospital stay.³⁸

CONCLUSIONS ON MANAGEMENT

Traditional measures intended to reduce the incidence of postoperative GI tract dysfunction—administration of prokinetic drugs, placement of nasogastric tubes, avoidance of food and fluids—are not beneficial and are often harmful. Administration of targeted amounts of fluid to optimize ventricular filling and end-organ perfusion has repeatedly been demonstrated to improve outcomes, particularly those related to GI tract perfusion and function. Administration of larger volumes of colloid, to achieve predetermined increases in stroke volume, improves gut perfusion and reduces the incidence of GI tract dysfunction.

Many simple, inexpensive, and readily available strategies for preventing or reversing postoperative GI tract dysfunction have some degree of evidence-based support and should be considered. I would recommend a multimodal approach that includes a limited surgical incision, regional local anesthesia without use of opioids, immediate postoperative mobilization, early enteral feeding, and postoperative gum chewing.¹ Such an approach promises to reduce GI tract dysfunction and other postoperative complications as well as to shorten hospital stay.

 

 

DISCUSSION

Question from the audience: You mentioned the selective use of nasogastric tubes. In which patients would you use them?

Dr. Mythen: For upper GI surgeries—esophagectomy, for example—a nasogastric tube is inevitable. Beyond that, the specific indications for tube placement are very limited. At our institution, we no longer place nasogastric tubes following the vast majority of GI tract operations, with esophagectomy being the exception.

Question from the audience: Would you comment on the selective contribution of thoracic epidural analgesia with respect to early feeding after abdominal or colon surgery?

Dr. Mythen: If you’re an enthusiast for thoracic epidurals, you can present the literature in a way that definitively demonstrates a huge advantage to thoracic epidurals. When they work well for the individual, they are fantastic, but you must have a very effective team and system to deliver success to the whole patient population. At our institution the failure rate 20 to 24 hours postoperatively is about 50%.

Question from the audience: I’m an internist and I’ve never heard of the esophageal Doppler-directed fluid bolus protocol—or of anyone using colloids at all. Is that something that is generally practiced in the United States?

Dr. Mythen: Some institutions are practicing goal-directed fluid management now. If you measure stroke volume and give small boluses of colloid, you need a lot less fluid to achieve a higher intravascular volume and goal. At our institution, we’ve repackaged it as “goal-directed fluid restriction” to gain acceptance among surgeons. Uptake has been slower in the United States, though studies here have reinforced the message and been supported by editorials. Guessing about fluids, which we’ve done historically, is not very smart. One thing that differentiates an anesthesiologist from an anesthetic technician is the ability to give goal-directed fluid therapy. The ability to act in a targeted fashion makes it possible to achieve an appropriate physiological goal, but it is more difficult.

Question from the audience: In terms of maintenance fluids and chloride toxicity, is there an alternative to D5 half-normal saline for maintenance fluid?

Dr. Mythen: We don’t have a very good postoperative maintenance fluid; D5 half-normal with some potassium is probably as good as it gets at present. I emphasize getting patients to drink as quickly as possible. If they’re not drinking (not using the GI tract), they need a very high level of physician input because fluid balance is rocket science. The GI tract is very clever. Once patients are drinking and eating, they’re fine, but if they still have an intravenous line in, close attention is required.

Question from the audience: Would you use lactated Ringer’s solution in a patient who is just not eating or drinking?

Dr. Mythen: I do, actually. I tend to mix it in with some D5 half-normal saline because lactated Ringer’s is a great solution. The body can use the lactate to make sugar if necessary. The brain is one of the few organs that will metabolize lactate.

Follow-up question: Would you use it at a lower rate to prevent volume overload?

Dr. Mythen: Yes, at 60 mL/hr. The important thing is that if intravenous fluids are still required, the patient needs to be in a fairly supervised, high-dependency environment. You must address the real issue: Why aren’t they drinking? If the patient is not drinking postoperatively, someone’s done a bad job or there is something that needs fixing.

Question from audience: In the operating room, do you have a preference between albumin and a high-molecular-weight hetastarch like Hextend?

Dr. Mythen: Europe is slightly different in its choice of colloids. We’ve pretty much abandoned the high-molecular-weight starches. We do not use albumin at our institution for cost reasons, and we can’t find any evidence to support its use. We would have to close one intensive care unit bed to be able to afford using albumin. We use low-molecular-weight hydroxyethyl starches, which I believe are now coming into the United States. They have no major coagulation effect.

CASE 1: RADICAL PROSTATECTOMY IN A MAN WITH ACUTE DEEP VEIN THROMBOSIS

A 69-year-old man is seen in the preoperative clinic 1 week before a scheduled radical prostatectomy. He has been diagnosed with femoral deep vein thrombosis (DVT) following a complaint of calf soreness.

Question 1.1: How would you treat him for his DVT?

A. Intravenous (IV) unfractionated heparin (UFH)

B. Low-molecular-weight heparin (LMWH)

C. Inferior vena cava (IVC) filter

D. Combination of pharmacologic therapy and then an IVC filter

Dr. Steven L. Cohn: The latest edition of the American College of Chest Physicians (ACCP) evidence-based guidelines on antithrombotic therapy recommends the use of therapeutic-dose subcutaneous LMWH over IV UFH for initial treatment of acute DVT in the outpatient or inpatient setting.¹ Additionally, indications for an IVC filter include the prevention of pulmonary embolism (PE) in a patient with DVT who requires full-dose anticoagulation but cannot receive it, as would be the case here if the patient proceeds with surgery as scheduled. So if surgery will be postponed, the best option is LMWH; if surgery will not be postponed, the best answer is a combination of pharmacologic therapy with low-dose LMWH and an IVC filter, preferably a retrievable one.²

Question 1.2: You recommend postponing surgery, but the patient is worried about metastatic disease. For how long should surgery be postponed?

A. 2 weeks

B. 1 month

C. 2 months

D. 3 months

E. 6 months

Dr. Cohn: In the absence of anticoagulation therapy, the risk of venous thromboembolism (VTE) is approximately 40% (~1% per day) during the first month following an acute VTE and then declines markedly, to approximately 10%, during the second and third months following the acute event.³ Therefore, I would suggest that the patient wait at least 1 month after an acute DVT before undergoing surgery.

Dr. BobbieJean Sweitzer: This patient is in a hypercoagulable state, and the surgery itself will induce excess hypercoagulability. With a femoral DVT already present, his risk of VTE or PE is likely to be greater than 1% per day during the first month. If he does develop a PE, it may potentially be fatal.

Question 1.3: According to the patient, the surgeon and the internist discussed options, but the surgeon “doesn’t believe in filters” and the patient doesn’t want to postpone the procedure, despite your recommendation. Two weeks later he shows up for surgery having stopped his LMWH 3 days before. What would you do?

A. Cancel the surgery and restart full-dose LMWH

B. Proceed with prophylactic-dose LMWH

C. Proceed after giving a full therapeutic dose

D. Insert a filter and give DVT prophylaxis

Dr. Cohn: A bridging protocol should have been discussed with the surgeon and anesthesiologist before the procedure. Therapeutic levels of LMWH persist as long as 18 hours after discontinuation; therefore, the ACCP recommends interrupting LMWH 24 hours before surgery.⁴

Dr. Sweitzer: The lack of a bridging protocol in this case created a problem. The patient was afraid to continue anticoagulation after hearing the internist and surgeon disagree about the plan, and thus stopped it entirely, and he did not want to delay surgery because he was fearful of metastasis. The surgeon was adamant that IVC filters don’t work. The internist was concerned that the patient was at high risk for a PE. Even though the documented risk of postponing radical prostatectomy for a short time is inconsequential, I was convinced that the patient would not believe this if metastasis were to develop in the future.

Question 1.4: How would you have managed his anticoagulation perioperatively?

A. Stop LMWH 12 hours before surgery and restart at full dose 12 to 24 hours after surgery

B. Stop LMWH 24 hours before surgery and restart at full dose 24 hours after surgery

C. Stop LMWH 24 hours before surgery and restart prophylactic dosing 12 to 24 hours after surgery, and then full-dose LMWH in 48 to 72 hours

D. Stop LMWH 24 hours before surgery and restart at full dose 72 hours after surgery

Dr. Cohn: The correct timing for stopping LMWH is 24 hours before surgery. As for how to resume anticoagulation in patients at high risk for VTE or those undergoing major surgery, the latest ACCP guidelines recommend the following⁴:

• Reinitiation of anticoagulation 12 to 24 hours postoperatively, assuming adequate hemostasis in patients not at high risk for bleeding
• Use of a prophylactic dose or no anticoagulation for up to 72 hours if the patient is at high risk for bleeding.

These recommendations are a departure from previous practice, in which we routinely restarted anticoagulation 6 to 12 hours postoperatively.

Dr. Sweitzer: According to guidelines from the American Society of Regional Anesthesia and Pain Medicine (ASRA),⁵ if twice-daily LMWH is stopped 24 hours ahead of time (as long as patients have normal renal function), it is safe to perform epidural or spinal anesthesia, if either is an option. If full-dose UFH is used, the partial thrombo­plastin time (PTT) is monitored and central neuraxial blockade may be done if the PTT is in the normal range, which typically is 2 to 6 hours after UFH is stopped.

Additionally, the platelet count should be checked every 3 days postoperatively while the patient is on UFH or LMWH. It may be just as important to monitor the platelet count preoperatively if the patient has been on UFH or LMWH for an extended duration, especially if a central neuraxial anesthetic technique is planned.

Dr. Cohn: The reason for monitoring the platelet count is the potential for heparin-induced thrombocytopenia in patients on UFH. I recently encountered a patient who developed postoperative heparin-induced thrombo­cytopenia with thrombosis while on LMWH, which is relatively uncommon compared with UFH.

Case resolution

After much discussion of the risk of a significant PE with the patient, family, urologist, and vascular surgeon, it is decided that a temporary IVC filter will be placed in the operating room immediately after induction of general anesthesia and before the prostatectomy. The operation is delayed about 1 hour to allow this option. The patient is successfully treated and has the IVC filter removed 1 month postoperatively.

 

 

CASE 2: RADICAL CYSTECTOMY IN ELDERLY MAN WITH CARDIAC RISK FACTORS

A 78-year-old obese Russian-speaking man is seen in the preoperative clinic prior to a scheduled radical cystectomy for highly invasive bladder cancer. He is a poor historian and argues with the several family members accompanying him, but it is determined that his medical history includes hypertension, diabetes mellitus, a myocardial infarction (MI) 5 years previously (in Russia), and stable angina that is determined to be class II.

He had no previous work-up and no electrocardiogram (ECG). His medications are aspirin, metoprolol, and metformin. His blood pressure is 190/100 mm Hg, heart rate 90 beats per minute, and body mass index 32. On examination, there is no murmur, S3 gallop, or rales. His blood glucose is 220 mg/dL, and his creatinine is slightly elevated (1.4 mg/dL). ECG verifies a prior MI.

Question 2.1: Which of the following additional tests should be ordered preoperatively?

A. Hemoglobin (Hb) A_1c

B. Lipid profile

C. Both

D. Neither

Dr. Sweitzer: Because the surgery is not elective, no immediate benefit would be achieved by ordering either an HbA_1c or a lipid profile. However, if you view the preoperative evaluation as an opportunity to manage risk factors over the long term, then it may be a good idea to order the lipid profile because this patient has rarely engaged the health care system. Likewise, the HbA_1c can be ordered to set in place his long-term management. Sometimes we focus on the preoperative visit only in the context of the surgery, but if a test or intervention is appropriate and needed for long-term management, then it is appropriate to do now.

Dr. Cohn: There is no evidence to support using the preoperative HbA_1c to alter management decisions. I would not postpone surgery based on the HbA_1c value, as I would if his glucose level were 600 mg/dL. Most of the studies that have assessed postoperative complications based on preoperative HbA_1c did not control for postoperative glucose levels. The incidence of complications varies based on the type of complication and the type of surgery.

Similarly, I would not use lipid values to guide management of this patient. Studies suggest that perioperative statin therapy may reduce postoperative morbidity and mortality in patients undergoing vascular surgery (see article by Poldermans on page S79 of this supplement), but our patient already has indications for a statin—a remote MI and diabetes—independent of what his lipid values are.

Question 2.2: How would you manage his elevated blood pressure (190/100 mm Hg)?

A. Discontinue metoprolol and start a different antihypertensive drug

B. Increase the metoprolol dose

C. Continue metoprolol and add a second drug

D. Observe him on his current regimen

Dr. Cohn: I would increase the dose of metoprolol and consider adding another drug, in view of his heart rate (90 beats per minute) and his cardiac status. Beta-blocker therapy should not be discontinued because doing so in the perioperative period is associated with an increased risk of adverse events such as cardiac death and MI.

Dr. Sweitzer: I would push up the metoprolol a bit to reduce the heart rate, knowing that beta-blockers are probably not the most efficacious antihypertensive agents. I would caution against starting an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) because he is scheduled to undergo a fairly significant procedure with expected blood loss and fluid shifts, and either of those agents in combination with a beta-blocker would be challenging to manage on the day of surgery.

Question 2.3: How would you manage his metformin perioperatively?

A. Discontinue it 48 hours preoperatively

B. Discontinue it 24 hours preoperatively

C. Withhold it on the morning of surgery

D. Continue it on the morning of surgery

Dr. Sweitzer: We routinely advise patients to hold all their oral diabetes medications the morning of surgery, primarily because many anesthesiologists are uncertain about the differing risks of hypoglycemia associated with the various oral agents.

Most of us will never see a patient who has lactic acidosis from metformin use. A systematic literature review and analysis found no increase in the risk of lactic acidosis with metformin compared with other oral hypoglycemics,⁶ so fear of lactic acidosis is not a valid reason to discontinue metformin. In fact, I think it is inappropriate to ever postpone or cancel surgery simply because the patient inadvertently took metformin on the morning of surgery. Some may argue that patients with renal insufficiency are at higher risk of lactic acidosis from metformin use on the morning of surgery, but keep in mind that renal insufficiency is a relative contra­indication to metformin use in the first place. Unless the patient is scheduled for a bilateral nephrectomy, his or her renal function is not going to be acutely reduced enough to enable a morning dose of metformin to cause lactic acidosis.

Dr. Cohn: Additionally, in a recent study of patients undergoing coronary artery bypass graft surgery (CABG), there was no increased risk of in-hospital morbidity or mortality in patients who received metformin on the morning of surgery,⁷ although I typically stop it 24 hours before major surgery.

Question 2.4: With respect to statin therapy, which course would you choose preoperatively?

A. Start a statin at a low dose

B. Start a statin at an intermediate dose

C. Start a statin at a high dose

D. Do not start a statin

Dr. Cohn: The answer to this question is not clear cut. The reason not to start a prophylactic statin would be the lack of evidence of benefit in patients undergoing noncardiac, nonvascular surgery, although there is evidence of potential benefit in patients undergoing vascular surgery.* The arguments in favor of starting a statin are that this patient has independent indications for a statin and the planned surgery is a high-risk procedure.

(* Editor’s note: In the time since this summit, results of the DECREASE-IV trial were published [Dunkelgrun et al, Ann Surg 2009; 249:921–926], showing a statisically nonsignificant trend toward improved outcomes at 30 days with fluvastatin in intermediate-risk patients undergoing noncardiovascular surgery.)

In cohort studies, perioperative death rates have been lower in statin recipients than in those not taking a statin.⁸ In the Dutch Echographic Cardiac Risk Evaluation Applying Stress Echo III (DECREASE III), which randomized noncardiac vascular surgery patients to perioperative fluvastatin or placebo, rates of MI and the composite end point of nonfatal MI or cardiovascular death were significantly lower in the statin group than in the placebo group.⁹

Question 2.5: Which of the following cardiac tests would you order preoperatively?

A. Exercise ECG

B. Dobutamine stress echocardiogram

C. Dipyridamole nuclear imaging

D. Coronary angiography

E. No further cardiac testing

Dr. Cohn: I wouldn’t do any cardiac testing since this patient needs surgery for his malignancy and the results of any testing would be highly unlikely to change management, in terms of canceling the surgery. This approach is consistent with the 2007 guidelines on perioperative cardiovascular evaluation for noncardiac surgery issued by the American College of Cardiology (ACC) and the American Heart Association (AHA).¹⁰

Dr. Sweitzer: I would differ on this question. This patient has not been evaluated adequately for his coronary artery disease. He has poor functional capacity that complicates assessment of his symptoms. He also has diabetes, so he is more likely to have silent myocardial ischemia. At age 78, he is understandably concerned about his survival: radical cystectomy is a major operation associated with significant blood loss, fluid shifts, and a long-term recuperative state. In this case, a cardiac evaluation may change management, not in terms of considering coronary revascularization before the surgery, but in terms of affecting the assessment of his chance of surviving this major operation, his life span following the operation, and his quality of life. For example, a highly positive dobutamine stress echo­cardiogram or certain wall motion abnormalities would suggest that he might not be protected even by optimal perioperative medical management.

Question 2.6: Which of the following would you do pre­operatively to assess pulmonary risk?

A. Obtain pulmonary function tests

B. Order a sleep study

C. Both

D. Neither

Dr. Sweitzer: There is no evidence supporting routine pulmonary function tests for patients undergoing procedures other than lung resection. If obstructive sleep apnea were suspected, I would order a sleep study only if I had access to one quickly to avoid delaying the surgery. Cancer surgery should never be delayed to get a sleep study. However, if this patient were seen in the primary care clinic, I would order a sleep study and, if indicated, put him on continuous positive airway pressure (CPAP). Whether or not preoperative CPAP makes a difference hasn’t been shown. No randomized controlled trials have been conducted, but there are some suggestions that the risks of ischemia and atrial arrhythmias in patients with known coronary artery disease can be reduced with CPAP. It is not always easy to initiate CPAP postoperatively because the number of CPAP machines is limited and titration by a respiratory technician is required, which is typically done in a sleep lab.

How the case was actually managed

Neither an HbA_1c measurement nor a lipid profile was ordered preoperatively, for lack of supportive evidence. The patient was continued on his beta-blocker and the dosage was increased sufficiently to control his blood pressure and heart rate. Metformin was continued, and statin therapy was begun preoperatively in light of the patient’s independent indications for it and the high-risk nature of the procedure. Stress testing was not ordered, in light of the lack of indication, given the patient’s stable angina. The patient refused a sleep study. The operation was lengthy and involved significant blood loss. The patient had a complicated postoperative course and ultimately died from multiorgan failure.

 

 

CASE 3: OPERATIONS OF VARIABLE RISK IN ELDERLY MAN WITH ACTIVE CARDIAC CONDITION

Scenario A: A 75-year-old man with diabetes, class III angina, and Q waves in inferior leads on his ECG is scheduled for elective femoropopliteal bypass surgery. His medications include isosorbide mononitrate (120 mg), amlodipine (10 mg), metoprolol controlled release (100 mg), atorvastatin (80 mg), insulin, and aspirin (81 mg). His heart rate is 64 beats per minute, blood pressure is controlled at 120/80 mm Hg, low-density lipoprotein cholesterol is 80 mg/dL, and creatinine is 1.5 μmol/L.

Scenario B: Consider the same patient undergoing elective cholecystectomy instead of a femoropopliteal bypass.

Scenario C: Consider the same patient scheduled for a cystoscopy instead of the other procedures. He had one episode of gross hematuria 1 week ago that resolved. Work-up by his urologist included a urinalysis and culture that were normal, cytology that was negative for malignancy, and a sonogram and computed tomography scan that were both negative. He has had no further bleeding and is not anemic. The urologist wants to do the cystoscopy for the sake of completeness.

Question 3.1: What would be your preoperative course of action in the above scenarios?

A. Order a dobutamine stress echocardiogram

B. Order nuclear imaging with dipyridamole or adenosine

C. Order coronary angiography

D. Order a resting two-dimensional echocardiogram

E. Continue his current medications and send to surgery with no further testing

Dr. Cohn: This is a man with an active cardiac condition and class III angina, which is considered severe angina in the ACC/AHA 2007 guidelines on peri­operative cardiac evaluation and care.¹⁰ The guidelines’ recommendation is to delay surgery for further evaluation and treatment. He is already on maximal medical therapy, which has failed to control his symptoms. He has poor exercise capacity. The only difference among the case scenarios is a variation in surgical risk.

This patient has independent indications for coronary angiography regardless of whether or not he’s undergoing surgery. He deserves evaluation for possible revascularization to improve his quality of life and symptoms.

I would send the patient to the catheterization lab in every one of these instances, with the possible exception of the cystoscopy scenario, where one could argue that revascularization with stenting would require antiplatelet therapy that might increase the bleeding risk, and also that the antiplatelet therapy would have to be interrupted for the cystoscopy, potentially increasing thrombotic risk.

Dr. Sweitzer: I disagree. The ACC/AHA 2007 guidelines do not recommend going directly to catheterization but rather recommend delaying surgery for further evaluation and treatment.¹⁰ We must ask whether this patient is truly receiving optimal medical management. After all, he is not on an ACE inhibitor or an ARB.

We must also consider whether the surgery is truly elective. In the first scenario, if he has peripheral vascular disease, he is likely to develop gangrene and have a further decrease in exercise capacity, which reduces his functional ability and increases his risk of comorbid conditions. He is at significant risk of developing worsening renal insufficiency or renal failure if he undergoes angiography. Coronary revascularization will delay treatment of his peripheral vascular disease. The Coronary Artery Revascularization Prophylaxis (CARP) trial showed no benefit of coronary revascularization relative to medical management in patients undergoing vascular surgery,¹¹ as is planned for this patient. I believe one must balance two competing risks and have an in-depth discussion with the patient.

In the second scenario, not treating gallstones or preventing cholelithiasis poses more risk to the health of this diabetic patient than does elective surgery if he needs a cholecystectomy. Emergency surgery, especially for acute cholecystitis, also significantly increases the risk of a cardiac event.

In the third scenario, the cystoscopy may uncover bladder cancer, which may be adversely affected by a delay of surgery. Regardless, the patient had gross hematuria and would be at risk for further bleeding should he undergo stenting with the requisite antiplatelet therapy.

Catheterization is not normally recommended unless CABG or stenting is being considered, yet I have seen no data that either of these procedures prolongs life except in very limited circumstances such as left main disease treated with bypass grafting. Though it is true that CABG reduces the incidence and severity of angina, it does not modify the physiologic cause of angina but rather may result in symptom improvement by damaging somatic nerve fibers to the heart. Putting a stent in this patient would be like applying a bandage: his symptoms will likely recur if he does not receive optimal medical management.

In a 2007 science advisory, several major medical societies cautioned against percutaneous coronary intervention (PCI) with drug-eluting stent placement in patients expected to undergo noncardiac surgery that would require interruption of antiplatelet therapy in the following 12 months (and against PCI with bare metal stent placement in patients undergoing such surgery in the following 4 to 6 weeks).¹² Therefore, I would not recommend catheterization for a patient whose noncardiac disease is likely to require surgery in the very near future, as is the case in each of the surgical scenarios above. One could consider noninvasive stress testing, which would be a safer approach and would almost certainly identify either significant stenosis of the left main coronary artery or three-vessel disease, which would be the only possible reasons to recommend CABG. I don’t believe there is any role for PCI for this patient.

Dr. Cohn: I argue for symptom relief even if it doesn’t prolong life. This patient cannot walk across the room without having symptoms despite taking multiple medications. I think he deserves a chance at revascularization if the angiogram shows he has a stenosis amenable to it, but I agree that a drug-eluting stent should not be placed if we know that he will undergo surgery within a few months.

 

 

CASE 4: VENTRAL HERNIA REPAIR IN A MIDDLE-AGED WOMAN

A 60-year-old woman is scheduled for ventral hernia repair. Her medical history is unremarkable, with the exception of hypertension. She denies any bleeding problems and had no complications after a laparoscopic cholecystectomy 10 years ago. She has no family history of bleeding disorders.

Question 4.1: Would you order a prothrombin time (PT)/partial thromboplastin time (PTT)?

A. Yes

B. No

Dr. Cohn: I would not.

Dr. Sweitzer: I agree.

Question 4.2: Although not requested, a PT/PTT was ordered anyway. The PT is normal (12.2 sec/12 sec) and the PTT is abnormal (40 sec/25 sec). What is the most likely cause of the PTT abnormality?

A. Laboratory error

B. Factor VII deficiency

C. Factor IX deficiency

D. Factor XI deficiency

E. Factor XII deficiency

Dr. Cohn: The most likely cause is a sample with insufficient blood in the tube. The test wasn’t indicated in the first place, but now it must be done again.

Question 4.3: The PTT is repeated and remains abnormal: 42 sec/25 sec. Mixing studies correct the abnormality to 29 sec/25 sec. Based on this information, what is the most likely cause of the PTT abnormality?

A. Laboratory error

B. Lupus anticoagulant

C. Prekallikrein factor deficiency

D. Factor XII deficiency

Dr. Cohn: This is not a case of lupus anticoagulant because the abnormal PTT was corrected by the mixing study. Causes of a prolonged PTT include deficiencies of factors XII, XI, and IX, so factor XII deficiency is the most likely explanation, though a deficiency higher up the coagulation cascade (ie, prekallikrein factor deficiency) is possible. In the absence of any personal or family bleeding history, it is unlikely to be a deficiency of factors VII or IX (the hemophiliac) or of factor XI, so a deficiency of factor XII or one of the prekallikrein factors is more likely.

Dr. Sweitzer: A mixing study is indeed the appropriate first step. It is ordered from the lab and involves mixing the patient’s blood with normal plasma and incubating the mixture. If the mixture corrects the PTT result, as was the case with this patient, it indicates a coagulation factor deficiency in the patient’s blood; if it doesn’t correct, that should prompt evaluation for lupus anticoagulant or the presence of some other protein or hormone that’s prolonging the PTT.

Question 4.4: How would you manage this patient perioperatively?

A. Fresh frozen plasma

B. Platelet transfusion

C. Cryoprecipitate

D. Factor VII

E. No treatment necessary

Dr. Cohn: No treatment is necessary. Factor XII deficiency does not cause bleeding, regardless of the PTT. Factor XI deficiency is associated with bleeding, but usually there is a family history or a personal history of bleeding with surgery.

Screening coagulation studies are not usually indicated in a patient without a personal or family history of bleeding, liver disease, alcohol or drug use, or current anticoagulant therapy. Such studies are usually normal in such patients, and when they are not, it’s usually because of a lab error or a disease (hypercoagulable state) or factor deficiency that does not cause bleeding

Dr. Sweitzer: However, if the PTT is prolonged, the cause should be identified, because if the patient is sent to the operating room without an explanation for the prolongation, the perioperative team might think the patient has a bleeding problem and use fresh frozen plasma too readily. Fresh frozen plasma is not appropriate for everyone and may actually make a potentially hypercoagulable state worse.

 

 

DISCUSSION

Question from the audience: It was said that use of ACE inhibitors and ARBs should be avoided around the time of surgery. I’ve done an extensive literature search and found minimal to no evidence to support this practice. To the contrary, I found fairly good evidence to indicate that heart failure can be exacerbated significantly and acutely, as early as within 24 hours, when patients are taken off their ACE inhibitor or ARB. I would like your viewpoint on this basic pathology in perioperative medicine.

Dr. Cohn: The literature on the use of ACE inhibitors or ARBs prior to noncardiac surgery consists of five studies with fewer than 500 patients in total, as recently reviewed by Rosenman et al.¹³ Although there was no excess of death or MI associated with taking these medications on the morning of surgery, they did increase the need for fluid and pressors.

Dr. Sweitzer: Patients with hypertension have bigger variations of blood pressure, both hypo- and hypertension, in the perioperative period. For this reason, it was standard of care 30 years ago to stop all antihypertensive drugs, including beta-blockers, preoperatively. We soon found that although this practice prevented many episodes of hypotension, it increased the occurrence of perioperative hypertension and the likelihood of cardiac events. It then became standard of care to always continue antihypertensive drugs on the morning of surgery. In the late 1980s and early 1990s, several studies showed that ACE inhibitors and ARBs were associated with a more profound drop in blood pressure upon induction of general anesthesia compared with other antihypertensives.

The usual ways we treat drops in blood pressure—with phenylephrine and ephedrine—are not very effective in treating hypotension associated with general anesthesia in patients taking ACE inhibitors or ARBs. Vasopressin is effective in treating refractory hypotension during surgery, but anesthesiologists don’t use it often. Reducing the doses of induction agents is another means of attenuating the hypotension induced by ACE inhibitors and ARBs.

We should not routinely stop ACE inhibitors and ARBs on the day of surgery, particularly in patients being treated for heart failure, angina, or a prior MI. My bias is to selectively hold ACE inhibitors and ARBs on the morning of surgery in patients who are undergoing a significant operation with a high likelihood of hypotension, have well-controlled preoperative blood pressure, are taking multiple antihypertensive agents, and do not have heart failure. Otherwise, patients should continue their ACE inhibitors and ARBs on the morning of surgery, and the anesthesiologist should be prepared for significant hypotension upon induction of anesthesia, alter anesthesia induction doses accordingly, have vasopressin handy, and avoid the temptation to treat hypotension with fluids or repeated doses of phenylephrine and ephedrine. The previous comment about concerns with ACE inhibitors and ARBs was in the context of initiating new therapies in the immediate preoperative period.

Question from the audience: Urinalysis is ordered for many patients undergoing orthopedic surgery, and invariably some bacteriuria is found. Can you comment on the value of urinalysis and subsequent treatment of abnormal results?

Dr. Cohn: I believe you should never order a urinalysis in an asymptomatic patient, with the exception of patients undergoing procedures that involve genitourinary or gynecologic instrumentation. Ordering a urinalysis before joint replacement has been promoted in the orthopedic literature on the theoretical grounds that bacteria might somehow seed and colonize the joint. Orthopedic surgeons like to do it, but I disregard their requests for it.

Dr. Sweitzer: One study showed that we’d need to spend $1.5 million on screening urinalysis for asymptomatic patients scheduled for joint replacement surgery in order to prevent one joint infection.¹⁴

Dr. Cohn: Also, patients are going to get their one dose of cephalosporin before surgery anyway, and that will probably knock out any bacteria that would be found on urinalysis.

Question from the audience: Can you clarify how the 2007 ACC/AHA perioperative guidelines define an active cardiac condition? The patient in your third case report had class III angina, or angina with less than usual activities, but nothing was presented to suggest that his symptoms were unstable. I would suggest that despite his class III symptoms, his angina was stable, and I would have continued down the algorithm rather than defining his cardiac condition as active and considering an intervention.

Dr. Cohn: An active cardiac condition is defined by the ACC as unstable coronary syndromes, which include acute (within the prior 7 days) or recent (within the prior 30 days) MI, unstable angina, and severe (class III or IV) angina.

CASE 1: RADICAL PROSTATECTOMY IN A MAN WITH ACUTE DEEP VEIN THROMBOSIS

A 69-year-old man is seen in the preoperative clinic 1 week before a scheduled radical prostatectomy. He has been diagnosed with femoral deep vein thrombosis (DVT) following a complaint of calf soreness.

Question 1.1: How would you treat him for his DVT?

A. Intravenous (IV) unfractionated heparin (UFH)

B. Low-molecular-weight heparin (LMWH)

C. Inferior vena cava (IVC) filter

D. Combination of pharmacologic therapy and then an IVC filter

Dr. Steven L. Cohn: The latest edition of the American College of Chest Physicians (ACCP) evidence-based guidelines on antithrombotic therapy recommends the use of therapeutic-dose subcutaneous LMWH over IV UFH for initial treatment of acute DVT in the outpatient or inpatient setting.¹ Additionally, indications for an IVC filter include the prevention of pulmonary embolism (PE) in a patient with DVT who requires full-dose anticoagulation but cannot receive it, as would be the case here if the patient proceeds with surgery as scheduled. So if surgery will be postponed, the best option is LMWH; if surgery will not be postponed, the best answer is a combination of pharmacologic therapy with low-dose LMWH and an IVC filter, preferably a retrievable one.²

Question 1.2: You recommend postponing surgery, but the patient is worried about metastatic disease. For how long should surgery be postponed?

A. 2 weeks

B. 1 month

C. 2 months

D. 3 months

E. 6 months

Dr. Cohn: In the absence of anticoagulation therapy, the risk of venous thromboembolism (VTE) is approximately 40% (~1% per day) during the first month following an acute VTE and then declines markedly, to approximately 10%, during the second and third months following the acute event.³ Therefore, I would suggest that the patient wait at least 1 month after an acute DVT before undergoing surgery.

Dr. BobbieJean Sweitzer: This patient is in a hypercoagulable state, and the surgery itself will induce excess hypercoagulability. With a femoral DVT already present, his risk of VTE or PE is likely to be greater than 1% per day during the first month. If he does develop a PE, it may potentially be fatal.

Question 1.3: According to the patient, the surgeon and the internist discussed options, but the surgeon “doesn’t believe in filters” and the patient doesn’t want to postpone the procedure, despite your recommendation. Two weeks later he shows up for surgery having stopped his LMWH 3 days before. What would you do?

A. Cancel the surgery and restart full-dose LMWH

B. Proceed with prophylactic-dose LMWH

C. Proceed after giving a full therapeutic dose

D. Insert a filter and give DVT prophylaxis

Dr. Cohn: A bridging protocol should have been discussed with the surgeon and anesthesiologist before the procedure. Therapeutic levels of LMWH persist as long as 18 hours after discontinuation; therefore, the ACCP recommends interrupting LMWH 24 hours before surgery.⁴

Dr. Sweitzer: The lack of a bridging protocol in this case created a problem. The patient was afraid to continue anticoagulation after hearing the internist and surgeon disagree about the plan, and thus stopped it entirely, and he did not want to delay surgery because he was fearful of metastasis. The surgeon was adamant that IVC filters don’t work. The internist was concerned that the patient was at high risk for a PE. Even though the documented risk of postponing radical prostatectomy for a short time is inconsequential, I was convinced that the patient would not believe this if metastasis were to develop in the future.

Question 1.4: How would you have managed his anticoagulation perioperatively?

A. Stop LMWH 12 hours before surgery and restart at full dose 12 to 24 hours after surgery

B. Stop LMWH 24 hours before surgery and restart at full dose 24 hours after surgery

C. Stop LMWH 24 hours before surgery and restart prophylactic dosing 12 to 24 hours after surgery, and then full-dose LMWH in 48 to 72 hours

D. Stop LMWH 24 hours before surgery and restart at full dose 72 hours after surgery

Dr. Cohn: The correct timing for stopping LMWH is 24 hours before surgery. As for how to resume anticoagulation in patients at high risk for VTE or those undergoing major surgery, the latest ACCP guidelines recommend the following⁴:

• Reinitiation of anticoagulation 12 to 24 hours postoperatively, assuming adequate hemostasis in patients not at high risk for bleeding
• Use of a prophylactic dose or no anticoagulation for up to 72 hours if the patient is at high risk for bleeding.

These recommendations are a departure from previous practice, in which we routinely restarted anticoagulation 6 to 12 hours postoperatively.

Dr. Sweitzer: According to guidelines from the American Society of Regional Anesthesia and Pain Medicine (ASRA),⁵ if twice-daily LMWH is stopped 24 hours ahead of time (as long as patients have normal renal function), it is safe to perform epidural or spinal anesthesia, if either is an option. If full-dose UFH is used, the partial thrombo­plastin time (PTT) is monitored and central neuraxial blockade may be done if the PTT is in the normal range, which typically is 2 to 6 hours after UFH is stopped.

Additionally, the platelet count should be checked every 3 days postoperatively while the patient is on UFH or LMWH. It may be just as important to monitor the platelet count preoperatively if the patient has been on UFH or LMWH for an extended duration, especially if a central neuraxial anesthetic technique is planned.

Dr. Cohn: The reason for monitoring the platelet count is the potential for heparin-induced thrombocytopenia in patients on UFH. I recently encountered a patient who developed postoperative heparin-induced thrombo­cytopenia with thrombosis while on LMWH, which is relatively uncommon compared with UFH.

Case resolution

After much discussion of the risk of a significant PE with the patient, family, urologist, and vascular surgeon, it is decided that a temporary IVC filter will be placed in the operating room immediately after induction of general anesthesia and before the prostatectomy. The operation is delayed about 1 hour to allow this option. The patient is successfully treated and has the IVC filter removed 1 month postoperatively.

 

 

CASE 2: RADICAL CYSTECTOMY IN ELDERLY MAN WITH CARDIAC RISK FACTORS

A 78-year-old obese Russian-speaking man is seen in the preoperative clinic prior to a scheduled radical cystectomy for highly invasive bladder cancer. He is a poor historian and argues with the several family members accompanying him, but it is determined that his medical history includes hypertension, diabetes mellitus, a myocardial infarction (MI) 5 years previously (in Russia), and stable angina that is determined to be class II.

He had no previous work-up and no electrocardiogram (ECG). His medications are aspirin, metoprolol, and metformin. His blood pressure is 190/100 mm Hg, heart rate 90 beats per minute, and body mass index 32. On examination, there is no murmur, S3 gallop, or rales. His blood glucose is 220 mg/dL, and his creatinine is slightly elevated (1.4 mg/dL). ECG verifies a prior MI.

Question 2.1: Which of the following additional tests should be ordered preoperatively?

A. Hemoglobin (Hb) A_1c

B. Lipid profile

C. Both

D. Neither

Dr. Sweitzer: Because the surgery is not elective, no immediate benefit would be achieved by ordering either an HbA_1c or a lipid profile. However, if you view the preoperative evaluation as an opportunity to manage risk factors over the long term, then it may be a good idea to order the lipid profile because this patient has rarely engaged the health care system. Likewise, the HbA_1c can be ordered to set in place his long-term management. Sometimes we focus on the preoperative visit only in the context of the surgery, but if a test or intervention is appropriate and needed for long-term management, then it is appropriate to do now.

Dr. Cohn: There is no evidence to support using the preoperative HbA_1c to alter management decisions. I would not postpone surgery based on the HbA_1c value, as I would if his glucose level were 600 mg/dL. Most of the studies that have assessed postoperative complications based on preoperative HbA_1c did not control for postoperative glucose levels. The incidence of complications varies based on the type of complication and the type of surgery.

Similarly, I would not use lipid values to guide management of this patient. Studies suggest that perioperative statin therapy may reduce postoperative morbidity and mortality in patients undergoing vascular surgery (see article by Poldermans on page S79 of this supplement), but our patient already has indications for a statin—a remote MI and diabetes—independent of what his lipid values are.

Question 2.2: How would you manage his elevated blood pressure (190/100 mm Hg)?

A. Discontinue metoprolol and start a different antihypertensive drug

B. Increase the metoprolol dose

C. Continue metoprolol and add a second drug

D. Observe him on his current regimen

Dr. Cohn: I would increase the dose of metoprolol and consider adding another drug, in view of his heart rate (90 beats per minute) and his cardiac status. Beta-blocker therapy should not be discontinued because doing so in the perioperative period is associated with an increased risk of adverse events such as cardiac death and MI.

Dr. Sweitzer: I would push up the metoprolol a bit to reduce the heart rate, knowing that beta-blockers are probably not the most efficacious antihypertensive agents. I would caution against starting an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) because he is scheduled to undergo a fairly significant procedure with expected blood loss and fluid shifts, and either of those agents in combination with a beta-blocker would be challenging to manage on the day of surgery.

Question 2.3: How would you manage his metformin perioperatively?

A. Discontinue it 48 hours preoperatively

B. Discontinue it 24 hours preoperatively

C. Withhold it on the morning of surgery

D. Continue it on the morning of surgery

Dr. Sweitzer: We routinely advise patients to hold all their oral diabetes medications the morning of surgery, primarily because many anesthesiologists are uncertain about the differing risks of hypoglycemia associated with the various oral agents.

Most of us will never see a patient who has lactic acidosis from metformin use. A systematic literature review and analysis found no increase in the risk of lactic acidosis with metformin compared with other oral hypoglycemics,⁶ so fear of lactic acidosis is not a valid reason to discontinue metformin. In fact, I think it is inappropriate to ever postpone or cancel surgery simply because the patient inadvertently took metformin on the morning of surgery. Some may argue that patients with renal insufficiency are at higher risk of lactic acidosis from metformin use on the morning of surgery, but keep in mind that renal insufficiency is a relative contra­indication to metformin use in the first place. Unless the patient is scheduled for a bilateral nephrectomy, his or her renal function is not going to be acutely reduced enough to enable a morning dose of metformin to cause lactic acidosis.

Dr. Cohn: Additionally, in a recent study of patients undergoing coronary artery bypass graft surgery (CABG), there was no increased risk of in-hospital morbidity or mortality in patients who received metformin on the morning of surgery,⁷ although I typically stop it 24 hours before major surgery.

Question 2.4: With respect to statin therapy, which course would you choose preoperatively?

A. Start a statin at a low dose

B. Start a statin at an intermediate dose

C. Start a statin at a high dose

D. Do not start a statin

Dr. Cohn: The answer to this question is not clear cut. The reason not to start a prophylactic statin would be the lack of evidence of benefit in patients undergoing noncardiac, nonvascular surgery, although there is evidence of potential benefit in patients undergoing vascular surgery.* The arguments in favor of starting a statin are that this patient has independent indications for a statin and the planned surgery is a high-risk procedure.

(* Editor’s note: In the time since this summit, results of the DECREASE-IV trial were published [Dunkelgrun et al, Ann Surg 2009; 249:921–926], showing a statisically nonsignificant trend toward improved outcomes at 30 days with fluvastatin in intermediate-risk patients undergoing noncardiovascular surgery.)

In cohort studies, perioperative death rates have been lower in statin recipients than in those not taking a statin.⁸ In the Dutch Echographic Cardiac Risk Evaluation Applying Stress Echo III (DECREASE III), which randomized noncardiac vascular surgery patients to perioperative fluvastatin or placebo, rates of MI and the composite end point of nonfatal MI or cardiovascular death were significantly lower in the statin group than in the placebo group.⁹

Question 2.5: Which of the following cardiac tests would you order preoperatively?

A. Exercise ECG

B. Dobutamine stress echocardiogram

C. Dipyridamole nuclear imaging

D. Coronary angiography

E. No further cardiac testing

Dr. Cohn: I wouldn’t do any cardiac testing since this patient needs surgery for his malignancy and the results of any testing would be highly unlikely to change management, in terms of canceling the surgery. This approach is consistent with the 2007 guidelines on perioperative cardiovascular evaluation for noncardiac surgery issued by the American College of Cardiology (ACC) and the American Heart Association (AHA).¹⁰

Dr. Sweitzer: I would differ on this question. This patient has not been evaluated adequately for his coronary artery disease. He has poor functional capacity that complicates assessment of his symptoms. He also has diabetes, so he is more likely to have silent myocardial ischemia. At age 78, he is understandably concerned about his survival: radical cystectomy is a major operation associated with significant blood loss, fluid shifts, and a long-term recuperative state. In this case, a cardiac evaluation may change management, not in terms of considering coronary revascularization before the surgery, but in terms of affecting the assessment of his chance of surviving this major operation, his life span following the operation, and his quality of life. For example, a highly positive dobutamine stress echo­cardiogram or certain wall motion abnormalities would suggest that he might not be protected even by optimal perioperative medical management.

Question 2.6: Which of the following would you do pre­operatively to assess pulmonary risk?

A. Obtain pulmonary function tests

B. Order a sleep study

C. Both

D. Neither

Dr. Sweitzer: There is no evidence supporting routine pulmonary function tests for patients undergoing procedures other than lung resection. If obstructive sleep apnea were suspected, I would order a sleep study only if I had access to one quickly to avoid delaying the surgery. Cancer surgery should never be delayed to get a sleep study. However, if this patient were seen in the primary care clinic, I would order a sleep study and, if indicated, put him on continuous positive airway pressure (CPAP). Whether or not preoperative CPAP makes a difference hasn’t been shown. No randomized controlled trials have been conducted, but there are some suggestions that the risks of ischemia and atrial arrhythmias in patients with known coronary artery disease can be reduced with CPAP. It is not always easy to initiate CPAP postoperatively because the number of CPAP machines is limited and titration by a respiratory technician is required, which is typically done in a sleep lab.

How the case was actually managed

Neither an HbA_1c measurement nor a lipid profile was ordered preoperatively, for lack of supportive evidence. The patient was continued on his beta-blocker and the dosage was increased sufficiently to control his blood pressure and heart rate. Metformin was continued, and statin therapy was begun preoperatively in light of the patient’s independent indications for it and the high-risk nature of the procedure. Stress testing was not ordered, in light of the lack of indication, given the patient’s stable angina. The patient refused a sleep study. The operation was lengthy and involved significant blood loss. The patient had a complicated postoperative course and ultimately died from multiorgan failure.

 

 

CASE 3: OPERATIONS OF VARIABLE RISK IN ELDERLY MAN WITH ACTIVE CARDIAC CONDITION

Scenario A: A 75-year-old man with diabetes, class III angina, and Q waves in inferior leads on his ECG is scheduled for elective femoropopliteal bypass surgery. His medications include isosorbide mononitrate (120 mg), amlodipine (10 mg), metoprolol controlled release (100 mg), atorvastatin (80 mg), insulin, and aspirin (81 mg). His heart rate is 64 beats per minute, blood pressure is controlled at 120/80 mm Hg, low-density lipoprotein cholesterol is 80 mg/dL, and creatinine is 1.5 μmol/L.

Scenario B: Consider the same patient undergoing elective cholecystectomy instead of a femoropopliteal bypass.

Scenario C: Consider the same patient scheduled for a cystoscopy instead of the other procedures. He had one episode of gross hematuria 1 week ago that resolved. Work-up by his urologist included a urinalysis and culture that were normal, cytology that was negative for malignancy, and a sonogram and computed tomography scan that were both negative. He has had no further bleeding and is not anemic. The urologist wants to do the cystoscopy for the sake of completeness.

Question 3.1: What would be your preoperative course of action in the above scenarios?

A. Order a dobutamine stress echocardiogram

B. Order nuclear imaging with dipyridamole or adenosine

C. Order coronary angiography

D. Order a resting two-dimensional echocardiogram

E. Continue his current medications and send to surgery with no further testing

Dr. Cohn: This is a man with an active cardiac condition and class III angina, which is considered severe angina in the ACC/AHA 2007 guidelines on peri­operative cardiac evaluation and care.¹⁰ The guidelines’ recommendation is to delay surgery for further evaluation and treatment. He is already on maximal medical therapy, which has failed to control his symptoms. He has poor exercise capacity. The only difference among the case scenarios is a variation in surgical risk.

This patient has independent indications for coronary angiography regardless of whether or not he’s undergoing surgery. He deserves evaluation for possible revascularization to improve his quality of life and symptoms.

I would send the patient to the catheterization lab in every one of these instances, with the possible exception of the cystoscopy scenario, where one could argue that revascularization with stenting would require antiplatelet therapy that might increase the bleeding risk, and also that the antiplatelet therapy would have to be interrupted for the cystoscopy, potentially increasing thrombotic risk.

Dr. Sweitzer: I disagree. The ACC/AHA 2007 guidelines do not recommend going directly to catheterization but rather recommend delaying surgery for further evaluation and treatment.¹⁰ We must ask whether this patient is truly receiving optimal medical management. After all, he is not on an ACE inhibitor or an ARB.

We must also consider whether the surgery is truly elective. In the first scenario, if he has peripheral vascular disease, he is likely to develop gangrene and have a further decrease in exercise capacity, which reduces his functional ability and increases his risk of comorbid conditions. He is at significant risk of developing worsening renal insufficiency or renal failure if he undergoes angiography. Coronary revascularization will delay treatment of his peripheral vascular disease. The Coronary Artery Revascularization Prophylaxis (CARP) trial showed no benefit of coronary revascularization relative to medical management in patients undergoing vascular surgery,¹¹ as is planned for this patient. I believe one must balance two competing risks and have an in-depth discussion with the patient.

In the second scenario, not treating gallstones or preventing cholelithiasis poses more risk to the health of this diabetic patient than does elective surgery if he needs a cholecystectomy. Emergency surgery, especially for acute cholecystitis, also significantly increases the risk of a cardiac event.

In the third scenario, the cystoscopy may uncover bladder cancer, which may be adversely affected by a delay of surgery. Regardless, the patient had gross hematuria and would be at risk for further bleeding should he undergo stenting with the requisite antiplatelet therapy.

Catheterization is not normally recommended unless CABG or stenting is being considered, yet I have seen no data that either of these procedures prolongs life except in very limited circumstances such as left main disease treated with bypass grafting. Though it is true that CABG reduces the incidence and severity of angina, it does not modify the physiologic cause of angina but rather may result in symptom improvement by damaging somatic nerve fibers to the heart. Putting a stent in this patient would be like applying a bandage: his symptoms will likely recur if he does not receive optimal medical management.

In a 2007 science advisory, several major medical societies cautioned against percutaneous coronary intervention (PCI) with drug-eluting stent placement in patients expected to undergo noncardiac surgery that would require interruption of antiplatelet therapy in the following 12 months (and against PCI with bare metal stent placement in patients undergoing such surgery in the following 4 to 6 weeks).¹² Therefore, I would not recommend catheterization for a patient whose noncardiac disease is likely to require surgery in the very near future, as is the case in each of the surgical scenarios above. One could consider noninvasive stress testing, which would be a safer approach and would almost certainly identify either significant stenosis of the left main coronary artery or three-vessel disease, which would be the only possible reasons to recommend CABG. I don’t believe there is any role for PCI for this patient.

Dr. Cohn: I argue for symptom relief even if it doesn’t prolong life. This patient cannot walk across the room without having symptoms despite taking multiple medications. I think he deserves a chance at revascularization if the angiogram shows he has a stenosis amenable to it, but I agree that a drug-eluting stent should not be placed if we know that he will undergo surgery within a few months.

 

 

CASE 4: VENTRAL HERNIA REPAIR IN A MIDDLE-AGED WOMAN

A 60-year-old woman is scheduled for ventral hernia repair. Her medical history is unremarkable, with the exception of hypertension. She denies any bleeding problems and had no complications after a laparoscopic cholecystectomy 10 years ago. She has no family history of bleeding disorders.

Question 4.1: Would you order a prothrombin time (PT)/partial thromboplastin time (PTT)?

A. Yes

B. No

Dr. Cohn: I would not.

Dr. Sweitzer: I agree.

Question 4.2: Although not requested, a PT/PTT was ordered anyway. The PT is normal (12.2 sec/12 sec) and the PTT is abnormal (40 sec/25 sec). What is the most likely cause of the PTT abnormality?

A. Laboratory error

B. Factor VII deficiency

C. Factor IX deficiency

D. Factor XI deficiency

E. Factor XII deficiency

Dr. Cohn: The most likely cause is a sample with insufficient blood in the tube. The test wasn’t indicated in the first place, but now it must be done again.

Question 4.3: The PTT is repeated and remains abnormal: 42 sec/25 sec. Mixing studies correct the abnormality to 29 sec/25 sec. Based on this information, what is the most likely cause of the PTT abnormality?

A. Laboratory error

B. Lupus anticoagulant

C. Prekallikrein factor deficiency

D. Factor XII deficiency

Dr. Cohn: This is not a case of lupus anticoagulant because the abnormal PTT was corrected by the mixing study. Causes of a prolonged PTT include deficiencies of factors XII, XI, and IX, so factor XII deficiency is the most likely explanation, though a deficiency higher up the coagulation cascade (ie, prekallikrein factor deficiency) is possible. In the absence of any personal or family bleeding history, it is unlikely to be a deficiency of factors VII or IX (the hemophiliac) or of factor XI, so a deficiency of factor XII or one of the prekallikrein factors is more likely.

Dr. Sweitzer: A mixing study is indeed the appropriate first step. It is ordered from the lab and involves mixing the patient’s blood with normal plasma and incubating the mixture. If the mixture corrects the PTT result, as was the case with this patient, it indicates a coagulation factor deficiency in the patient’s blood; if it doesn’t correct, that should prompt evaluation for lupus anticoagulant or the presence of some other protein or hormone that’s prolonging the PTT.

Question 4.4: How would you manage this patient perioperatively?

A. Fresh frozen plasma

B. Platelet transfusion

C. Cryoprecipitate

D. Factor VII

E. No treatment necessary

Dr. Cohn: No treatment is necessary. Factor XII deficiency does not cause bleeding, regardless of the PTT. Factor XI deficiency is associated with bleeding, but usually there is a family history or a personal history of bleeding with surgery.

Screening coagulation studies are not usually indicated in a patient without a personal or family history of bleeding, liver disease, alcohol or drug use, or current anticoagulant therapy. Such studies are usually normal in such patients, and when they are not, it’s usually because of a lab error or a disease (hypercoagulable state) or factor deficiency that does not cause bleeding

Dr. Sweitzer: However, if the PTT is prolonged, the cause should be identified, because if the patient is sent to the operating room without an explanation for the prolongation, the perioperative team might think the patient has a bleeding problem and use fresh frozen plasma too readily. Fresh frozen plasma is not appropriate for everyone and may actually make a potentially hypercoagulable state worse.

 

 

DISCUSSION

Question from the audience: It was said that use of ACE inhibitors and ARBs should be avoided around the time of surgery. I’ve done an extensive literature search and found minimal to no evidence to support this practice. To the contrary, I found fairly good evidence to indicate that heart failure can be exacerbated significantly and acutely, as early as within 24 hours, when patients are taken off their ACE inhibitor or ARB. I would like your viewpoint on this basic pathology in perioperative medicine.

Dr. Cohn: The literature on the use of ACE inhibitors or ARBs prior to noncardiac surgery consists of five studies with fewer than 500 patients in total, as recently reviewed by Rosenman et al.¹³ Although there was no excess of death or MI associated with taking these medications on the morning of surgery, they did increase the need for fluid and pressors.

Dr. Sweitzer: Patients with hypertension have bigger variations of blood pressure, both hypo- and hypertension, in the perioperative period. For this reason, it was standard of care 30 years ago to stop all antihypertensive drugs, including beta-blockers, preoperatively. We soon found that although this practice prevented many episodes of hypotension, it increased the occurrence of perioperative hypertension and the likelihood of cardiac events. It then became standard of care to always continue antihypertensive drugs on the morning of surgery. In the late 1980s and early 1990s, several studies showed that ACE inhibitors and ARBs were associated with a more profound drop in blood pressure upon induction of general anesthesia compared with other antihypertensives.

The usual ways we treat drops in blood pressure—with phenylephrine and ephedrine—are not very effective in treating hypotension associated with general anesthesia in patients taking ACE inhibitors or ARBs. Vasopressin is effective in treating refractory hypotension during surgery, but anesthesiologists don’t use it often. Reducing the doses of induction agents is another means of attenuating the hypotension induced by ACE inhibitors and ARBs.

We should not routinely stop ACE inhibitors and ARBs on the day of surgery, particularly in patients being treated for heart failure, angina, or a prior MI. My bias is to selectively hold ACE inhibitors and ARBs on the morning of surgery in patients who are undergoing a significant operation with a high likelihood of hypotension, have well-controlled preoperative blood pressure, are taking multiple antihypertensive agents, and do not have heart failure. Otherwise, patients should continue their ACE inhibitors and ARBs on the morning of surgery, and the anesthesiologist should be prepared for significant hypotension upon induction of anesthesia, alter anesthesia induction doses accordingly, have vasopressin handy, and avoid the temptation to treat hypotension with fluids or repeated doses of phenylephrine and ephedrine. The previous comment about concerns with ACE inhibitors and ARBs was in the context of initiating new therapies in the immediate preoperative period.

Question from the audience: Urinalysis is ordered for many patients undergoing orthopedic surgery, and invariably some bacteriuria is found. Can you comment on the value of urinalysis and subsequent treatment of abnormal results?

Dr. Cohn: I believe you should never order a urinalysis in an asymptomatic patient, with the exception of patients undergoing procedures that involve genitourinary or gynecologic instrumentation. Ordering a urinalysis before joint replacement has been promoted in the orthopedic literature on the theoretical grounds that bacteria might somehow seed and colonize the joint. Orthopedic surgeons like to do it, but I disregard their requests for it.

Dr. Sweitzer: One study showed that we’d need to spend $1.5 million on screening urinalysis for asymptomatic patients scheduled for joint replacement surgery in order to prevent one joint infection.¹⁴

Dr. Cohn: Also, patients are going to get their one dose of cephalosporin before surgery anyway, and that will probably knock out any bacteria that would be found on urinalysis.

Question from the audience: Can you clarify how the 2007 ACC/AHA perioperative guidelines define an active cardiac condition? The patient in your third case report had class III angina, or angina with less than usual activities, but nothing was presented to suggest that his symptoms were unstable. I would suggest that despite his class III symptoms, his angina was stable, and I would have continued down the algorithm rather than defining his cardiac condition as active and considering an intervention.

Dr. Cohn: An active cardiac condition is defined by the ACC as unstable coronary syndromes, which include acute (within the prior 7 days) or recent (within the prior 30 days) MI, unstable angina, and severe (class III or IV) angina.