Clinical Care Conundrums

The approach to clinical conundrums by an expert clinician is revealed through the presentation of an actual patient’s case in an approach typical of a morning report. Similarly to patient care, sequential pieces of information are provided to the clinician, who is unfamiliar with the case. The focus is on the thought processes of both the clinical team caring for the patient and the discussant. The bolded text represents the patient’s case. Each paragraph that follows represents the discussant’s thoughts.

A 75-year-old man was brought by ambulance to the emergency department (ED) after the acute onset of palpitations, lightheadedness, and confusion. His medical history, provided by his wife, included osteoarthritis and remote cholecystectomy. He was not a smoker but drank 2 to 4 cans of beer daily. His medications were aspirin 162 mg daily and naproxen as needed. There was no history of bruising, diarrhea, melena, or bleeding.

Palpitations may represent an arrhythmia arising from an ischemic or alcoholic cardiomyopathy. Mental status changes usually have metabolic, infectious, structural (eg, hemorrhage, tumor), or toxic causes. Lightheadedness and confusion could occur with arrhythmia-associated cerebral hypoperfusion or a seizure. Daily alcohol use could cause confusion through acute intoxication, thiamine or B₁₂ deficiency, repeated head trauma, or liver failure.

The patient’s systolic blood pressure (BP) was 60 mm Hg, heart rate (HR) was 120 beats per minute (bpm), and oral temperature was 98.4°F. Rousing him was difficult. There were no localizing neurologic abnormalities, and the rest of the physical examination findings were normal. Point-of-care blood glucose level was 155 mg/dL. Blood cultures were obtained and broad-spectrum antibiotics initiated. After fluid resuscitation, BP improved to 116/87 mm Hg, HR fell to 105 bpm, and the patient became alert and oriented. He denied chest pain, fever, or diaphoresis.

The patient’s improvement with intravenous (IV) fluids makes cardiogenic shock unlikely but does not exclude an underlying compensated cardiomyopathy that may be predisposing to arrhythmia. Hypotension, tachycardia, and somnolence may represent sepsis, but the near normalization of vital signs and mental status shortly after administration of IV fluids, the normal temperature, and the absence of localizing signs of infection favor withholding additional antibiotics. Other causes of hypotension are hypovolemia, medication effects, adrenal insufficiency, anaphylaxis, and autonomic insufficiency. There was no reported nausea, vomiting, diarrhea, bleeding, polyuria, or impaired oral intake to support hypovolemia, though the response to IV fluids suggests hypovolemia may still be playing a role.

White blood cell (WBC) count was 15,450/µL with a normal differential; hemoglobin level was 15.8 g/dL; and platelet count was 176,000/µL. Electrolytes, liver function tests, cardiac enzymes, and urinalysis were normal. Electrocardiogram showed sinus tachycardia with premature atrial complexes and no ST-segment abnormalities. Radiograph of the chest and computed tomography scan of the head were normal. Echocardiogram showed moderate left ventricular hypertrophy with a normal ejection fraction and no valvular abnormalities. Exercise nuclear cardiac stress test was negative for ischemia. Blood cultures were sterile. The patient quickly became asymptomatic and remained so during his 3-day hospitalization. There were no arrhythmias on telemetry. The patient was discharged with follow-up scheduled with his primary care physician.

The nonlocalizing history and physical examination findings, normal chest radiograph and urinalysis, absence of fevers, negative blood cultures, and quick recovery make infection unlikely, despite the moderate leukocytosis. Conditions that present with acute and transient hypotension and altered mental status include arrhythmias, seizures, and reactions to drugs or toxins. Given the cardiac test results, a chronic cardiomyopathy seems unlikely, but arrhythmia is still possible. Continuous outpatient monitoring is required to assess the palpitations and the frequency of the premature atrial complexes.

Two days after discharge, the patient suddenly became diaphoretic and lost consciousness while walking to the bathroom. He was taken to the ED, where his BP was 90/60 mm Hg and HR was 108 bpm. Family members reported that he had appeared flushed during the syncopal episode, showed no seizure activity, and been unconscious for 15 to 20 minutes. The patient denied chest pain, dyspnea, fever, bowel or bladder incontinence, focal weakness, slurred speech, visual changes, nausea or vomiting either before or after the episode. Physical examination revealed a tongue laceration and facial erythema; all other findings were normal. In the ED, there was an asymptomatic 7-beat run of nonsustained ventricular tachycardia, and the hypotension resolved after fluid resuscitation. The patient now reported 2 similar syncopal episodes in the past. The first occurred in a restaurant 6 years earlier, and the second occurred 3 years later, at which time he was hospitalized and no etiology was found.

The loss of consciousness is attributable to cerebral hypoperfusion. Hypotension has 3 principal categories: hypovolemic, cardiogenic, and distributive. With syncopal episodes recurring over several years, hypovolemia seems unlikely. Given the palpitations and ventricular tachycardia, it is reasonable to suspect a cardiogenic cause. Although his heart appears to be structurally normal on echocardiogram, genetic, electrophysiologic, or magnetic resonance imaging (MRI) testing will occasionally reveal an unsuspected substrate for arrhythmia.

 

The recurring yet self-limited nature, diaphoresis, flushing, and facial erythema suggest a non-sepsis distributive cause of hypotension. It is possible the patient is recurrently exposed to a toxin (eg, alcohol) that causes both flushing and dehydration. Flushing disorders include carcinoid syndrome, pheochromocytoma, drug reaction with eosinophilia and systemic symptoms (DRESS), and mastocytosis. Carcinoid syndrome is characterized by bronchospasm and diarrhea and, in some cases, right-sided valvulopathy, all of which are absent in this patient. Pheochromocytoma is associated with orthostasis, but patients typically are hypertensive at baseline. DRESS, which may arise from nonsteroidal anti-inflammatory drug (NSAID) or aspirin use, can cause facial erythema and swelling but is also characterized by liver, renal, and hematologic abnormalities, none of which was demonstrated. Furthermore, DRESS typically does not cause hypotension. Mastocytosis can manifest as isolated or recurrent anaphylaxis.

It is important to investigate antecedents of these syncopal episodes. If the earlier episodes were food-related—one occurred at a restaurant—then deglutition syncope (syncope precipitated by swallowing) should be considered. If an NSAID or aspirin was ingested before each episode, then medication hypersensitivity or mast cell degranulation (which can be triggered by these medications) should be further examined. Loss of consciousness lasting 20 minutes without causing any neurologic sequelae is unusual for most causes of recurrent syncope. This feature raises the possibility that a toxin or mediator might still be present in the patient’s system.

Serial cardiac enzymes and electrocardiogram were normal. A tilt-table study was negative. The cortisol response to ACTH (cosyntropin) stimulation was normal. The level of serum tryptase, drawn 2 days after syncope, was 18.4 ng/dL (normal, <11.5 ng/dL). Computed tomography scan of chest and abdomen was negative for pulmonary embolism but showed a 1.4×1.3-cm hypervascular lesion in the tail of pancreas. The following neuroendocrine tests were within normal limits: serum and urine catecholamines; urine 5-hydroxyindoleacetic acid (5-HIAA); and serum chromogranin A, insulin, serotonin, vasoactive intestinal polypeptide (VIP), and somatostatin (Table 1). The patient remained asymptomatic during his hospital stay and was discharged home with appointments for cardiology follow-up and endoscopic ultrasound-guided biopsy of the pancreatic mass.

Pheochromocytoma is unlikely with normal serum and urine catecholamine levels and normal adrenal images. The differential diagnosis for a pancreatic mass includes pancreatic carcinoma, lymphoma, cystic neoplasm, and neuroendocrine tumor. All markers of neuroendocrine excess are normal, though elevations can be episodic. The normal 5-HIAA level makes carcinoid syndrome unlikely. VIPomas are associated with flushing, but the absence of profound and protracted diarrhea makes a VIPoma unlikely.

As hypoglycemia from a pancreatic insulinoma is plausible as a cause of episodic loss of consciousness lasting 15 minutes or more, it is important to inquire if giving food or drink helped resolve previous episodes. The normal insulin level reported here is of limited value, because it is the combination of insulin and C-peptide levels at time of hypoglycemia that is diagnostic. The normal glucose level recorded during one of the earlier episodes and the hypotension argue against hypoglycemia.

The elevated tryptase level is an indicator of mast cell degranulation. Tryptase levels are transiently elevated during the initial 2 to 4 hours after an anaphylactic episode and then normalize. An elevated level many hours or days later is considered a sign of mast cell excess. Although there is no evidence of the multi-organ disease (eg, cytopenia, bone disease, hepatosplenomegaly) seen in patients with a high systemic burden of mast cells, mast cell disorders exist on a spectrum. There may be a focal excess of mast cells confined to one organ or an isolated mass.

The same day as discharge, the patient’s wife drove them to the grocery store. He remained in the car while she shopped. When she returned, she found him confused and minimally responsive with subsequent brief loss of consciousness. He was taken to an ED, where he was flushed and hypotensive (systolic BP, 60 mm Hg) and tachycardic. Other examination findings were normal. After fluid resuscitation he became alert and oriented. WBC count was 20,850/μL with 89% neutrophils, hemoglobin level was 14.6 g/dL, and platelet count was 168,000/μL. Serum lactate level was 3.7 mmol/L (normal, <2.3 mmol/L). Chest radiograph was normal. He was treated with broad-spectrum antibiotic therapy and admitted to the hospital. Blood and urine cultures were sterile. Fine-needle aspiration of the pancreatic mass demonstrated nonspecific inflammation. Four days after admission (3 days after pancreatic mass biopsy) the patient developed palpitations, felt unwell, and had marked flushing of the face and trunk, with concomitant BP of 90/50 mm Hg and HR of 140 bpm.

The salient features of this case are recurrent hypotension, tachycardia, and flushing. Autonomic insufficiency, to which elderly patients are prone, causes hemodynamic perturbations but rarely flushing. The patient does not have diabetes mellitus, Parkinson disease, or another condition that puts him at risk for dysautonomia. Pancreatic neuroendocrine tumors secrete mediators that lead to vasodilation and hypotension but are unlikely given the clinical and biochemical data.

 

The patient’s symptoms are consistent with anaphylaxis, though prototypical immunoglobulin E (IgE)–mediated anaphylaxis is usually accompanied by urticaria, angioedema, and wheezing, which have been absent during his presentations. There are no clear food, pharmacologic, or environmental precipitants.

Recurrent anaphylaxis can be a manifestation of mast cell excess (eg, cutaneous or systemic mastocytosis). A markedly elevated tryptase level during an anaphylactic episode is consistent with mastocytosis or IgE-mediated anaphylaxis. An elevated baseline tryptase level days after an anaphylactic episode signals increased mast cell burden. There may be a reservoir of mast cells in the bone marrow. Alternatively, the hypervascular pancreatic mass may be a mastocytoma or a mast cell sarcoma (missed because of inadequate sampling or staining).

The lactic acidosis likely reflects global tissue hypoperfusion from vasodilatory hypotension. The leukocytosis may reflect WBC mobilization secondary to endogenous corticosteroids and catecholamines in response to hypotension or may be a direct response to the release of mast cell–derived mediators of inflammation.

The patient was treated with diphenhydramine and ranitidine. Serum tryptase level was 46.8 ng/mL (normal, <11.5 ng/mL), and 24-hour urine histamine level was 95 µ g/dL (normal, <60 µ g/dL). Bone marrow biopsy results showed multifocal dense infiltrative aggregates of mast cells (>15 cells/aggregate), which were confirmed by CD117 (Kit) and tryptase positivity (Figure). Mutation analysis for Kit Asp816Val, which is present in 80% to 90% of patients with mastocytosis, was positive. He fulfilled the 2008 World Health Organization criteria for systemic mastocytosis (Table 2). Prednisone, histamine inhibitors, and montelukast were prescribed. Six months later, magnetic resonance imaging of the abdomen showed no change in the pancreatic mass, which was now characterized as a possible splenule. The patient had no additional episodes of flushing or syncope over 2 years.

 

DISCUSSION

Cardiovascular collapse (hypotension, tachycardia, syncope) in an elderly patient prompts clinicians to focus on life-threatening conditions, such as acute coronary syndrome, pulmonary embolus, arrhythmia, and sepsis. Each of these diagnoses was considered early in the course of this patient’s presentations, but each was deemed unlikely as it became apparent that the episodes were self-limited and recurrent over years. Incorporating flushing into the diagnostic problem representation allowed the clinicians to focus on a subset of causes of hypotension.

Flushing disorders may be classified by whether they are mediated by the autonomic nervous system (wet flushes, because they are usually accompanied by diaphoresis) or by exogenous or endogenous vasoactive substances (dry flushes).¹ Autonomic nervous system flushing is triggered by emotions, fever, exercise, perimenopause (hot flashes), and neurologic conditions (eg, Parkinson disease, spinal cord injury, multiple sclerosis). Vasoactive flushing precipitants include drugs (eg, niacin); alcohol (secondary to cutaneous vasodilation, or acetaldehyde particularly in people with insufficient acetaldehyde dehydrogenase activity)²; foods that contain capsaicin, tyramine, sulfites, or histamine (eg, eating improperly handled fish can cause scombroid poisoning); and anaphylaxis. Rare causes of vasoactive flushing include carcinoid syndrome, pheochromocytoma, medullary thyroid carcinoma, VIPoma, and mastocytosis.²

Mastocytosis is a rare clonal disorder characterized by the accumulation of abnormal mast cells in the skin (cutaneous mastocytosis), in multiple organs (systemic mastocytosis), or in a solid tumor (mastocytoma). Urticaria pigmentosa is the most common form of cutaneous mastocytosis; it is seen more often in children than in adults and typically is associated with a maculopapular rash and dermatographism. Systemic mastocytosis is the most common form of the disorder in adults.³ Symptoms are related to mast cell infiltration or mast cell mediator–related effects, which range from itching, flushing, and diarrhea to hypotension and anaphylaxis. Other manifestations are fatigue, urticaria pigmentosa, osteoporosis, hepatosplenomegaly, bone pain, cytopenias, and lymphadenopathy.⁴

Systemic mastocytosis can occur at any age and should be considered in patients with recurrent unexplained flushing, syncope, or hypotension. Eighty percent to 90% of patients with systemic mastocytosis have a mutation in Kit,⁵ a transmembrane tyrosine kinase that is the receptor for stem cell factor. The Asp816Val mutation leads to increased proliferation and reduced apoptosis of mast cells.^3,6,7 Proposed diagnostic algorithms^8-11 involve measurement of serum tryptase levels and examination of bone marrow. Bone marrow biopsy and testing for the Asp816Val Kit mutation should be considered in patients with modestly elevated baseline tryptase levels (11.5-20 ng/mL) if clinical findings are consistent with mastocytosis.¹²

The primary goals of treatment are managing mast cell–mediated symptoms and, in advanced cases, achieving cytoreduction. Alcohol can trigger mast cell degranulation in indolent systemic mastocytosis and should be avoided. Mast cell–mediated symptoms are managed with histamine blockers, leukotriene antagonists, and mast cell stabilizers.¹² Targeted therapy with tyrosine kinase inhibitors (eg, imatinib) in patients with transmembrane Kit mutation (eg, Phe522Cys, Lys509Ile) associated with systemic mastocytosis has had promising results.^13,14 However, this patient’s Asp816Val mutation is in the Kit catalytic domain, not the transmembrane region, and therefore would not be expected to respond to imatinib. A recent open-label trial of the multikinase inhibitor midostaurin demonstrated resolution of organ damage, reduced bone marrow burden, and lowered serum tryptase levels in patients with advanced systemic mastocytosis.¹⁵ Interferon, cladribine, and high-dose corticosteroids are prescribed in patients for whom other therapies have been ineffective.⁸

The differential diagnosis is broad for both hypotension and for flushing, but the differential diagnosis for recurrent hypotension and flushing is limited. Recognizing that flushing was an essential feature of this patient’s hypotensive condition, and not an epiphenomenon of syncope, allowed the clinicians to focus on the overlap and make a shocking diagnosis.

 

Acknowledgment

The authors thank David Bosler, MD (Cleveland Clinic) for interpreting the pathology image.

Disclosure

Nothing to report.

The approach to clinical conundrums by an expert clinician is revealed through the presentation of an actual patient’s case in an approach typical of a morning report. Similarly to patient care, sequential pieces of information are provided to the clinician, who is unfamiliar with the case. The focus is on the thought processes of both the clinical team caring for the patient and the discussant. The bolded text represents the patient’s case. Each paragraph that follows represents the discussant’s thoughts.

A 75-year-old man was brought by ambulance to the emergency department (ED) after the acute onset of palpitations, lightheadedness, and confusion. His medical history, provided by his wife, included osteoarthritis and remote cholecystectomy. He was not a smoker but drank 2 to 4 cans of beer daily. His medications were aspirin 162 mg daily and naproxen as needed. There was no history of bruising, diarrhea, melena, or bleeding.

Palpitations may represent an arrhythmia arising from an ischemic or alcoholic cardiomyopathy. Mental status changes usually have metabolic, infectious, structural (eg, hemorrhage, tumor), or toxic causes. Lightheadedness and confusion could occur with arrhythmia-associated cerebral hypoperfusion or a seizure. Daily alcohol use could cause confusion through acute intoxication, thiamine or B₁₂ deficiency, repeated head trauma, or liver failure.

The patient’s systolic blood pressure (BP) was 60 mm Hg, heart rate (HR) was 120 beats per minute (bpm), and oral temperature was 98.4°F. Rousing him was difficult. There were no localizing neurologic abnormalities, and the rest of the physical examination findings were normal. Point-of-care blood glucose level was 155 mg/dL. Blood cultures were obtained and broad-spectrum antibiotics initiated. After fluid resuscitation, BP improved to 116/87 mm Hg, HR fell to 105 bpm, and the patient became alert and oriented. He denied chest pain, fever, or diaphoresis.

The patient’s improvement with intravenous (IV) fluids makes cardiogenic shock unlikely but does not exclude an underlying compensated cardiomyopathy that may be predisposing to arrhythmia. Hypotension, tachycardia, and somnolence may represent sepsis, but the near normalization of vital signs and mental status shortly after administration of IV fluids, the normal temperature, and the absence of localizing signs of infection favor withholding additional antibiotics. Other causes of hypotension are hypovolemia, medication effects, adrenal insufficiency, anaphylaxis, and autonomic insufficiency. There was no reported nausea, vomiting, diarrhea, bleeding, polyuria, or impaired oral intake to support hypovolemia, though the response to IV fluids suggests hypovolemia may still be playing a role.

White blood cell (WBC) count was 15,450/µL with a normal differential; hemoglobin level was 15.8 g/dL; and platelet count was 176,000/µL. Electrolytes, liver function tests, cardiac enzymes, and urinalysis were normal. Electrocardiogram showed sinus tachycardia with premature atrial complexes and no ST-segment abnormalities. Radiograph of the chest and computed tomography scan of the head were normal. Echocardiogram showed moderate left ventricular hypertrophy with a normal ejection fraction and no valvular abnormalities. Exercise nuclear cardiac stress test was negative for ischemia. Blood cultures were sterile. The patient quickly became asymptomatic and remained so during his 3-day hospitalization. There were no arrhythmias on telemetry. The patient was discharged with follow-up scheduled with his primary care physician.

The nonlocalizing history and physical examination findings, normal chest radiograph and urinalysis, absence of fevers, negative blood cultures, and quick recovery make infection unlikely, despite the moderate leukocytosis. Conditions that present with acute and transient hypotension and altered mental status include arrhythmias, seizures, and reactions to drugs or toxins. Given the cardiac test results, a chronic cardiomyopathy seems unlikely, but arrhythmia is still possible. Continuous outpatient monitoring is required to assess the palpitations and the frequency of the premature atrial complexes.

Two days after discharge, the patient suddenly became diaphoretic and lost consciousness while walking to the bathroom. He was taken to the ED, where his BP was 90/60 mm Hg and HR was 108 bpm. Family members reported that he had appeared flushed during the syncopal episode, showed no seizure activity, and been unconscious for 15 to 20 minutes. The patient denied chest pain, dyspnea, fever, bowel or bladder incontinence, focal weakness, slurred speech, visual changes, nausea or vomiting either before or after the episode. Physical examination revealed a tongue laceration and facial erythema; all other findings were normal. In the ED, there was an asymptomatic 7-beat run of nonsustained ventricular tachycardia, and the hypotension resolved after fluid resuscitation. The patient now reported 2 similar syncopal episodes in the past. The first occurred in a restaurant 6 years earlier, and the second occurred 3 years later, at which time he was hospitalized and no etiology was found.

The loss of consciousness is attributable to cerebral hypoperfusion. Hypotension has 3 principal categories: hypovolemic, cardiogenic, and distributive. With syncopal episodes recurring over several years, hypovolemia seems unlikely. Given the palpitations and ventricular tachycardia, it is reasonable to suspect a cardiogenic cause. Although his heart appears to be structurally normal on echocardiogram, genetic, electrophysiologic, or magnetic resonance imaging (MRI) testing will occasionally reveal an unsuspected substrate for arrhythmia.

 

The recurring yet self-limited nature, diaphoresis, flushing, and facial erythema suggest a non-sepsis distributive cause of hypotension. It is possible the patient is recurrently exposed to a toxin (eg, alcohol) that causes both flushing and dehydration. Flushing disorders include carcinoid syndrome, pheochromocytoma, drug reaction with eosinophilia and systemic symptoms (DRESS), and mastocytosis. Carcinoid syndrome is characterized by bronchospasm and diarrhea and, in some cases, right-sided valvulopathy, all of which are absent in this patient. Pheochromocytoma is associated with orthostasis, but patients typically are hypertensive at baseline. DRESS, which may arise from nonsteroidal anti-inflammatory drug (NSAID) or aspirin use, can cause facial erythema and swelling but is also characterized by liver, renal, and hematologic abnormalities, none of which was demonstrated. Furthermore, DRESS typically does not cause hypotension. Mastocytosis can manifest as isolated or recurrent anaphylaxis.

It is important to investigate antecedents of these syncopal episodes. If the earlier episodes were food-related—one occurred at a restaurant—then deglutition syncope (syncope precipitated by swallowing) should be considered. If an NSAID or aspirin was ingested before each episode, then medication hypersensitivity or mast cell degranulation (which can be triggered by these medications) should be further examined. Loss of consciousness lasting 20 minutes without causing any neurologic sequelae is unusual for most causes of recurrent syncope. This feature raises the possibility that a toxin or mediator might still be present in the patient’s system.

Serial cardiac enzymes and electrocardiogram were normal. A tilt-table study was negative. The cortisol response to ACTH (cosyntropin) stimulation was normal. The level of serum tryptase, drawn 2 days after syncope, was 18.4 ng/dL (normal, <11.5 ng/dL). Computed tomography scan of chest and abdomen was negative for pulmonary embolism but showed a 1.4×1.3-cm hypervascular lesion in the tail of pancreas. The following neuroendocrine tests were within normal limits: serum and urine catecholamines; urine 5-hydroxyindoleacetic acid (5-HIAA); and serum chromogranin A, insulin, serotonin, vasoactive intestinal polypeptide (VIP), and somatostatin (Table 1). The patient remained asymptomatic during his hospital stay and was discharged home with appointments for cardiology follow-up and endoscopic ultrasound-guided biopsy of the pancreatic mass.

Pheochromocytoma is unlikely with normal serum and urine catecholamine levels and normal adrenal images. The differential diagnosis for a pancreatic mass includes pancreatic carcinoma, lymphoma, cystic neoplasm, and neuroendocrine tumor. All markers of neuroendocrine excess are normal, though elevations can be episodic. The normal 5-HIAA level makes carcinoid syndrome unlikely. VIPomas are associated with flushing, but the absence of profound and protracted diarrhea makes a VIPoma unlikely.

As hypoglycemia from a pancreatic insulinoma is plausible as a cause of episodic loss of consciousness lasting 15 minutes or more, it is important to inquire if giving food or drink helped resolve previous episodes. The normal insulin level reported here is of limited value, because it is the combination of insulin and C-peptide levels at time of hypoglycemia that is diagnostic. The normal glucose level recorded during one of the earlier episodes and the hypotension argue against hypoglycemia.

The elevated tryptase level is an indicator of mast cell degranulation. Tryptase levels are transiently elevated during the initial 2 to 4 hours after an anaphylactic episode and then normalize. An elevated level many hours or days later is considered a sign of mast cell excess. Although there is no evidence of the multi-organ disease (eg, cytopenia, bone disease, hepatosplenomegaly) seen in patients with a high systemic burden of mast cells, mast cell disorders exist on a spectrum. There may be a focal excess of mast cells confined to one organ or an isolated mass.

The same day as discharge, the patient’s wife drove them to the grocery store. He remained in the car while she shopped. When she returned, she found him confused and minimally responsive with subsequent brief loss of consciousness. He was taken to an ED, where he was flushed and hypotensive (systolic BP, 60 mm Hg) and tachycardic. Other examination findings were normal. After fluid resuscitation he became alert and oriented. WBC count was 20,850/μL with 89% neutrophils, hemoglobin level was 14.6 g/dL, and platelet count was 168,000/μL. Serum lactate level was 3.7 mmol/L (normal, <2.3 mmol/L). Chest radiograph was normal. He was treated with broad-spectrum antibiotic therapy and admitted to the hospital. Blood and urine cultures were sterile. Fine-needle aspiration of the pancreatic mass demonstrated nonspecific inflammation. Four days after admission (3 days after pancreatic mass biopsy) the patient developed palpitations, felt unwell, and had marked flushing of the face and trunk, with concomitant BP of 90/50 mm Hg and HR of 140 bpm.

The salient features of this case are recurrent hypotension, tachycardia, and flushing. Autonomic insufficiency, to which elderly patients are prone, causes hemodynamic perturbations but rarely flushing. The patient does not have diabetes mellitus, Parkinson disease, or another condition that puts him at risk for dysautonomia. Pancreatic neuroendocrine tumors secrete mediators that lead to vasodilation and hypotension but are unlikely given the clinical and biochemical data.

 

The patient’s symptoms are consistent with anaphylaxis, though prototypical immunoglobulin E (IgE)–mediated anaphylaxis is usually accompanied by urticaria, angioedema, and wheezing, which have been absent during his presentations. There are no clear food, pharmacologic, or environmental precipitants.

Recurrent anaphylaxis can be a manifestation of mast cell excess (eg, cutaneous or systemic mastocytosis). A markedly elevated tryptase level during an anaphylactic episode is consistent with mastocytosis or IgE-mediated anaphylaxis. An elevated baseline tryptase level days after an anaphylactic episode signals increased mast cell burden. There may be a reservoir of mast cells in the bone marrow. Alternatively, the hypervascular pancreatic mass may be a mastocytoma or a mast cell sarcoma (missed because of inadequate sampling or staining).

The lactic acidosis likely reflects global tissue hypoperfusion from vasodilatory hypotension. The leukocytosis may reflect WBC mobilization secondary to endogenous corticosteroids and catecholamines in response to hypotension or may be a direct response to the release of mast cell–derived mediators of inflammation.

The patient was treated with diphenhydramine and ranitidine. Serum tryptase level was 46.8 ng/mL (normal, <11.5 ng/mL), and 24-hour urine histamine level was 95 µ g/dL (normal, <60 µ g/dL). Bone marrow biopsy results showed multifocal dense infiltrative aggregates of mast cells (>15 cells/aggregate), which were confirmed by CD117 (Kit) and tryptase positivity (Figure). Mutation analysis for Kit Asp816Val, which is present in 80% to 90% of patients with mastocytosis, was positive. He fulfilled the 2008 World Health Organization criteria for systemic mastocytosis (Table 2). Prednisone, histamine inhibitors, and montelukast were prescribed. Six months later, magnetic resonance imaging of the abdomen showed no change in the pancreatic mass, which was now characterized as a possible splenule. The patient had no additional episodes of flushing or syncope over 2 years.

 

DISCUSSION

Cardiovascular collapse (hypotension, tachycardia, syncope) in an elderly patient prompts clinicians to focus on life-threatening conditions, such as acute coronary syndrome, pulmonary embolus, arrhythmia, and sepsis. Each of these diagnoses was considered early in the course of this patient’s presentations, but each was deemed unlikely as it became apparent that the episodes were self-limited and recurrent over years. Incorporating flushing into the diagnostic problem representation allowed the clinicians to focus on a subset of causes of hypotension.

Flushing disorders may be classified by whether they are mediated by the autonomic nervous system (wet flushes, because they are usually accompanied by diaphoresis) or by exogenous or endogenous vasoactive substances (dry flushes).¹ Autonomic nervous system flushing is triggered by emotions, fever, exercise, perimenopause (hot flashes), and neurologic conditions (eg, Parkinson disease, spinal cord injury, multiple sclerosis). Vasoactive flushing precipitants include drugs (eg, niacin); alcohol (secondary to cutaneous vasodilation, or acetaldehyde particularly in people with insufficient acetaldehyde dehydrogenase activity)²; foods that contain capsaicin, tyramine, sulfites, or histamine (eg, eating improperly handled fish can cause scombroid poisoning); and anaphylaxis. Rare causes of vasoactive flushing include carcinoid syndrome, pheochromocytoma, medullary thyroid carcinoma, VIPoma, and mastocytosis.²

Mastocytosis is a rare clonal disorder characterized by the accumulation of abnormal mast cells in the skin (cutaneous mastocytosis), in multiple organs (systemic mastocytosis), or in a solid tumor (mastocytoma). Urticaria pigmentosa is the most common form of cutaneous mastocytosis; it is seen more often in children than in adults and typically is associated with a maculopapular rash and dermatographism. Systemic mastocytosis is the most common form of the disorder in adults.³ Symptoms are related to mast cell infiltration or mast cell mediator–related effects, which range from itching, flushing, and diarrhea to hypotension and anaphylaxis. Other manifestations are fatigue, urticaria pigmentosa, osteoporosis, hepatosplenomegaly, bone pain, cytopenias, and lymphadenopathy.⁴

Systemic mastocytosis can occur at any age and should be considered in patients with recurrent unexplained flushing, syncope, or hypotension. Eighty percent to 90% of patients with systemic mastocytosis have a mutation in Kit,⁵ a transmembrane tyrosine kinase that is the receptor for stem cell factor. The Asp816Val mutation leads to increased proliferation and reduced apoptosis of mast cells.^3,6,7 Proposed diagnostic algorithms^8-11 involve measurement of serum tryptase levels and examination of bone marrow. Bone marrow biopsy and testing for the Asp816Val Kit mutation should be considered in patients with modestly elevated baseline tryptase levels (11.5-20 ng/mL) if clinical findings are consistent with mastocytosis.¹²

The primary goals of treatment are managing mast cell–mediated symptoms and, in advanced cases, achieving cytoreduction. Alcohol can trigger mast cell degranulation in indolent systemic mastocytosis and should be avoided. Mast cell–mediated symptoms are managed with histamine blockers, leukotriene antagonists, and mast cell stabilizers.¹² Targeted therapy with tyrosine kinase inhibitors (eg, imatinib) in patients with transmembrane Kit mutation (eg, Phe522Cys, Lys509Ile) associated with systemic mastocytosis has had promising results.^13,14 However, this patient’s Asp816Val mutation is in the Kit catalytic domain, not the transmembrane region, and therefore would not be expected to respond to imatinib. A recent open-label trial of the multikinase inhibitor midostaurin demonstrated resolution of organ damage, reduced bone marrow burden, and lowered serum tryptase levels in patients with advanced systemic mastocytosis.¹⁵ Interferon, cladribine, and high-dose corticosteroids are prescribed in patients for whom other therapies have been ineffective.⁸

The differential diagnosis is broad for both hypotension and for flushing, but the differential diagnosis for recurrent hypotension and flushing is limited. Recognizing that flushing was an essential feature of this patient’s hypotensive condition, and not an epiphenomenon of syncope, allowed the clinicians to focus on the overlap and make a shocking diagnosis.

 

Acknowledgment

The authors thank David Bosler, MD (Cleveland Clinic) for interpreting the pathology image.

Disclosure

Nothing to report.

The approach to clinical conundrums by an expert clinician is revealed through the presentation of an actual patient’s case in an approach typical of a morning report. Similarly to patient care, sequential pieces of information are provided to the clinician, who is unfamiliar with the case. The focus is on the thought processes of both the clinical team caring for the patient and the discussant. The bolded text represents the patient’s case. Each paragraph that follows represents the discussant’s thoughts.

A 75-year-old man was brought by ambulance to the emergency department (ED) after the acute onset of palpitations, lightheadedness, and confusion. His medical history, provided by his wife, included osteoarthritis and remote cholecystectomy. He was not a smoker but drank 2 to 4 cans of beer daily. His medications were aspirin 162 mg daily and naproxen as needed. There was no history of bruising, diarrhea, melena, or bleeding.

Palpitations may represent an arrhythmia arising from an ischemic or alcoholic cardiomyopathy. Mental status changes usually have metabolic, infectious, structural (eg, hemorrhage, tumor), or toxic causes. Lightheadedness and confusion could occur with arrhythmia-associated cerebral hypoperfusion or a seizure. Daily alcohol use could cause confusion through acute intoxication, thiamine or B₁₂ deficiency, repeated head trauma, or liver failure.

The patient’s systolic blood pressure (BP) was 60 mm Hg, heart rate (HR) was 120 beats per minute (bpm), and oral temperature was 98.4°F. Rousing him was difficult. There were no localizing neurologic abnormalities, and the rest of the physical examination findings were normal. Point-of-care blood glucose level was 155 mg/dL. Blood cultures were obtained and broad-spectrum antibiotics initiated. After fluid resuscitation, BP improved to 116/87 mm Hg, HR fell to 105 bpm, and the patient became alert and oriented. He denied chest pain, fever, or diaphoresis.

The patient’s improvement with intravenous (IV) fluids makes cardiogenic shock unlikely but does not exclude an underlying compensated cardiomyopathy that may be predisposing to arrhythmia. Hypotension, tachycardia, and somnolence may represent sepsis, but the near normalization of vital signs and mental status shortly after administration of IV fluids, the normal temperature, and the absence of localizing signs of infection favor withholding additional antibiotics. Other causes of hypotension are hypovolemia, medication effects, adrenal insufficiency, anaphylaxis, and autonomic insufficiency. There was no reported nausea, vomiting, diarrhea, bleeding, polyuria, or impaired oral intake to support hypovolemia, though the response to IV fluids suggests hypovolemia may still be playing a role.

White blood cell (WBC) count was 15,450/µL with a normal differential; hemoglobin level was 15.8 g/dL; and platelet count was 176,000/µL. Electrolytes, liver function tests, cardiac enzymes, and urinalysis were normal. Electrocardiogram showed sinus tachycardia with premature atrial complexes and no ST-segment abnormalities. Radiograph of the chest and computed tomography scan of the head were normal. Echocardiogram showed moderate left ventricular hypertrophy with a normal ejection fraction and no valvular abnormalities. Exercise nuclear cardiac stress test was negative for ischemia. Blood cultures were sterile. The patient quickly became asymptomatic and remained so during his 3-day hospitalization. There were no arrhythmias on telemetry. The patient was discharged with follow-up scheduled with his primary care physician.

The nonlocalizing history and physical examination findings, normal chest radiograph and urinalysis, absence of fevers, negative blood cultures, and quick recovery make infection unlikely, despite the moderate leukocytosis. Conditions that present with acute and transient hypotension and altered mental status include arrhythmias, seizures, and reactions to drugs or toxins. Given the cardiac test results, a chronic cardiomyopathy seems unlikely, but arrhythmia is still possible. Continuous outpatient monitoring is required to assess the palpitations and the frequency of the premature atrial complexes.

Two days after discharge, the patient suddenly became diaphoretic and lost consciousness while walking to the bathroom. He was taken to the ED, where his BP was 90/60 mm Hg and HR was 108 bpm. Family members reported that he had appeared flushed during the syncopal episode, showed no seizure activity, and been unconscious for 15 to 20 minutes. The patient denied chest pain, dyspnea, fever, bowel or bladder incontinence, focal weakness, slurred speech, visual changes, nausea or vomiting either before or after the episode. Physical examination revealed a tongue laceration and facial erythema; all other findings were normal. In the ED, there was an asymptomatic 7-beat run of nonsustained ventricular tachycardia, and the hypotension resolved after fluid resuscitation. The patient now reported 2 similar syncopal episodes in the past. The first occurred in a restaurant 6 years earlier, and the second occurred 3 years later, at which time he was hospitalized and no etiology was found.

The loss of consciousness is attributable to cerebral hypoperfusion. Hypotension has 3 principal categories: hypovolemic, cardiogenic, and distributive. With syncopal episodes recurring over several years, hypovolemia seems unlikely. Given the palpitations and ventricular tachycardia, it is reasonable to suspect a cardiogenic cause. Although his heart appears to be structurally normal on echocardiogram, genetic, electrophysiologic, or magnetic resonance imaging (MRI) testing will occasionally reveal an unsuspected substrate for arrhythmia.

 

The recurring yet self-limited nature, diaphoresis, flushing, and facial erythema suggest a non-sepsis distributive cause of hypotension. It is possible the patient is recurrently exposed to a toxin (eg, alcohol) that causes both flushing and dehydration. Flushing disorders include carcinoid syndrome, pheochromocytoma, drug reaction with eosinophilia and systemic symptoms (DRESS), and mastocytosis. Carcinoid syndrome is characterized by bronchospasm and diarrhea and, in some cases, right-sided valvulopathy, all of which are absent in this patient. Pheochromocytoma is associated with orthostasis, but patients typically are hypertensive at baseline. DRESS, which may arise from nonsteroidal anti-inflammatory drug (NSAID) or aspirin use, can cause facial erythema and swelling but is also characterized by liver, renal, and hematologic abnormalities, none of which was demonstrated. Furthermore, DRESS typically does not cause hypotension. Mastocytosis can manifest as isolated or recurrent anaphylaxis.

It is important to investigate antecedents of these syncopal episodes. If the earlier episodes were food-related—one occurred at a restaurant—then deglutition syncope (syncope precipitated by swallowing) should be considered. If an NSAID or aspirin was ingested before each episode, then medication hypersensitivity or mast cell degranulation (which can be triggered by these medications) should be further examined. Loss of consciousness lasting 20 minutes without causing any neurologic sequelae is unusual for most causes of recurrent syncope. This feature raises the possibility that a toxin or mediator might still be present in the patient’s system.

Serial cardiac enzymes and electrocardiogram were normal. A tilt-table study was negative. The cortisol response to ACTH (cosyntropin) stimulation was normal. The level of serum tryptase, drawn 2 days after syncope, was 18.4 ng/dL (normal, <11.5 ng/dL). Computed tomography scan of chest and abdomen was negative for pulmonary embolism but showed a 1.4×1.3-cm hypervascular lesion in the tail of pancreas. The following neuroendocrine tests were within normal limits: serum and urine catecholamines; urine 5-hydroxyindoleacetic acid (5-HIAA); and serum chromogranin A, insulin, serotonin, vasoactive intestinal polypeptide (VIP), and somatostatin (Table 1). The patient remained asymptomatic during his hospital stay and was discharged home with appointments for cardiology follow-up and endoscopic ultrasound-guided biopsy of the pancreatic mass.

Pheochromocytoma is unlikely with normal serum and urine catecholamine levels and normal adrenal images. The differential diagnosis for a pancreatic mass includes pancreatic carcinoma, lymphoma, cystic neoplasm, and neuroendocrine tumor. All markers of neuroendocrine excess are normal, though elevations can be episodic. The normal 5-HIAA level makes carcinoid syndrome unlikely. VIPomas are associated with flushing, but the absence of profound and protracted diarrhea makes a VIPoma unlikely.

As hypoglycemia from a pancreatic insulinoma is plausible as a cause of episodic loss of consciousness lasting 15 minutes or more, it is important to inquire if giving food or drink helped resolve previous episodes. The normal insulin level reported here is of limited value, because it is the combination of insulin and C-peptide levels at time of hypoglycemia that is diagnostic. The normal glucose level recorded during one of the earlier episodes and the hypotension argue against hypoglycemia.

The elevated tryptase level is an indicator of mast cell degranulation. Tryptase levels are transiently elevated during the initial 2 to 4 hours after an anaphylactic episode and then normalize. An elevated level many hours or days later is considered a sign of mast cell excess. Although there is no evidence of the multi-organ disease (eg, cytopenia, bone disease, hepatosplenomegaly) seen in patients with a high systemic burden of mast cells, mast cell disorders exist on a spectrum. There may be a focal excess of mast cells confined to one organ or an isolated mass.

The same day as discharge, the patient’s wife drove them to the grocery store. He remained in the car while she shopped. When she returned, she found him confused and minimally responsive with subsequent brief loss of consciousness. He was taken to an ED, where he was flushed and hypotensive (systolic BP, 60 mm Hg) and tachycardic. Other examination findings were normal. After fluid resuscitation he became alert and oriented. WBC count was 20,850/μL with 89% neutrophils, hemoglobin level was 14.6 g/dL, and platelet count was 168,000/μL. Serum lactate level was 3.7 mmol/L (normal, <2.3 mmol/L). Chest radiograph was normal. He was treated with broad-spectrum antibiotic therapy and admitted to the hospital. Blood and urine cultures were sterile. Fine-needle aspiration of the pancreatic mass demonstrated nonspecific inflammation. Four days after admission (3 days after pancreatic mass biopsy) the patient developed palpitations, felt unwell, and had marked flushing of the face and trunk, with concomitant BP of 90/50 mm Hg and HR of 140 bpm.

The salient features of this case are recurrent hypotension, tachycardia, and flushing. Autonomic insufficiency, to which elderly patients are prone, causes hemodynamic perturbations but rarely flushing. The patient does not have diabetes mellitus, Parkinson disease, or another condition that puts him at risk for dysautonomia. Pancreatic neuroendocrine tumors secrete mediators that lead to vasodilation and hypotension but are unlikely given the clinical and biochemical data.

 

The patient’s symptoms are consistent with anaphylaxis, though prototypical immunoglobulin E (IgE)–mediated anaphylaxis is usually accompanied by urticaria, angioedema, and wheezing, which have been absent during his presentations. There are no clear food, pharmacologic, or environmental precipitants.

Recurrent anaphylaxis can be a manifestation of mast cell excess (eg, cutaneous or systemic mastocytosis). A markedly elevated tryptase level during an anaphylactic episode is consistent with mastocytosis or IgE-mediated anaphylaxis. An elevated baseline tryptase level days after an anaphylactic episode signals increased mast cell burden. There may be a reservoir of mast cells in the bone marrow. Alternatively, the hypervascular pancreatic mass may be a mastocytoma or a mast cell sarcoma (missed because of inadequate sampling or staining).

The lactic acidosis likely reflects global tissue hypoperfusion from vasodilatory hypotension. The leukocytosis may reflect WBC mobilization secondary to endogenous corticosteroids and catecholamines in response to hypotension or may be a direct response to the release of mast cell–derived mediators of inflammation.

The patient was treated with diphenhydramine and ranitidine. Serum tryptase level was 46.8 ng/mL (normal, <11.5 ng/mL), and 24-hour urine histamine level was 95 µ g/dL (normal, <60 µ g/dL). Bone marrow biopsy results showed multifocal dense infiltrative aggregates of mast cells (>15 cells/aggregate), which were confirmed by CD117 (Kit) and tryptase positivity (Figure). Mutation analysis for Kit Asp816Val, which is present in 80% to 90% of patients with mastocytosis, was positive. He fulfilled the 2008 World Health Organization criteria for systemic mastocytosis (Table 2). Prednisone, histamine inhibitors, and montelukast were prescribed. Six months later, magnetic resonance imaging of the abdomen showed no change in the pancreatic mass, which was now characterized as a possible splenule. The patient had no additional episodes of flushing or syncope over 2 years.

 

DISCUSSION

Cardiovascular collapse (hypotension, tachycardia, syncope) in an elderly patient prompts clinicians to focus on life-threatening conditions, such as acute coronary syndrome, pulmonary embolus, arrhythmia, and sepsis. Each of these diagnoses was considered early in the course of this patient’s presentations, but each was deemed unlikely as it became apparent that the episodes were self-limited and recurrent over years. Incorporating flushing into the diagnostic problem representation allowed the clinicians to focus on a subset of causes of hypotension.

Flushing disorders may be classified by whether they are mediated by the autonomic nervous system (wet flushes, because they are usually accompanied by diaphoresis) or by exogenous or endogenous vasoactive substances (dry flushes).¹ Autonomic nervous system flushing is triggered by emotions, fever, exercise, perimenopause (hot flashes), and neurologic conditions (eg, Parkinson disease, spinal cord injury, multiple sclerosis). Vasoactive flushing precipitants include drugs (eg, niacin); alcohol (secondary to cutaneous vasodilation, or acetaldehyde particularly in people with insufficient acetaldehyde dehydrogenase activity)²; foods that contain capsaicin, tyramine, sulfites, or histamine (eg, eating improperly handled fish can cause scombroid poisoning); and anaphylaxis. Rare causes of vasoactive flushing include carcinoid syndrome, pheochromocytoma, medullary thyroid carcinoma, VIPoma, and mastocytosis.²

Mastocytosis is a rare clonal disorder characterized by the accumulation of abnormal mast cells in the skin (cutaneous mastocytosis), in multiple organs (systemic mastocytosis), or in a solid tumor (mastocytoma). Urticaria pigmentosa is the most common form of cutaneous mastocytosis; it is seen more often in children than in adults and typically is associated with a maculopapular rash and dermatographism. Systemic mastocytosis is the most common form of the disorder in adults.³ Symptoms are related to mast cell infiltration or mast cell mediator–related effects, which range from itching, flushing, and diarrhea to hypotension and anaphylaxis. Other manifestations are fatigue, urticaria pigmentosa, osteoporosis, hepatosplenomegaly, bone pain, cytopenias, and lymphadenopathy.⁴

Systemic mastocytosis can occur at any age and should be considered in patients with recurrent unexplained flushing, syncope, or hypotension. Eighty percent to 90% of patients with systemic mastocytosis have a mutation in Kit,⁵ a transmembrane tyrosine kinase that is the receptor for stem cell factor. The Asp816Val mutation leads to increased proliferation and reduced apoptosis of mast cells.^3,6,7 Proposed diagnostic algorithms^8-11 involve measurement of serum tryptase levels and examination of bone marrow. Bone marrow biopsy and testing for the Asp816Val Kit mutation should be considered in patients with modestly elevated baseline tryptase levels (11.5-20 ng/mL) if clinical findings are consistent with mastocytosis.¹²

The primary goals of treatment are managing mast cell–mediated symptoms and, in advanced cases, achieving cytoreduction. Alcohol can trigger mast cell degranulation in indolent systemic mastocytosis and should be avoided. Mast cell–mediated symptoms are managed with histamine blockers, leukotriene antagonists, and mast cell stabilizers.¹² Targeted therapy with tyrosine kinase inhibitors (eg, imatinib) in patients with transmembrane Kit mutation (eg, Phe522Cys, Lys509Ile) associated with systemic mastocytosis has had promising results.^13,14 However, this patient’s Asp816Val mutation is in the Kit catalytic domain, not the transmembrane region, and therefore would not be expected to respond to imatinib. A recent open-label trial of the multikinase inhibitor midostaurin demonstrated resolution of organ damage, reduced bone marrow burden, and lowered serum tryptase levels in patients with advanced systemic mastocytosis.¹⁵ Interferon, cladribine, and high-dose corticosteroids are prescribed in patients for whom other therapies have been ineffective.⁸

The differential diagnosis is broad for both hypotension and for flushing, but the differential diagnosis for recurrent hypotension and flushing is limited. Recognizing that flushing was an essential feature of this patient’s hypotensive condition, and not an epiphenomenon of syncope, allowed the clinicians to focus on the overlap and make a shocking diagnosis.

 

Acknowledgment

The authors thank David Bosler, MD (Cleveland Clinic) for interpreting the pathology image.

Disclosure

Nothing to report.

The Case

A 74-year-old man with Alzheimer’s dementia presents with urinary tract infection (UTI), hypovolemia, and hypernatremia. He also has chronic dysphagia with a history of aspiration pneumonia and has been on thickened liquids at home for the past five months. As his infection is treated, he improves and requests water to drink.

Background

Dysphagia is a very common problem, particularly among elderly patients. The exact prevalence is unknown, but it is estimated to occur in up to 30% of the elderly population. Dysphagia is defined as difficulty or discomfort in swallowing and is traditionally classified as either oropharyngeal or esophageal in origin. Normal aging as well as chronic illness may lead to decreased connective tissue elasticity, muscle mass, and oral secretions, which affect swallowing performance.1 Stroke is a common predisposing condition.2 Dysphagia predisposes patients to dehydration, malnutrition, and electrolyte derangements. The most feared immediate complication is aspiration pneumonia (AP) resulting from impaired clearance of oral secretions.3

The diagnosis of dysphagia is clinical, and assessments from patients and family are often sufficient. The optimal test to assess the severity of dysphagia is a bedside swallow evaluation using small amounts of water.1 Video-assisted fluoroscopic examinations can identify problem areas within the oropharynx and esophagus and may help determine the etiology of dysphagia.

What evidence supports various treatment options for dysphagia?

Access to Water

Water is a thin liquid with low viscosity, which allows for rapid transit through the oropharynx. In debilitated and elderly patients, thin liquids easily reach the epiglottis and enter the trachea before pharyngeal muscles compensate. As such, access to water and other thin liquids is often restricted in patients suspected to have dysphagia.4

However, allowing access to water improves patient satisfaction, reduces the development of dehydration, and does not increase the incidence of AP. Bedside therapy interventions such as correct positioning and chin-tuck and sipping technique as well as attention to oral hygiene are recommended prior to more noxious options such as thickened liquids.1 The Frazier water protocol may help provide logistical guidance for facilities interested in improving access to water for patients with dysphagia.

Liquid Modification

Many clinicians manage dysphagia through restricting access to all thin liquids. In the hospital setting where video fluoroscopy and speech therapy are readily available, clinicians frequently employ the use of modified diets with thickened liquids in order to minimize the risk of aspiration despite the lack of high-quality evidence supporting liquid modification.2 Patients associate thickened liquids and restricted diets with a reduction in quality of life. Compliance studies have shown that only a minority of patients are compliant with thickened liquids at five days. In addition, thickening liquids has not been shown to decrease the risk of AP nor improve nutritional status, and it may actually cause harm by increasing the risk of dehydration and UTI.4

Tube Feeding

In patients with severe dysphagia in whom conservative management is not feasible or has failed, maintaining adequate nutrition can be a challenge. There are encouraging data with nutritionally enriching and modifying the texture of solid foods.1 Alternative methods of enteral nutrition delivery are often also considered. The most common vehicles of delivery are nasogastric tubes, post-pyloric feeding tubes, and percutaneous endoscopic gastrostomy (PEG) tubes. In theory, bypassing the pharynx and esophagus could result in fewer aspiration events and less AP.3 However, nasogastric, post-pyloric, or PEG feeding does not decrease the risk of AP. For patients with advanced dementia, there have been no randomized trials demonstrating an improvement in mortality with tube feeds.4 Tube feeding also carries with it a slight procedural risk and a high incidence of associated diarrhea, plus is associated with electrolyte derangements such as hypernatremia. The decision to pursue tube feeding should be weighed heavily in every patient and is highly influenced by the etiology and anticipated duration of dysphagia.

 

Selective Digestive Decontamination

Selective digestive decontamination (SDD) is a protocol-based treatment that aims to eradicate potentially pathogenic gut flora, particularly aerobic gram-negatives, in critically ill patients to reduce the impact of aspiration events. The utilization of SDD and the available literature center firmly on critically ill and ventilated patients. Subsequent studies have demonstrated recolonization after protocol cessation, and long-term effects are currently undefined.5 Until it can be studied in broader populations and proven to have clinical benefit, employing SSD in non-critically ill patients with dysphagia remains unsupported.

Multimodal Approach

Many rehabilitation centers incorporate a therapist-driven swallowing treatment program. Evidence suggests patient and family counseling alone may not be effective, so these programs variably incorporate diet/liquid modification, strengthening exercises, sensory processing techniques, and even neuromuscular electrical stimulation for muscle building.1 Accordingly, these programs are resource-intensive.

Management

Dysphagia remains a significant clinical problem for hospitalized patients. The existing literature and practice guidelines generally support a “less is more” approach. Though liquid/diet modification is common practice, it is not based in solid evidence and may contribute to unnecessary tube feeding. The best current evidence supports allowing access to water and ice chips. The ideal management plan for each patient will differ and should incorporate patient and family preferences in a multidisciplinary approach.

Back to the Case

Our patient requests water. He coughs after drinking during a bedside swallow evaluation. The risks of potential aspiration and AP are explained, and he expresses his understanding. He reiterates his choice to be allowed access to water as it is important to his quality of life. The speech therapy team is consulted and provides instruction on chin-tuck positioning, oral care, and timing water between meals rather than while eating food. He does well for the remainder of the hospital stay, and by time of discharge, his electrolytes are corrected, and he is much more comfortable being allowed to drink water. He is discharged home and encouraged to continue with these conservative measures.

Bottom Line

Evidence to support many common interventions for dysphagia is lacking; patients with dysphagia are best managed via a multidisciplinary, multimodal approach that provides access to water whenever possible. TH

---

Vijay G. Paryani, MD, is an internal medicine resident in the department of internal medicine at the University of Kentucky. Joseph R. Sweigart, MD, is a hospitalist and assistant professor of hospital medicine in the division of hospital medicine at the University of Kentucky. Laura C. Fanucchi, MD, is a hospitalist and assistant professor of hospital medicine in the division of hospital medicine at the University of Kentucky.

References

1. Karagiannis MJ, Chivers L, Karagiannis TC. Effects of oral intake of water in patients with oropharyngeal dysphagia. BMC Geriatr. 2011;11(2):9.
2. Foley N, Teasell R, Salter K, Kruger E, Martino R. Dysphagia treatment post stroke: a systematic review of randomized controlled trials. Age Ageing. 2008;37(3):258-264.
3. Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med. 2001;344(9):665-671.
4. Loeb MB, Becker M, Eady A, Walker-Dilks C. Interventions to prevent aspiration pneumonia in older adults: a systematic review. J Am Geriatr Soc. 2003;51(7):1018-1022.
5. Gosney M, Martin MV, Wright AE. The role of selective decontamination of the digestive tract in acute stroke. Age Ageing 2006;35(1):42-47.

 

The Case

A 74-year-old man with Alzheimer’s dementia presents with urinary tract infection (UTI), hypovolemia, and hypernatremia. He also has chronic dysphagia with a history of aspiration pneumonia and has been on thickened liquids at home for the past five months. As his infection is treated, he improves and requests water to drink.

Background

Dysphagia is a very common problem, particularly among elderly patients. The exact prevalence is unknown, but it is estimated to occur in up to 30% of the elderly population. Dysphagia is defined as difficulty or discomfort in swallowing and is traditionally classified as either oropharyngeal or esophageal in origin. Normal aging as well as chronic illness may lead to decreased connective tissue elasticity, muscle mass, and oral secretions, which affect swallowing performance.1 Stroke is a common predisposing condition.2 Dysphagia predisposes patients to dehydration, malnutrition, and electrolyte derangements. The most feared immediate complication is aspiration pneumonia (AP) resulting from impaired clearance of oral secretions.3

The diagnosis of dysphagia is clinical, and assessments from patients and family are often sufficient. The optimal test to assess the severity of dysphagia is a bedside swallow evaluation using small amounts of water.1 Video-assisted fluoroscopic examinations can identify problem areas within the oropharynx and esophagus and may help determine the etiology of dysphagia.

What evidence supports various treatment options for dysphagia?

Access to Water

Water is a thin liquid with low viscosity, which allows for rapid transit through the oropharynx. In debilitated and elderly patients, thin liquids easily reach the epiglottis and enter the trachea before pharyngeal muscles compensate. As such, access to water and other thin liquids is often restricted in patients suspected to have dysphagia.4

However, allowing access to water improves patient satisfaction, reduces the development of dehydration, and does not increase the incidence of AP. Bedside therapy interventions such as correct positioning and chin-tuck and sipping technique as well as attention to oral hygiene are recommended prior to more noxious options such as thickened liquids.1 The Frazier water protocol may help provide logistical guidance for facilities interested in improving access to water for patients with dysphagia.

Liquid Modification

Many clinicians manage dysphagia through restricting access to all thin liquids. In the hospital setting where video fluoroscopy and speech therapy are readily available, clinicians frequently employ the use of modified diets with thickened liquids in order to minimize the risk of aspiration despite the lack of high-quality evidence supporting liquid modification.2 Patients associate thickened liquids and restricted diets with a reduction in quality of life. Compliance studies have shown that only a minority of patients are compliant with thickened liquids at five days. In addition, thickening liquids has not been shown to decrease the risk of AP nor improve nutritional status, and it may actually cause harm by increasing the risk of dehydration and UTI.4

Tube Feeding

In patients with severe dysphagia in whom conservative management is not feasible or has failed, maintaining adequate nutrition can be a challenge. There are encouraging data with nutritionally enriching and modifying the texture of solid foods.1 Alternative methods of enteral nutrition delivery are often also considered. The most common vehicles of delivery are nasogastric tubes, post-pyloric feeding tubes, and percutaneous endoscopic gastrostomy (PEG) tubes. In theory, bypassing the pharynx and esophagus could result in fewer aspiration events and less AP.3 However, nasogastric, post-pyloric, or PEG feeding does not decrease the risk of AP. For patients with advanced dementia, there have been no randomized trials demonstrating an improvement in mortality with tube feeds.4 Tube feeding also carries with it a slight procedural risk and a high incidence of associated diarrhea, plus is associated with electrolyte derangements such as hypernatremia. The decision to pursue tube feeding should be weighed heavily in every patient and is highly influenced by the etiology and anticipated duration of dysphagia.

 

Selective Digestive Decontamination

Selective digestive decontamination (SDD) is a protocol-based treatment that aims to eradicate potentially pathogenic gut flora, particularly aerobic gram-negatives, in critically ill patients to reduce the impact of aspiration events. The utilization of SDD and the available literature center firmly on critically ill and ventilated patients. Subsequent studies have demonstrated recolonization after protocol cessation, and long-term effects are currently undefined.5 Until it can be studied in broader populations and proven to have clinical benefit, employing SSD in non-critically ill patients with dysphagia remains unsupported.

Multimodal Approach

Many rehabilitation centers incorporate a therapist-driven swallowing treatment program. Evidence suggests patient and family counseling alone may not be effective, so these programs variably incorporate diet/liquid modification, strengthening exercises, sensory processing techniques, and even neuromuscular electrical stimulation for muscle building.1 Accordingly, these programs are resource-intensive.

Management

Dysphagia remains a significant clinical problem for hospitalized patients. The existing literature and practice guidelines generally support a “less is more” approach. Though liquid/diet modification is common practice, it is not based in solid evidence and may contribute to unnecessary tube feeding. The best current evidence supports allowing access to water and ice chips. The ideal management plan for each patient will differ and should incorporate patient and family preferences in a multidisciplinary approach.

Back to the Case

Our patient requests water. He coughs after drinking during a bedside swallow evaluation. The risks of potential aspiration and AP are explained, and he expresses his understanding. He reiterates his choice to be allowed access to water as it is important to his quality of life. The speech therapy team is consulted and provides instruction on chin-tuck positioning, oral care, and timing water between meals rather than while eating food. He does well for the remainder of the hospital stay, and by time of discharge, his electrolytes are corrected, and he is much more comfortable being allowed to drink water. He is discharged home and encouraged to continue with these conservative measures.

Bottom Line

Evidence to support many common interventions for dysphagia is lacking; patients with dysphagia are best managed via a multidisciplinary, multimodal approach that provides access to water whenever possible. TH

---

Vijay G. Paryani, MD, is an internal medicine resident in the department of internal medicine at the University of Kentucky. Joseph R. Sweigart, MD, is a hospitalist and assistant professor of hospital medicine in the division of hospital medicine at the University of Kentucky. Laura C. Fanucchi, MD, is a hospitalist and assistant professor of hospital medicine in the division of hospital medicine at the University of Kentucky.

References

1. Karagiannis MJ, Chivers L, Karagiannis TC. Effects of oral intake of water in patients with oropharyngeal dysphagia. BMC Geriatr. 2011;11(2):9.
2. Foley N, Teasell R, Salter K, Kruger E, Martino R. Dysphagia treatment post stroke: a systematic review of randomized controlled trials. Age Ageing. 2008;37(3):258-264.
3. Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med. 2001;344(9):665-671.
4. Loeb MB, Becker M, Eady A, Walker-Dilks C. Interventions to prevent aspiration pneumonia in older adults: a systematic review. J Am Geriatr Soc. 2003;51(7):1018-1022.
5. Gosney M, Martin MV, Wright AE. The role of selective decontamination of the digestive tract in acute stroke. Age Ageing 2006;35(1):42-47.

 

The Case

A 74-year-old man with Alzheimer’s dementia presents with urinary tract infection (UTI), hypovolemia, and hypernatremia. He also has chronic dysphagia with a history of aspiration pneumonia and has been on thickened liquids at home for the past five months. As his infection is treated, he improves and requests water to drink.

Background

Dysphagia is a very common problem, particularly among elderly patients. The exact prevalence is unknown, but it is estimated to occur in up to 30% of the elderly population. Dysphagia is defined as difficulty or discomfort in swallowing and is traditionally classified as either oropharyngeal or esophageal in origin. Normal aging as well as chronic illness may lead to decreased connective tissue elasticity, muscle mass, and oral secretions, which affect swallowing performance.1 Stroke is a common predisposing condition.2 Dysphagia predisposes patients to dehydration, malnutrition, and electrolyte derangements. The most feared immediate complication is aspiration pneumonia (AP) resulting from impaired clearance of oral secretions.3

The diagnosis of dysphagia is clinical, and assessments from patients and family are often sufficient. The optimal test to assess the severity of dysphagia is a bedside swallow evaluation using small amounts of water.1 Video-assisted fluoroscopic examinations can identify problem areas within the oropharynx and esophagus and may help determine the etiology of dysphagia.

What evidence supports various treatment options for dysphagia?

Access to Water

Water is a thin liquid with low viscosity, which allows for rapid transit through the oropharynx. In debilitated and elderly patients, thin liquids easily reach the epiglottis and enter the trachea before pharyngeal muscles compensate. As such, access to water and other thin liquids is often restricted in patients suspected to have dysphagia.4

However, allowing access to water improves patient satisfaction, reduces the development of dehydration, and does not increase the incidence of AP. Bedside therapy interventions such as correct positioning and chin-tuck and sipping technique as well as attention to oral hygiene are recommended prior to more noxious options such as thickened liquids.1 The Frazier water protocol may help provide logistical guidance for facilities interested in improving access to water for patients with dysphagia.

Liquid Modification

Many clinicians manage dysphagia through restricting access to all thin liquids. In the hospital setting where video fluoroscopy and speech therapy are readily available, clinicians frequently employ the use of modified diets with thickened liquids in order to minimize the risk of aspiration despite the lack of high-quality evidence supporting liquid modification.2 Patients associate thickened liquids and restricted diets with a reduction in quality of life. Compliance studies have shown that only a minority of patients are compliant with thickened liquids at five days. In addition, thickening liquids has not been shown to decrease the risk of AP nor improve nutritional status, and it may actually cause harm by increasing the risk of dehydration and UTI.4

Tube Feeding

In patients with severe dysphagia in whom conservative management is not feasible or has failed, maintaining adequate nutrition can be a challenge. There are encouraging data with nutritionally enriching and modifying the texture of solid foods.1 Alternative methods of enteral nutrition delivery are often also considered. The most common vehicles of delivery are nasogastric tubes, post-pyloric feeding tubes, and percutaneous endoscopic gastrostomy (PEG) tubes. In theory, bypassing the pharynx and esophagus could result in fewer aspiration events and less AP.3 However, nasogastric, post-pyloric, or PEG feeding does not decrease the risk of AP. For patients with advanced dementia, there have been no randomized trials demonstrating an improvement in mortality with tube feeds.4 Tube feeding also carries with it a slight procedural risk and a high incidence of associated diarrhea, plus is associated with electrolyte derangements such as hypernatremia. The decision to pursue tube feeding should be weighed heavily in every patient and is highly influenced by the etiology and anticipated duration of dysphagia.

 

Selective Digestive Decontamination

Selective digestive decontamination (SDD) is a protocol-based treatment that aims to eradicate potentially pathogenic gut flora, particularly aerobic gram-negatives, in critically ill patients to reduce the impact of aspiration events. The utilization of SDD and the available literature center firmly on critically ill and ventilated patients. Subsequent studies have demonstrated recolonization after protocol cessation, and long-term effects are currently undefined.5 Until it can be studied in broader populations and proven to have clinical benefit, employing SSD in non-critically ill patients with dysphagia remains unsupported.

Multimodal Approach

Many rehabilitation centers incorporate a therapist-driven swallowing treatment program. Evidence suggests patient and family counseling alone may not be effective, so these programs variably incorporate diet/liquid modification, strengthening exercises, sensory processing techniques, and even neuromuscular electrical stimulation for muscle building.1 Accordingly, these programs are resource-intensive.

Management

Dysphagia remains a significant clinical problem for hospitalized patients. The existing literature and practice guidelines generally support a “less is more” approach. Though liquid/diet modification is common practice, it is not based in solid evidence and may contribute to unnecessary tube feeding. The best current evidence supports allowing access to water and ice chips. The ideal management plan for each patient will differ and should incorporate patient and family preferences in a multidisciplinary approach.

Back to the Case

Our patient requests water. He coughs after drinking during a bedside swallow evaluation. The risks of potential aspiration and AP are explained, and he expresses his understanding. He reiterates his choice to be allowed access to water as it is important to his quality of life. The speech therapy team is consulted and provides instruction on chin-tuck positioning, oral care, and timing water between meals rather than while eating food. He does well for the remainder of the hospital stay, and by time of discharge, his electrolytes are corrected, and he is much more comfortable being allowed to drink water. He is discharged home and encouraged to continue with these conservative measures.

Bottom Line

Evidence to support many common interventions for dysphagia is lacking; patients with dysphagia are best managed via a multidisciplinary, multimodal approach that provides access to water whenever possible. TH

---

Vijay G. Paryani, MD, is an internal medicine resident in the department of internal medicine at the University of Kentucky. Joseph R. Sweigart, MD, is a hospitalist and assistant professor of hospital medicine in the division of hospital medicine at the University of Kentucky. Laura C. Fanucchi, MD, is a hospitalist and assistant professor of hospital medicine in the division of hospital medicine at the University of Kentucky.

References

1. Karagiannis MJ, Chivers L, Karagiannis TC. Effects of oral intake of water in patients with oropharyngeal dysphagia. BMC Geriatr. 2011;11(2):9.
2. Foley N, Teasell R, Salter K, Kruger E, Martino R. Dysphagia treatment post stroke: a systematic review of randomized controlled trials. Age Ageing. 2008;37(3):258-264.
3. Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med. 2001;344(9):665-671.
4. Loeb MB, Becker M, Eady A, Walker-Dilks C. Interventions to prevent aspiration pneumonia in older adults: a systematic review. J Am Geriatr Soc. 2003;51(7):1018-1022.
5. Gosney M, Martin MV, Wright AE. The role of selective decontamination of the digestive tract in acute stroke. Age Ageing 2006;35(1):42-47.

 

The Case

A 50-year-old man with no known medical history presents with two months of increasing abdominal distension. Exam is notable for scleral icterus, telangiectasias on the upper chest, abdominal distention with a positive fluid wave, and bilateral pitting lower-extremity edema. An abdominal ultrasound shows large ascites and a nodular liver consistent with cirrhosis. How should this patient with newly diagnosed cirrhosis be evaluated and managed?

Background

Cirrhosis is a leading cause of death among people ages 25–64 and associated with a mortality rate of 11.5 per 100,000 people.1 In 2010, 101,000 people were discharged from the hospital with chronic liver disease and cirrhosis as the first-listed diagnosis.2 Given the myriad etiologies and the asymptomatic nature of many of these conditions, hospitalists frequently encounter patients presenting with advanced disease.

Evaluation

The first step in evaluation is to differentiate cirrhotic from non-cirrhotic liver disease. Figure 1 lists physical exam and laboratory findings helpful in staging liver disease. Imaging (ultrasound, computerized tomography [CT], or magnetic resonance imaging [MRI]) is not diagnostic in isolation but can be used to confirm cirrhosis in the presence of associated findings on exam and laboratory studies.

The gold standard for diagnosis is liver biopsy, although this is now usually reserved for atypical cases or where the etiology of cirrhosis is unclear. Alcohol and viral hepatitis (B and C) are the most common causes of chronic liver disease, with nonalcoholic steatohepatitis (NASH) increasing in prevalence. Other less common etiologies and characteristic test findings are listed in Figure 2.

Recently, the Centers for Disease Control and Prevention (CDC) recommended that adults born between 1945 and 1965 receive one-time testing for hepatitis C virus (HCV) infection, regardless of other risk factors, given the higher prevalence in this birth cohort and the introduction of newer oral treatments that achieve sustained virologic response.3

Management

The three classic complications of cirrhosis that will typically prompt inpatient admission are volume overload/ascites, gastrointestinal variceal bleeding, and hepatic encephalopathy.

Volume overload/ascites. Ascites is the most common major complication of cirrhosis, with roughly 50% of patients with asymptomatic cirrhosis developing ascites within 10 years.4 Ascites development portends a poor prognosis, with a mortality of 15% within one year and 44% within five years of diagnosis.4 Patients presenting with new-onset ascites should have a diagnostic paracentesis performed to determine the etiology and evaluate for infection.

Ascitic fluid should be sent for an albumin level and a cell count with differential. A serum-ascites albumin gradient (SAAG) of greater than or equal to 1.1 g/dL is consistent with portal hypertension and cirrhosis, while values less than 1.1 g/dL suggest a non-cirrhotic cause, such as infection or malignancy. Due to the high prevalence of spontaneous bacterial peritonitis (SBP) in hospitalized patients, fluid should also be immediately inoculated in aerobic and anaerobic culture bottles at the bedside, as this has been shown to improve the yield compared to inoculation of culture bottles in the laboratory. Other testing (such as cytology for the evaluation of malignancy) should only be performed if there is significant concern for a particular disease since the vast majority of cases are secondary to uncomplicated cirrhosis.4

In patients with a large amount of ascites and related symptoms (eg, abdominal pain, shortness of breath), therapeutic paracentesis should be performed. Although there is controversy over the need for routine albumin administration, guidelines currently recommend the infusion of 6–8 g of albumin per liter of ascites removed for paracentesis volumes of greater than 4–5 liters.4

No data support the routine administration of fresh frozen plasma (FFP) or platelets prior to paracentesis. Although significant complications of paracentesis (including bowel perforation and hemorrhage) may occur, these are exceedingly rare. Ultrasonography can be used to decrease risks and identify suitable pockets of fluid to tap, even when fluid is not obvious on physical exam alone.5

 

For patients with significant edema or ascites that is due to portal hypertension (SAAG >1.1 g/dL), the first-line therapy is sodium restriction to less than 2,000 mg/day. Consulting a nutritionist may be beneficial for patient education.

For patients with significant natriuresis (>78 mmol daily urine sodium excretion), dietary restriction alone can manage fluid retention. Most patients (85%–90%), however, require diuretics to increase sodium output. Single-agent spironolactone is more efficacious than single-agent furosemide, but diuresis is improved when both agents are used.4 A dosing regimen of once-daily 40 mg furosemide and 100 mg spironolactone is the recommended starting regimen to promote diuresis while maintaining normokalemia. Due to the long half-life of spironolactone, the dose can be increased every three to five days if needed for diuresis.4

Gastroesophageal variceal bleeding. Approximately 50% of patients with cirrhosis have gastroesophageal varices as a consequence of portal hypertension, with prevalence increasing in those with more severe disease.6 As many patients with cirrhosis have advanced disease at the time of diagnosis, it is recommended that patients be referred for endoscopic screening when diagnosed.6 Nonselective beta-blockers decrease the risk of bleeding in patients with known varices but should not be initiated empirically in all patients with cirrhosis given significant side effects, including worsening of ascites.

There is increasing evidence that there is a “window” period for beta-blocker use in cirrhosis with the window opening after the diagnosis of varices and the window closing at advanced stages of disease (marked by an episode of spontaneous bacterial peritonitis, refractory ascites, or hepatorenal syndrome, for example).7

Hepatic encephalopathy. Hepatic encephalopathy (HE) is another complication of portal hypertension and is seen in 10%–14% of patients at the time of cirrhosis diagnosis.8 Overt HE is estimated to occur in 30%–40% of patients with cirrhosis at some point during their disease course, and more subtle forms (minimal or covert HE) are seen in up to 80%.8 HE can cause numerous neurologic and psychiatric issues including personality changes, poor memory, sleep-wake disturbances, and alterations in consciousness.

In patients with an episode of encephalopathy, precipitating factors should be evaluated. Typical precipitants include infections, bleeding, electrolyte disorders, and constipation. Ammonia levels are frequently drawn as part of the evaluation of hepatic encephalopathy, but elevated levels do not significantly change diagnostic probabilities or add prognostic information.8 A low ammonia level, on the other hand, may be useful in lowering the probability of hepatic encephalopathy in a patient with altered mental status of unknown etiology.8

Routine primary prophylaxis of HE in all patients with cirrhosis is not currently recommended. Treatment is only recommended in patients with overt HE, with secondary prophylaxis administered following an episode due to the high risk for recurrence.

Other Issues

VTE prophylaxis. Although patients with cirrhosis are often presumed to be “auto-anticoagulated” due to an elevated international normalized ratio (INR), they experience thrombotic complications during hospitalization at the same rate or higher than patients with other chronic illnesses.9 Unfortunately, studies examining venous thromboembolism (VTE) prophylaxis in hospitalized patients have generally excluded cirrhotics. Therefore, risks/benefits of prophylaxis need to be considered on an individual basis, taking into account the presence of varices (if known), platelet count, and other VTE risk factors.

Drugs to avoid. As detailed above, nonselective beta-blockers should be avoided when outside the “window” period of benefit. Patients with cirrhosis should be counseled to avoid nonsteroidal anti-inflammatory drugs (NSAIDs) due to an increased risk of bleeding and renal dysfunction. ACE inhibitors (ACE-Is) and angiotensin-receptor blockers (ARBs) can also precipitate renal dysfunction and should generally be avoided unless strongly indicated for another diagnosis.

There is conflicting evidence with regard to whether the use of proton-pump inhibitors (PPIs) in cirrhotics increases the risk of SBP.10,11 Nevertheless, it is prudent to reevaluate the need for PPIs in patients with cirrhosis to determine where a true indication exists.

 

Post-hospitalization care. Patients with a new diagnosis of cirrhosis require screening for esophageal varices and hepatocellular carcinoma (HCC), with frequency of subsequent testing based on initial results. They should also be immunized against hepatitis A (HAV) and hepatitis B (HBV), if not already immune. Specific treatments are available for many causes of cirrhosis, including new antiviral agents against hepatitis C (HCV), and liver transplantation is an option for select patients. Given the complexity of subsequent diagnostic and treatment options, patients with new cirrhosis should be referred to a gastroenterologist or hepatologist, if possible.

Back to the Case

The patient is hospitalized, and a large-volume paracentesis is performed. Four liters are removed without the administration of albumin. Ascitic fluid analysis reveals a SAAG of greater than 1.1 g/dL and a polymorphonuclear cell count of 50 cell/mm3, suggesting ascites due to portal hypertension and ruling out infection. Nutrition is consulted and educates the patient on a restricted-sodium diet. Furosemide is started at 40 mg daily; spironolactone is started at 100 mg daily. Initial workup and serologies demonstrate active HCV infection (HCV RNA positive), with immunity to HBV due to vaccination. HAV vaccination is administered given lack of seropositivity. The patient is screened for alcohol and found not to drink alcohol. By the time of discharge, the patient is experiencing daily 0.5 kg weight loss due to diuretics and has stable renal function. The patient is referred to outpatient gastroenterology for gastroesophageal variceal screening and consideration of HCV treatment and/or liver transplantation.

Bottom Line

Workup and management of cirrhosis should focus on revealing the underlying etiology, managing complications, and discharging patients with a comprehensive follow-up plan. TH

Dr. Sehgal and Dr. Hanson are hospitalists in the division of hospital medicine at the University of Texas Health Science Center at San Antonio and the South Texas Veterans Health Care System.

References

1. Heron M. Deaths: leading causes for 2012. Natl Vital Stat Rep. 2015;64(10):1-93.
2. Chronic liver disease and cirrhosis. Centers for Disease Control and Prevention website. Accessed March 17, 2016.
3. Smith BD, Morgan RL, Beckett GA, Falck-Ytter Y, Holtzman D, Ward JW. Hepatitis C virus testing of persons born during 1945-1965: recommendations from the Centers for Disease Control and Prevention. Ann Intern Med. 2012;157(11):817-822. doi:10.7326/0003-4819-157-9-201211060-00529.
4. Runyon BA, AASLD. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology. 2013;57(4):1651-1653. doi:10.1002/hep.26359.
5. Udell JA, Wang CS, Tinmouth J, et al. Does this patient with liver disease have cirrhosis? JAMA. 2012;307(8):832-842. doi:10.1001/jama.2012.186.
6. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W, Practice Guidelines Committee of the American Association for the Study of Liver Diseases, Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46(3):922-938. doi:10.1002/hep.21907.
7. Mandorfer M, Bota S, Schwabl P, et al. Nonselective β blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterology. 2014;146(7):1680-90.e1. doi:10.1053/j.gastro.2014.03.005.
8. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715-735. doi:10.1002/hep.27210.
9. Khoury T, Ayman AR, Cohen J, Daher S, Shmuel C, Mizrahi M. The complex role of anticoagulation in cirrhosis: an updated review of where we are and where we are going. Digestion. 2016;93(2):149-159. doi:10.1159/000442877.
10. Terg R, Casciato P, Garbe C, et al. Proton pump inhibitor therapy does not increase the incidence of spontaneous bacterial peritonitis in cirrhosis: a multicenter prospective study. J Hepatol. 2015;62(5):1056-1060. doi:10.1016/j.jhep.2014.11.036.
11. Deshpande A, Pasupuleti V, Thota P, et al. Acid-suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. J Gastroenterol Hepatol. 2013;28(2):235-242. doi:10.1111/jgh.12065.

 

Key Points

• Cirrhosis has many etiologies, and new diagnoses require further investigation as to the underlying etiology.
• Initial management should focus on evaluation and treatment of complications, including ascites, esophageal varices, and hepatic encephalopathy.
• A diagnostic paracentesis, salt restriction, and a nutrition consult are the initial therapies for ascites although most patients will also require diuretics to increase sodium excretion.
• Once stabilized, the cirrhotic patient will require specialty care for possible liver biopsy (if etiology remains unclear), treatment (eg, HCV antivirals), and/or referral for liver transplantation.

The Case

A 50-year-old man with no known medical history presents with two months of increasing abdominal distension. Exam is notable for scleral icterus, telangiectasias on the upper chest, abdominal distention with a positive fluid wave, and bilateral pitting lower-extremity edema. An abdominal ultrasound shows large ascites and a nodular liver consistent with cirrhosis. How should this patient with newly diagnosed cirrhosis be evaluated and managed?

Background

Cirrhosis is a leading cause of death among people ages 25–64 and associated with a mortality rate of 11.5 per 100,000 people.1 In 2010, 101,000 people were discharged from the hospital with chronic liver disease and cirrhosis as the first-listed diagnosis.2 Given the myriad etiologies and the asymptomatic nature of many of these conditions, hospitalists frequently encounter patients presenting with advanced disease.

Evaluation

The first step in evaluation is to differentiate cirrhotic from non-cirrhotic liver disease. Figure 1 lists physical exam and laboratory findings helpful in staging liver disease. Imaging (ultrasound, computerized tomography [CT], or magnetic resonance imaging [MRI]) is not diagnostic in isolation but can be used to confirm cirrhosis in the presence of associated findings on exam and laboratory studies.

The gold standard for diagnosis is liver biopsy, although this is now usually reserved for atypical cases or where the etiology of cirrhosis is unclear. Alcohol and viral hepatitis (B and C) are the most common causes of chronic liver disease, with nonalcoholic steatohepatitis (NASH) increasing in prevalence. Other less common etiologies and characteristic test findings are listed in Figure 2.

Recently, the Centers for Disease Control and Prevention (CDC) recommended that adults born between 1945 and 1965 receive one-time testing for hepatitis C virus (HCV) infection, regardless of other risk factors, given the higher prevalence in this birth cohort and the introduction of newer oral treatments that achieve sustained virologic response.3

Management

The three classic complications of cirrhosis that will typically prompt inpatient admission are volume overload/ascites, gastrointestinal variceal bleeding, and hepatic encephalopathy.

Volume overload/ascites. Ascites is the most common major complication of cirrhosis, with roughly 50% of patients with asymptomatic cirrhosis developing ascites within 10 years.4 Ascites development portends a poor prognosis, with a mortality of 15% within one year and 44% within five years of diagnosis.4 Patients presenting with new-onset ascites should have a diagnostic paracentesis performed to determine the etiology and evaluate for infection.

Ascitic fluid should be sent for an albumin level and a cell count with differential. A serum-ascites albumin gradient (SAAG) of greater than or equal to 1.1 g/dL is consistent with portal hypertension and cirrhosis, while values less than 1.1 g/dL suggest a non-cirrhotic cause, such as infection or malignancy. Due to the high prevalence of spontaneous bacterial peritonitis (SBP) in hospitalized patients, fluid should also be immediately inoculated in aerobic and anaerobic culture bottles at the bedside, as this has been shown to improve the yield compared to inoculation of culture bottles in the laboratory. Other testing (such as cytology for the evaluation of malignancy) should only be performed if there is significant concern for a particular disease since the vast majority of cases are secondary to uncomplicated cirrhosis.4

In patients with a large amount of ascites and related symptoms (eg, abdominal pain, shortness of breath), therapeutic paracentesis should be performed. Although there is controversy over the need for routine albumin administration, guidelines currently recommend the infusion of 6–8 g of albumin per liter of ascites removed for paracentesis volumes of greater than 4–5 liters.4

No data support the routine administration of fresh frozen plasma (FFP) or platelets prior to paracentesis. Although significant complications of paracentesis (including bowel perforation and hemorrhage) may occur, these are exceedingly rare. Ultrasonography can be used to decrease risks and identify suitable pockets of fluid to tap, even when fluid is not obvious on physical exam alone.5

 

For patients with significant edema or ascites that is due to portal hypertension (SAAG >1.1 g/dL), the first-line therapy is sodium restriction to less than 2,000 mg/day. Consulting a nutritionist may be beneficial for patient education.

For patients with significant natriuresis (>78 mmol daily urine sodium excretion), dietary restriction alone can manage fluid retention. Most patients (85%–90%), however, require diuretics to increase sodium output. Single-agent spironolactone is more efficacious than single-agent furosemide, but diuresis is improved when both agents are used.4 A dosing regimen of once-daily 40 mg furosemide and 100 mg spironolactone is the recommended starting regimen to promote diuresis while maintaining normokalemia. Due to the long half-life of spironolactone, the dose can be increased every three to five days if needed for diuresis.4

Gastroesophageal variceal bleeding. Approximately 50% of patients with cirrhosis have gastroesophageal varices as a consequence of portal hypertension, with prevalence increasing in those with more severe disease.6 As many patients with cirrhosis have advanced disease at the time of diagnosis, it is recommended that patients be referred for endoscopic screening when diagnosed.6 Nonselective beta-blockers decrease the risk of bleeding in patients with known varices but should not be initiated empirically in all patients with cirrhosis given significant side effects, including worsening of ascites.

There is increasing evidence that there is a “window” period for beta-blocker use in cirrhosis with the window opening after the diagnosis of varices and the window closing at advanced stages of disease (marked by an episode of spontaneous bacterial peritonitis, refractory ascites, or hepatorenal syndrome, for example).7

Hepatic encephalopathy. Hepatic encephalopathy (HE) is another complication of portal hypertension and is seen in 10%–14% of patients at the time of cirrhosis diagnosis.8 Overt HE is estimated to occur in 30%–40% of patients with cirrhosis at some point during their disease course, and more subtle forms (minimal or covert HE) are seen in up to 80%.8 HE can cause numerous neurologic and psychiatric issues including personality changes, poor memory, sleep-wake disturbances, and alterations in consciousness.

In patients with an episode of encephalopathy, precipitating factors should be evaluated. Typical precipitants include infections, bleeding, electrolyte disorders, and constipation. Ammonia levels are frequently drawn as part of the evaluation of hepatic encephalopathy, but elevated levels do not significantly change diagnostic probabilities or add prognostic information.8 A low ammonia level, on the other hand, may be useful in lowering the probability of hepatic encephalopathy in a patient with altered mental status of unknown etiology.8

Routine primary prophylaxis of HE in all patients with cirrhosis is not currently recommended. Treatment is only recommended in patients with overt HE, with secondary prophylaxis administered following an episode due to the high risk for recurrence.

Other Issues

VTE prophylaxis. Although patients with cirrhosis are often presumed to be “auto-anticoagulated” due to an elevated international normalized ratio (INR), they experience thrombotic complications during hospitalization at the same rate or higher than patients with other chronic illnesses.9 Unfortunately, studies examining venous thromboembolism (VTE) prophylaxis in hospitalized patients have generally excluded cirrhotics. Therefore, risks/benefits of prophylaxis need to be considered on an individual basis, taking into account the presence of varices (if known), platelet count, and other VTE risk factors.

Drugs to avoid. As detailed above, nonselective beta-blockers should be avoided when outside the “window” period of benefit. Patients with cirrhosis should be counseled to avoid nonsteroidal anti-inflammatory drugs (NSAIDs) due to an increased risk of bleeding and renal dysfunction. ACE inhibitors (ACE-Is) and angiotensin-receptor blockers (ARBs) can also precipitate renal dysfunction and should generally be avoided unless strongly indicated for another diagnosis.

There is conflicting evidence with regard to whether the use of proton-pump inhibitors (PPIs) in cirrhotics increases the risk of SBP.10,11 Nevertheless, it is prudent to reevaluate the need for PPIs in patients with cirrhosis to determine where a true indication exists.

 

Post-hospitalization care. Patients with a new diagnosis of cirrhosis require screening for esophageal varices and hepatocellular carcinoma (HCC), with frequency of subsequent testing based on initial results. They should also be immunized against hepatitis A (HAV) and hepatitis B (HBV), if not already immune. Specific treatments are available for many causes of cirrhosis, including new antiviral agents against hepatitis C (HCV), and liver transplantation is an option for select patients. Given the complexity of subsequent diagnostic and treatment options, patients with new cirrhosis should be referred to a gastroenterologist or hepatologist, if possible.

Back to the Case

The patient is hospitalized, and a large-volume paracentesis is performed. Four liters are removed without the administration of albumin. Ascitic fluid analysis reveals a SAAG of greater than 1.1 g/dL and a polymorphonuclear cell count of 50 cell/mm3, suggesting ascites due to portal hypertension and ruling out infection. Nutrition is consulted and educates the patient on a restricted-sodium diet. Furosemide is started at 40 mg daily; spironolactone is started at 100 mg daily. Initial workup and serologies demonstrate active HCV infection (HCV RNA positive), with immunity to HBV due to vaccination. HAV vaccination is administered given lack of seropositivity. The patient is screened for alcohol and found not to drink alcohol. By the time of discharge, the patient is experiencing daily 0.5 kg weight loss due to diuretics and has stable renal function. The patient is referred to outpatient gastroenterology for gastroesophageal variceal screening and consideration of HCV treatment and/or liver transplantation.

Bottom Line

Workup and management of cirrhosis should focus on revealing the underlying etiology, managing complications, and discharging patients with a comprehensive follow-up plan. TH

Dr. Sehgal and Dr. Hanson are hospitalists in the division of hospital medicine at the University of Texas Health Science Center at San Antonio and the South Texas Veterans Health Care System.

References

1. Heron M. Deaths: leading causes for 2012. Natl Vital Stat Rep. 2015;64(10):1-93.
2. Chronic liver disease and cirrhosis. Centers for Disease Control and Prevention website. Accessed March 17, 2016.
3. Smith BD, Morgan RL, Beckett GA, Falck-Ytter Y, Holtzman D, Ward JW. Hepatitis C virus testing of persons born during 1945-1965: recommendations from the Centers for Disease Control and Prevention. Ann Intern Med. 2012;157(11):817-822. doi:10.7326/0003-4819-157-9-201211060-00529.
4. Runyon BA, AASLD. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology. 2013;57(4):1651-1653. doi:10.1002/hep.26359.
5. Udell JA, Wang CS, Tinmouth J, et al. Does this patient with liver disease have cirrhosis? JAMA. 2012;307(8):832-842. doi:10.1001/jama.2012.186.
6. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W, Practice Guidelines Committee of the American Association for the Study of Liver Diseases, Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46(3):922-938. doi:10.1002/hep.21907.
7. Mandorfer M, Bota S, Schwabl P, et al. Nonselective β blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterology. 2014;146(7):1680-90.e1. doi:10.1053/j.gastro.2014.03.005.
8. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715-735. doi:10.1002/hep.27210.
9. Khoury T, Ayman AR, Cohen J, Daher S, Shmuel C, Mizrahi M. The complex role of anticoagulation in cirrhosis: an updated review of where we are and where we are going. Digestion. 2016;93(2):149-159. doi:10.1159/000442877.
10. Terg R, Casciato P, Garbe C, et al. Proton pump inhibitor therapy does not increase the incidence of spontaneous bacterial peritonitis in cirrhosis: a multicenter prospective study. J Hepatol. 2015;62(5):1056-1060. doi:10.1016/j.jhep.2014.11.036.
11. Deshpande A, Pasupuleti V, Thota P, et al. Acid-suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. J Gastroenterol Hepatol. 2013;28(2):235-242. doi:10.1111/jgh.12065.

 

Key Points

• Cirrhosis has many etiologies, and new diagnoses require further investigation as to the underlying etiology.
• Initial management should focus on evaluation and treatment of complications, including ascites, esophageal varices, and hepatic encephalopathy.
• A diagnostic paracentesis, salt restriction, and a nutrition consult are the initial therapies for ascites although most patients will also require diuretics to increase sodium excretion.
• Once stabilized, the cirrhotic patient will require specialty care for possible liver biopsy (if etiology remains unclear), treatment (eg, HCV antivirals), and/or referral for liver transplantation.

The Case

A 50-year-old man with no known medical history presents with two months of increasing abdominal distension. Exam is notable for scleral icterus, telangiectasias on the upper chest, abdominal distention with a positive fluid wave, and bilateral pitting lower-extremity edema. An abdominal ultrasound shows large ascites and a nodular liver consistent with cirrhosis. How should this patient with newly diagnosed cirrhosis be evaluated and managed?

Background

Cirrhosis is a leading cause of death among people ages 25–64 and associated with a mortality rate of 11.5 per 100,000 people.1 In 2010, 101,000 people were discharged from the hospital with chronic liver disease and cirrhosis as the first-listed diagnosis.2 Given the myriad etiologies and the asymptomatic nature of many of these conditions, hospitalists frequently encounter patients presenting with advanced disease.

Evaluation

The first step in evaluation is to differentiate cirrhotic from non-cirrhotic liver disease. Figure 1 lists physical exam and laboratory findings helpful in staging liver disease. Imaging (ultrasound, computerized tomography [CT], or magnetic resonance imaging [MRI]) is not diagnostic in isolation but can be used to confirm cirrhosis in the presence of associated findings on exam and laboratory studies.

The gold standard for diagnosis is liver biopsy, although this is now usually reserved for atypical cases or where the etiology of cirrhosis is unclear. Alcohol and viral hepatitis (B and C) are the most common causes of chronic liver disease, with nonalcoholic steatohepatitis (NASH) increasing in prevalence. Other less common etiologies and characteristic test findings are listed in Figure 2.

Recently, the Centers for Disease Control and Prevention (CDC) recommended that adults born between 1945 and 1965 receive one-time testing for hepatitis C virus (HCV) infection, regardless of other risk factors, given the higher prevalence in this birth cohort and the introduction of newer oral treatments that achieve sustained virologic response.3

Management

The three classic complications of cirrhosis that will typically prompt inpatient admission are volume overload/ascites, gastrointestinal variceal bleeding, and hepatic encephalopathy.

Volume overload/ascites. Ascites is the most common major complication of cirrhosis, with roughly 50% of patients with asymptomatic cirrhosis developing ascites within 10 years.4 Ascites development portends a poor prognosis, with a mortality of 15% within one year and 44% within five years of diagnosis.4 Patients presenting with new-onset ascites should have a diagnostic paracentesis performed to determine the etiology and evaluate for infection.

Ascitic fluid should be sent for an albumin level and a cell count with differential. A serum-ascites albumin gradient (SAAG) of greater than or equal to 1.1 g/dL is consistent with portal hypertension and cirrhosis, while values less than 1.1 g/dL suggest a non-cirrhotic cause, such as infection or malignancy. Due to the high prevalence of spontaneous bacterial peritonitis (SBP) in hospitalized patients, fluid should also be immediately inoculated in aerobic and anaerobic culture bottles at the bedside, as this has been shown to improve the yield compared to inoculation of culture bottles in the laboratory. Other testing (such as cytology for the evaluation of malignancy) should only be performed if there is significant concern for a particular disease since the vast majority of cases are secondary to uncomplicated cirrhosis.4

In patients with a large amount of ascites and related symptoms (eg, abdominal pain, shortness of breath), therapeutic paracentesis should be performed. Although there is controversy over the need for routine albumin administration, guidelines currently recommend the infusion of 6–8 g of albumin per liter of ascites removed for paracentesis volumes of greater than 4–5 liters.4

No data support the routine administration of fresh frozen plasma (FFP) or platelets prior to paracentesis. Although significant complications of paracentesis (including bowel perforation and hemorrhage) may occur, these are exceedingly rare. Ultrasonography can be used to decrease risks and identify suitable pockets of fluid to tap, even when fluid is not obvious on physical exam alone.5

 

For patients with significant edema or ascites that is due to portal hypertension (SAAG >1.1 g/dL), the first-line therapy is sodium restriction to less than 2,000 mg/day. Consulting a nutritionist may be beneficial for patient education.

For patients with significant natriuresis (>78 mmol daily urine sodium excretion), dietary restriction alone can manage fluid retention. Most patients (85%–90%), however, require diuretics to increase sodium output. Single-agent spironolactone is more efficacious than single-agent furosemide, but diuresis is improved when both agents are used.4 A dosing regimen of once-daily 40 mg furosemide and 100 mg spironolactone is the recommended starting regimen to promote diuresis while maintaining normokalemia. Due to the long half-life of spironolactone, the dose can be increased every three to five days if needed for diuresis.4

Gastroesophageal variceal bleeding. Approximately 50% of patients with cirrhosis have gastroesophageal varices as a consequence of portal hypertension, with prevalence increasing in those with more severe disease.6 As many patients with cirrhosis have advanced disease at the time of diagnosis, it is recommended that patients be referred for endoscopic screening when diagnosed.6 Nonselective beta-blockers decrease the risk of bleeding in patients with known varices but should not be initiated empirically in all patients with cirrhosis given significant side effects, including worsening of ascites.

There is increasing evidence that there is a “window” period for beta-blocker use in cirrhosis with the window opening after the diagnosis of varices and the window closing at advanced stages of disease (marked by an episode of spontaneous bacterial peritonitis, refractory ascites, or hepatorenal syndrome, for example).7

Hepatic encephalopathy. Hepatic encephalopathy (HE) is another complication of portal hypertension and is seen in 10%–14% of patients at the time of cirrhosis diagnosis.8 Overt HE is estimated to occur in 30%–40% of patients with cirrhosis at some point during their disease course, and more subtle forms (minimal or covert HE) are seen in up to 80%.8 HE can cause numerous neurologic and psychiatric issues including personality changes, poor memory, sleep-wake disturbances, and alterations in consciousness.

In patients with an episode of encephalopathy, precipitating factors should be evaluated. Typical precipitants include infections, bleeding, electrolyte disorders, and constipation. Ammonia levels are frequently drawn as part of the evaluation of hepatic encephalopathy, but elevated levels do not significantly change diagnostic probabilities or add prognostic information.8 A low ammonia level, on the other hand, may be useful in lowering the probability of hepatic encephalopathy in a patient with altered mental status of unknown etiology.8

Routine primary prophylaxis of HE in all patients with cirrhosis is not currently recommended. Treatment is only recommended in patients with overt HE, with secondary prophylaxis administered following an episode due to the high risk for recurrence.

Other Issues

VTE prophylaxis. Although patients with cirrhosis are often presumed to be “auto-anticoagulated” due to an elevated international normalized ratio (INR), they experience thrombotic complications during hospitalization at the same rate or higher than patients with other chronic illnesses.9 Unfortunately, studies examining venous thromboembolism (VTE) prophylaxis in hospitalized patients have generally excluded cirrhotics. Therefore, risks/benefits of prophylaxis need to be considered on an individual basis, taking into account the presence of varices (if known), platelet count, and other VTE risk factors.

Drugs to avoid. As detailed above, nonselective beta-blockers should be avoided when outside the “window” period of benefit. Patients with cirrhosis should be counseled to avoid nonsteroidal anti-inflammatory drugs (NSAIDs) due to an increased risk of bleeding and renal dysfunction. ACE inhibitors (ACE-Is) and angiotensin-receptor blockers (ARBs) can also precipitate renal dysfunction and should generally be avoided unless strongly indicated for another diagnosis.

There is conflicting evidence with regard to whether the use of proton-pump inhibitors (PPIs) in cirrhotics increases the risk of SBP.10,11 Nevertheless, it is prudent to reevaluate the need for PPIs in patients with cirrhosis to determine where a true indication exists.

 

Post-hospitalization care. Patients with a new diagnosis of cirrhosis require screening for esophageal varices and hepatocellular carcinoma (HCC), with frequency of subsequent testing based on initial results. They should also be immunized against hepatitis A (HAV) and hepatitis B (HBV), if not already immune. Specific treatments are available for many causes of cirrhosis, including new antiviral agents against hepatitis C (HCV), and liver transplantation is an option for select patients. Given the complexity of subsequent diagnostic and treatment options, patients with new cirrhosis should be referred to a gastroenterologist or hepatologist, if possible.

Back to the Case

The patient is hospitalized, and a large-volume paracentesis is performed. Four liters are removed without the administration of albumin. Ascitic fluid analysis reveals a SAAG of greater than 1.1 g/dL and a polymorphonuclear cell count of 50 cell/mm3, suggesting ascites due to portal hypertension and ruling out infection. Nutrition is consulted and educates the patient on a restricted-sodium diet. Furosemide is started at 40 mg daily; spironolactone is started at 100 mg daily. Initial workup and serologies demonstrate active HCV infection (HCV RNA positive), with immunity to HBV due to vaccination. HAV vaccination is administered given lack of seropositivity. The patient is screened for alcohol and found not to drink alcohol. By the time of discharge, the patient is experiencing daily 0.5 kg weight loss due to diuretics and has stable renal function. The patient is referred to outpatient gastroenterology for gastroesophageal variceal screening and consideration of HCV treatment and/or liver transplantation.

Bottom Line

Workup and management of cirrhosis should focus on revealing the underlying etiology, managing complications, and discharging patients with a comprehensive follow-up plan. TH

Dr. Sehgal and Dr. Hanson are hospitalists in the division of hospital medicine at the University of Texas Health Science Center at San Antonio and the South Texas Veterans Health Care System.

References

1. Heron M. Deaths: leading causes for 2012. Natl Vital Stat Rep. 2015;64(10):1-93.
2. Chronic liver disease and cirrhosis. Centers for Disease Control and Prevention website. Accessed March 17, 2016.
3. Smith BD, Morgan RL, Beckett GA, Falck-Ytter Y, Holtzman D, Ward JW. Hepatitis C virus testing of persons born during 1945-1965: recommendations from the Centers for Disease Control and Prevention. Ann Intern Med. 2012;157(11):817-822. doi:10.7326/0003-4819-157-9-201211060-00529.
4. Runyon BA, AASLD. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology. 2013;57(4):1651-1653. doi:10.1002/hep.26359.
5. Udell JA, Wang CS, Tinmouth J, et al. Does this patient with liver disease have cirrhosis? JAMA. 2012;307(8):832-842. doi:10.1001/jama.2012.186.
6. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W, Practice Guidelines Committee of the American Association for the Study of Liver Diseases, Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46(3):922-938. doi:10.1002/hep.21907.
7. Mandorfer M, Bota S, Schwabl P, et al. Nonselective β blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterology. 2014;146(7):1680-90.e1. doi:10.1053/j.gastro.2014.03.005.
8. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715-735. doi:10.1002/hep.27210.
9. Khoury T, Ayman AR, Cohen J, Daher S, Shmuel C, Mizrahi M. The complex role of anticoagulation in cirrhosis: an updated review of where we are and where we are going. Digestion. 2016;93(2):149-159. doi:10.1159/000442877.
10. Terg R, Casciato P, Garbe C, et al. Proton pump inhibitor therapy does not increase the incidence of spontaneous bacterial peritonitis in cirrhosis: a multicenter prospective study. J Hepatol. 2015;62(5):1056-1060. doi:10.1016/j.jhep.2014.11.036.
11. Deshpande A, Pasupuleti V, Thota P, et al. Acid-suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. J Gastroenterol Hepatol. 2013;28(2):235-242. doi:10.1111/jgh.12065.

 

Key Points

• Cirrhosis has many etiologies, and new diagnoses require further investigation as to the underlying etiology.
• Initial management should focus on evaluation and treatment of complications, including ascites, esophageal varices, and hepatic encephalopathy.
• A diagnostic paracentesis, salt restriction, and a nutrition consult are the initial therapies for ascites although most patients will also require diuretics to increase sodium excretion.
• Once stabilized, the cirrhotic patient will require specialty care for possible liver biopsy (if etiology remains unclear), treatment (eg, HCV antivirals), and/or referral for liver transplantation.

NEW YORK - Greater access to alcohol is linked with more atrial fibrillation but less myocardial infarction and congestive heart failure, researchers report.

Dr. Gregory M. Marcus, from the Division of Cardiology at the University of California, San Francisco, and colleagues conducted an observational cohort study of differences in health outcomes based on alcohol sales laws by county in Texas.

All patients were residents of Texas, 21 years old or older, and were admitted to hospitals in Texas between 2005 and 2010. More than 1 million patients were included in the analysis.

Of the counties, 47 were wet (no restrictions on the sale of alcohol) and 29 were dry (prohibition of alcohol sales). Seven of them changed from dry to wet during the study period.

The main cardiovascular outcomes were atrial fibrillation, acute myocardial infarction, and congestive heart failure.

After multivariable adjustment, wet county residents had a greater prevalence (odds ratio 1.05, p=0.007) and incidence (HR 1.07, p=0.014) of atrial fibrillation.

Prevalence of myocardial infarction was lower (OR 0.83, p&lt;0.001), as was its incidence (HR 0.91, p=0.019). Prevalence of congestive heart failure was also lower (OR 0.87, p&lt;0.001).

In the seven dry counties that changed their status to wet, the post-conversion interval (from dry to wet county status) was associated with greater odds of hospitalization for atrial fibrillation (OR 1.07, p=0.001) and congestive heart failure (OR 1.07, p&lt;0.001).

The researchers found no difference in acute myocardial infarction (OR 0.99, p=0.746).

"Cardiovascular disease is the most common cause of death worldwide, and alcohol is the most widely consumed drug in the United States," said Dr. Rory Brett Weiner, a cardiologist at Massachusetts General Hospital in Boston.

He said that studying the impact of alcohol intake on incident cardiovascular disease is important for its public health implications.

"Differences in laws affecting access to alcohol are associated with changes in health outcomes, both harmful and protective," said Dr. Marcus, "but the study's findings shouldn't be used to change any specific legislation."

Dr. Weiner agreed. "The study design minimizes confounders commonly seen in prior research that relied on self-report," he said, "but it still doesn't provide conclusive evidence with regard to the use of alcohol and incident cardiovascular disease."

Dr. Weiner said that the study did not contain information on the level of individual alcohol exposure, and therefore, the impact of the 'dose' of alcohol on cardiovascular outcomes could not be ascertained.

"Based on the question at hand -- the impact of alcohol -- it's unlikely that a randomized controlled study will ever be performed," he said, "so analyses like the current one are important."

According to Dr. Marcus, "We still don't understand the mechanisms underlying the relationship between alcohol and cardiovascular disease, and have a long way to go to achieve the sort of personalized medicine needed to figure out how to counsel an individual patient on their particular "prescribed" amount, if any, of alcohol."

The National Institute on Alcohol Abuse and Alcoholism supported this research. Dr. Marcus reported research support from Medtronic and Pfizer and equity interest in InCarda.

SOURCE: http://bit.ly/1tlx1cx

BMJ 2016

NEW YORK - Greater access to alcohol is linked with more atrial fibrillation but less myocardial infarction and congestive heart failure, researchers report.

Dr. Gregory M. Marcus, from the Division of Cardiology at the University of California, San Francisco, and colleagues conducted an observational cohort study of differences in health outcomes based on alcohol sales laws by county in Texas.

All patients were residents of Texas, 21 years old or older, and were admitted to hospitals in Texas between 2005 and 2010. More than 1 million patients were included in the analysis.

Of the counties, 47 were wet (no restrictions on the sale of alcohol) and 29 were dry (prohibition of alcohol sales). Seven of them changed from dry to wet during the study period.

The main cardiovascular outcomes were atrial fibrillation, acute myocardial infarction, and congestive heart failure.

After multivariable adjustment, wet county residents had a greater prevalence (odds ratio 1.05, p=0.007) and incidence (HR 1.07, p=0.014) of atrial fibrillation.

Prevalence of myocardial infarction was lower (OR 0.83, p&lt;0.001), as was its incidence (HR 0.91, p=0.019). Prevalence of congestive heart failure was also lower (OR 0.87, p&lt;0.001).

In the seven dry counties that changed their status to wet, the post-conversion interval (from dry to wet county status) was associated with greater odds of hospitalization for atrial fibrillation (OR 1.07, p=0.001) and congestive heart failure (OR 1.07, p&lt;0.001).

The researchers found no difference in acute myocardial infarction (OR 0.99, p=0.746).

"Cardiovascular disease is the most common cause of death worldwide, and alcohol is the most widely consumed drug in the United States," said Dr. Rory Brett Weiner, a cardiologist at Massachusetts General Hospital in Boston.

He said that studying the impact of alcohol intake on incident cardiovascular disease is important for its public health implications.

"Differences in laws affecting access to alcohol are associated with changes in health outcomes, both harmful and protective," said Dr. Marcus, "but the study's findings shouldn't be used to change any specific legislation."

Dr. Weiner agreed. "The study design minimizes confounders commonly seen in prior research that relied on self-report," he said, "but it still doesn't provide conclusive evidence with regard to the use of alcohol and incident cardiovascular disease."

Dr. Weiner said that the study did not contain information on the level of individual alcohol exposure, and therefore, the impact of the 'dose' of alcohol on cardiovascular outcomes could not be ascertained.

"Based on the question at hand -- the impact of alcohol -- it's unlikely that a randomized controlled study will ever be performed," he said, "so analyses like the current one are important."

According to Dr. Marcus, "We still don't understand the mechanisms underlying the relationship between alcohol and cardiovascular disease, and have a long way to go to achieve the sort of personalized medicine needed to figure out how to counsel an individual patient on their particular "prescribed" amount, if any, of alcohol."

The National Institute on Alcohol Abuse and Alcoholism supported this research. Dr. Marcus reported research support from Medtronic and Pfizer and equity interest in InCarda.

SOURCE: http://bit.ly/1tlx1cx

BMJ 2016

NEW YORK - Greater access to alcohol is linked with more atrial fibrillation but less myocardial infarction and congestive heart failure, researchers report.

Dr. Gregory M. Marcus, from the Division of Cardiology at the University of California, San Francisco, and colleagues conducted an observational cohort study of differences in health outcomes based on alcohol sales laws by county in Texas.

All patients were residents of Texas, 21 years old or older, and were admitted to hospitals in Texas between 2005 and 2010. More than 1 million patients were included in the analysis.

Of the counties, 47 were wet (no restrictions on the sale of alcohol) and 29 were dry (prohibition of alcohol sales). Seven of them changed from dry to wet during the study period.

The main cardiovascular outcomes were atrial fibrillation, acute myocardial infarction, and congestive heart failure.

After multivariable adjustment, wet county residents had a greater prevalence (odds ratio 1.05, p=0.007) and incidence (HR 1.07, p=0.014) of atrial fibrillation.

Prevalence of myocardial infarction was lower (OR 0.83, p&lt;0.001), as was its incidence (HR 0.91, p=0.019). Prevalence of congestive heart failure was also lower (OR 0.87, p&lt;0.001).

In the seven dry counties that changed their status to wet, the post-conversion interval (from dry to wet county status) was associated with greater odds of hospitalization for atrial fibrillation (OR 1.07, p=0.001) and congestive heart failure (OR 1.07, p&lt;0.001).

The researchers found no difference in acute myocardial infarction (OR 0.99, p=0.746).

"Cardiovascular disease is the most common cause of death worldwide, and alcohol is the most widely consumed drug in the United States," said Dr. Rory Brett Weiner, a cardiologist at Massachusetts General Hospital in Boston.

He said that studying the impact of alcohol intake on incident cardiovascular disease is important for its public health implications.

"Differences in laws affecting access to alcohol are associated with changes in health outcomes, both harmful and protective," said Dr. Marcus, "but the study's findings shouldn't be used to change any specific legislation."

Dr. Weiner agreed. "The study design minimizes confounders commonly seen in prior research that relied on self-report," he said, "but it still doesn't provide conclusive evidence with regard to the use of alcohol and incident cardiovascular disease."

Dr. Weiner said that the study did not contain information on the level of individual alcohol exposure, and therefore, the impact of the 'dose' of alcohol on cardiovascular outcomes could not be ascertained.

"Based on the question at hand -- the impact of alcohol -- it's unlikely that a randomized controlled study will ever be performed," he said, "so analyses like the current one are important."

According to Dr. Marcus, "We still don't understand the mechanisms underlying the relationship between alcohol and cardiovascular disease, and have a long way to go to achieve the sort of personalized medicine needed to figure out how to counsel an individual patient on their particular "prescribed" amount, if any, of alcohol."

The National Institute on Alcohol Abuse and Alcoholism supported this research. Dr. Marcus reported research support from Medtronic and Pfizer and equity interest in InCarda.

SOURCE: http://bit.ly/1tlx1cx

BMJ 2016

NEW YORK - CT scans identify all clinically significant cervical spine injuries in intoxicated patients with blunt trauma, according to a new study.

"I don't think any of the results were particularly surprising to any of us who regularly do trauma care, but what I do think is remarkable about them is that they dispel several long-held myths about the c-spine, intoxicated patients, and the clearance process," Dr. Matthew J. Martin from Legacy Emanuel Medical Center, Portland, Oregon told Reuters Health.

"I think it again confirms that modern CT scan is highly reliable for identifying significant c-spine injuries, but also that the majority of so called 'intoxicated' patients are examinable enough to determine whether the collar can be removed (when combined with the CT scan)," he said.

Up to half of trauma patients are intoxicated, making clearance of the cervical spine a commonly encountered dilemma with both medical and medicolegal implications. Most guidelines indicate that the cervical spine should not be cleared in such patients, resulting in prolonged immobilization or additional imaging even in the face of a normal CT scan.

Dr. Martin's team examined cervical spine clearance practices for intoxicated trauma patients, examined the reliability of cervical spine CT scans for identifying clinically significant injuries (CSIs), and looked for CSIs that might have been missed by CT scans.

Among 1,429 patients who had an alcohol or drug screen performed, 44.2% were intoxicated, the researchers report in JAMA Surgery, online June 15.

Cervical spine injuries were identified in 11.3% of the sober group, 8.1% of the alcohol-intoxicated group, and 12.0% of the drug-intoxicated group.

CT scans yielded negative predictive values of 99.2% for all injuries and 99.8% for unstable injuries. There were five false-negative CT scans, including four central cord syndromes without associated fractures and one potentially unstable injury in a drug-intoxicated patient who presented with clear quadriplegia on examination.

Half of the intoxicated patients were admitted with continued cervical spine immobilization only on the basis of their intoxication. There were no missed CSIs in this group, and all patients were discharged without evidence of an injury or neurologic deficit. They underwent cervical spine immobilization for an average of 15.1 hours, about four times the average time to cervical spine clearance among sober patients (3.7 hours).

"The finding of how long we are keeping these patients in a c-collar based solely on intoxication should raise some eyebrows, and identifies an easy target for process improvement," Dr. Martin said.

"Cervical collars and immobilization are not therapeutic for the vast majority of c-spine injuries; they are really only to prevent inadvertent motion of an unstable c-spine injury," Dr. Martin said. "This is exceedingly rare in a patient who presents with no gross motor deficit, and a high quality CT scan will identify these unstable injuries very reliably. In addition, there are multiple adverse effects of prolonged immobilization, and even of getting an MRI."

"When these are factored in, I think the risk:benefit analysis falls squarely on the side of early clearance based on CT scan," he concluded.

"A key point is that this should be done by experts who are familiar with not only the global concept (the collar can be removed with a negative CT scan), but also the finer points where you could potentially cause harm, or where you should not remove the collar," Dr. Martin added. "This is where a very clear written protocol comes into play and reduces variation or errors that could cause patient harm."

"The results of this study suggest that it is unnecessary to delay cervical spine clearance until intoxicated patients are sober or until magnetic resonance imaging is performed," write Dr. Olubode A. Olufajo and Dr. Ali Salim from Brigham and Women's Hospital, Boston, in a related editorial. "However, caution must be taken in making conclusions based on these data."

"Although the authors conducted the study at an institution with high-quality CT technology and well-trained radiologists, they still recorded a false-negative CT report consistent with a misread," they note. "With the higher potential for this nature of error in lower-resourced settings, it becomes important to compare the costs and benefits of early removal of cervical collars."

 

They wonder, "With our knowledge that intoxicated patients form up to half of the population of trauma patients, is it really safe to risk irreversible injuries in 1% of the population to save a few hours in cervical clearance times?"

Dr. Stephen Asha from the University of New South Wales in Sydney, Australia, who has reported on various aspects of cervical spine imaging, told Reuters Health by email, "I think this study confirms what clinical experience as well as much of the more recent studies on cervical spine CT scanning tells us, which is that if there is nothing abnormal detected on a new generation, multi-slice CT, then the neck can be cleared."

"Of course there were a few missed injuries, but this needs to be put into context: no one just does a test in isolation, it is always combined with a clinical assessment, and a consideration the mechanism of injury," said Dr. Asha, who was not involved in the new work. "In this case there were five injuries not apparent on the CT scan, but all had obvious spinal cord injury on clinical examination before the CT was done, so these injuries were never going to be missed in a real clinical setting."

"MRI use should be carefully considered because the problem with MRI is that it can be over-sensitive, demonstrating abnormal signal suggesting ligamentous injury in patient who simply have a ligamentous 'strain,'" Dr. Asha explained. "The false-positive results then lead to further periods of inappropriate immobilization and testing, with the accompanying costs, inconvenience, and complications."

"In patients in whom the clinical assessment raises no concerns for injury, then a normal CT should herald the end of investigations," he said. "MRI should be reserved for those where the clinical assessment is abnormal or where the CT is abnormal and further evaluation for ligamentous or spinal injury is required."

Dr. Asha concluded, "If the clinical exam is not concerning and the CT is normal, then clear the neck."

SOURCE: http://bit.ly/28MxHxA and http://bit.ly/28MxHO5

JAMA Surg 2016.

NEW YORK - CT scans identify all clinically significant cervical spine injuries in intoxicated patients with blunt trauma, according to a new study.

"I don't think any of the results were particularly surprising to any of us who regularly do trauma care, but what I do think is remarkable about them is that they dispel several long-held myths about the c-spine, intoxicated patients, and the clearance process," Dr. Matthew J. Martin from Legacy Emanuel Medical Center, Portland, Oregon told Reuters Health.

"I think it again confirms that modern CT scan is highly reliable for identifying significant c-spine injuries, but also that the majority of so called 'intoxicated' patients are examinable enough to determine whether the collar can be removed (when combined with the CT scan)," he said.

Up to half of trauma patients are intoxicated, making clearance of the cervical spine a commonly encountered dilemma with both medical and medicolegal implications. Most guidelines indicate that the cervical spine should not be cleared in such patients, resulting in prolonged immobilization or additional imaging even in the face of a normal CT scan.

Dr. Martin's team examined cervical spine clearance practices for intoxicated trauma patients, examined the reliability of cervical spine CT scans for identifying clinically significant injuries (CSIs), and looked for CSIs that might have been missed by CT scans.

Among 1,429 patients who had an alcohol or drug screen performed, 44.2% were intoxicated, the researchers report in JAMA Surgery, online June 15.

Cervical spine injuries were identified in 11.3% of the sober group, 8.1% of the alcohol-intoxicated group, and 12.0% of the drug-intoxicated group.

CT scans yielded negative predictive values of 99.2% for all injuries and 99.8% for unstable injuries. There were five false-negative CT scans, including four central cord syndromes without associated fractures and one potentially unstable injury in a drug-intoxicated patient who presented with clear quadriplegia on examination.

Half of the intoxicated patients were admitted with continued cervical spine immobilization only on the basis of their intoxication. There were no missed CSIs in this group, and all patients were discharged without evidence of an injury or neurologic deficit. They underwent cervical spine immobilization for an average of 15.1 hours, about four times the average time to cervical spine clearance among sober patients (3.7 hours).

"The finding of how long we are keeping these patients in a c-collar based solely on intoxication should raise some eyebrows, and identifies an easy target for process improvement," Dr. Martin said.

"Cervical collars and immobilization are not therapeutic for the vast majority of c-spine injuries; they are really only to prevent inadvertent motion of an unstable c-spine injury," Dr. Martin said. "This is exceedingly rare in a patient who presents with no gross motor deficit, and a high quality CT scan will identify these unstable injuries very reliably. In addition, there are multiple adverse effects of prolonged immobilization, and even of getting an MRI."

"When these are factored in, I think the risk:benefit analysis falls squarely on the side of early clearance based on CT scan," he concluded.

"A key point is that this should be done by experts who are familiar with not only the global concept (the collar can be removed with a negative CT scan), but also the finer points where you could potentially cause harm, or where you should not remove the collar," Dr. Martin added. "This is where a very clear written protocol comes into play and reduces variation or errors that could cause patient harm."

"The results of this study suggest that it is unnecessary to delay cervical spine clearance until intoxicated patients are sober or until magnetic resonance imaging is performed," write Dr. Olubode A. Olufajo and Dr. Ali Salim from Brigham and Women's Hospital, Boston, in a related editorial. "However, caution must be taken in making conclusions based on these data."

"Although the authors conducted the study at an institution with high-quality CT technology and well-trained radiologists, they still recorded a false-negative CT report consistent with a misread," they note. "With the higher potential for this nature of error in lower-resourced settings, it becomes important to compare the costs and benefits of early removal of cervical collars."

 

They wonder, "With our knowledge that intoxicated patients form up to half of the population of trauma patients, is it really safe to risk irreversible injuries in 1% of the population to save a few hours in cervical clearance times?"

Dr. Stephen Asha from the University of New South Wales in Sydney, Australia, who has reported on various aspects of cervical spine imaging, told Reuters Health by email, "I think this study confirms what clinical experience as well as much of the more recent studies on cervical spine CT scanning tells us, which is that if there is nothing abnormal detected on a new generation, multi-slice CT, then the neck can be cleared."

"Of course there were a few missed injuries, but this needs to be put into context: no one just does a test in isolation, it is always combined with a clinical assessment, and a consideration the mechanism of injury," said Dr. Asha, who was not involved in the new work. "In this case there were five injuries not apparent on the CT scan, but all had obvious spinal cord injury on clinical examination before the CT was done, so these injuries were never going to be missed in a real clinical setting."

"MRI use should be carefully considered because the problem with MRI is that it can be over-sensitive, demonstrating abnormal signal suggesting ligamentous injury in patient who simply have a ligamentous 'strain,'" Dr. Asha explained. "The false-positive results then lead to further periods of inappropriate immobilization and testing, with the accompanying costs, inconvenience, and complications."

"In patients in whom the clinical assessment raises no concerns for injury, then a normal CT should herald the end of investigations," he said. "MRI should be reserved for those where the clinical assessment is abnormal or where the CT is abnormal and further evaluation for ligamentous or spinal injury is required."

Dr. Asha concluded, "If the clinical exam is not concerning and the CT is normal, then clear the neck."

SOURCE: http://bit.ly/28MxHxA and http://bit.ly/28MxHO5

JAMA Surg 2016.

NEW YORK - CT scans identify all clinically significant cervical spine injuries in intoxicated patients with blunt trauma, according to a new study.

"I don't think any of the results were particularly surprising to any of us who regularly do trauma care, but what I do think is remarkable about them is that they dispel several long-held myths about the c-spine, intoxicated patients, and the clearance process," Dr. Matthew J. Martin from Legacy Emanuel Medical Center, Portland, Oregon told Reuters Health.

"I think it again confirms that modern CT scan is highly reliable for identifying significant c-spine injuries, but also that the majority of so called 'intoxicated' patients are examinable enough to determine whether the collar can be removed (when combined with the CT scan)," he said.

Up to half of trauma patients are intoxicated, making clearance of the cervical spine a commonly encountered dilemma with both medical and medicolegal implications. Most guidelines indicate that the cervical spine should not be cleared in such patients, resulting in prolonged immobilization or additional imaging even in the face of a normal CT scan.

Dr. Martin's team examined cervical spine clearance practices for intoxicated trauma patients, examined the reliability of cervical spine CT scans for identifying clinically significant injuries (CSIs), and looked for CSIs that might have been missed by CT scans.

Among 1,429 patients who had an alcohol or drug screen performed, 44.2% were intoxicated, the researchers report in JAMA Surgery, online June 15.

Cervical spine injuries were identified in 11.3% of the sober group, 8.1% of the alcohol-intoxicated group, and 12.0% of the drug-intoxicated group.

CT scans yielded negative predictive values of 99.2% for all injuries and 99.8% for unstable injuries. There were five false-negative CT scans, including four central cord syndromes without associated fractures and one potentially unstable injury in a drug-intoxicated patient who presented with clear quadriplegia on examination.

Half of the intoxicated patients were admitted with continued cervical spine immobilization only on the basis of their intoxication. There were no missed CSIs in this group, and all patients were discharged without evidence of an injury or neurologic deficit. They underwent cervical spine immobilization for an average of 15.1 hours, about four times the average time to cervical spine clearance among sober patients (3.7 hours).

"The finding of how long we are keeping these patients in a c-collar based solely on intoxication should raise some eyebrows, and identifies an easy target for process improvement," Dr. Martin said.

"Cervical collars and immobilization are not therapeutic for the vast majority of c-spine injuries; they are really only to prevent inadvertent motion of an unstable c-spine injury," Dr. Martin said. "This is exceedingly rare in a patient who presents with no gross motor deficit, and a high quality CT scan will identify these unstable injuries very reliably. In addition, there are multiple adverse effects of prolonged immobilization, and even of getting an MRI."

"When these are factored in, I think the risk:benefit analysis falls squarely on the side of early clearance based on CT scan," he concluded.

"A key point is that this should be done by experts who are familiar with not only the global concept (the collar can be removed with a negative CT scan), but also the finer points where you could potentially cause harm, or where you should not remove the collar," Dr. Martin added. "This is where a very clear written protocol comes into play and reduces variation or errors that could cause patient harm."

"The results of this study suggest that it is unnecessary to delay cervical spine clearance until intoxicated patients are sober or until magnetic resonance imaging is performed," write Dr. Olubode A. Olufajo and Dr. Ali Salim from Brigham and Women's Hospital, Boston, in a related editorial. "However, caution must be taken in making conclusions based on these data."

"Although the authors conducted the study at an institution with high-quality CT technology and well-trained radiologists, they still recorded a false-negative CT report consistent with a misread," they note. "With the higher potential for this nature of error in lower-resourced settings, it becomes important to compare the costs and benefits of early removal of cervical collars."

 

They wonder, "With our knowledge that intoxicated patients form up to half of the population of trauma patients, is it really safe to risk irreversible injuries in 1% of the population to save a few hours in cervical clearance times?"

Dr. Stephen Asha from the University of New South Wales in Sydney, Australia, who has reported on various aspects of cervical spine imaging, told Reuters Health by email, "I think this study confirms what clinical experience as well as much of the more recent studies on cervical spine CT scanning tells us, which is that if there is nothing abnormal detected on a new generation, multi-slice CT, then the neck can be cleared."

"Of course there were a few missed injuries, but this needs to be put into context: no one just does a test in isolation, it is always combined with a clinical assessment, and a consideration the mechanism of injury," said Dr. Asha, who was not involved in the new work. "In this case there were five injuries not apparent on the CT scan, but all had obvious spinal cord injury on clinical examination before the CT was done, so these injuries were never going to be missed in a real clinical setting."

"MRI use should be carefully considered because the problem with MRI is that it can be over-sensitive, demonstrating abnormal signal suggesting ligamentous injury in patient who simply have a ligamentous 'strain,'" Dr. Asha explained. "The false-positive results then lead to further periods of inappropriate immobilization and testing, with the accompanying costs, inconvenience, and complications."

"In patients in whom the clinical assessment raises no concerns for injury, then a normal CT should herald the end of investigations," he said. "MRI should be reserved for those where the clinical assessment is abnormal or where the CT is abnormal and further evaluation for ligamentous or spinal injury is required."

Dr. Asha concluded, "If the clinical exam is not concerning and the CT is normal, then clear the neck."

SOURCE: http://bit.ly/28MxHxA and http://bit.ly/28MxHO5

JAMA Surg 2016.

Case

A 42-year-old female with a history of intravenous (IV) drug use presents with severe neck pain, gait instability, and bilateral C5 motor weakness. A cervical MRI shows inflammation consistent with infection of her cervical spine at C5 and C6 and significant boney destruction. The patient undergoes kyphoplasty and debridement of her cervical spine. Operative cultures are significant for Pseudomonas aeruginosa. Infectious disease consultants recommend parenteral ceftriaxone for six weeks. The patient has no insurance, and efforts to obtain long-term placement are unsuccessful. The patient states that her last use of IV drugs was three months ago, and she insists that she will abstain from illicit IV drug abuse going forward.

Background

Outpatient parenteral antibiotic treatment (OPAT) has proven to be a cost-effective and relatively safe treatment option for most patients.1 For these reasons, it has been encouraged for use among a wide a variety of clinical situations. Intravenous drug users (IDUs) are often underinsured and have few options other than costly treatment in an inpatient acute-care facility.

A history of illicit injection drug use frequently raises questions about the appropriateness of OPAT. Some of our most vulnerable patients are those who abuse illicit drugs. Due to psychiatric, social, and financial factors, their ability to adequately transition to outpatient care may be limited. They are often underinsured, and appropriate options for inpatient post-acute care may not exist. Hospitalists often feel pressure to discharge these patients despite the lack of optimal follow-up care, and they must weigh the risks and benefits in each case.

The enrollment of IDUs into an OPAT service using a peripherally inserted central catheter (PICC) is controversial and often avoided. No clear-cut guidelines concerning the use of OPAT in IDUs by national medical societies exist.2 Consultants are often reluctant to recommend options that deviate from the typical standard of inpatient or directly observed care. The obvious risk is that a PICC line provides easy and tempting access to veins for continued drug abuse. In addition, there is an increased risk of infection and/or thrombosis if the PICC is abused.3

The safety and efficacy of PICC line use for OPAT in IDUs are unknown, and studies addressing these issues are limited. In one study at the National University Hospital of Singapore, 29 IDU patients received OPAT without complications.4 Patients were closely monitored, including by use of a tamper-proof security seal on the PICC. Infective endocarditis was the primary diagnosis in 42% of the cases studied. There were no deaths or cases of PICC abuse reported. In another abstract presentation, 39 IDU patients at Henry Ford Health System in Detroit were discharged to outpatient therapy with a PICC line and demonstrated a high cure rate (73.3%). Nine patients were lost to follow-up.5

No studies have compared OPAT therapy to inpatient therapy in IDU patients.

Back to the Case

Despite multiple attempts and due to financial considerations, no long-term care facility is able to admit the patient for therapy. The frequency of required antibiotics makes outpatient therapy in an infusion center problematic. The primary service is reluctant to discharge the patient home with a PICC line in place due to the potential of abuse and complications. A “Goals of Care” committee, consisting of several physicians from multiple specialties, legal counsel, and case management, is convened to review the case. The committee concludes that, in this particular case, it would be a reasonable option to discharge the patient to home with a PICC line in place to complete OPAT. A patient agreement document is drafted; it describes the complications of PICC line abuse and stipulates that the patient agrees to drug testing throughout the duration of her treatment. A similar agreement is required by the home infusion company. Both documents are signed by the patient, and she is subsequently discharged home.

 

Bottom Line

Our strategy is to deal with each of these cases as unique situations because no policies, procedures, protocols, or guidelines currently exist. One of the guiding principles should be, despite financial pressures, that the primary focus is on appropriate care of this vulnerable population. A type of “Goals of Care” committee (or organizational equivalent) can be utilized to offer assistance in decision making. Unfortunately, the safety and efficacy of OPAT in IDU patients are uncertain, and there is a lack of studies to support definitive protocols. In select cases, OPAT in IDU patients may be considered, but signed consent of the risks and the patient’s responsibilities concerning OPAT should be clearly documented in the medical record by the discharging team. TH

Dr. Conrad is a hospitalist with Ochsner Health System in New Orleans.

References

1. Tice AD, Hoaglund PA, Nolet B, McKinnon PS, Mozaffari E. Cost perspectives for outpatient intravenous antimicrobial therapy. Pharmacotherapy. 2002;22(2, pt 2):63S-70S.
2. Tice AD, Rehm SJ, Dalovisio JR, et al. Practice guidelines for outpatient parenteral antimicrobial therapy. IDSA guidelines. Clin Infect Dis. 2004;38(12):1651-1672.
3. Chemaly R, de Parres JB, Rehm SJ, et al. Venous thrombosis associated with peripherally inserted central catheters: a retrospective analysis of the Cleveland Clinic experience. Clin Infect Dis. 2002;34(9):1179-1183.
4. Ho J, Archuleta S, Sulaiman Z, Fisher D. Safe and successful treatment of intravenous drug users with a peripherally inserted central catheter in an outpatient parenteral antibiotic treatment service. J Antimicrobial Chemotherapy. 2010;65(12):2641-2644.
5. Papalekas E, Patel N, Neph A, Moreno D, Zervos M, Reyes K. Outpatient parenteral antimicrobial therapy (OPAT) in intravenous drug users (IVDUs): epidemiology and outcomes. Oral abstract presented at: IDWeek; October 2014; Philadelphia.

Case

A 42-year-old female with a history of intravenous (IV) drug use presents with severe neck pain, gait instability, and bilateral C5 motor weakness. A cervical MRI shows inflammation consistent with infection of her cervical spine at C5 and C6 and significant boney destruction. The patient undergoes kyphoplasty and debridement of her cervical spine. Operative cultures are significant for Pseudomonas aeruginosa. Infectious disease consultants recommend parenteral ceftriaxone for six weeks. The patient has no insurance, and efforts to obtain long-term placement are unsuccessful. The patient states that her last use of IV drugs was three months ago, and she insists that she will abstain from illicit IV drug abuse going forward.

Background

Outpatient parenteral antibiotic treatment (OPAT) has proven to be a cost-effective and relatively safe treatment option for most patients.1 For these reasons, it has been encouraged for use among a wide a variety of clinical situations. Intravenous drug users (IDUs) are often underinsured and have few options other than costly treatment in an inpatient acute-care facility.

A history of illicit injection drug use frequently raises questions about the appropriateness of OPAT. Some of our most vulnerable patients are those who abuse illicit drugs. Due to psychiatric, social, and financial factors, their ability to adequately transition to outpatient care may be limited. They are often underinsured, and appropriate options for inpatient post-acute care may not exist. Hospitalists often feel pressure to discharge these patients despite the lack of optimal follow-up care, and they must weigh the risks and benefits in each case.

The enrollment of IDUs into an OPAT service using a peripherally inserted central catheter (PICC) is controversial and often avoided. No clear-cut guidelines concerning the use of OPAT in IDUs by national medical societies exist.2 Consultants are often reluctant to recommend options that deviate from the typical standard of inpatient or directly observed care. The obvious risk is that a PICC line provides easy and tempting access to veins for continued drug abuse. In addition, there is an increased risk of infection and/or thrombosis if the PICC is abused.3

The safety and efficacy of PICC line use for OPAT in IDUs are unknown, and studies addressing these issues are limited. In one study at the National University Hospital of Singapore, 29 IDU patients received OPAT without complications.4 Patients were closely monitored, including by use of a tamper-proof security seal on the PICC. Infective endocarditis was the primary diagnosis in 42% of the cases studied. There were no deaths or cases of PICC abuse reported. In another abstract presentation, 39 IDU patients at Henry Ford Health System in Detroit were discharged to outpatient therapy with a PICC line and demonstrated a high cure rate (73.3%). Nine patients were lost to follow-up.5

No studies have compared OPAT therapy to inpatient therapy in IDU patients.

Back to the Case

Despite multiple attempts and due to financial considerations, no long-term care facility is able to admit the patient for therapy. The frequency of required antibiotics makes outpatient therapy in an infusion center problematic. The primary service is reluctant to discharge the patient home with a PICC line in place due to the potential of abuse and complications. A “Goals of Care” committee, consisting of several physicians from multiple specialties, legal counsel, and case management, is convened to review the case. The committee concludes that, in this particular case, it would be a reasonable option to discharge the patient to home with a PICC line in place to complete OPAT. A patient agreement document is drafted; it describes the complications of PICC line abuse and stipulates that the patient agrees to drug testing throughout the duration of her treatment. A similar agreement is required by the home infusion company. Both documents are signed by the patient, and she is subsequently discharged home.

 

Bottom Line

Our strategy is to deal with each of these cases as unique situations because no policies, procedures, protocols, or guidelines currently exist. One of the guiding principles should be, despite financial pressures, that the primary focus is on appropriate care of this vulnerable population. A type of “Goals of Care” committee (or organizational equivalent) can be utilized to offer assistance in decision making. Unfortunately, the safety and efficacy of OPAT in IDU patients are uncertain, and there is a lack of studies to support definitive protocols. In select cases, OPAT in IDU patients may be considered, but signed consent of the risks and the patient’s responsibilities concerning OPAT should be clearly documented in the medical record by the discharging team. TH

Dr. Conrad is a hospitalist with Ochsner Health System in New Orleans.

References

1. Tice AD, Hoaglund PA, Nolet B, McKinnon PS, Mozaffari E. Cost perspectives for outpatient intravenous antimicrobial therapy. Pharmacotherapy. 2002;22(2, pt 2):63S-70S.
2. Tice AD, Rehm SJ, Dalovisio JR, et al. Practice guidelines for outpatient parenteral antimicrobial therapy. IDSA guidelines. Clin Infect Dis. 2004;38(12):1651-1672.
3. Chemaly R, de Parres JB, Rehm SJ, et al. Venous thrombosis associated with peripherally inserted central catheters: a retrospective analysis of the Cleveland Clinic experience. Clin Infect Dis. 2002;34(9):1179-1183.
4. Ho J, Archuleta S, Sulaiman Z, Fisher D. Safe and successful treatment of intravenous drug users with a peripherally inserted central catheter in an outpatient parenteral antibiotic treatment service. J Antimicrobial Chemotherapy. 2010;65(12):2641-2644.
5. Papalekas E, Patel N, Neph A, Moreno D, Zervos M, Reyes K. Outpatient parenteral antimicrobial therapy (OPAT) in intravenous drug users (IVDUs): epidemiology and outcomes. Oral abstract presented at: IDWeek; October 2014; Philadelphia.

Case

A 42-year-old female with a history of intravenous (IV) drug use presents with severe neck pain, gait instability, and bilateral C5 motor weakness. A cervical MRI shows inflammation consistent with infection of her cervical spine at C5 and C6 and significant boney destruction. The patient undergoes kyphoplasty and debridement of her cervical spine. Operative cultures are significant for Pseudomonas aeruginosa. Infectious disease consultants recommend parenteral ceftriaxone for six weeks. The patient has no insurance, and efforts to obtain long-term placement are unsuccessful. The patient states that her last use of IV drugs was three months ago, and she insists that she will abstain from illicit IV drug abuse going forward.

Background

Outpatient parenteral antibiotic treatment (OPAT) has proven to be a cost-effective and relatively safe treatment option for most patients.1 For these reasons, it has been encouraged for use among a wide a variety of clinical situations. Intravenous drug users (IDUs) are often underinsured and have few options other than costly treatment in an inpatient acute-care facility.

A history of illicit injection drug use frequently raises questions about the appropriateness of OPAT. Some of our most vulnerable patients are those who abuse illicit drugs. Due to psychiatric, social, and financial factors, their ability to adequately transition to outpatient care may be limited. They are often underinsured, and appropriate options for inpatient post-acute care may not exist. Hospitalists often feel pressure to discharge these patients despite the lack of optimal follow-up care, and they must weigh the risks and benefits in each case.

The enrollment of IDUs into an OPAT service using a peripherally inserted central catheter (PICC) is controversial and often avoided. No clear-cut guidelines concerning the use of OPAT in IDUs by national medical societies exist.2 Consultants are often reluctant to recommend options that deviate from the typical standard of inpatient or directly observed care. The obvious risk is that a PICC line provides easy and tempting access to veins for continued drug abuse. In addition, there is an increased risk of infection and/or thrombosis if the PICC is abused.3

The safety and efficacy of PICC line use for OPAT in IDUs are unknown, and studies addressing these issues are limited. In one study at the National University Hospital of Singapore, 29 IDU patients received OPAT without complications.4 Patients were closely monitored, including by use of a tamper-proof security seal on the PICC. Infective endocarditis was the primary diagnosis in 42% of the cases studied. There were no deaths or cases of PICC abuse reported. In another abstract presentation, 39 IDU patients at Henry Ford Health System in Detroit were discharged to outpatient therapy with a PICC line and demonstrated a high cure rate (73.3%). Nine patients were lost to follow-up.5

No studies have compared OPAT therapy to inpatient therapy in IDU patients.

Back to the Case

Despite multiple attempts and due to financial considerations, no long-term care facility is able to admit the patient for therapy. The frequency of required antibiotics makes outpatient therapy in an infusion center problematic. The primary service is reluctant to discharge the patient home with a PICC line in place due to the potential of abuse and complications. A “Goals of Care” committee, consisting of several physicians from multiple specialties, legal counsel, and case management, is convened to review the case. The committee concludes that, in this particular case, it would be a reasonable option to discharge the patient to home with a PICC line in place to complete OPAT. A patient agreement document is drafted; it describes the complications of PICC line abuse and stipulates that the patient agrees to drug testing throughout the duration of her treatment. A similar agreement is required by the home infusion company. Both documents are signed by the patient, and she is subsequently discharged home.

 

Bottom Line

Our strategy is to deal with each of these cases as unique situations because no policies, procedures, protocols, or guidelines currently exist. One of the guiding principles should be, despite financial pressures, that the primary focus is on appropriate care of this vulnerable population. A type of “Goals of Care” committee (or organizational equivalent) can be utilized to offer assistance in decision making. Unfortunately, the safety and efficacy of OPAT in IDU patients are uncertain, and there is a lack of studies to support definitive protocols. In select cases, OPAT in IDU patients may be considered, but signed consent of the risks and the patient’s responsibilities concerning OPAT should be clearly documented in the medical record by the discharging team. TH

Dr. Conrad is a hospitalist with Ochsner Health System in New Orleans.

References

1. Tice AD, Hoaglund PA, Nolet B, McKinnon PS, Mozaffari E. Cost perspectives for outpatient intravenous antimicrobial therapy. Pharmacotherapy. 2002;22(2, pt 2):63S-70S.
2. Tice AD, Rehm SJ, Dalovisio JR, et al. Practice guidelines for outpatient parenteral antimicrobial therapy. IDSA guidelines. Clin Infect Dis. 2004;38(12):1651-1672.
3. Chemaly R, de Parres JB, Rehm SJ, et al. Venous thrombosis associated with peripherally inserted central catheters: a retrospective analysis of the Cleveland Clinic experience. Clin Infect Dis. 2002;34(9):1179-1183.
4. Ho J, Archuleta S, Sulaiman Z, Fisher D. Safe and successful treatment of intravenous drug users with a peripherally inserted central catheter in an outpatient parenteral antibiotic treatment service. J Antimicrobial Chemotherapy. 2010;65(12):2641-2644.
5. Papalekas E, Patel N, Neph A, Moreno D, Zervos M, Reyes K. Outpatient parenteral antimicrobial therapy (OPAT) in intravenous drug users (IVDUs): epidemiology and outcomes. Oral abstract presented at: IDWeek; October 2014; Philadelphia.