Healthcare systems are targeting effective strategies to improve patient safety and reduce hospital readmissions. Hospital readmissions can be detrimental to patients’ health, a source of avoidable healthcare costs, and are frequently a reflection of the quality of patient care during transitions of care. Medication reconciliation (Med Rec) was identified as 1 of 12 interventions that may reduce 30-day readmissions; however, rigorously designed studies are scarce.^1,2 Published systematic reviews and meta-analyses have produced mixed conclusions regarding the impact of Med Rec on unplanned 30-day readmissions.^2-4

In several studies, researchers have established the positive impact of Med Rec on reducing patient medication discrepancies and potential adverse drug events.^4-8 Pharmacy-led Med Rec interventions have been shown to easily identify more clinically relevant and higher impact medication discrepancies when compared to usual care.⁸ In a systematic review, Mueller et al.² suggest that there are several interrelated elements that determine if a Med Rec intervention will influence hospital readmissions. These elements form a multicomponent “bundle” of interventions, including a systematic medication history process, admission reconciliation, patient education on discharge, discharge reconciliation, and communication to outpatient providers.⁹ Several prospective randomized controlled studies have demonstrated lower readmission rates and fewer visits to the emergency department (ED) after implementing a comprehensive, interprofessional, bundled intervention (including Med Rec) from admission to discharge.^10-13 A 2016 systematic review and meta-analysis specifically evaluated pharmacy-led Med Rec programs (the majority of which included interventions involving multicomponent bundles) and demonstrated a significant reduction in posthospital healthcare utilization.¹⁴

Although comprehensive, interprofessional, bundled interventions have been shown to reduce readmission rates and ED visits in randomized controlled trials (RCTs), limited resources often prevent hospitals from consistently implementing all aspects of these multicomponent interventions. In practice, clinicians may provide varying components of the bundle, such as the combination of admission medication history by the pharmacist and discharge Med Rec completed by the physician alone. The unique impact of combined pharmacist and prescriber Med Rec interventions from admission to discharge on readmissions remains inconclusive. Further, it is unclear which high-risk patient groups will benefit the most from these interventions. We set out to evaluate the impact of an enhanced, interprofessional Med Rec process from admission to discharge (characterized within the context of a novel taxonomy continuum that specifies clinician involvement and intensity of services) on readmissions to hospital and ED visits within 30 days of discharge.

We conducted a retrospective, observational, analytical cohort study using QuadraMed’s Computerized Patient Record and the EMITT (Electronic Medication Information Transfer Tool)¹⁵ to collect data from 2007 to 2011.

Setting

The study was conducted at a 417-bed tertiary care teaching hospital in Toronto, Ontario, Canada.

Med Rec Process and Description of Exposure (Intervention)

The targeted clinical areas had sustained interprofessional models of patient care in place from admission to discharge. They also were actively using an in-house EMITT to facilitate the documentation and tracking of Med Rec efforts throughout patient admission, transfer, and discharge.¹⁵ On admission, the pharmacist conducted a best possible medication history (BPMH). A BPMH provides the cornerstone for Med Rec. It differs from a routine medication history in that it involves (1) a systematic process for interviewing the patient (or family) and (2) a review of at least one other reliable source of information (eg, a provincial medication database, an inspection of medication vials, or contact with the community pharmacy) to obtain and verify patient medications (prescribed and nonprescribed). The pharmacist recorded the BPMH in the electronic patient record. The application supported admission and discharge Med Rec. On discharge, there were 2 options: (1) the prescriber alone would review and complete the discharge Med Rec and generate electronic prescriptions (Table 1, Silver level care) or (2) the pharmacist would collaborate with the prescriber to complete the discharge reconciliation and the prescriber would electronically generate prescriptions (Table 1, Gold level care). All clinical areas had a combined pharmacist and prescriber Med Rec model in place at admission, but the proportion of patients receiving discharge reconciliation completed by pharmacist and prescriber versus the prescriber-alone varied based on the individual clinician’s practices.

Patient Selection

All consecutive hospitalized patients admitted and discharged by the general internal medicine [GIM] service from March 2007 to December 2011 were included. The GIM service was chosen for the main analysis because they had been performing the intervention for the longest period of time and had the largest population of patients. Patients were identified via their hospital-specific medical record identification number and specific hospital-visit number. Patients were excluded if any of the following occurred: (1) the length of stay of their index admission was less than 24 hours; (2) they died during the visit; (3) they were transferred to a separate acute care inpatient facility; or (4) they left hospital against medical advice. Patient visits were excluded as index cases from the analysis if they were returning within 90 days of a previous discharge.

Outcomes

The primary study outcome was the occurrence of an inpatient readmission or ED visit within 30 days of discharge. In our secondary analyses, we examined the impact of the intervention on high-risk patient populations, such as those ≥65 years of age, with a length of stay, acuity of admission, Charlson comorbidity index, and emergency department visits in past 6 months (LACE) index score ≥10 (see supplementary Appendix 1 for LACE score description), on high-alert medications (1 or more of warfarin, insulin, digoxin, and opioids), and on ≥10 medications.

Data Collection

Identification of Exposure of Interest

We used the electronic database to capture all patients who received pharmacist and prescriber supported admission-to-discharge reconciliation. We explicitly defined increasing intensity of Med Rec care in categories of Bronze, Silver, and Gold care levels (Table 1). The exposed (intervention) group received an enhanced Med Rec bundle (patients receiving Gold level care). The control group was made of patients receiving a partial Med Rec Bundle (patients receiving Silver or Bronze level of care or below).

Determination of Hospital Visits

A search of administrative databases was used to determine if patients admitted to the targeted services had an ED visit or urgent inpatient admission to the study hospital within 30 days.

Statistical Analysis

A logistic regression for outcomes was performed. This yielded an adjusted odds ratio with a 95% confidence interval (CI) between the intervention and control groups. Statistical significance was determined with a 2-sided α level of 0.05. In the analysis, we used Statistical Analysis Software version 9.2.

In our multivariate logistic regression model, we adjusted for confounding factors that might influence the patients’ risk of readmission or the type of Med Rec they received upon discharge. By using administrative databases, patient level demographics, and the Charlson comorbidity index, the most responsible diagnosis and disease burden were collected. Medication-related factors collected included the number of medications on discharge and the presence of predefined high-alert medications. The number of medications on the medication discharge list was determined by using the electronic database. The final adjustment model included age, gender, the number of medications on discharge, and the LACE index score (supplementary Appendix 1). The LACE index score has been validated in Ontario, Canada, populations to quantify the risk of death or unplanned readmission within 30 days of discharge.²⁴

Propensity Score Adjustment

Propensity scoring (probability of treatment assignment conditional on observed baseline characteristics) was planned a priori to account for possible factors that would impact whether a patient received the intervention or control care levels. The propensity score for receiving Med Rec was computed from a logistic model using Med Rec as the outcome. A structured iterative approach was used to refine this model to achieve covariate balance within the matched pairs. Covariate balance was measured by the standardized difference, in which an absolute standardized difference >10% represents meaningful imbalance.²⁵ From the original cohort, we attempted to match patients who had the intervention to patients from the control by means of a matching algorithm using the logit of the propensity score for receiving the intervention.²⁶

Subgroup Analysis

We also examined the impact of the intervention on high-risk patient populations such as those ≥65 years of age, with a LACE index score ≥10, on high-alert medications, and on ≥10 medications. A univariate analysis was conducted to identify patient-related risk predictors that may be independently correlated with a higher risk of hospital visits.

Baseline Characteristics

A total of 8678 patients representing 9931 unique visits met the inclusion criteria for analysis. There were 2541 unique visits (approximately 26% of visits) in the intervention group that received Gold level care and 7390 unique visits in the control group. The patients in the control group were largely patients who received the original standard of care at the institution, Silver level care (67% of the control group). Patients who received Bronze level care or less comprised 33% of the control group.

Patients in the intervention group were significantly older (average of 68 years old versus 64 years old) and on more medications. They also notably had a longer duration of stay in hospital, an increased percentage of visits with a LACE index score ≥10, and were more likely to be discharged home on a high-alert medication and with supports (Table 2).

Main Analysis

The main unadjusted analysis of GIM patients (n = 9931 visits) did not detect a difference in 30-day ED visits and readmissions between the intervention group (540 out of 2541; 21.2%) and control (1423 out of 7390; 19.3%; Table 3). By using a multivariate logistic regression model to account for age, sex, LACE index, and number of medications on discharge, the adjusted odds ratio was 1.06 (95% CI, 0.95-1.19; P = 0.33). After propensity score adjustment, the relative risk of readmission was 0.88 (16.7% vs 18.9%; 95% CI, 0.59-1.32; P = 0.54).

Secondary Analyses

In each predefined high-risk patient subgroup (age ≥65, LACE index score ≥10, number of discharge medications ≥10, and the presence of high-alert medications), analyses of our primary endpoint did not detect significant adjusted odds ratios (Table 4). In our univariate analysis, increasing number of medications, LACE index score, and male gender were independently correlated with a higher risk of hospital visits (supplementary Appendix 2).

Med Rec is widely recommended as a patient safety strategy to prevent clinically significant medication discrepancies at transitions in care.^4-9 However, Med Rec varies widely in terms of what it entails and who delivers it, with the preponderance of evidence suggesting an impact on clinically significant medication discrepancies only when interprofessional care delivered includes a central role for pharmacists.²⁷ Furthermore, Med Rec appears to impact short term readmissions only when embedded in a broader, multifaceted, bundled intervention in which pharmacists or other team members educate patients about their medications and deliver postdischarge follow-up phone calls.^10-13

As very few hospitals have the resources to sustainably deliver intensive care bundles that are represented in RCTs (characterized by Platinum and Diamond levels of care in Table 1), in our observational study, we sought to explore whether a resource-attainable, enhanced Med Rec care bundle (Gold level) had an impact on hospital utilization compared to partial Med Rec care bundles (Bronze and Silver levels). In our findings, we did not detect a significant difference on ED visits and readmissions within 30 days between enhanced and partial care bundles. In a secondary analysis of the influence of the intervention on prespecified high-risk patient subgroups, we also did not detect a difference.

As far as we are aware, our long-term, observational study is the largest to date to explore a real-life, enhanced Med Rec intervention and examine its impact on meaningful patient outcomes. We extrapolated that our intervention group received several critical attributes of a successful bundle as discussed by Mueller in a systematic review.² Our intervention included the following: (1) a systematic BPMH process on admission; (2) integrated admission-to-discharge reconciliation processes; (3) discharge delineation of medication changes since admission; (4) pharmacist involvement in reconciliation from admission to discharge; (5) an electronic platform; and (6) formal discharge reconciliation with interprofessional collaboration. Additional components in the bundle described by Mueller included the following: patient education at discharge, postdischarge communication with the patient, and communication with outpatient providers and medication management.

In our results, we did not find a difference in outcomes between the intervention and control groups. Therefore, it is possible that the enhanced bundle’s focus on interprofessional involvement in discharge reconciliation (Gold care level) has no impact on hospital utilization compared to partial care bundles (Silver and Bronze levels). Kwan et al.³ describe similar findings in their systematic review, in which they evaluated the effects of hospital-based Med Rec on unintentional discrepancies with nontrivial risks for harm to patients on 30-day postdischarge hospital visits. Kwan et al.³ concluded that larger well-designed studies are required to further evaluate this outcome, but authors of current published studies suggest that Med Rec alone probably does not reduce postdischarge hospital utilization within 30 days. Med Rec may have a more significant impact on utilization when bundled with other interventions that improve discharge coordination.³

There may be several reasons why we were unable to detect a significant difference between the intervention and control groups. One limitation is that our nonrandomized, retrospective design may have led to unmeasured confounders that impacted allocation into the intervention group versus the control group. It was notable that patients in the intervention group had an increased age, longer duration of hospital stay, more medications, and high-alert medications on discharge compared to the control group and that may have biased our results towards the null hypothesis. Although the propensity score analysis attempted to adjust for this, it also did not detect a significant difference between groups.

In addition, the existing standard of care during the study period allowed for patients in the control group to receive varying levels of Med Rec. Ideally, we would have compared the intervention to a placebo group that did not receive any Med Rec-related care elements. However, as this was a real-life observational study, the majority of patients received some Med Rec services as a part of the standard of care. As a result, 67% of patients in the control group received Silver level Med Rec with a BPMH, admission reconciliation, and prescriber-only discharge reconciliation. This may have made it more difficult to show an incremental benefit on readmissions between the intervention and control.

Also, our primary outcome of all-cause ED or hospital readmissions within 30 days may not have been sensitive enough to detect the effect of Med Rec interventions alone. Only a small proportion of readmissions within 30 days of discharge are preventable and many patient and community level factors responsible for readmissions cannot be controlled by the hospital’s actions.²⁸ Comprehensive pharmacy interventions have demonstrated decreased hospitalizations and emergency visits at 12 months; however, the largest impact was seen on the more specific outcome of medication-related hospitalizations (80% reduction).²⁹ Lastly, another limitation was that we were unable to capture hospital visits to other centres. However, in our region, almost 75% of readmissions are to the same site as the initial hospitalization.³⁰

Overall, our findings in this study and novel characterization of Med Rec services are relevant to many hospital sites that are striving to implement integrated Med Rec with limited healthcare resources. Although interprofessional Med Rec likely reduces clinically significant medication discrepancies, enhanced interprofessional Med Rec on discharge (Gold Med Rec) alone may not be enough to impact hospital utilization compared to partial Med Rec services (Silver and Bronze Med Rec). Further research into practical, targeted Med Rec bundles on more specific outcomes (such as preventable postdischarge adverse events, “avoidable” hospital readmissions, and medication-related readmissions) may detect a significant benefit.

A long-term observational evaluation of interprofessional Med Rec did not detect a difference in 30-day postdischarge patient hospital visits between patients who received enhanced versus partial Med Rec patient care bundles. Researchers of future prospective studies could focus on evaluating high-risk populations or specific elements of Med Rec services on avoidable medication-related hospital admissions and postdischarge adverse drug events.

Acknowledgments

The authors thank Nita Dhir, MBA.

Presented as a poster and oral presentation at the 2012 American College of Clinical Pharmacy Annual Meeting, Hollywood, Florida, October 21-24, 2012, and as an encore poster presentation at the Canadian Society of Hospital Pharmacists Professional Practice Conference, Toronto, Canada, Feb 3, 2013.

Disclosure

The authors declare no conflicts of interest related to the manuscript submitted. All monies used for the research came from the University Health Network Department of Pharmacy Budget, including the pharmacy residency program.

Healthcare systems are targeting effective strategies to improve patient safety and reduce hospital readmissions. Hospital readmissions can be detrimental to patients’ health, a source of avoidable healthcare costs, and are frequently a reflection of the quality of patient care during transitions of care. Medication reconciliation (Med Rec) was identified as 1 of 12 interventions that may reduce 30-day readmissions; however, rigorously designed studies are scarce.^1,2 Published systematic reviews and meta-analyses have produced mixed conclusions regarding the impact of Med Rec on unplanned 30-day readmissions.^2-4

In several studies, researchers have established the positive impact of Med Rec on reducing patient medication discrepancies and potential adverse drug events.^4-8 Pharmacy-led Med Rec interventions have been shown to easily identify more clinically relevant and higher impact medication discrepancies when compared to usual care.⁸ In a systematic review, Mueller et al.² suggest that there are several interrelated elements that determine if a Med Rec intervention will influence hospital readmissions. These elements form a multicomponent “bundle” of interventions, including a systematic medication history process, admission reconciliation, patient education on discharge, discharge reconciliation, and communication to outpatient providers.⁹ Several prospective randomized controlled studies have demonstrated lower readmission rates and fewer visits to the emergency department (ED) after implementing a comprehensive, interprofessional, bundled intervention (including Med Rec) from admission to discharge.^10-13 A 2016 systematic review and meta-analysis specifically evaluated pharmacy-led Med Rec programs (the majority of which included interventions involving multicomponent bundles) and demonstrated a significant reduction in posthospital healthcare utilization.¹⁴

Although comprehensive, interprofessional, bundled interventions have been shown to reduce readmission rates and ED visits in randomized controlled trials (RCTs), limited resources often prevent hospitals from consistently implementing all aspects of these multicomponent interventions. In practice, clinicians may provide varying components of the bundle, such as the combination of admission medication history by the pharmacist and discharge Med Rec completed by the physician alone. The unique impact of combined pharmacist and prescriber Med Rec interventions from admission to discharge on readmissions remains inconclusive. Further, it is unclear which high-risk patient groups will benefit the most from these interventions. We set out to evaluate the impact of an enhanced, interprofessional Med Rec process from admission to discharge (characterized within the context of a novel taxonomy continuum that specifies clinician involvement and intensity of services) on readmissions to hospital and ED visits within 30 days of discharge.

We conducted a retrospective, observational, analytical cohort study using QuadraMed’s Computerized Patient Record and the EMITT (Electronic Medication Information Transfer Tool)¹⁵ to collect data from 2007 to 2011.

Setting

The study was conducted at a 417-bed tertiary care teaching hospital in Toronto, Ontario, Canada.

Med Rec Process and Description of Exposure (Intervention)

The targeted clinical areas had sustained interprofessional models of patient care in place from admission to discharge. They also were actively using an in-house EMITT to facilitate the documentation and tracking of Med Rec efforts throughout patient admission, transfer, and discharge.¹⁵ On admission, the pharmacist conducted a best possible medication history (BPMH). A BPMH provides the cornerstone for Med Rec. It differs from a routine medication history in that it involves (1) a systematic process for interviewing the patient (or family) and (2) a review of at least one other reliable source of information (eg, a provincial medication database, an inspection of medication vials, or contact with the community pharmacy) to obtain and verify patient medications (prescribed and nonprescribed). The pharmacist recorded the BPMH in the electronic patient record. The application supported admission and discharge Med Rec. On discharge, there were 2 options: (1) the prescriber alone would review and complete the discharge Med Rec and generate electronic prescriptions (Table 1, Silver level care) or (2) the pharmacist would collaborate with the prescriber to complete the discharge reconciliation and the prescriber would electronically generate prescriptions (Table 1, Gold level care). All clinical areas had a combined pharmacist and prescriber Med Rec model in place at admission, but the proportion of patients receiving discharge reconciliation completed by pharmacist and prescriber versus the prescriber-alone varied based on the individual clinician’s practices.

Patient Selection

All consecutive hospitalized patients admitted and discharged by the general internal medicine [GIM] service from March 2007 to December 2011 were included. The GIM service was chosen for the main analysis because they had been performing the intervention for the longest period of time and had the largest population of patients. Patients were identified via their hospital-specific medical record identification number and specific hospital-visit number. Patients were excluded if any of the following occurred: (1) the length of stay of their index admission was less than 24 hours; (2) they died during the visit; (3) they were transferred to a separate acute care inpatient facility; or (4) they left hospital against medical advice. Patient visits were excluded as index cases from the analysis if they were returning within 90 days of a previous discharge.

Outcomes

The primary study outcome was the occurrence of an inpatient readmission or ED visit within 30 days of discharge. In our secondary analyses, we examined the impact of the intervention on high-risk patient populations, such as those ≥65 years of age, with a length of stay, acuity of admission, Charlson comorbidity index, and emergency department visits in past 6 months (LACE) index score ≥10 (see supplementary Appendix 1 for LACE score description), on high-alert medications (1 or more of warfarin, insulin, digoxin, and opioids), and on ≥10 medications.

Data Collection

Identification of Exposure of Interest

We used the electronic database to capture all patients who received pharmacist and prescriber supported admission-to-discharge reconciliation. We explicitly defined increasing intensity of Med Rec care in categories of Bronze, Silver, and Gold care levels (Table 1). The exposed (intervention) group received an enhanced Med Rec bundle (patients receiving Gold level care). The control group was made of patients receiving a partial Med Rec Bundle (patients receiving Silver or Bronze level of care or below).

Determination of Hospital Visits

A search of administrative databases was used to determine if patients admitted to the targeted services had an ED visit or urgent inpatient admission to the study hospital within 30 days.

Statistical Analysis

A logistic regression for outcomes was performed. This yielded an adjusted odds ratio with a 95% confidence interval (CI) between the intervention and control groups. Statistical significance was determined with a 2-sided α level of 0.05. In the analysis, we used Statistical Analysis Software version 9.2.

In our multivariate logistic regression model, we adjusted for confounding factors that might influence the patients’ risk of readmission or the type of Med Rec they received upon discharge. By using administrative databases, patient level demographics, and the Charlson comorbidity index, the most responsible diagnosis and disease burden were collected. Medication-related factors collected included the number of medications on discharge and the presence of predefined high-alert medications. The number of medications on the medication discharge list was determined by using the electronic database. The final adjustment model included age, gender, the number of medications on discharge, and the LACE index score (supplementary Appendix 1). The LACE index score has been validated in Ontario, Canada, populations to quantify the risk of death or unplanned readmission within 30 days of discharge.²⁴

Propensity Score Adjustment

Propensity scoring (probability of treatment assignment conditional on observed baseline characteristics) was planned a priori to account for possible factors that would impact whether a patient received the intervention or control care levels. The propensity score for receiving Med Rec was computed from a logistic model using Med Rec as the outcome. A structured iterative approach was used to refine this model to achieve covariate balance within the matched pairs. Covariate balance was measured by the standardized difference, in which an absolute standardized difference >10% represents meaningful imbalance.²⁵ From the original cohort, we attempted to match patients who had the intervention to patients from the control by means of a matching algorithm using the logit of the propensity score for receiving the intervention.²⁶

Subgroup Analysis

We also examined the impact of the intervention on high-risk patient populations such as those ≥65 years of age, with a LACE index score ≥10, on high-alert medications, and on ≥10 medications. A univariate analysis was conducted to identify patient-related risk predictors that may be independently correlated with a higher risk of hospital visits.

Baseline Characteristics

A total of 8678 patients representing 9931 unique visits met the inclusion criteria for analysis. There were 2541 unique visits (approximately 26% of visits) in the intervention group that received Gold level care and 7390 unique visits in the control group. The patients in the control group were largely patients who received the original standard of care at the institution, Silver level care (67% of the control group). Patients who received Bronze level care or less comprised 33% of the control group.

Patients in the intervention group were significantly older (average of 68 years old versus 64 years old) and on more medications. They also notably had a longer duration of stay in hospital, an increased percentage of visits with a LACE index score ≥10, and were more likely to be discharged home on a high-alert medication and with supports (Table 2).

Main Analysis

The main unadjusted analysis of GIM patients (n = 9931 visits) did not detect a difference in 30-day ED visits and readmissions between the intervention group (540 out of 2541; 21.2%) and control (1423 out of 7390; 19.3%; Table 3). By using a multivariate logistic regression model to account for age, sex, LACE index, and number of medications on discharge, the adjusted odds ratio was 1.06 (95% CI, 0.95-1.19; P = 0.33). After propensity score adjustment, the relative risk of readmission was 0.88 (16.7% vs 18.9%; 95% CI, 0.59-1.32; P = 0.54).

Secondary Analyses

In each predefined high-risk patient subgroup (age ≥65, LACE index score ≥10, number of discharge medications ≥10, and the presence of high-alert medications), analyses of our primary endpoint did not detect significant adjusted odds ratios (Table 4). In our univariate analysis, increasing number of medications, LACE index score, and male gender were independently correlated with a higher risk of hospital visits (supplementary Appendix 2).

Med Rec is widely recommended as a patient safety strategy to prevent clinically significant medication discrepancies at transitions in care.^4-9 However, Med Rec varies widely in terms of what it entails and who delivers it, with the preponderance of evidence suggesting an impact on clinically significant medication discrepancies only when interprofessional care delivered includes a central role for pharmacists.²⁷ Furthermore, Med Rec appears to impact short term readmissions only when embedded in a broader, multifaceted, bundled intervention in which pharmacists or other team members educate patients about their medications and deliver postdischarge follow-up phone calls.^10-13

As very few hospitals have the resources to sustainably deliver intensive care bundles that are represented in RCTs (characterized by Platinum and Diamond levels of care in Table 1), in our observational study, we sought to explore whether a resource-attainable, enhanced Med Rec care bundle (Gold level) had an impact on hospital utilization compared to partial Med Rec care bundles (Bronze and Silver levels). In our findings, we did not detect a significant difference on ED visits and readmissions within 30 days between enhanced and partial care bundles. In a secondary analysis of the influence of the intervention on prespecified high-risk patient subgroups, we also did not detect a difference.

As far as we are aware, our long-term, observational study is the largest to date to explore a real-life, enhanced Med Rec intervention and examine its impact on meaningful patient outcomes. We extrapolated that our intervention group received several critical attributes of a successful bundle as discussed by Mueller in a systematic review.² Our intervention included the following: (1) a systematic BPMH process on admission; (2) integrated admission-to-discharge reconciliation processes; (3) discharge delineation of medication changes since admission; (4) pharmacist involvement in reconciliation from admission to discharge; (5) an electronic platform; and (6) formal discharge reconciliation with interprofessional collaboration. Additional components in the bundle described by Mueller included the following: patient education at discharge, postdischarge communication with the patient, and communication with outpatient providers and medication management.

In our results, we did not find a difference in outcomes between the intervention and control groups. Therefore, it is possible that the enhanced bundle’s focus on interprofessional involvement in discharge reconciliation (Gold care level) has no impact on hospital utilization compared to partial care bundles (Silver and Bronze levels). Kwan et al.³ describe similar findings in their systematic review, in which they evaluated the effects of hospital-based Med Rec on unintentional discrepancies with nontrivial risks for harm to patients on 30-day postdischarge hospital visits. Kwan et al.³ concluded that larger well-designed studies are required to further evaluate this outcome, but authors of current published studies suggest that Med Rec alone probably does not reduce postdischarge hospital utilization within 30 days. Med Rec may have a more significant impact on utilization when bundled with other interventions that improve discharge coordination.³

There may be several reasons why we were unable to detect a significant difference between the intervention and control groups. One limitation is that our nonrandomized, retrospective design may have led to unmeasured confounders that impacted allocation into the intervention group versus the control group. It was notable that patients in the intervention group had an increased age, longer duration of hospital stay, more medications, and high-alert medications on discharge compared to the control group and that may have biased our results towards the null hypothesis. Although the propensity score analysis attempted to adjust for this, it also did not detect a significant difference between groups.

In addition, the existing standard of care during the study period allowed for patients in the control group to receive varying levels of Med Rec. Ideally, we would have compared the intervention to a placebo group that did not receive any Med Rec-related care elements. However, as this was a real-life observational study, the majority of patients received some Med Rec services as a part of the standard of care. As a result, 67% of patients in the control group received Silver level Med Rec with a BPMH, admission reconciliation, and prescriber-only discharge reconciliation. This may have made it more difficult to show an incremental benefit on readmissions between the intervention and control.

Also, our primary outcome of all-cause ED or hospital readmissions within 30 days may not have been sensitive enough to detect the effect of Med Rec interventions alone. Only a small proportion of readmissions within 30 days of discharge are preventable and many patient and community level factors responsible for readmissions cannot be controlled by the hospital’s actions.²⁸ Comprehensive pharmacy interventions have demonstrated decreased hospitalizations and emergency visits at 12 months; however, the largest impact was seen on the more specific outcome of medication-related hospitalizations (80% reduction).²⁹ Lastly, another limitation was that we were unable to capture hospital visits to other centres. However, in our region, almost 75% of readmissions are to the same site as the initial hospitalization.³⁰

Overall, our findings in this study and novel characterization of Med Rec services are relevant to many hospital sites that are striving to implement integrated Med Rec with limited healthcare resources. Although interprofessional Med Rec likely reduces clinically significant medication discrepancies, enhanced interprofessional Med Rec on discharge (Gold Med Rec) alone may not be enough to impact hospital utilization compared to partial Med Rec services (Silver and Bronze Med Rec). Further research into practical, targeted Med Rec bundles on more specific outcomes (such as preventable postdischarge adverse events, “avoidable” hospital readmissions, and medication-related readmissions) may detect a significant benefit.

A long-term observational evaluation of interprofessional Med Rec did not detect a difference in 30-day postdischarge patient hospital visits between patients who received enhanced versus partial Med Rec patient care bundles. Researchers of future prospective studies could focus on evaluating high-risk populations or specific elements of Med Rec services on avoidable medication-related hospital admissions and postdischarge adverse drug events.

Acknowledgments

The authors thank Nita Dhir, MBA.

Presented as a poster and oral presentation at the 2012 American College of Clinical Pharmacy Annual Meeting, Hollywood, Florida, October 21-24, 2012, and as an encore poster presentation at the Canadian Society of Hospital Pharmacists Professional Practice Conference, Toronto, Canada, Feb 3, 2013.

Disclosure

The authors declare no conflicts of interest related to the manuscript submitted. All monies used for the research came from the University Health Network Department of Pharmacy Budget, including the pharmacy residency program.

Healthcare systems are targeting effective strategies to improve patient safety and reduce hospital readmissions. Hospital readmissions can be detrimental to patients’ health, a source of avoidable healthcare costs, and are frequently a reflection of the quality of patient care during transitions of care. Medication reconciliation (Med Rec) was identified as 1 of 12 interventions that may reduce 30-day readmissions; however, rigorously designed studies are scarce.^1,2 Published systematic reviews and meta-analyses have produced mixed conclusions regarding the impact of Med Rec on unplanned 30-day readmissions.^2-4

In several studies, researchers have established the positive impact of Med Rec on reducing patient medication discrepancies and potential adverse drug events.^4-8 Pharmacy-led Med Rec interventions have been shown to easily identify more clinically relevant and higher impact medication discrepancies when compared to usual care.⁸ In a systematic review, Mueller et al.² suggest that there are several interrelated elements that determine if a Med Rec intervention will influence hospital readmissions. These elements form a multicomponent “bundle” of interventions, including a systematic medication history process, admission reconciliation, patient education on discharge, discharge reconciliation, and communication to outpatient providers.⁹ Several prospective randomized controlled studies have demonstrated lower readmission rates and fewer visits to the emergency department (ED) after implementing a comprehensive, interprofessional, bundled intervention (including Med Rec) from admission to discharge.^10-13 A 2016 systematic review and meta-analysis specifically evaluated pharmacy-led Med Rec programs (the majority of which included interventions involving multicomponent bundles) and demonstrated a significant reduction in posthospital healthcare utilization.¹⁴

Although comprehensive, interprofessional, bundled interventions have been shown to reduce readmission rates and ED visits in randomized controlled trials (RCTs), limited resources often prevent hospitals from consistently implementing all aspects of these multicomponent interventions. In practice, clinicians may provide varying components of the bundle, such as the combination of admission medication history by the pharmacist and discharge Med Rec completed by the physician alone. The unique impact of combined pharmacist and prescriber Med Rec interventions from admission to discharge on readmissions remains inconclusive. Further, it is unclear which high-risk patient groups will benefit the most from these interventions. We set out to evaluate the impact of an enhanced, interprofessional Med Rec process from admission to discharge (characterized within the context of a novel taxonomy continuum that specifies clinician involvement and intensity of services) on readmissions to hospital and ED visits within 30 days of discharge.

We conducted a retrospective, observational, analytical cohort study using QuadraMed’s Computerized Patient Record and the EMITT (Electronic Medication Information Transfer Tool)¹⁵ to collect data from 2007 to 2011.

Setting

The study was conducted at a 417-bed tertiary care teaching hospital in Toronto, Ontario, Canada.

Med Rec Process and Description of Exposure (Intervention)

The targeted clinical areas had sustained interprofessional models of patient care in place from admission to discharge. They also were actively using an in-house EMITT to facilitate the documentation and tracking of Med Rec efforts throughout patient admission, transfer, and discharge.¹⁵ On admission, the pharmacist conducted a best possible medication history (BPMH). A BPMH provides the cornerstone for Med Rec. It differs from a routine medication history in that it involves (1) a systematic process for interviewing the patient (or family) and (2) a review of at least one other reliable source of information (eg, a provincial medication database, an inspection of medication vials, or contact with the community pharmacy) to obtain and verify patient medications (prescribed and nonprescribed). The pharmacist recorded the BPMH in the electronic patient record. The application supported admission and discharge Med Rec. On discharge, there were 2 options: (1) the prescriber alone would review and complete the discharge Med Rec and generate electronic prescriptions (Table 1, Silver level care) or (2) the pharmacist would collaborate with the prescriber to complete the discharge reconciliation and the prescriber would electronically generate prescriptions (Table 1, Gold level care). All clinical areas had a combined pharmacist and prescriber Med Rec model in place at admission, but the proportion of patients receiving discharge reconciliation completed by pharmacist and prescriber versus the prescriber-alone varied based on the individual clinician’s practices.

Patient Selection

All consecutive hospitalized patients admitted and discharged by the general internal medicine [GIM] service from March 2007 to December 2011 were included. The GIM service was chosen for the main analysis because they had been performing the intervention for the longest period of time and had the largest population of patients. Patients were identified via their hospital-specific medical record identification number and specific hospital-visit number. Patients were excluded if any of the following occurred: (1) the length of stay of their index admission was less than 24 hours; (2) they died during the visit; (3) they were transferred to a separate acute care inpatient facility; or (4) they left hospital against medical advice. Patient visits were excluded as index cases from the analysis if they were returning within 90 days of a previous discharge.

Outcomes

The primary study outcome was the occurrence of an inpatient readmission or ED visit within 30 days of discharge. In our secondary analyses, we examined the impact of the intervention on high-risk patient populations, such as those ≥65 years of age, with a length of stay, acuity of admission, Charlson comorbidity index, and emergency department visits in past 6 months (LACE) index score ≥10 (see supplementary Appendix 1 for LACE score description), on high-alert medications (1 or more of warfarin, insulin, digoxin, and opioids), and on ≥10 medications.

Data Collection

Identification of Exposure of Interest

We used the electronic database to capture all patients who received pharmacist and prescriber supported admission-to-discharge reconciliation. We explicitly defined increasing intensity of Med Rec care in categories of Bronze, Silver, and Gold care levels (Table 1). The exposed (intervention) group received an enhanced Med Rec bundle (patients receiving Gold level care). The control group was made of patients receiving a partial Med Rec Bundle (patients receiving Silver or Bronze level of care or below).

Determination of Hospital Visits

A search of administrative databases was used to determine if patients admitted to the targeted services had an ED visit or urgent inpatient admission to the study hospital within 30 days.

Statistical Analysis

A logistic regression for outcomes was performed. This yielded an adjusted odds ratio with a 95% confidence interval (CI) between the intervention and control groups. Statistical significance was determined with a 2-sided α level of 0.05. In the analysis, we used Statistical Analysis Software version 9.2.

In our multivariate logistic regression model, we adjusted for confounding factors that might influence the patients’ risk of readmission or the type of Med Rec they received upon discharge. By using administrative databases, patient level demographics, and the Charlson comorbidity index, the most responsible diagnosis and disease burden were collected. Medication-related factors collected included the number of medications on discharge and the presence of predefined high-alert medications. The number of medications on the medication discharge list was determined by using the electronic database. The final adjustment model included age, gender, the number of medications on discharge, and the LACE index score (supplementary Appendix 1). The LACE index score has been validated in Ontario, Canada, populations to quantify the risk of death or unplanned readmission within 30 days of discharge.²⁴

Propensity Score Adjustment

Propensity scoring (probability of treatment assignment conditional on observed baseline characteristics) was planned a priori to account for possible factors that would impact whether a patient received the intervention or control care levels. The propensity score for receiving Med Rec was computed from a logistic model using Med Rec as the outcome. A structured iterative approach was used to refine this model to achieve covariate balance within the matched pairs. Covariate balance was measured by the standardized difference, in which an absolute standardized difference >10% represents meaningful imbalance.²⁵ From the original cohort, we attempted to match patients who had the intervention to patients from the control by means of a matching algorithm using the logit of the propensity score for receiving the intervention.²⁶

Subgroup Analysis

We also examined the impact of the intervention on high-risk patient populations such as those ≥65 years of age, with a LACE index score ≥10, on high-alert medications, and on ≥10 medications. A univariate analysis was conducted to identify patient-related risk predictors that may be independently correlated with a higher risk of hospital visits.

Baseline Characteristics

A total of 8678 patients representing 9931 unique visits met the inclusion criteria for analysis. There were 2541 unique visits (approximately 26% of visits) in the intervention group that received Gold level care and 7390 unique visits in the control group. The patients in the control group were largely patients who received the original standard of care at the institution, Silver level care (67% of the control group). Patients who received Bronze level care or less comprised 33% of the control group.

Patients in the intervention group were significantly older (average of 68 years old versus 64 years old) and on more medications. They also notably had a longer duration of stay in hospital, an increased percentage of visits with a LACE index score ≥10, and were more likely to be discharged home on a high-alert medication and with supports (Table 2).

Main Analysis

The main unadjusted analysis of GIM patients (n = 9931 visits) did not detect a difference in 30-day ED visits and readmissions between the intervention group (540 out of 2541; 21.2%) and control (1423 out of 7390; 19.3%; Table 3). By using a multivariate logistic regression model to account for age, sex, LACE index, and number of medications on discharge, the adjusted odds ratio was 1.06 (95% CI, 0.95-1.19; P = 0.33). After propensity score adjustment, the relative risk of readmission was 0.88 (16.7% vs 18.9%; 95% CI, 0.59-1.32; P = 0.54).

Secondary Analyses

In each predefined high-risk patient subgroup (age ≥65, LACE index score ≥10, number of discharge medications ≥10, and the presence of high-alert medications), analyses of our primary endpoint did not detect significant adjusted odds ratios (Table 4). In our univariate analysis, increasing number of medications, LACE index score, and male gender were independently correlated with a higher risk of hospital visits (supplementary Appendix 2).

Med Rec is widely recommended as a patient safety strategy to prevent clinically significant medication discrepancies at transitions in care.^4-9 However, Med Rec varies widely in terms of what it entails and who delivers it, with the preponderance of evidence suggesting an impact on clinically significant medication discrepancies only when interprofessional care delivered includes a central role for pharmacists.²⁷ Furthermore, Med Rec appears to impact short term readmissions only when embedded in a broader, multifaceted, bundled intervention in which pharmacists or other team members educate patients about their medications and deliver postdischarge follow-up phone calls.^10-13

As very few hospitals have the resources to sustainably deliver intensive care bundles that are represented in RCTs (characterized by Platinum and Diamond levels of care in Table 1), in our observational study, we sought to explore whether a resource-attainable, enhanced Med Rec care bundle (Gold level) had an impact on hospital utilization compared to partial Med Rec care bundles (Bronze and Silver levels). In our findings, we did not detect a significant difference on ED visits and readmissions within 30 days between enhanced and partial care bundles. In a secondary analysis of the influence of the intervention on prespecified high-risk patient subgroups, we also did not detect a difference.

As far as we are aware, our long-term, observational study is the largest to date to explore a real-life, enhanced Med Rec intervention and examine its impact on meaningful patient outcomes. We extrapolated that our intervention group received several critical attributes of a successful bundle as discussed by Mueller in a systematic review.² Our intervention included the following: (1) a systematic BPMH process on admission; (2) integrated admission-to-discharge reconciliation processes; (3) discharge delineation of medication changes since admission; (4) pharmacist involvement in reconciliation from admission to discharge; (5) an electronic platform; and (6) formal discharge reconciliation with interprofessional collaboration. Additional components in the bundle described by Mueller included the following: patient education at discharge, postdischarge communication with the patient, and communication with outpatient providers and medication management.

In our results, we did not find a difference in outcomes between the intervention and control groups. Therefore, it is possible that the enhanced bundle’s focus on interprofessional involvement in discharge reconciliation (Gold care level) has no impact on hospital utilization compared to partial care bundles (Silver and Bronze levels). Kwan et al.³ describe similar findings in their systematic review, in which they evaluated the effects of hospital-based Med Rec on unintentional discrepancies with nontrivial risks for harm to patients on 30-day postdischarge hospital visits. Kwan et al.³ concluded that larger well-designed studies are required to further evaluate this outcome, but authors of current published studies suggest that Med Rec alone probably does not reduce postdischarge hospital utilization within 30 days. Med Rec may have a more significant impact on utilization when bundled with other interventions that improve discharge coordination.³

There may be several reasons why we were unable to detect a significant difference between the intervention and control groups. One limitation is that our nonrandomized, retrospective design may have led to unmeasured confounders that impacted allocation into the intervention group versus the control group. It was notable that patients in the intervention group had an increased age, longer duration of hospital stay, more medications, and high-alert medications on discharge compared to the control group and that may have biased our results towards the null hypothesis. Although the propensity score analysis attempted to adjust for this, it also did not detect a significant difference between groups.

In addition, the existing standard of care during the study period allowed for patients in the control group to receive varying levels of Med Rec. Ideally, we would have compared the intervention to a placebo group that did not receive any Med Rec-related care elements. However, as this was a real-life observational study, the majority of patients received some Med Rec services as a part of the standard of care. As a result, 67% of patients in the control group received Silver level Med Rec with a BPMH, admission reconciliation, and prescriber-only discharge reconciliation. This may have made it more difficult to show an incremental benefit on readmissions between the intervention and control.

Also, our primary outcome of all-cause ED or hospital readmissions within 30 days may not have been sensitive enough to detect the effect of Med Rec interventions alone. Only a small proportion of readmissions within 30 days of discharge are preventable and many patient and community level factors responsible for readmissions cannot be controlled by the hospital’s actions.²⁸ Comprehensive pharmacy interventions have demonstrated decreased hospitalizations and emergency visits at 12 months; however, the largest impact was seen on the more specific outcome of medication-related hospitalizations (80% reduction).²⁹ Lastly, another limitation was that we were unable to capture hospital visits to other centres. However, in our region, almost 75% of readmissions are to the same site as the initial hospitalization.³⁰

Overall, our findings in this study and novel characterization of Med Rec services are relevant to many hospital sites that are striving to implement integrated Med Rec with limited healthcare resources. Although interprofessional Med Rec likely reduces clinically significant medication discrepancies, enhanced interprofessional Med Rec on discharge (Gold Med Rec) alone may not be enough to impact hospital utilization compared to partial Med Rec services (Silver and Bronze Med Rec). Further research into practical, targeted Med Rec bundles on more specific outcomes (such as preventable postdischarge adverse events, “avoidable” hospital readmissions, and medication-related readmissions) may detect a significant benefit.

A long-term observational evaluation of interprofessional Med Rec did not detect a difference in 30-day postdischarge patient hospital visits between patients who received enhanced versus partial Med Rec patient care bundles. Researchers of future prospective studies could focus on evaluating high-risk populations or specific elements of Med Rec services on avoidable medication-related hospital admissions and postdischarge adverse drug events.

Acknowledgments

The authors thank Nita Dhir, MBA.

Presented as a poster and oral presentation at the 2012 American College of Clinical Pharmacy Annual Meeting, Hollywood, Florida, October 21-24, 2012, and as an encore poster presentation at the Canadian Society of Hospital Pharmacists Professional Practice Conference, Toronto, Canada, Feb 3, 2013.

Disclosure

The authors declare no conflicts of interest related to the manuscript submitted. All monies used for the research came from the University Health Network Department of Pharmacy Budget, including the pharmacy residency program.

The lack of mentorship in hospital medicine has been previously documented,^1-3 but there is scant literature about solutions to the problem.⁴ In other disciplines, data suggest that the guidance of a mentor has a positive influence on academic productivity and professional satisfaction. Mentored faculty at all levels in their careers are more successful at producing peer-reviewed publications, procuring grant support, and maintaining confidence in their career trajectory.^5,6 In one study, mentored faculty physicians reported receiving career advice, improving communication skills, and growing their professional networks.⁷ Another study found that the primary benefits of physician mentoring were improved professional and personal well-being.⁸ Whether early-career hospitalists would have similarly favorable responses to a structured mentorship program is unknown. We report our experience in implementing a pilot mentorship program to support junior hospitalists at a large academic medical center.

The mentorship program was implemented from October 2015 to June 2016 in the Hospital Medicine Unit (HMU) of the Massachusetts General Hospital (MGH), a teaching affiliate of Harvard Medical School.  

Program Goals, Design, and Development

In collaboration with the MGH Center for Faculty Development (CFD), we offered 3 training sessions over a period of 9 months, for both mentors and mentees, on how to maximize mentorship success. Funding was provided by the MGH Division of General Internal Medicine and CFD. There were no external funding sources. This study was exempt by the Partners Institutional Review Board.

Participants

Mentees had to be hired at >0.5 full-time equivalent and have 3 years or fewer of hospitalist experience. Mentors were physicians with at least 7 years of hospital medicine experience. All HMU faculty who met the criteria were invited to participate on a voluntary basis.

Mentor–Mentee Matching

Mentors were paired with 1 or 2 mentees. Participant information such as history of mentorship and areas of interest for mentorship was collected. Two authors matched mentors and mentees to maximize similarities in these areas. Four mentors were paired with 2 mentees each, and 12 mentors were paired with 1 mentee each.

Mentorship Training Sessions

The program provided 3 mentorship-training lunch sessions for both mentees and mentors during the 9-month program. To enrich attendance, mentees were provided coverage for their clinical duties. The initial training session provided an opportunity to meet, articulate expectations and challenges, and develop action plans with individualized goals for the mentoring relationship. The second training session occurred at the midpoint. Pairs considered their mentorship status, evaluated their progress, and discussed strategies for optimizing their experience. At the final training session, participants reflected on their mentoring relationships, identified their extended network of mentoring support, and set expectations regarding whether the mentoring relationship would continue.

Mentorship Meetings

In addition to the training sessions, mentee–mentor pairs were expected to meet a minimum of 2 times during the formal mentorship program. CFD experts performed participant outreach via e-mail to assess progress. Mentees were given dining facility gift cards to support meetings with their mentors.

Program Evaluation

Confidential, anonymous semiquantitative surveys were used to assess the efficacy of this prospective, nonrandomized intervention study. An online survey platform was utilized to assess the frequency of mentorship meetings, satisfaction and challenges with mentorship, perception of support, degree of career satisfaction, and perceived need for and value of mentoring. Data were collected from both mentors and mentees prior to the first training session and after completion of the program. To preserve anonymity and encourage responses, surveys did not contain identifying information. As such, individual respondent data were not directly matched pre- and postintervention.

Statistical Analysis

Individual satisfaction scores (ranked 1 to 5, with 5 being very satisfied) were assigned to each response within each of the 18 domains. A composite satisfaction score was then calculated for each respondent both pre- and postintervention. An unpaired Student’s t test was first used to assess change in overall satisfaction scores pre- and postintervention. As there was a statistically significant change in this aggregate score, Wilcoxon rank sum testing was used to compare ordinal scores pre- and postintervention within each of the 18 domains. The proportion of respondents ranking their satisfaction in each domain as satisfied or very satisfied was also compared pre- and postmentorship. This approach of modified “top-box” reporting is similar to prior major national survey-based experiences.⁹

Program Participation and Response Rate

Of the 25 eligible mentees, 16 (64%) participated in the mentorship program. Of the 20 eligible mentors, 12 (60%) participated. One participating mentee and 1 mentor left the institution during the intervention period. Fourteen mentees (response rate: 88%) and 9 mentors (response rate: 75%) completed the preintervention survey. Ten mentees (response rate: 63%) and 8 mentors (response rate: 67%) completed the postintervention survey.

Mentor Characteristics

Ninety-two percent of mentors were clinician educators. The mentors had 21 peer-reviewed publications during the year of the study, 25% of the mentors had external research funding, 75% had internal funding for projects or administrative roles, and 75% were above the rank of instructor. Most mentors were married with children.

Mentorship Meetings and the Mentorship Network

All participants attended at least 2 of the 3 trainings. For the mentees who completed the postintervention survey, 9 (90%) met with their mentors 3 or more additional times, and 8 (80%) were connected by their mentor to at least 1 additional faculty mentor.

Perceptions and Overall Satisfaction with Mentorship

Prior to starting the mentoring relationship, 86% of mentees and 78% of mentors anticipated that differing career goals would be a challenge to a successful mentor–mentee relationship. At the end of the program, only 30% of mentees and 38% of mentors felt that such differences were a challenge. Ninety percent of mentees and 88% of mentors were satisfied or very satisfied with their mentorship match. Forty-three percent of mentees felt supported by the HMU prior to the mentorship program, while 90% felt supported after the program. All the mentees agreed that future HMU faculty should participate in a similar program.

Impact of Mentorship on Critical Domains

At baseline, the following domains were most commonly rated as very important by mentees: career planning, professional connectedness, producing scholarly work, finding an area of expertise, balancing work and family life, and job satisfaction (Figure 1). There was a significant improvement in composite satisfaction scores after completion of the mentorship program (54.5 ± 6.2 vs 65 ± 14.9, P = 0.02). The influence of the mentorship program on all domains is shown in Figure 2. After completion of the mentorship program, there was a significant improvement in mentee satisfaction in the following domains: career planning, professional connectedness, self-reflection, research skills, and mentoring skills.

Our pilot structured mentorship program for junior hospitalists was feasible and led to improved satisfaction in select key career domains. Other mentoring or faculty coaching programs have been studied in several fields of medicine^10-12; however, to our knowledge, there have not been published data studying a structured mentorship program for junior faculty in hospital medicine. Our intervention prioritized not only optimizing mentorship matches but also formalizing training sessions led by content experts.

After experiencing a structured mentoring relationship, most mentees felt a greater sense of support, were satisfied with their mentoring experiences, were connected to additional faculty, and had significant improvement in satisfaction in key career domains. Satisfaction with other self-identified “very important” domains, including scholarly activity, finding an area of expertise, job satisfaction, and work and family-life balance, did not significantly improve by the end of the program.

Perceived challenges to mentoring did not persist to the same degree with the implementation of a structured program. This highlights the importance of building mentorship skill sets (such as mentoring across differences and goal setting) through expert-led training sessions and perhaps also the importance of matching based on career goals.

This study has several limitations, including a small sample size, modest response rate, and short study period. Additionally, the assessment relied on self-reporting. This study was performed at a large academic institution, and mentors were almost all clinician educators with some research experience, which limits generalizability. Surveys were entirely anonymized and did not contain identifying information, so individual respondent data could not be matched pre- and postintervention. Given that this was an observational study without a control group, mentorship can only be said to be associated with, and not necessarily causally linked to, the observed improvements. Other cointerventions occurring during the same time frame that may have impacted satisfaction include annual career conferences, changing leadership, and other faculty development seminars. Finally, given the study design and the reliance on survey-based data, the net improvement in satisfaction scores may be influenced by the Hawthorne effect.

Effective and sustainable career development requires mentorship. In our pilot study, implementing a personalized and structured mentorship program for junior hospitalists focusing on building mentor–mentee relationships was feasible and was met with satisfaction. Indeed, the proportion of junior hospitalists who felt supported more than doubled, which could potentially improve academic productivity, recruitment, and retention. Larger prospective studies with a longer follow-up are needed to assess the impact of a structured mentorship program on hospitalist careers.

Acknowledgments

The authors would like to thank each of the participants in the HMU Mentorship Program and the MGH CFD and Division of General Internal Medicine for supporting this effort.

Disclosure 

Funding was provided by the MGH DGIM and CFD. Dr. Regina O’Neill reports the following relevant financial relationship: Massachusetts General Hospital Center for Faculty Development (consultant). All other authors report no other financial or other conflicts of interest to disclose.

The lack of mentorship in hospital medicine has been previously documented,^1-3 but there is scant literature about solutions to the problem.⁴ In other disciplines, data suggest that the guidance of a mentor has a positive influence on academic productivity and professional satisfaction. Mentored faculty at all levels in their careers are more successful at producing peer-reviewed publications, procuring grant support, and maintaining confidence in their career trajectory.^5,6 In one study, mentored faculty physicians reported receiving career advice, improving communication skills, and growing their professional networks.⁷ Another study found that the primary benefits of physician mentoring were improved professional and personal well-being.⁸ Whether early-career hospitalists would have similarly favorable responses to a structured mentorship program is unknown. We report our experience in implementing a pilot mentorship program to support junior hospitalists at a large academic medical center.

The mentorship program was implemented from October 2015 to June 2016 in the Hospital Medicine Unit (HMU) of the Massachusetts General Hospital (MGH), a teaching affiliate of Harvard Medical School.  

Program Goals, Design, and Development

In collaboration with the MGH Center for Faculty Development (CFD), we offered 3 training sessions over a period of 9 months, for both mentors and mentees, on how to maximize mentorship success. Funding was provided by the MGH Division of General Internal Medicine and CFD. There were no external funding sources. This study was exempt by the Partners Institutional Review Board.

Participants

Mentees had to be hired at >0.5 full-time equivalent and have 3 years or fewer of hospitalist experience. Mentors were physicians with at least 7 years of hospital medicine experience. All HMU faculty who met the criteria were invited to participate on a voluntary basis.

Mentor–Mentee Matching

Mentors were paired with 1 or 2 mentees. Participant information such as history of mentorship and areas of interest for mentorship was collected. Two authors matched mentors and mentees to maximize similarities in these areas. Four mentors were paired with 2 mentees each, and 12 mentors were paired with 1 mentee each.

Mentorship Training Sessions

The program provided 3 mentorship-training lunch sessions for both mentees and mentors during the 9-month program. To enrich attendance, mentees were provided coverage for their clinical duties. The initial training session provided an opportunity to meet, articulate expectations and challenges, and develop action plans with individualized goals for the mentoring relationship. The second training session occurred at the midpoint. Pairs considered their mentorship status, evaluated their progress, and discussed strategies for optimizing their experience. At the final training session, participants reflected on their mentoring relationships, identified their extended network of mentoring support, and set expectations regarding whether the mentoring relationship would continue.

Mentorship Meetings

In addition to the training sessions, mentee–mentor pairs were expected to meet a minimum of 2 times during the formal mentorship program. CFD experts performed participant outreach via e-mail to assess progress. Mentees were given dining facility gift cards to support meetings with their mentors.

Program Evaluation

Confidential, anonymous semiquantitative surveys were used to assess the efficacy of this prospective, nonrandomized intervention study. An online survey platform was utilized to assess the frequency of mentorship meetings, satisfaction and challenges with mentorship, perception of support, degree of career satisfaction, and perceived need for and value of mentoring. Data were collected from both mentors and mentees prior to the first training session and after completion of the program. To preserve anonymity and encourage responses, surveys did not contain identifying information. As such, individual respondent data were not directly matched pre- and postintervention.

Statistical Analysis

Individual satisfaction scores (ranked 1 to 5, with 5 being very satisfied) were assigned to each response within each of the 18 domains. A composite satisfaction score was then calculated for each respondent both pre- and postintervention. An unpaired Student’s t test was first used to assess change in overall satisfaction scores pre- and postintervention. As there was a statistically significant change in this aggregate score, Wilcoxon rank sum testing was used to compare ordinal scores pre- and postintervention within each of the 18 domains. The proportion of respondents ranking their satisfaction in each domain as satisfied or very satisfied was also compared pre- and postmentorship. This approach of modified “top-box” reporting is similar to prior major national survey-based experiences.⁹

Program Participation and Response Rate

Of the 25 eligible mentees, 16 (64%) participated in the mentorship program. Of the 20 eligible mentors, 12 (60%) participated. One participating mentee and 1 mentor left the institution during the intervention period. Fourteen mentees (response rate: 88%) and 9 mentors (response rate: 75%) completed the preintervention survey. Ten mentees (response rate: 63%) and 8 mentors (response rate: 67%) completed the postintervention survey.

Mentor Characteristics

Ninety-two percent of mentors were clinician educators. The mentors had 21 peer-reviewed publications during the year of the study, 25% of the mentors had external research funding, 75% had internal funding for projects or administrative roles, and 75% were above the rank of instructor. Most mentors were married with children.

Mentorship Meetings and the Mentorship Network

All participants attended at least 2 of the 3 trainings. For the mentees who completed the postintervention survey, 9 (90%) met with their mentors 3 or more additional times, and 8 (80%) were connected by their mentor to at least 1 additional faculty mentor.

Perceptions and Overall Satisfaction with Mentorship

Prior to starting the mentoring relationship, 86% of mentees and 78% of mentors anticipated that differing career goals would be a challenge to a successful mentor–mentee relationship. At the end of the program, only 30% of mentees and 38% of mentors felt that such differences were a challenge. Ninety percent of mentees and 88% of mentors were satisfied or very satisfied with their mentorship match. Forty-three percent of mentees felt supported by the HMU prior to the mentorship program, while 90% felt supported after the program. All the mentees agreed that future HMU faculty should participate in a similar program.

Impact of Mentorship on Critical Domains

At baseline, the following domains were most commonly rated as very important by mentees: career planning, professional connectedness, producing scholarly work, finding an area of expertise, balancing work and family life, and job satisfaction (Figure 1). There was a significant improvement in composite satisfaction scores after completion of the mentorship program (54.5 ± 6.2 vs 65 ± 14.9, P = 0.02). The influence of the mentorship program on all domains is shown in Figure 2. After completion of the mentorship program, there was a significant improvement in mentee satisfaction in the following domains: career planning, professional connectedness, self-reflection, research skills, and mentoring skills.

Our pilot structured mentorship program for junior hospitalists was feasible and led to improved satisfaction in select key career domains. Other mentoring or faculty coaching programs have been studied in several fields of medicine^10-12; however, to our knowledge, there have not been published data studying a structured mentorship program for junior faculty in hospital medicine. Our intervention prioritized not only optimizing mentorship matches but also formalizing training sessions led by content experts.

After experiencing a structured mentoring relationship, most mentees felt a greater sense of support, were satisfied with their mentoring experiences, were connected to additional faculty, and had significant improvement in satisfaction in key career domains. Satisfaction with other self-identified “very important” domains, including scholarly activity, finding an area of expertise, job satisfaction, and work and family-life balance, did not significantly improve by the end of the program.

Perceived challenges to mentoring did not persist to the same degree with the implementation of a structured program. This highlights the importance of building mentorship skill sets (such as mentoring across differences and goal setting) through expert-led training sessions and perhaps also the importance of matching based on career goals.

This study has several limitations, including a small sample size, modest response rate, and short study period. Additionally, the assessment relied on self-reporting. This study was performed at a large academic institution, and mentors were almost all clinician educators with some research experience, which limits generalizability. Surveys were entirely anonymized and did not contain identifying information, so individual respondent data could not be matched pre- and postintervention. Given that this was an observational study without a control group, mentorship can only be said to be associated with, and not necessarily causally linked to, the observed improvements. Other cointerventions occurring during the same time frame that may have impacted satisfaction include annual career conferences, changing leadership, and other faculty development seminars. Finally, given the study design and the reliance on survey-based data, the net improvement in satisfaction scores may be influenced by the Hawthorne effect.

Effective and sustainable career development requires mentorship. In our pilot study, implementing a personalized and structured mentorship program for junior hospitalists focusing on building mentor–mentee relationships was feasible and was met with satisfaction. Indeed, the proportion of junior hospitalists who felt supported more than doubled, which could potentially improve academic productivity, recruitment, and retention. Larger prospective studies with a longer follow-up are needed to assess the impact of a structured mentorship program on hospitalist careers.

Acknowledgments

The authors would like to thank each of the participants in the HMU Mentorship Program and the MGH CFD and Division of General Internal Medicine for supporting this effort.

Disclosure 

Funding was provided by the MGH DGIM and CFD. Dr. Regina O’Neill reports the following relevant financial relationship: Massachusetts General Hospital Center for Faculty Development (consultant). All other authors report no other financial or other conflicts of interest to disclose.

The lack of mentorship in hospital medicine has been previously documented,^1-3 but there is scant literature about solutions to the problem.⁴ In other disciplines, data suggest that the guidance of a mentor has a positive influence on academic productivity and professional satisfaction. Mentored faculty at all levels in their careers are more successful at producing peer-reviewed publications, procuring grant support, and maintaining confidence in their career trajectory.^5,6 In one study, mentored faculty physicians reported receiving career advice, improving communication skills, and growing their professional networks.⁷ Another study found that the primary benefits of physician mentoring were improved professional and personal well-being.⁸ Whether early-career hospitalists would have similarly favorable responses to a structured mentorship program is unknown. We report our experience in implementing a pilot mentorship program to support junior hospitalists at a large academic medical center.

The mentorship program was implemented from October 2015 to June 2016 in the Hospital Medicine Unit (HMU) of the Massachusetts General Hospital (MGH), a teaching affiliate of Harvard Medical School.  

Program Goals, Design, and Development

In collaboration with the MGH Center for Faculty Development (CFD), we offered 3 training sessions over a period of 9 months, for both mentors and mentees, on how to maximize mentorship success. Funding was provided by the MGH Division of General Internal Medicine and CFD. There were no external funding sources. This study was exempt by the Partners Institutional Review Board.

Participants

Mentees had to be hired at >0.5 full-time equivalent and have 3 years or fewer of hospitalist experience. Mentors were physicians with at least 7 years of hospital medicine experience. All HMU faculty who met the criteria were invited to participate on a voluntary basis.

Mentor–Mentee Matching

Mentors were paired with 1 or 2 mentees. Participant information such as history of mentorship and areas of interest for mentorship was collected. Two authors matched mentors and mentees to maximize similarities in these areas. Four mentors were paired with 2 mentees each, and 12 mentors were paired with 1 mentee each.

Mentorship Training Sessions

The program provided 3 mentorship-training lunch sessions for both mentees and mentors during the 9-month program. To enrich attendance, mentees were provided coverage for their clinical duties. The initial training session provided an opportunity to meet, articulate expectations and challenges, and develop action plans with individualized goals for the mentoring relationship. The second training session occurred at the midpoint. Pairs considered their mentorship status, evaluated their progress, and discussed strategies for optimizing their experience. At the final training session, participants reflected on their mentoring relationships, identified their extended network of mentoring support, and set expectations regarding whether the mentoring relationship would continue.

Mentorship Meetings

In addition to the training sessions, mentee–mentor pairs were expected to meet a minimum of 2 times during the formal mentorship program. CFD experts performed participant outreach via e-mail to assess progress. Mentees were given dining facility gift cards to support meetings with their mentors.

Program Evaluation

Confidential, anonymous semiquantitative surveys were used to assess the efficacy of this prospective, nonrandomized intervention study. An online survey platform was utilized to assess the frequency of mentorship meetings, satisfaction and challenges with mentorship, perception of support, degree of career satisfaction, and perceived need for and value of mentoring. Data were collected from both mentors and mentees prior to the first training session and after completion of the program. To preserve anonymity and encourage responses, surveys did not contain identifying information. As such, individual respondent data were not directly matched pre- and postintervention.

Statistical Analysis

Individual satisfaction scores (ranked 1 to 5, with 5 being very satisfied) were assigned to each response within each of the 18 domains. A composite satisfaction score was then calculated for each respondent both pre- and postintervention. An unpaired Student’s t test was first used to assess change in overall satisfaction scores pre- and postintervention. As there was a statistically significant change in this aggregate score, Wilcoxon rank sum testing was used to compare ordinal scores pre- and postintervention within each of the 18 domains. The proportion of respondents ranking their satisfaction in each domain as satisfied or very satisfied was also compared pre- and postmentorship. This approach of modified “top-box” reporting is similar to prior major national survey-based experiences.⁹

Program Participation and Response Rate

Of the 25 eligible mentees, 16 (64%) participated in the mentorship program. Of the 20 eligible mentors, 12 (60%) participated. One participating mentee and 1 mentor left the institution during the intervention period. Fourteen mentees (response rate: 88%) and 9 mentors (response rate: 75%) completed the preintervention survey. Ten mentees (response rate: 63%) and 8 mentors (response rate: 67%) completed the postintervention survey.

Mentor Characteristics

Ninety-two percent of mentors were clinician educators. The mentors had 21 peer-reviewed publications during the year of the study, 25% of the mentors had external research funding, 75% had internal funding for projects or administrative roles, and 75% were above the rank of instructor. Most mentors were married with children.

Mentorship Meetings and the Mentorship Network

All participants attended at least 2 of the 3 trainings. For the mentees who completed the postintervention survey, 9 (90%) met with their mentors 3 or more additional times, and 8 (80%) were connected by their mentor to at least 1 additional faculty mentor.

Perceptions and Overall Satisfaction with Mentorship

Prior to starting the mentoring relationship, 86% of mentees and 78% of mentors anticipated that differing career goals would be a challenge to a successful mentor–mentee relationship. At the end of the program, only 30% of mentees and 38% of mentors felt that such differences were a challenge. Ninety percent of mentees and 88% of mentors were satisfied or very satisfied with their mentorship match. Forty-three percent of mentees felt supported by the HMU prior to the mentorship program, while 90% felt supported after the program. All the mentees agreed that future HMU faculty should participate in a similar program.

Impact of Mentorship on Critical Domains

At baseline, the following domains were most commonly rated as very important by mentees: career planning, professional connectedness, producing scholarly work, finding an area of expertise, balancing work and family life, and job satisfaction (Figure 1). There was a significant improvement in composite satisfaction scores after completion of the mentorship program (54.5 ± 6.2 vs 65 ± 14.9, P = 0.02). The influence of the mentorship program on all domains is shown in Figure 2. After completion of the mentorship program, there was a significant improvement in mentee satisfaction in the following domains: career planning, professional connectedness, self-reflection, research skills, and mentoring skills.

Our pilot structured mentorship program for junior hospitalists was feasible and led to improved satisfaction in select key career domains. Other mentoring or faculty coaching programs have been studied in several fields of medicine^10-12; however, to our knowledge, there have not been published data studying a structured mentorship program for junior faculty in hospital medicine. Our intervention prioritized not only optimizing mentorship matches but also formalizing training sessions led by content experts.

After experiencing a structured mentoring relationship, most mentees felt a greater sense of support, were satisfied with their mentoring experiences, were connected to additional faculty, and had significant improvement in satisfaction in key career domains. Satisfaction with other self-identified “very important” domains, including scholarly activity, finding an area of expertise, job satisfaction, and work and family-life balance, did not significantly improve by the end of the program.

Perceived challenges to mentoring did not persist to the same degree with the implementation of a structured program. This highlights the importance of building mentorship skill sets (such as mentoring across differences and goal setting) through expert-led training sessions and perhaps also the importance of matching based on career goals.

This study has several limitations, including a small sample size, modest response rate, and short study period. Additionally, the assessment relied on self-reporting. This study was performed at a large academic institution, and mentors were almost all clinician educators with some research experience, which limits generalizability. Surveys were entirely anonymized and did not contain identifying information, so individual respondent data could not be matched pre- and postintervention. Given that this was an observational study without a control group, mentorship can only be said to be associated with, and not necessarily causally linked to, the observed improvements. Other cointerventions occurring during the same time frame that may have impacted satisfaction include annual career conferences, changing leadership, and other faculty development seminars. Finally, given the study design and the reliance on survey-based data, the net improvement in satisfaction scores may be influenced by the Hawthorne effect.

Effective and sustainable career development requires mentorship. In our pilot study, implementing a personalized and structured mentorship program for junior hospitalists focusing on building mentor–mentee relationships was feasible and was met with satisfaction. Indeed, the proportion of junior hospitalists who felt supported more than doubled, which could potentially improve academic productivity, recruitment, and retention. Larger prospective studies with a longer follow-up are needed to assess the impact of a structured mentorship program on hospitalist careers.

Acknowledgments

The authors would like to thank each of the participants in the HMU Mentorship Program and the MGH CFD and Division of General Internal Medicine for supporting this effort.

Disclosure 

Funding was provided by the MGH DGIM and CFD. Dr. Regina O’Neill reports the following relevant financial relationship: Massachusetts General Hospital Center for Faculty Development (consultant). All other authors report no other financial or other conflicts of interest to disclose.

Public reporting of readmission rates on the Nursing Home Compare website is mandated to begin on October 1, 2017, with skilled nursing facilities (SNFs) set to receive a Medicare bonus or penalty beginning a year later.¹ The Centers for Medicare & Medicaid Services (CMS) began public reporting of hospitals’ 30-day readmission rates for selected conditions in 2009, and the Patient Protection and Affordable Care Act of 2010 mandated financial penalties for excess readmissions through the Hospital Readmission Reduction Program.² In response, most hospitals have focused on patients who return home following discharge. Innovative interventions have proven successful, such as the Transitional Care model developed by Naylor and Coleman’s Care Transitions Intervention.^3-5 Approximately 20% of Medicare beneficiaries are discharged from hospitals to SNFs, and these patients have higher readmission rates than those discharged home. CMS reported that in 2010, 23.3% of those with an SNF stay were readmitted within 30 days, compared with 18.8% for those with other discharge dispositions.⁶

Some work has been undertaken in this arena. In 2012, the Center for Medicare and Medicaid Innovation (CMMI) and the Medicare-Medicaid Coordination Office jointly launched the Initiative to Reduce Avoidable Hospitalizations among Nursing Facility Residents.⁷ This partnership established 7 Enhanced Care and Coordination Provider organizations and was designed to improve care by reducing hospitalizations among long-stay, dual-eligible nursing facility residents at 143 nursing homes in 7 states.⁸ At the time of the most recent project report, there were mixed results regarding program effects on hospitalizations and spending, with 2 states showing strongly positive patterns, 3 states with reductions that were consistent though not statistically strong, and mixed results in the remaining states. Quality measures did not show any pattern suggesting a program effect.⁹ Interventions to Reduce Acute Care Transfers (INTERACT) II was a 6-month, collaborative, quality-improvement project implemented in 2009 at 30 nursing homes in 3 states.¹⁰ The project evaluation found a statistically significant, 17% decrease in self-reported hospital admissions among the 25 SNFs that completed the intervention, compared with the same 6 months in the prior year. The Cleveland Clinic recently reported favorable results implementing its Connected Care model, which relied on staff physicians and advanced practice professionals to visit patients 4 to 5 times per week and be on call 24/7 at 7 intervention SNFs.¹¹ Through this intervention, it successfully reduced its 30-day hospital readmission rate from SNFs from 28.1% to 21.7% (P < 0.001), and the authors posed the question as to whether its model and results were reproducible in other healthcare systems.

Herein, we report on the results of a collaborative initiative named the Enhanced Care Program (ECP), which offers the services of clinical providers and administrative staff to assist with the care of patients at 8 partner SNFs. The 3 components of ECP (described below) were specifically designed to address commonly recognized gaps and opportunities in routine SNF care. In contrast to the Cleveland Clinic’s Connected Care model (which involved hospital-employed physicians serving as the SNF attendings and excluded patients followed by their own physicians), ECP was designed to integrate into a pluralistic, community model whereby independent physicians continued to follow their own patients at the SNFs. The Connected Care analysis compared participating versus nonparticipating SNFs; both the Connected Care model and the INTERACT II evaluation relied on pre–post comparisons; the CMMI evaluation used a difference-in-differences model to compare the outcomes of the program SNFs with those of a matched comparison group of nonparticipating SNFs. The evaluation of ECP differs from these other initiatives, using a concurrent comparison group of patients discharged to the same SNFs but who were not enrolled in ECP.

Setting

Cedars-Sinai Medical Center (CSMC) is an 850-bed, acute care facility located in an urban area of Los Angeles. Eight SNFs, ranging in size from 49 to 150 beds and located between 0.6 and 2.2 miles from CSMC, were invited to partner with the ECP. The physician community encompasses more than 2000 physicians on the medical staff, including private practitioners, nonteaching hospitalists, full-time faculty hospitalists, and faculty specialists.

Study Design and Patients

This was an observational, retrospective cohort analysis of 30-day same-hospital readmissions among 3951 patients discharged from CSMC to 8 SNFs between January 1, 2014, and June 30, 2015. A total of 2394 patients were enrolled in the ECP, and 1557 patients were not enrolled.

ECP Enrollment Protocol

Every patient discharged from CSMC to 1 of the 8 partner SNFs was eligible to participate in the program. To respect the autonomy of the SNF attending physicians and to facilitate a collaborative relationship, the decision to enroll a patient in the ECP rested with the SNF attending physician. The ECP team maintained a database that tracked whether each SNF attending physician (1) opted to automatically enroll all his or her patients in the ECP, (2) opted to enroll patients on a case-by-case basis (in which case an ECP nurse practitioner [NP] contacted the attending physician for each eligible patient), or (3) opted out of the ECP completely. When a new SNF attending physician was encountered, the ECP medical director called the physician to explain the ECP and offer enrollment of his or her patient(s). Ultimately, patients (or their decision-makers) retained the right to opt in or out of the ECP at any time, regardless of the decision of the attending physicians.

Program Description

Patients enrolled in the ECP experienced the standard care provided by the SNF staff and attending physicians plus a clinical care program delivered by 9 full-time NPs, 1 full-time pharmacist, 1 pharmacy technician, 1 full-time nurse educator, a program administrator, and a medical director.

The program included the following 3 major components:

1. Direct patient care and 24/7 NP availability: Program enrollment began with an on-site, bedside evaluation by an ECP NP at the SNF within 24 hours of arrival and continued with weekly NP rounding (or more frequently, if clinically indicated) on the patient. Each encounter included a review of the medical record; a dialogue with the patient’s SNF attending physician to formulate treatment plans and place orders; discussions with nurses, family members, and other caregivers; and documentation in the medical record. The ECP team was on-site at the SNFs 7 days a week and on call 24/7 to address questions and concerns. Patients remained enrolled in the ECP from SNF admission to discharge even if their stay extended beyond 30 days.

2. Medication reconciliation: The ECP pharmacy team completed a review of a patient’s SNF medication administration record (MAR) within 72 hours of SNF admission. This process involved the pharmacy technician gathering medication lists from the SNFs and CSMC and providing this information to the pharmacist for a medication reconciliation and clinical evaluation. Discrepancies and pharmacist recommendations were communicated to the ECP NPs, and all identified issues were resolved.

3. Educational in-services: Building upon the INTERACT II model, the ECP team identified high-yield, clinically relevant topics, which the ECP nurse educator turned into monthly educational sessions for the SNF nursing staff at each of the participating SNFs.¹⁰

Primary Outcome Measure

An inpatient readmission to CSMC within 30 days of the hospital discharge date was counted as a readmission, whether the patient returned directly from an SNF or was readmitted from home after an SNF discharge.

Data

ECP patients were identified using a log maintained by the ECP program manager. Non-ECP patients discharged to the same SNFs during the study period were identified from CSMC’s electronic registry of SNF discharges. Covariates known to be associated with increased risk of 30-day readmission were obtained from CSMC’s electronic data warehouse, including demographic information, length of stay (LOS) of index hospitalization, and payer.¹² Eleven clinical service lines represented patients’ clinical conditions based on Medicare-Severity Diagnosis-Related groupings. The discharge severity of illness score was calculated using 3M All Patients Refined Diagnosis Related Group software, version 33.¹³

Analysis

Characteristics of the ECP and non-ECP patients were compared using the χ² test. A multivariable logistic regression model with fixed effects for SNF was created to determine the program’s impact on 30-day hospital readmission, adjusting for patient characteristics. The Pearson χ² goodness-of-fit test and the link test for model specification were used to evaluate model specification. The sensitivity of the results to differences in patient characteristics was assessed in 2 ways. First, the ECP and non-ECP populations were stratified based on race and/or ethnicity and payer, and the multivariable regression model was run within the strata associated with the highest readmission rates. Second, a propensity analysis using inverse probability of treatment weighting (IPTW) was performed to control for group differences. Results of all comparisons were considered statistically significant when P < 0.05. Stata version 13 was used to perform the main analyses.¹⁴ The propensity analysis was conducted using R version 3.2.3. The CSMC Institutional Review Board (IRB) determined that this study qualified as a quality-improvement activity and did not require IRB approval or exemption.

The average unadjusted 30-day readmission rate for ECP patients over the 18-month study period was 17.2%, compared to 23.0% for patients not enrolled in ECP (P < 0.001) (Figure 1). After adjusting for patient characteristics, ECP patients had 29% lower odds (95% confidence interval [CI], 0.60-0.85) of being readmitted to the medical center within 30 days than non-ECP patients at the same SNFs. The characteristics of the ECP and comparison patient cohorts are shown in Table 1. There were significant differences in sociodemographic characteristics: The ECP group had a higher proportion of non-Hispanic white patients, while the comparison group had a higher proportion of patients who were African American or Hispanic. ECP patients were more likely to prefer speaking English, while Russian, Farsi, and Spanish were preferred more frequently in the comparison group. There were also differences in payer mix, with the ECP group including proportionately more Medicare fee-for-service (52.9% vs 35.0%, P < 0.001), while the comparison group had a correspondingly larger proportion of dual-eligible (Medicare and Medicaid) patients (55.0% vs 35.1%, P < 0.001).

Sensitivity Analyses

The results were robust when tested within strata of the study population, including analyses limited to dual-eligible patients, African American patients, patients admitted to all except the highest volume facility, and patients admitted to any service line other than orthopedic surgery. Similar results were obtained when the study population was restricted to patients living within the medical center’s primary service area and to patients living in zip codes in which the proportion of adults living in households with income below 100% of the poverty level was 15% or greater (see Supplementary Material for results).

The effect of the program on readmission was also consistent when the full logistic regression model was run with IPTW using the propensity score. The evaluation of standardized cluster differences between the ECP and non-ECP groups before and after IPTW showed that the differences were reduced to <10% for being African American; speaking Russian or Farsi; having dual-eligible insurance coverage; having orthopedic surgery; being discharged from the clinical service lines of gastroenterology, pulmonary, other surgery, and other services; and having an index hospital LOS of 4 to 5 days or 10 or more days (results are provided in the Supplementary Material).

Hospitals continue to experience significant pressure to manage LOS, and SNFs and hospitals are being held accountable for readmission rates. The setting of this study is representative of many large, urban hospitals in the United States whose communities include a heterogeneous mix of hospitalists, primary care physicians who follow their patients in SNFs, and independent SNFs.¹⁵ The current regulations have not kept up with the increasing acuity and complexity of SNF patients. Specifically, Medicare guidelines allow the SNF attending physician up to 72 hours to complete a history and physical (or 7 days if he or she was the hospital attending physician for the index hospitalization) and only require monthly follow-up visits. It is the opinion of the ECP designers that these relatively lax requirements present unnecessary risk for vulnerable patients. While the INTERACT II model was focused largely on educational initiatives (with an advanced practice nurse available in a consultative role, as needed), the central tenet of ECP was similar to the Connected Care model in that the focus was on adding an extra layer of direct clinical support. Protocols that provided timely initial assessments by an NP (within 24 hours), weekly NP rounding (at a minimum), and 24/7 on-call availability all contributed to helping patients stay on track. Although the ECP had patients visited less frequently than the Connected Care model, and the Cleveland Clinic started with a higher baseline 30-day readmission rate from SNFs, similar overall reductions in 30-day readmissions were observed. The key point from both initiatives is that an increase in clinical touchpoints and ease of access to clinicians generates myriad opportunities to identify and address small issues before they become clinical emergencies requiring hospital transfers and readmissions.

Correcting medication discrepancies between hospital discharge summaries and SNF admission orders through a systematic medication reconciliation using a clinical pharmacist has previously been shown to improve outcomes.^16-18 The ECP pharmacy technician and ECP clinical pharmacist discovered and corrected errors on a daily basis that ranged from incidental to potentially life-threatening. If the SNF staff does not provide the patient’s MAR within 48 hours of arrival, the pharmacy technician contacts the facility to obtain the information. As a result, all patients enrolled in the ECP during the study period received this intervention (unless they were rehospitalized or left the SNF before the process was completed), and 54% of ECP patients required some form of intervention after medication reconciliation was completed (data not shown).

This type of program requires hospital leadership and SNF administrators to be fully committed to developing strong working relationships, and in fact, there is evidence that SNF baseline readmission rates have a greater influence on patients’ risk of rehospitalization than the discharging hospital itself.^19-21 Monthly educational in-services are delivered at the partner SNFs to enhance SNF nursing staff knowledge and clinical acumen. High-impact topics identified by the ECP team include the following: fall prevention, hand hygiene, venous thromboembolism, cardiovascular health, how to report change in condition, and advanced care planning, among others. While no formal pre–post assessments of the SNF nurses’ knowledge were conducted, a log of in-services was kept, subjective feedback was collected for performance improvement purposes, and continuing educational units were provided to the SNF nurses who attended.

This study has limitations. As a single-hospital study, generalizability may be limited. While adherence to the program components was closely monitored daily, service gaps may have occurred that were not captured. The program design makes it difficult to quantify the relative impact of the 3 program components on the outcome. Furthermore, the study was observational, so the differences in readmission rates may have been due to unmeasured variables. The decision to enroll patients in the ECP was made by each patient’s SNF attending physician, and those who chose to (or not to) participate in the program may manifest other, unmeasured practice patterns that made readmissions more or less likely. Participating physicians also had the option to enroll their patients on a case-by-case basis, introducing further potential bias in patient selection; however, <5% of physicians exercised this option. Patients may have also been readmitted to hospitals other than CSMC, producing an observed readmission rate for 1 or both groups that underrepresents the true outcome. On this point, while we did not systematically track these other-hospital readmissions for both groups, there is no reason to believe that this occurred preferentially for ECP or non-ECP patients.

Multiple sensitivity analyses were performed to address the observed differences between ECP and non-ECP patients. These included stratified examinations of variables differing between populations, examination of clustering effects between SNFs, and an analysis adjusted for the propensity to be included in the ECP. The calculated effect of the intervention on readmission remained robust, although we acknowledge that differences in the populations may persist and have influenced the outcomes even after controlling for multiple variables.^22-25

In conclusion, the results of this intervention are compelling and add to the growing body of literature suggesting that a comprehensive, multipronged effort to enhance clinical oversight and coordination of care for SNF patients can improve outcomes. Given CMS’s plans to report SNF readmission rates in 2017 followed by the application of financial incentives in 2018, a favorable climate currently exists for greater coordination between hospitals and SNFs.²⁶ We are currently undertaking an economic evaluation of the program.

Acknowledgments

The authors would like to thank the following people for their contributions: Mae Saunders, Rita Shane, Dr. Jon Kea, Miranda Li, the ECP NPs, the ECP pharmacy team, CSMC’s performance improvement team, and Alan Matus.

Disclosure

 No conflicts of interest or disclosures.

Public reporting of readmission rates on the Nursing Home Compare website is mandated to begin on October 1, 2017, with skilled nursing facilities (SNFs) set to receive a Medicare bonus or penalty beginning a year later.¹ The Centers for Medicare & Medicaid Services (CMS) began public reporting of hospitals’ 30-day readmission rates for selected conditions in 2009, and the Patient Protection and Affordable Care Act of 2010 mandated financial penalties for excess readmissions through the Hospital Readmission Reduction Program.² In response, most hospitals have focused on patients who return home following discharge. Innovative interventions have proven successful, such as the Transitional Care model developed by Naylor and Coleman’s Care Transitions Intervention.^3-5 Approximately 20% of Medicare beneficiaries are discharged from hospitals to SNFs, and these patients have higher readmission rates than those discharged home. CMS reported that in 2010, 23.3% of those with an SNF stay were readmitted within 30 days, compared with 18.8% for those with other discharge dispositions.⁶

Some work has been undertaken in this arena. In 2012, the Center for Medicare and Medicaid Innovation (CMMI) and the Medicare-Medicaid Coordination Office jointly launched the Initiative to Reduce Avoidable Hospitalizations among Nursing Facility Residents.⁷ This partnership established 7 Enhanced Care and Coordination Provider organizations and was designed to improve care by reducing hospitalizations among long-stay, dual-eligible nursing facility residents at 143 nursing homes in 7 states.⁸ At the time of the most recent project report, there were mixed results regarding program effects on hospitalizations and spending, with 2 states showing strongly positive patterns, 3 states with reductions that were consistent though not statistically strong, and mixed results in the remaining states. Quality measures did not show any pattern suggesting a program effect.⁹ Interventions to Reduce Acute Care Transfers (INTERACT) II was a 6-month, collaborative, quality-improvement project implemented in 2009 at 30 nursing homes in 3 states.¹⁰ The project evaluation found a statistically significant, 17% decrease in self-reported hospital admissions among the 25 SNFs that completed the intervention, compared with the same 6 months in the prior year. The Cleveland Clinic recently reported favorable results implementing its Connected Care model, which relied on staff physicians and advanced practice professionals to visit patients 4 to 5 times per week and be on call 24/7 at 7 intervention SNFs.¹¹ Through this intervention, it successfully reduced its 30-day hospital readmission rate from SNFs from 28.1% to 21.7% (P < 0.001), and the authors posed the question as to whether its model and results were reproducible in other healthcare systems.

Herein, we report on the results of a collaborative initiative named the Enhanced Care Program (ECP), which offers the services of clinical providers and administrative staff to assist with the care of patients at 8 partner SNFs. The 3 components of ECP (described below) were specifically designed to address commonly recognized gaps and opportunities in routine SNF care. In contrast to the Cleveland Clinic’s Connected Care model (which involved hospital-employed physicians serving as the SNF attendings and excluded patients followed by their own physicians), ECP was designed to integrate into a pluralistic, community model whereby independent physicians continued to follow their own patients at the SNFs. The Connected Care analysis compared participating versus nonparticipating SNFs; both the Connected Care model and the INTERACT II evaluation relied on pre–post comparisons; the CMMI evaluation used a difference-in-differences model to compare the outcomes of the program SNFs with those of a matched comparison group of nonparticipating SNFs. The evaluation of ECP differs from these other initiatives, using a concurrent comparison group of patients discharged to the same SNFs but who were not enrolled in ECP.

Setting

Cedars-Sinai Medical Center (CSMC) is an 850-bed, acute care facility located in an urban area of Los Angeles. Eight SNFs, ranging in size from 49 to 150 beds and located between 0.6 and 2.2 miles from CSMC, were invited to partner with the ECP. The physician community encompasses more than 2000 physicians on the medical staff, including private practitioners, nonteaching hospitalists, full-time faculty hospitalists, and faculty specialists.

Study Design and Patients

This was an observational, retrospective cohort analysis of 30-day same-hospital readmissions among 3951 patients discharged from CSMC to 8 SNFs between January 1, 2014, and June 30, 2015. A total of 2394 patients were enrolled in the ECP, and 1557 patients were not enrolled.

ECP Enrollment Protocol

Every patient discharged from CSMC to 1 of the 8 partner SNFs was eligible to participate in the program. To respect the autonomy of the SNF attending physicians and to facilitate a collaborative relationship, the decision to enroll a patient in the ECP rested with the SNF attending physician. The ECP team maintained a database that tracked whether each SNF attending physician (1) opted to automatically enroll all his or her patients in the ECP, (2) opted to enroll patients on a case-by-case basis (in which case an ECP nurse practitioner [NP] contacted the attending physician for each eligible patient), or (3) opted out of the ECP completely. When a new SNF attending physician was encountered, the ECP medical director called the physician to explain the ECP and offer enrollment of his or her patient(s). Ultimately, patients (or their decision-makers) retained the right to opt in or out of the ECP at any time, regardless of the decision of the attending physicians.

Program Description

Patients enrolled in the ECP experienced the standard care provided by the SNF staff and attending physicians plus a clinical care program delivered by 9 full-time NPs, 1 full-time pharmacist, 1 pharmacy technician, 1 full-time nurse educator, a program administrator, and a medical director.

The program included the following 3 major components:

1. Direct patient care and 24/7 NP availability: Program enrollment began with an on-site, bedside evaluation by an ECP NP at the SNF within 24 hours of arrival and continued with weekly NP rounding (or more frequently, if clinically indicated) on the patient. Each encounter included a review of the medical record; a dialogue with the patient’s SNF attending physician to formulate treatment plans and place orders; discussions with nurses, family members, and other caregivers; and documentation in the medical record. The ECP team was on-site at the SNFs 7 days a week and on call 24/7 to address questions and concerns. Patients remained enrolled in the ECP from SNF admission to discharge even if their stay extended beyond 30 days.

2. Medication reconciliation: The ECP pharmacy team completed a review of a patient’s SNF medication administration record (MAR) within 72 hours of SNF admission. This process involved the pharmacy technician gathering medication lists from the SNFs and CSMC and providing this information to the pharmacist for a medication reconciliation and clinical evaluation. Discrepancies and pharmacist recommendations were communicated to the ECP NPs, and all identified issues were resolved.

3. Educational in-services: Building upon the INTERACT II model, the ECP team identified high-yield, clinically relevant topics, which the ECP nurse educator turned into monthly educational sessions for the SNF nursing staff at each of the participating SNFs.¹⁰

Primary Outcome Measure

An inpatient readmission to CSMC within 30 days of the hospital discharge date was counted as a readmission, whether the patient returned directly from an SNF or was readmitted from home after an SNF discharge.

Data

ECP patients were identified using a log maintained by the ECP program manager. Non-ECP patients discharged to the same SNFs during the study period were identified from CSMC’s electronic registry of SNF discharges. Covariates known to be associated with increased risk of 30-day readmission were obtained from CSMC’s electronic data warehouse, including demographic information, length of stay (LOS) of index hospitalization, and payer.¹² Eleven clinical service lines represented patients’ clinical conditions based on Medicare-Severity Diagnosis-Related groupings. The discharge severity of illness score was calculated using 3M All Patients Refined Diagnosis Related Group software, version 33.¹³

Analysis

Characteristics of the ECP and non-ECP patients were compared using the χ² test. A multivariable logistic regression model with fixed effects for SNF was created to determine the program’s impact on 30-day hospital readmission, adjusting for patient characteristics. The Pearson χ² goodness-of-fit test and the link test for model specification were used to evaluate model specification. The sensitivity of the results to differences in patient characteristics was assessed in 2 ways. First, the ECP and non-ECP populations were stratified based on race and/or ethnicity and payer, and the multivariable regression model was run within the strata associated with the highest readmission rates. Second, a propensity analysis using inverse probability of treatment weighting (IPTW) was performed to control for group differences. Results of all comparisons were considered statistically significant when P < 0.05. Stata version 13 was used to perform the main analyses.¹⁴ The propensity analysis was conducted using R version 3.2.3. The CSMC Institutional Review Board (IRB) determined that this study qualified as a quality-improvement activity and did not require IRB approval or exemption.

The average unadjusted 30-day readmission rate for ECP patients over the 18-month study period was 17.2%, compared to 23.0% for patients not enrolled in ECP (P < 0.001) (Figure 1). After adjusting for patient characteristics, ECP patients had 29% lower odds (95% confidence interval [CI], 0.60-0.85) of being readmitted to the medical center within 30 days than non-ECP patients at the same SNFs. The characteristics of the ECP and comparison patient cohorts are shown in Table 1. There were significant differences in sociodemographic characteristics: The ECP group had a higher proportion of non-Hispanic white patients, while the comparison group had a higher proportion of patients who were African American or Hispanic. ECP patients were more likely to prefer speaking English, while Russian, Farsi, and Spanish were preferred more frequently in the comparison group. There were also differences in payer mix, with the ECP group including proportionately more Medicare fee-for-service (52.9% vs 35.0%, P < 0.001), while the comparison group had a correspondingly larger proportion of dual-eligible (Medicare and Medicaid) patients (55.0% vs 35.1%, P < 0.001).

Sensitivity Analyses

The results were robust when tested within strata of the study population, including analyses limited to dual-eligible patients, African American patients, patients admitted to all except the highest volume facility, and patients admitted to any service line other than orthopedic surgery. Similar results were obtained when the study population was restricted to patients living within the medical center’s primary service area and to patients living in zip codes in which the proportion of adults living in households with income below 100% of the poverty level was 15% or greater (see Supplementary Material for results).

The effect of the program on readmission was also consistent when the full logistic regression model was run with IPTW using the propensity score. The evaluation of standardized cluster differences between the ECP and non-ECP groups before and after IPTW showed that the differences were reduced to <10% for being African American; speaking Russian or Farsi; having dual-eligible insurance coverage; having orthopedic surgery; being discharged from the clinical service lines of gastroenterology, pulmonary, other surgery, and other services; and having an index hospital LOS of 4 to 5 days or 10 or more days (results are provided in the Supplementary Material).

Hospitals continue to experience significant pressure to manage LOS, and SNFs and hospitals are being held accountable for readmission rates. The setting of this study is representative of many large, urban hospitals in the United States whose communities include a heterogeneous mix of hospitalists, primary care physicians who follow their patients in SNFs, and independent SNFs.¹⁵ The current regulations have not kept up with the increasing acuity and complexity of SNF patients. Specifically, Medicare guidelines allow the SNF attending physician up to 72 hours to complete a history and physical (or 7 days if he or she was the hospital attending physician for the index hospitalization) and only require monthly follow-up visits. It is the opinion of the ECP designers that these relatively lax requirements present unnecessary risk for vulnerable patients. While the INTERACT II model was focused largely on educational initiatives (with an advanced practice nurse available in a consultative role, as needed), the central tenet of ECP was similar to the Connected Care model in that the focus was on adding an extra layer of direct clinical support. Protocols that provided timely initial assessments by an NP (within 24 hours), weekly NP rounding (at a minimum), and 24/7 on-call availability all contributed to helping patients stay on track. Although the ECP had patients visited less frequently than the Connected Care model, and the Cleveland Clinic started with a higher baseline 30-day readmission rate from SNFs, similar overall reductions in 30-day readmissions were observed. The key point from both initiatives is that an increase in clinical touchpoints and ease of access to clinicians generates myriad opportunities to identify and address small issues before they become clinical emergencies requiring hospital transfers and readmissions.

Correcting medication discrepancies between hospital discharge summaries and SNF admission orders through a systematic medication reconciliation using a clinical pharmacist has previously been shown to improve outcomes.^16-18 The ECP pharmacy technician and ECP clinical pharmacist discovered and corrected errors on a daily basis that ranged from incidental to potentially life-threatening. If the SNF staff does not provide the patient’s MAR within 48 hours of arrival, the pharmacy technician contacts the facility to obtain the information. As a result, all patients enrolled in the ECP during the study period received this intervention (unless they were rehospitalized or left the SNF before the process was completed), and 54% of ECP patients required some form of intervention after medication reconciliation was completed (data not shown).

This type of program requires hospital leadership and SNF administrators to be fully committed to developing strong working relationships, and in fact, there is evidence that SNF baseline readmission rates have a greater influence on patients’ risk of rehospitalization than the discharging hospital itself.^19-21 Monthly educational in-services are delivered at the partner SNFs to enhance SNF nursing staff knowledge and clinical acumen. High-impact topics identified by the ECP team include the following: fall prevention, hand hygiene, venous thromboembolism, cardiovascular health, how to report change in condition, and advanced care planning, among others. While no formal pre–post assessments of the SNF nurses’ knowledge were conducted, a log of in-services was kept, subjective feedback was collected for performance improvement purposes, and continuing educational units were provided to the SNF nurses who attended.

This study has limitations. As a single-hospital study, generalizability may be limited. While adherence to the program components was closely monitored daily, service gaps may have occurred that were not captured. The program design makes it difficult to quantify the relative impact of the 3 program components on the outcome. Furthermore, the study was observational, so the differences in readmission rates may have been due to unmeasured variables. The decision to enroll patients in the ECP was made by each patient’s SNF attending physician, and those who chose to (or not to) participate in the program may manifest other, unmeasured practice patterns that made readmissions more or less likely. Participating physicians also had the option to enroll their patients on a case-by-case basis, introducing further potential bias in patient selection; however, <5% of physicians exercised this option. Patients may have also been readmitted to hospitals other than CSMC, producing an observed readmission rate for 1 or both groups that underrepresents the true outcome. On this point, while we did not systematically track these other-hospital readmissions for both groups, there is no reason to believe that this occurred preferentially for ECP or non-ECP patients.

Multiple sensitivity analyses were performed to address the observed differences between ECP and non-ECP patients. These included stratified examinations of variables differing between populations, examination of clustering effects between SNFs, and an analysis adjusted for the propensity to be included in the ECP. The calculated effect of the intervention on readmission remained robust, although we acknowledge that differences in the populations may persist and have influenced the outcomes even after controlling for multiple variables.^22-25

In conclusion, the results of this intervention are compelling and add to the growing body of literature suggesting that a comprehensive, multipronged effort to enhance clinical oversight and coordination of care for SNF patients can improve outcomes. Given CMS’s plans to report SNF readmission rates in 2017 followed by the application of financial incentives in 2018, a favorable climate currently exists for greater coordination between hospitals and SNFs.²⁶ We are currently undertaking an economic evaluation of the program.

Acknowledgments

The authors would like to thank the following people for their contributions: Mae Saunders, Rita Shane, Dr. Jon Kea, Miranda Li, the ECP NPs, the ECP pharmacy team, CSMC’s performance improvement team, and Alan Matus.

Disclosure

 No conflicts of interest or disclosures.

Public reporting of readmission rates on the Nursing Home Compare website is mandated to begin on October 1, 2017, with skilled nursing facilities (SNFs) set to receive a Medicare bonus or penalty beginning a year later.¹ The Centers for Medicare & Medicaid Services (CMS) began public reporting of hospitals’ 30-day readmission rates for selected conditions in 2009, and the Patient Protection and Affordable Care Act of 2010 mandated financial penalties for excess readmissions through the Hospital Readmission Reduction Program.² In response, most hospitals have focused on patients who return home following discharge. Innovative interventions have proven successful, such as the Transitional Care model developed by Naylor and Coleman’s Care Transitions Intervention.^3-5 Approximately 20% of Medicare beneficiaries are discharged from hospitals to SNFs, and these patients have higher readmission rates than those discharged home. CMS reported that in 2010, 23.3% of those with an SNF stay were readmitted within 30 days, compared with 18.8% for those with other discharge dispositions.⁶

Some work has been undertaken in this arena. In 2012, the Center for Medicare and Medicaid Innovation (CMMI) and the Medicare-Medicaid Coordination Office jointly launched the Initiative to Reduce Avoidable Hospitalizations among Nursing Facility Residents.⁷ This partnership established 7 Enhanced Care and Coordination Provider organizations and was designed to improve care by reducing hospitalizations among long-stay, dual-eligible nursing facility residents at 143 nursing homes in 7 states.⁸ At the time of the most recent project report, there were mixed results regarding program effects on hospitalizations and spending, with 2 states showing strongly positive patterns, 3 states with reductions that were consistent though not statistically strong, and mixed results in the remaining states. Quality measures did not show any pattern suggesting a program effect.⁹ Interventions to Reduce Acute Care Transfers (INTERACT) II was a 6-month, collaborative, quality-improvement project implemented in 2009 at 30 nursing homes in 3 states.¹⁰ The project evaluation found a statistically significant, 17% decrease in self-reported hospital admissions among the 25 SNFs that completed the intervention, compared with the same 6 months in the prior year. The Cleveland Clinic recently reported favorable results implementing its Connected Care model, which relied on staff physicians and advanced practice professionals to visit patients 4 to 5 times per week and be on call 24/7 at 7 intervention SNFs.¹¹ Through this intervention, it successfully reduced its 30-day hospital readmission rate from SNFs from 28.1% to 21.7% (P < 0.001), and the authors posed the question as to whether its model and results were reproducible in other healthcare systems.

Herein, we report on the results of a collaborative initiative named the Enhanced Care Program (ECP), which offers the services of clinical providers and administrative staff to assist with the care of patients at 8 partner SNFs. The 3 components of ECP (described below) were specifically designed to address commonly recognized gaps and opportunities in routine SNF care. In contrast to the Cleveland Clinic’s Connected Care model (which involved hospital-employed physicians serving as the SNF attendings and excluded patients followed by their own physicians), ECP was designed to integrate into a pluralistic, community model whereby independent physicians continued to follow their own patients at the SNFs. The Connected Care analysis compared participating versus nonparticipating SNFs; both the Connected Care model and the INTERACT II evaluation relied on pre–post comparisons; the CMMI evaluation used a difference-in-differences model to compare the outcomes of the program SNFs with those of a matched comparison group of nonparticipating SNFs. The evaluation of ECP differs from these other initiatives, using a concurrent comparison group of patients discharged to the same SNFs but who were not enrolled in ECP.

Setting

Cedars-Sinai Medical Center (CSMC) is an 850-bed, acute care facility located in an urban area of Los Angeles. Eight SNFs, ranging in size from 49 to 150 beds and located between 0.6 and 2.2 miles from CSMC, were invited to partner with the ECP. The physician community encompasses more than 2000 physicians on the medical staff, including private practitioners, nonteaching hospitalists, full-time faculty hospitalists, and faculty specialists.

Study Design and Patients

This was an observational, retrospective cohort analysis of 30-day same-hospital readmissions among 3951 patients discharged from CSMC to 8 SNFs between January 1, 2014, and June 30, 2015. A total of 2394 patients were enrolled in the ECP, and 1557 patients were not enrolled.

ECP Enrollment Protocol

Every patient discharged from CSMC to 1 of the 8 partner SNFs was eligible to participate in the program. To respect the autonomy of the SNF attending physicians and to facilitate a collaborative relationship, the decision to enroll a patient in the ECP rested with the SNF attending physician. The ECP team maintained a database that tracked whether each SNF attending physician (1) opted to automatically enroll all his or her patients in the ECP, (2) opted to enroll patients on a case-by-case basis (in which case an ECP nurse practitioner [NP] contacted the attending physician for each eligible patient), or (3) opted out of the ECP completely. When a new SNF attending physician was encountered, the ECP medical director called the physician to explain the ECP and offer enrollment of his or her patient(s). Ultimately, patients (or their decision-makers) retained the right to opt in or out of the ECP at any time, regardless of the decision of the attending physicians.

Program Description

Patients enrolled in the ECP experienced the standard care provided by the SNF staff and attending physicians plus a clinical care program delivered by 9 full-time NPs, 1 full-time pharmacist, 1 pharmacy technician, 1 full-time nurse educator, a program administrator, and a medical director.

The program included the following 3 major components:

1. Direct patient care and 24/7 NP availability: Program enrollment began with an on-site, bedside evaluation by an ECP NP at the SNF within 24 hours of arrival and continued with weekly NP rounding (or more frequently, if clinically indicated) on the patient. Each encounter included a review of the medical record; a dialogue with the patient’s SNF attending physician to formulate treatment plans and place orders; discussions with nurses, family members, and other caregivers; and documentation in the medical record. The ECP team was on-site at the SNFs 7 days a week and on call 24/7 to address questions and concerns. Patients remained enrolled in the ECP from SNF admission to discharge even if their stay extended beyond 30 days.

2. Medication reconciliation: The ECP pharmacy team completed a review of a patient’s SNF medication administration record (MAR) within 72 hours of SNF admission. This process involved the pharmacy technician gathering medication lists from the SNFs and CSMC and providing this information to the pharmacist for a medication reconciliation and clinical evaluation. Discrepancies and pharmacist recommendations were communicated to the ECP NPs, and all identified issues were resolved.

3. Educational in-services: Building upon the INTERACT II model, the ECP team identified high-yield, clinically relevant topics, which the ECP nurse educator turned into monthly educational sessions for the SNF nursing staff at each of the participating SNFs.¹⁰

Primary Outcome Measure

An inpatient readmission to CSMC within 30 days of the hospital discharge date was counted as a readmission, whether the patient returned directly from an SNF or was readmitted from home after an SNF discharge.

Data

ECP patients were identified using a log maintained by the ECP program manager. Non-ECP patients discharged to the same SNFs during the study period were identified from CSMC’s electronic registry of SNF discharges. Covariates known to be associated with increased risk of 30-day readmission were obtained from CSMC’s electronic data warehouse, including demographic information, length of stay (LOS) of index hospitalization, and payer.¹² Eleven clinical service lines represented patients’ clinical conditions based on Medicare-Severity Diagnosis-Related groupings. The discharge severity of illness score was calculated using 3M All Patients Refined Diagnosis Related Group software, version 33.¹³

Analysis

Characteristics of the ECP and non-ECP patients were compared using the χ² test. A multivariable logistic regression model with fixed effects for SNF was created to determine the program’s impact on 30-day hospital readmission, adjusting for patient characteristics. The Pearson χ² goodness-of-fit test and the link test for model specification were used to evaluate model specification. The sensitivity of the results to differences in patient characteristics was assessed in 2 ways. First, the ECP and non-ECP populations were stratified based on race and/or ethnicity and payer, and the multivariable regression model was run within the strata associated with the highest readmission rates. Second, a propensity analysis using inverse probability of treatment weighting (IPTW) was performed to control for group differences. Results of all comparisons were considered statistically significant when P < 0.05. Stata version 13 was used to perform the main analyses.¹⁴ The propensity analysis was conducted using R version 3.2.3. The CSMC Institutional Review Board (IRB) determined that this study qualified as a quality-improvement activity and did not require IRB approval or exemption.

The average unadjusted 30-day readmission rate for ECP patients over the 18-month study period was 17.2%, compared to 23.0% for patients not enrolled in ECP (P < 0.001) (Figure 1). After adjusting for patient characteristics, ECP patients had 29% lower odds (95% confidence interval [CI], 0.60-0.85) of being readmitted to the medical center within 30 days than non-ECP patients at the same SNFs. The characteristics of the ECP and comparison patient cohorts are shown in Table 1. There were significant differences in sociodemographic characteristics: The ECP group had a higher proportion of non-Hispanic white patients, while the comparison group had a higher proportion of patients who were African American or Hispanic. ECP patients were more likely to prefer speaking English, while Russian, Farsi, and Spanish were preferred more frequently in the comparison group. There were also differences in payer mix, with the ECP group including proportionately more Medicare fee-for-service (52.9% vs 35.0%, P < 0.001), while the comparison group had a correspondingly larger proportion of dual-eligible (Medicare and Medicaid) patients (55.0% vs 35.1%, P < 0.001).

Sensitivity Analyses

The results were robust when tested within strata of the study population, including analyses limited to dual-eligible patients, African American patients, patients admitted to all except the highest volume facility, and patients admitted to any service line other than orthopedic surgery. Similar results were obtained when the study population was restricted to patients living within the medical center’s primary service area and to patients living in zip codes in which the proportion of adults living in households with income below 100% of the poverty level was 15% or greater (see Supplementary Material for results).

The effect of the program on readmission was also consistent when the full logistic regression model was run with IPTW using the propensity score. The evaluation of standardized cluster differences between the ECP and non-ECP groups before and after IPTW showed that the differences were reduced to <10% for being African American; speaking Russian or Farsi; having dual-eligible insurance coverage; having orthopedic surgery; being discharged from the clinical service lines of gastroenterology, pulmonary, other surgery, and other services; and having an index hospital LOS of 4 to 5 days or 10 or more days (results are provided in the Supplementary Material).

Hospitals continue to experience significant pressure to manage LOS, and SNFs and hospitals are being held accountable for readmission rates. The setting of this study is representative of many large, urban hospitals in the United States whose communities include a heterogeneous mix of hospitalists, primary care physicians who follow their patients in SNFs, and independent SNFs.¹⁵ The current regulations have not kept up with the increasing acuity and complexity of SNF patients. Specifically, Medicare guidelines allow the SNF attending physician up to 72 hours to complete a history and physical (or 7 days if he or she was the hospital attending physician for the index hospitalization) and only require monthly follow-up visits. It is the opinion of the ECP designers that these relatively lax requirements present unnecessary risk for vulnerable patients. While the INTERACT II model was focused largely on educational initiatives (with an advanced practice nurse available in a consultative role, as needed), the central tenet of ECP was similar to the Connected Care model in that the focus was on adding an extra layer of direct clinical support. Protocols that provided timely initial assessments by an NP (within 24 hours), weekly NP rounding (at a minimum), and 24/7 on-call availability all contributed to helping patients stay on track. Although the ECP had patients visited less frequently than the Connected Care model, and the Cleveland Clinic started with a higher baseline 30-day readmission rate from SNFs, similar overall reductions in 30-day readmissions were observed. The key point from both initiatives is that an increase in clinical touchpoints and ease of access to clinicians generates myriad opportunities to identify and address small issues before they become clinical emergencies requiring hospital transfers and readmissions.

Correcting medication discrepancies between hospital discharge summaries and SNF admission orders through a systematic medication reconciliation using a clinical pharmacist has previously been shown to improve outcomes.^16-18 The ECP pharmacy technician and ECP clinical pharmacist discovered and corrected errors on a daily basis that ranged from incidental to potentially life-threatening. If the SNF staff does not provide the patient’s MAR within 48 hours of arrival, the pharmacy technician contacts the facility to obtain the information. As a result, all patients enrolled in the ECP during the study period received this intervention (unless they were rehospitalized or left the SNF before the process was completed), and 54% of ECP patients required some form of intervention after medication reconciliation was completed (data not shown).

This type of program requires hospital leadership and SNF administrators to be fully committed to developing strong working relationships, and in fact, there is evidence that SNF baseline readmission rates have a greater influence on patients’ risk of rehospitalization than the discharging hospital itself.^19-21 Monthly educational in-services are delivered at the partner SNFs to enhance SNF nursing staff knowledge and clinical acumen. High-impact topics identified by the ECP team include the following: fall prevention, hand hygiene, venous thromboembolism, cardiovascular health, how to report change in condition, and advanced care planning, among others. While no formal pre–post assessments of the SNF nurses’ knowledge were conducted, a log of in-services was kept, subjective feedback was collected for performance improvement purposes, and continuing educational units were provided to the SNF nurses who attended.

This study has limitations. As a single-hospital study, generalizability may be limited. While adherence to the program components was closely monitored daily, service gaps may have occurred that were not captured. The program design makes it difficult to quantify the relative impact of the 3 program components on the outcome. Furthermore, the study was observational, so the differences in readmission rates may have been due to unmeasured variables. The decision to enroll patients in the ECP was made by each patient’s SNF attending physician, and those who chose to (or not to) participate in the program may manifest other, unmeasured practice patterns that made readmissions more or less likely. Participating physicians also had the option to enroll their patients on a case-by-case basis, introducing further potential bias in patient selection; however, <5% of physicians exercised this option. Patients may have also been readmitted to hospitals other than CSMC, producing an observed readmission rate for 1 or both groups that underrepresents the true outcome. On this point, while we did not systematically track these other-hospital readmissions for both groups, there is no reason to believe that this occurred preferentially for ECP or non-ECP patients.

Multiple sensitivity analyses were performed to address the observed differences between ECP and non-ECP patients. These included stratified examinations of variables differing between populations, examination of clustering effects between SNFs, and an analysis adjusted for the propensity to be included in the ECP. The calculated effect of the intervention on readmission remained robust, although we acknowledge that differences in the populations may persist and have influenced the outcomes even after controlling for multiple variables.^22-25

In conclusion, the results of this intervention are compelling and add to the growing body of literature suggesting that a comprehensive, multipronged effort to enhance clinical oversight and coordination of care for SNF patients can improve outcomes. Given CMS’s plans to report SNF readmission rates in 2017 followed by the application of financial incentives in 2018, a favorable climate currently exists for greater coordination between hospitals and SNFs.²⁶ We are currently undertaking an economic evaluation of the program.

Acknowledgments

The authors would like to thank the following people for their contributions: Mae Saunders, Rita Shane, Dr. Jon Kea, Miranda Li, the ECP NPs, the ECP pharmacy team, CSMC’s performance improvement team, and Alan Matus.

Disclosure

 No conflicts of interest or disclosures.

Take-Home Points

• Reconstruction of a torn ITB is important in restoration of native anatomy and function given its properties in anterolateral stabilization and resistance to varus stress and internal tibial rotation.
• Restoration of posterolateral instability primarily involves reconstructing the FCL, PLT, and popliteofibular ligament.
• For combined PLC injuries, concurrent reconstruction of the cruciate ligaments in one stage is highly recommended.
• Post-surgery, a 6-week non-weight-bearing, limited flexion rehab protocol utilizing a dynamic PCL brace, such as the PCL Rebound brace, is recommended to prevent posterior tibial sag.
• Arthrofibrosis and decreased ROM can be seen following a violent knee injury which requires extensive multiligament reconstruction surgeries, occasionally requiring a secondary surgery for further restoration of knee motion.

Tibiofemoral knee dislocations are uncommon injuries that have devastating complications and potentially result in complex surgeries.¹ Knee dislocations (KDs) can be classified with the Schenck system.² KD-I is a multiligament injury involving the anterior cruciate ligament (ACL) or the posterior cruciate ligament (PCL), and the scale increases in severity/number of ligaments involved, with KD-V being a multiligament injury with periarticular fracture.²

In this article, we report the case of a complex multiligament knee reconstruction performed with a midsubstance iliotibial band (ITB) repair. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 27-year-old man presented 12 days after a paraskiing crash in which he collided with a tree at 45 mph and fell 40 feet before hitting snow. Physical examination revealed a large hemarthrosis of the left lower extremity and ecchymosis about the posterolateral aspect of the knee and popliteal fossa. Range of motion (ROM) was limited from 5° of hyperextension to 90° of flexion. Additional motion was deferred secondary to pain. Varus stress testing at 0° and 30° of knee flexion demonstrated significant side-to-side differences. The Lachman test, posterior drawer test, and posterolateral drawer test were all 3+. The dial test was 3 to 4+ compared with the contralateral knee. Valgus stress testing at 0° and 30° of flexion did not reveal any side-to-side laxity. The calf was nontender, and all compartments were soft. The patient reported no neurovascular symptoms and had no neuromotor deficits other than mild common peroneal nerve dysesthesias.

Varus stress radiographs showed increased side-to-side gapping (8 mm) of the lateral compartment of the injured knee. Kneeling posterior stress radiographs, limited because of the patient’s inability to apply full stress on the injured knee secondary to pain, showed a difference of 6 mm in increased posterior translation on the uninjured leg (Figures 1A-1D).

First Surgery

1. PLC Approach. A lateral hockey-stick skin incision was made along the ITB and extended distally between the fibular head and the Gerdy tubercle. The subcutaneous tissue was then dissected, and a posteriorly based flap was developed for preservation of vascular support to the superficial tissues. The ITB and the lateral capsule had completely torn off of the femur, allowing exposure directly into the joint. The long and short heads of the biceps femoris were exposed, with about 50% of the biceps attachment torn. The FCL was torn midsubstance, and the PLT had no remnant attachment left on the femur.

2. ITB and Lateral Capsule Tag Stitched. The torn ends of the ITB were dissected and tag stitches placed in each end. Tag stitches were also placed in the lateral capsule in preparation for a direct repair.

3. Neurolysis. The common peroneal nerve was found encased in a significant amount of scar tissue, and extensive neurolysis was required. Slow, methodical dissection was performed under the partially torn long head of the biceps femoris and was continued through the scar tissue and adhesions. Distally, 5 mm to 7 mm of the peroneus longus fascia was incised as part of the neurolysis in order to prevent nerve irritation or foot drop caused by postoperative swelling.

4. PLC Tunnels. The margin between the lateral gastrocnemius tendon and the soleus muscle was identified by blunt dissection that allowed palpation of the posteromedial aspect of the fibular styloid and the popliteus musculotendinous junction. The underlying biceps bursa was incised in order to locate the midportion of the FCL remnant, which typically is tag-stitched with No. 2 FiberWire to help identify the femoral attachment (this was not done because of the complete tear at the midsubstance of the FCL).
Subperiosteal dissection of the lateral aspect of the fibular head was performed anterior to posterior and distally extended to the champagne-glass drop-off of the fibular head. Continuing the dissection distally beyond this point can endanger the common peroneal nerve. A small sulcus can be palpated where the distal FCL inserts on the fibular head. Posteriorly, a small elevator was used to dissect the soleus muscle off of the posteromedial aspect of the fibular head, where the fibular tunnel would later be created.

A Chandler retractor was placed posterior to the fibular head to protect the neurovascular bundle. With the aid of a collateral ligament aiming device, a guide pin was drilled from the lateral aspect of the fibular head (FCL attachment) to the posteromedial downslope of the fibular styloid (popliteofibular ligament attachment). The entry point of the guide pin was immediately above the champagne- glass drop-off, at the distal insertion site of the FCL, which was described as being 28.4 mm from the styloid tip and 8.2 mm posterior to the anterior margin of the fibular head.3 Care should be taken not to ream the tunnel too proximal, as doing so increases the risk of iatrogenic fracture. A 7-mm reamer was then used to drill the fibular tunnel. To facilitate later passage of the graft, a passing suture was placed through the tunnel, leaving the loop anterolateral.

Next, the starting point for the tibial tunnel was located on the flat spot of the anterolateral tibia distal and medial to the Gerdy tubercle, just lateral to the tibial tubercle. The tibial popliteal sulcus was identified by palpation of the posterolateral tibial plateau to localize the site of the popliteus musculotendinous junction, which is the ideal location of the posterior aperture of the tibial tunnel. This point is 1 cm proximal and 1 cm medial to the posteromedial exit of the fibular tunnel. A Chandler retractor was placed anterior to the lateral gastrocnemius to protect the neurovascular bundle. In the locations described earlier, a cruciate aiming device was used to place a guide pin anterior to posterior. A 9-mm tunnel was overreamed and a passing suture placed, leaving the loop posterior to facilitate graft passage.

The femoral insertions of the FCL and the PLT were then identified. ITB splitting was not necessary, given the complete midsubstance tear of this structure. The FCL attachment was identified 1.4 mm proximal and 3.1 mm posterior to the lateral epicondyle.3 Sharp dissection was performed in this location, proximal to distal, exposing the lateral epicondyle and the small sulcus at the FCL attachment site. A collateral ligament reconstruction aiming sleeve was used to drill a guide pin over the FCL femoral attachment site and out the medial aspect of the distal thigh, about 5 cm proximal and anterior to the adductor tubercle.

The femoral attachment of the PLT was reported located 18.5 mm anterior to the FCL insertion, in the anterior fifth of the popliteal sulcus.³ Although arthrotomy is usually required in order to access the PLT attachment, it was not necessary in this case, given the lateral capsule tear. A guide pin was inserted at the PLT attachment site, parallel to the FCL pin. After proper placement was verified, a 9-mm reamer was used to drill the FCL and PLT tunnels to a depth of 25 mm (socket), and a passing suture was placed into each tunnel to facilitate graft passage.

5. ACL Graft Harvest. The central third of the ipsilateral patellar tendon was harvested for use in the ACL reconstruction. Included were a 10-mm × 20-mm bone plug from the patella and a 10-mm × 25-mm bone plug from the tibial tubercle. The patella defect was then bone-grafted, and the patellar tendon closed side-to-side.

6. Graft Preparation. For the PLC, we used a split Achilles tendon allograft that had two 9-mm × 25-mm bone plugs proximally and were tubularized distally. For the PCL, we used an anterolateral bundle (ALB), which consisted of an Achilles tendon allograft that had an 11-mm × 25-mm bone plug proximally and was tubularized distally, and a posteromedial bundle (PMB), which consisted of a tibialis anterior allograft that was tubularized at both ends. For the ACL, we used a bone–patellar tendon–bone autograft 10 mm in diameter with a 20-mm femoral bone plug and a 25-mm tibial bone plug distally.

7. Arthroscopy. We created standard anterolateral and anteromedial parapatellar portals and performed arthroscopy, including lysis of adhesions. Cartilage and menisci were lesion-free.

8. PCL Femoral Tunnels. The ALB attachment was identified and outlined with a coagulator between the trochlear point and the medial arch point, adjacent to the edge of the articular cartilage. Similarly, the PMB attachment was marked about 8 mm or 9 mm posterior to the edge of the articular cartilage of the medial femoral condyle and slightly posterior to the ALB tunnel.⁴

In the anterolateral tunnel, an acorn reamer 11 mm in diameter was used to score the entry point of the ALB femoral tunnel. An eyelet pin was then drilled through the reamer anteromedially out the knee. Then a closed socket tunnel was reamed over the eyelet pin to a depth of 25 mm. A passing suture was pulled through the tunnel in preparation for graft passage. 

With use of the same technique, a 7-mm reamer was placed against the outline of the PMB attachment site, and an eyelet pin was drilled through this reamer and out the anteromedial aspect of the knee. Again, a 25-mm deep closed socket was reamed. A bone bridge distance of 2 mm was maintained between the 2 femoral PCL bundle tunnels.

9. ACL Femoral Tunnel. The femoral ACL attachment was identified and outlined. An over-the-top guide was used to determine proper placement of the 10-mm low-profile reamer. A guide pin was drilled through the center of the reamer. The reamer was used to create a 25-mm deep closed socket tunnel, and a passing stitch was placed. 

10. PCL Tibial Tunnel. With use of a 70° arthroscope for visualization, a posteromedial arthroscopic portal was created, and a shaver and a coagulator were used to identify the tibial PCL attachment, located distally along the PCL facet, until the proximal aspect of the popliteus muscle fibers were visualized. A guide pin was drilled starting at the anteromedial aspect of the tibia, about 6 cm distal to the joint line and centered between the anterior tibial crest and the medial tibial border. The pin exited posteriorly at the center of the PCL tibial attachment along the PCL bundle ridge, which was reported located between the ALB and the PMB on the tibia.5 Pin placement was verified with intraoperative lateral and anteroposterior radiographs. On the lateral radiograph, the pin should be about 6 mm or 7 mm proximal to the champagne-glass drop-off at the PCL facet on the posterior aspect of the tibia. On the anteroposterior radiograph, the pin should be 1 mm to 2 mm distal to the joint line and at the medial aspect of the lateral tibial eminence. A large curette was passed through the posteromedial arthroscopic portal both to retract the posterior tissues away from the reamer and to protect against guide-pin protrusion The guide pin was then overreamed with a 12-mm acorn reamer.

A large smoother was passed proximally up the tibial tunnel and then pulled out the anteromedial portal with a grasper. The smoother was gently cycled to smooth the intra-articular tibial tunnel aperture to remove any bony spicules that could interfere with graft passage. The smoother was then pulled back into the joint, passed out the anterolateral arthroscopic portal, and secured with a small clamp.⁴

11. ACL Tibial Tunnel. The ACL tibial attachment site was identified and cleaned of soft tissue. A guide pin was placed and then overreamed with a 10-mm acorn reamer.

12. PCL Femoral Fixation. The PMB graft was passed into its tunnel and secured with a 7-mm × 23-mm titanium screw. Next, the ALB was secured to the femur with a 7-mm × 20-mm titanium screw. The smoother was used to pull both grafts down through the tibial tunnel.

13. ACL Femoral Fixation. A 7-mm × 20-mm titanium screw was then used to fix the ACL autograft inside the femur. Traction was applied to the 3 cruciate grafts. There was no sign of impingement.

14. PLC Femoral Fixation. The FCL and the popliteus bone plugs were passed into their respective femoral sockets and secured with 7-mm × 20-mm titanium screws.

15. Lateral Capsule Femoral Anchors. Two suture anchors were placed into the femur, and the sutures were passed through the femoral portion of the lateral capsule for later repair.

16. PCL Tibial Fixation. Both grafts were fixed with a fully threaded bicortical 6.5-mm × 40-mm cannulated cancellous screw and an 18-mm spiked washer. The ALB was fixed first, with the knee flexed to 90°, traction on the graft, and the tibia in neutral rotation. Restoration of the normal tibiofemoral step-off was verified. The PMB was then fixed with the knee in full extension. A posterior drawer test was performed to verify restoration of stability.

17. PLC Fibula Fixation. The PLT graft was passed down the popliteal hiatus, and the FCL graft was passed under the remnant of the biceps bursa on the fibular head and then through the fibular head, anterolateral to posteromedial. The FCL graft was fixed in the fibular tunnel with the knee in 20° of flexion, a slight valgus reduction force, the tibia in neutral rotation, and traction on the graft. A 7-mm × 23-mm bioabsorbable screw was used.

18. Lateral Capsular Repair. The lateral capsule was directly repaired with the previously placed sutures. The sutures were tied with the knee in 20° of flexion.

19. PLC Tibial Fixation. The grafts were passed together, posterior to anterior, through the tibial tunnel. The knee was cycled several times through complete flexion/extension ROM. A 9-mm × 23-mm bioabsorbable screw was then used to fix the grafts to the tibia. During this fixation, the knee was kept in 60° of flexion and neutral rotation while traction was being applied to the distal end of both grafts.

20. ACL Tibial Fixation. A 9-mm × 20-mm titanium screw was used to fix the ACL graft with the knee in full extension. The graft was then viewed intra-articularly to confirm there was no impingement. The Lachman, posterior drawer, posterolateral drawer, dial, and varus stress tests were performed to ensure restoration of stability.

21. ITB Repair. A portion of the remaining Achilles tendon allograft was used to perform ITB reconstruction (reconstitution of the gaped portion of the ITB). Orthocord (DePuy Synthes) and Vicryl (Ethicon) sutures were used for this reconstruction. Knee stability was deemed restored, and the incisions were closed in standard layered fashion.

First Surgery: Postoperative Management

The patient remained non-weight-bearing the first 6 weeks after surgery, with prone knee flexion limited (0°-90°) the first 2 weeks. In addition, a PCL Jack brace (Albrecht) was placed 1 week after surgery and was to be worn at all times to decrease stress on the PCL grafts.

As ROM was not progressing as expected, the patient was instructed to use a continuous passive motion (CPM) machine 2 hours 3 times a day. About 4 weeks after surgery, with ROM still not progressing, the frequency of use of this machine was increased.

Despite continued physical therapy, use of the CPM machine, and pain management, ROM was limited (11°-90° of flexion) 5.5 months after left knee multiligament reconstruction. However, stress radiographs showed excellent stability. Varus stress radiographs showed a side-to-side difference of 0.3 mm less on the left (injured) knee, and kneeling PCL stress radiographs showed a side-to-side difference of 1.3 mm more on the left knee (Figures 3A-3D).

Second Surgery and Postoperative Management

As gentle manipulation under anesthesia was unsuccessful, the patient underwent knee arthroscopy, including 4-compartment lysis of adhesions, arthroscopically assisted posteromedial capsular release, and post-débridement manipulation under anesthesia. During manipulation, full extension and knee flexion up to 135° were achieved. ACL, PCL, and popliteus grafts were visualized and confirmed to be intact. 

After this second surgery, the patient was to resume physical therapy and begin weight- bearing as tolerated. Active ROM was prioritized in an attempt to reach full ROM. In addition, a CPM machine was to be used from 0° to 135° of knee flexion 4 hours 3 times a day for 6 weeks.

Two weeks after surgery, the patient had continued pain, and extracapsular swelling in the left knee. However, ROM (0°-115° of flexion) was improved relative to before surgery (11°-90° of flexion), though it remained below the range on the contralateral side. Of note, the patient reported having a flexion contracture (~10°) in the immediate postoperative period. He had woken up with it after sleeping with the CPM machine the night before. The contracture delayed his physical therapy for several hours and resulted in a redesign of his therapy protocol to emphasize full, active knee extension and patellar mobilization, as well as discontinuation of use of the CPM machine. Corticosteroids were initiated to help with the extracapsular swelling, and the new therapy regimen brought adequate progress in ROM. Four months after the second surgery, the patient had full extension and 135° of flexion and was transitioned into wearing the PCL Rebound brace.

Discussion

This case was unique because of the midsubstance ITB tear and simultaneous multiligament injury caused by a KD-IIIL, a KD involving the ACL, the PCL, and the PLC with the medial side intact. There is limited research on ITB repair generally, with or without KD involvement. In a retrospective review of acute knee trauma cases, ITB pathologies were seen on 45% of reviewed MRI scans, and only 3% of the injuries were grade III; in addition, only 9 (5%) of the 200 cases involved both ITB and multiligament (ACL, PCL) knee injuries.⁶

After our patient’s ACL, PCL, and PLC were reconstructed, a fan piece of the Achilles tendon allograft from the PLC reconstruction was used to repair the ITB. The graft was used to reconstitute the torn gapped portion of the band in multiple locations, and this repair helped restore stability. The literature has reported numerous surgical uses for a portion of the ITB but few studies on repairing this anatomical structure. Preservation of the ITB is important to restoration of native anatomy and function. The ITB helps with anterolateral stabilization of the knee and with resistance of varus stress and internal tibial rotation.

The PLC reconstruction used in this case has been biomechanically validated as restoring the knee to near native stability through anatomical reconstruction of the PLC’s 3 main static stabilizers: the FCL, the PLT, and the popliteofibular ligament.^7-9 First described in 2004,⁷ this anatomical PLC reconstruction technique has improved subjective and objective patient outcomes.^10,11 For combined PLC injuries (eg, our patient’s injuries), Geeslin and LaPrade¹⁰ recommended concurrent reconstruction of the cruciate ligaments. In addition to the PLC reconstruction, the anatomical double-bundle PCL reconstruction used in this case has demonstrated significant improvements in subjective and objective outcome scores and objective knee stability.¹²

Although the stability and anatomy of this patient’s injured knee were reestablished, his development of arthrofibrosis is important. Many have discussed the commonality of arthrofibrosis or decreased ROM after extensive multiligament reconstruction surgeries.^13,14 One study involving surgical management and outcomes of multiligament knee injuries found that, in more than half of its cases, restoration of full ROM required at least one operation after the initial one.¹³ Therefore, it is not unusual that our patient required a second operation for decreased ROM.

Conclusion

After surgery, excellent stabilization was achieved. Although the patient had setbacks related to pain and decreased ROM, his second surgery and continued physical therapy likely will help him return to his preoperative recreational activity levels.

Take-Home Points

• Reconstruction of a torn ITB is important in restoration of native anatomy and function given its properties in anterolateral stabilization and resistance to varus stress and internal tibial rotation.
• Restoration of posterolateral instability primarily involves reconstructing the FCL, PLT, and popliteofibular ligament.
• For combined PLC injuries, concurrent reconstruction of the cruciate ligaments in one stage is highly recommended.
• Post-surgery, a 6-week non-weight-bearing, limited flexion rehab protocol utilizing a dynamic PCL brace, such as the PCL Rebound brace, is recommended to prevent posterior tibial sag.
• Arthrofibrosis and decreased ROM can be seen following a violent knee injury which requires extensive multiligament reconstruction surgeries, occasionally requiring a secondary surgery for further restoration of knee motion.

Tibiofemoral knee dislocations are uncommon injuries that have devastating complications and potentially result in complex surgeries.¹ Knee dislocations (KDs) can be classified with the Schenck system.² KD-I is a multiligament injury involving the anterior cruciate ligament (ACL) or the posterior cruciate ligament (PCL), and the scale increases in severity/number of ligaments involved, with KD-V being a multiligament injury with periarticular fracture.²

In this article, we report the case of a complex multiligament knee reconstruction performed with a midsubstance iliotibial band (ITB) repair. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 27-year-old man presented 12 days after a paraskiing crash in which he collided with a tree at 45 mph and fell 40 feet before hitting snow. Physical examination revealed a large hemarthrosis of the left lower extremity and ecchymosis about the posterolateral aspect of the knee and popliteal fossa. Range of motion (ROM) was limited from 5° of hyperextension to 90° of flexion. Additional motion was deferred secondary to pain. Varus stress testing at 0° and 30° of knee flexion demonstrated significant side-to-side differences. The Lachman test, posterior drawer test, and posterolateral drawer test were all 3+. The dial test was 3 to 4+ compared with the contralateral knee. Valgus stress testing at 0° and 30° of flexion did not reveal any side-to-side laxity. The calf was nontender, and all compartments were soft. The patient reported no neurovascular symptoms and had no neuromotor deficits other than mild common peroneal nerve dysesthesias.

Varus stress radiographs showed increased side-to-side gapping (8 mm) of the lateral compartment of the injured knee. Kneeling posterior stress radiographs, limited because of the patient’s inability to apply full stress on the injured knee secondary to pain, showed a difference of 6 mm in increased posterior translation on the uninjured leg (Figures 1A-1D).

First Surgery

1. PLC Approach. A lateral hockey-stick skin incision was made along the ITB and extended distally between the fibular head and the Gerdy tubercle. The subcutaneous tissue was then dissected, and a posteriorly based flap was developed for preservation of vascular support to the superficial tissues. The ITB and the lateral capsule had completely torn off of the femur, allowing exposure directly into the joint. The long and short heads of the biceps femoris were exposed, with about 50% of the biceps attachment torn. The FCL was torn midsubstance, and the PLT had no remnant attachment left on the femur.

2. ITB and Lateral Capsule Tag Stitched. The torn ends of the ITB were dissected and tag stitches placed in each end. Tag stitches were also placed in the lateral capsule in preparation for a direct repair.

3. Neurolysis. The common peroneal nerve was found encased in a significant amount of scar tissue, and extensive neurolysis was required. Slow, methodical dissection was performed under the partially torn long head of the biceps femoris and was continued through the scar tissue and adhesions. Distally, 5 mm to 7 mm of the peroneus longus fascia was incised as part of the neurolysis in order to prevent nerve irritation or foot drop caused by postoperative swelling.

4. PLC Tunnels. The margin between the lateral gastrocnemius tendon and the soleus muscle was identified by blunt dissection that allowed palpation of the posteromedial aspect of the fibular styloid and the popliteus musculotendinous junction. The underlying biceps bursa was incised in order to locate the midportion of the FCL remnant, which typically is tag-stitched with No. 2 FiberWire to help identify the femoral attachment (this was not done because of the complete tear at the midsubstance of the FCL).
Subperiosteal dissection of the lateral aspect of the fibular head was performed anterior to posterior and distally extended to the champagne-glass drop-off of the fibular head. Continuing the dissection distally beyond this point can endanger the common peroneal nerve. A small sulcus can be palpated where the distal FCL inserts on the fibular head. Posteriorly, a small elevator was used to dissect the soleus muscle off of the posteromedial aspect of the fibular head, where the fibular tunnel would later be created.

A Chandler retractor was placed posterior to the fibular head to protect the neurovascular bundle. With the aid of a collateral ligament aiming device, a guide pin was drilled from the lateral aspect of the fibular head (FCL attachment) to the posteromedial downslope of the fibular styloid (popliteofibular ligament attachment). The entry point of the guide pin was immediately above the champagne- glass drop-off, at the distal insertion site of the FCL, which was described as being 28.4 mm from the styloid tip and 8.2 mm posterior to the anterior margin of the fibular head.3 Care should be taken not to ream the tunnel too proximal, as doing so increases the risk of iatrogenic fracture. A 7-mm reamer was then used to drill the fibular tunnel. To facilitate later passage of the graft, a passing suture was placed through the tunnel, leaving the loop anterolateral.

Next, the starting point for the tibial tunnel was located on the flat spot of the anterolateral tibia distal and medial to the Gerdy tubercle, just lateral to the tibial tubercle. The tibial popliteal sulcus was identified by palpation of the posterolateral tibial plateau to localize the site of the popliteus musculotendinous junction, which is the ideal location of the posterior aperture of the tibial tunnel. This point is 1 cm proximal and 1 cm medial to the posteromedial exit of the fibular tunnel. A Chandler retractor was placed anterior to the lateral gastrocnemius to protect the neurovascular bundle. In the locations described earlier, a cruciate aiming device was used to place a guide pin anterior to posterior. A 9-mm tunnel was overreamed and a passing suture placed, leaving the loop posterior to facilitate graft passage.

The femoral insertions of the FCL and the PLT were then identified. ITB splitting was not necessary, given the complete midsubstance tear of this structure. The FCL attachment was identified 1.4 mm proximal and 3.1 mm posterior to the lateral epicondyle.3 Sharp dissection was performed in this location, proximal to distal, exposing the lateral epicondyle and the small sulcus at the FCL attachment site. A collateral ligament reconstruction aiming sleeve was used to drill a guide pin over the FCL femoral attachment site and out the medial aspect of the distal thigh, about 5 cm proximal and anterior to the adductor tubercle.

The femoral attachment of the PLT was reported located 18.5 mm anterior to the FCL insertion, in the anterior fifth of the popliteal sulcus.³ Although arthrotomy is usually required in order to access the PLT attachment, it was not necessary in this case, given the lateral capsule tear. A guide pin was inserted at the PLT attachment site, parallel to the FCL pin. After proper placement was verified, a 9-mm reamer was used to drill the FCL and PLT tunnels to a depth of 25 mm (socket), and a passing suture was placed into each tunnel to facilitate graft passage.

5. ACL Graft Harvest. The central third of the ipsilateral patellar tendon was harvested for use in the ACL reconstruction. Included were a 10-mm × 20-mm bone plug from the patella and a 10-mm × 25-mm bone plug from the tibial tubercle. The patella defect was then bone-grafted, and the patellar tendon closed side-to-side.

6. Graft Preparation. For the PLC, we used a split Achilles tendon allograft that had two 9-mm × 25-mm bone plugs proximally and were tubularized distally. For the PCL, we used an anterolateral bundle (ALB), which consisted of an Achilles tendon allograft that had an 11-mm × 25-mm bone plug proximally and was tubularized distally, and a posteromedial bundle (PMB), which consisted of a tibialis anterior allograft that was tubularized at both ends. For the ACL, we used a bone–patellar tendon–bone autograft 10 mm in diameter with a 20-mm femoral bone plug and a 25-mm tibial bone plug distally.

7. Arthroscopy. We created standard anterolateral and anteromedial parapatellar portals and performed arthroscopy, including lysis of adhesions. Cartilage and menisci were lesion-free.

8. PCL Femoral Tunnels. The ALB attachment was identified and outlined with a coagulator between the trochlear point and the medial arch point, adjacent to the edge of the articular cartilage. Similarly, the PMB attachment was marked about 8 mm or 9 mm posterior to the edge of the articular cartilage of the medial femoral condyle and slightly posterior to the ALB tunnel.⁴

In the anterolateral tunnel, an acorn reamer 11 mm in diameter was used to score the entry point of the ALB femoral tunnel. An eyelet pin was then drilled through the reamer anteromedially out the knee. Then a closed socket tunnel was reamed over the eyelet pin to a depth of 25 mm. A passing suture was pulled through the tunnel in preparation for graft passage. 

With use of the same technique, a 7-mm reamer was placed against the outline of the PMB attachment site, and an eyelet pin was drilled through this reamer and out the anteromedial aspect of the knee. Again, a 25-mm deep closed socket was reamed. A bone bridge distance of 2 mm was maintained between the 2 femoral PCL bundle tunnels.

9. ACL Femoral Tunnel. The femoral ACL attachment was identified and outlined. An over-the-top guide was used to determine proper placement of the 10-mm low-profile reamer. A guide pin was drilled through the center of the reamer. The reamer was used to create a 25-mm deep closed socket tunnel, and a passing stitch was placed. 

10. PCL Tibial Tunnel. With use of a 70° arthroscope for visualization, a posteromedial arthroscopic portal was created, and a shaver and a coagulator were used to identify the tibial PCL attachment, located distally along the PCL facet, until the proximal aspect of the popliteus muscle fibers were visualized. A guide pin was drilled starting at the anteromedial aspect of the tibia, about 6 cm distal to the joint line and centered between the anterior tibial crest and the medial tibial border. The pin exited posteriorly at the center of the PCL tibial attachment along the PCL bundle ridge, which was reported located between the ALB and the PMB on the tibia.5 Pin placement was verified with intraoperative lateral and anteroposterior radiographs. On the lateral radiograph, the pin should be about 6 mm or 7 mm proximal to the champagne-glass drop-off at the PCL facet on the posterior aspect of the tibia. On the anteroposterior radiograph, the pin should be 1 mm to 2 mm distal to the joint line and at the medial aspect of the lateral tibial eminence. A large curette was passed through the posteromedial arthroscopic portal both to retract the posterior tissues away from the reamer and to protect against guide-pin protrusion The guide pin was then overreamed with a 12-mm acorn reamer.

A large smoother was passed proximally up the tibial tunnel and then pulled out the anteromedial portal with a grasper. The smoother was gently cycled to smooth the intra-articular tibial tunnel aperture to remove any bony spicules that could interfere with graft passage. The smoother was then pulled back into the joint, passed out the anterolateral arthroscopic portal, and secured with a small clamp.⁴

11. ACL Tibial Tunnel. The ACL tibial attachment site was identified and cleaned of soft tissue. A guide pin was placed and then overreamed with a 10-mm acorn reamer.

12. PCL Femoral Fixation. The PMB graft was passed into its tunnel and secured with a 7-mm × 23-mm titanium screw. Next, the ALB was secured to the femur with a 7-mm × 20-mm titanium screw. The smoother was used to pull both grafts down through the tibial tunnel.

13. ACL Femoral Fixation. A 7-mm × 20-mm titanium screw was then used to fix the ACL autograft inside the femur. Traction was applied to the 3 cruciate grafts. There was no sign of impingement.

14. PLC Femoral Fixation. The FCL and the popliteus bone plugs were passed into their respective femoral sockets and secured with 7-mm × 20-mm titanium screws.

15. Lateral Capsule Femoral Anchors. Two suture anchors were placed into the femur, and the sutures were passed through the femoral portion of the lateral capsule for later repair.

16. PCL Tibial Fixation. Both grafts were fixed with a fully threaded bicortical 6.5-mm × 40-mm cannulated cancellous screw and an 18-mm spiked washer. The ALB was fixed first, with the knee flexed to 90°, traction on the graft, and the tibia in neutral rotation. Restoration of the normal tibiofemoral step-off was verified. The PMB was then fixed with the knee in full extension. A posterior drawer test was performed to verify restoration of stability.

17. PLC Fibula Fixation. The PLT graft was passed down the popliteal hiatus, and the FCL graft was passed under the remnant of the biceps bursa on the fibular head and then through the fibular head, anterolateral to posteromedial. The FCL graft was fixed in the fibular tunnel with the knee in 20° of flexion, a slight valgus reduction force, the tibia in neutral rotation, and traction on the graft. A 7-mm × 23-mm bioabsorbable screw was used.

18. Lateral Capsular Repair. The lateral capsule was directly repaired with the previously placed sutures. The sutures were tied with the knee in 20° of flexion.

19. PLC Tibial Fixation. The grafts were passed together, posterior to anterior, through the tibial tunnel. The knee was cycled several times through complete flexion/extension ROM. A 9-mm × 23-mm bioabsorbable screw was then used to fix the grafts to the tibia. During this fixation, the knee was kept in 60° of flexion and neutral rotation while traction was being applied to the distal end of both grafts.

20. ACL Tibial Fixation. A 9-mm × 20-mm titanium screw was used to fix the ACL graft with the knee in full extension. The graft was then viewed intra-articularly to confirm there was no impingement. The Lachman, posterior drawer, posterolateral drawer, dial, and varus stress tests were performed to ensure restoration of stability.

21. ITB Repair. A portion of the remaining Achilles tendon allograft was used to perform ITB reconstruction (reconstitution of the gaped portion of the ITB). Orthocord (DePuy Synthes) and Vicryl (Ethicon) sutures were used for this reconstruction. Knee stability was deemed restored, and the incisions were closed in standard layered fashion.

First Surgery: Postoperative Management

The patient remained non-weight-bearing the first 6 weeks after surgery, with prone knee flexion limited (0°-90°) the first 2 weeks. In addition, a PCL Jack brace (Albrecht) was placed 1 week after surgery and was to be worn at all times to decrease stress on the PCL grafts.

As ROM was not progressing as expected, the patient was instructed to use a continuous passive motion (CPM) machine 2 hours 3 times a day. About 4 weeks after surgery, with ROM still not progressing, the frequency of use of this machine was increased.

Despite continued physical therapy, use of the CPM machine, and pain management, ROM was limited (11°-90° of flexion) 5.5 months after left knee multiligament reconstruction. However, stress radiographs showed excellent stability. Varus stress radiographs showed a side-to-side difference of 0.3 mm less on the left (injured) knee, and kneeling PCL stress radiographs showed a side-to-side difference of 1.3 mm more on the left knee (Figures 3A-3D).

Second Surgery and Postoperative Management

As gentle manipulation under anesthesia was unsuccessful, the patient underwent knee arthroscopy, including 4-compartment lysis of adhesions, arthroscopically assisted posteromedial capsular release, and post-débridement manipulation under anesthesia. During manipulation, full extension and knee flexion up to 135° were achieved. ACL, PCL, and popliteus grafts were visualized and confirmed to be intact. 

After this second surgery, the patient was to resume physical therapy and begin weight- bearing as tolerated. Active ROM was prioritized in an attempt to reach full ROM. In addition, a CPM machine was to be used from 0° to 135° of knee flexion 4 hours 3 times a day for 6 weeks.

Two weeks after surgery, the patient had continued pain, and extracapsular swelling in the left knee. However, ROM (0°-115° of flexion) was improved relative to before surgery (11°-90° of flexion), though it remained below the range on the contralateral side. Of note, the patient reported having a flexion contracture (~10°) in the immediate postoperative period. He had woken up with it after sleeping with the CPM machine the night before. The contracture delayed his physical therapy for several hours and resulted in a redesign of his therapy protocol to emphasize full, active knee extension and patellar mobilization, as well as discontinuation of use of the CPM machine. Corticosteroids were initiated to help with the extracapsular swelling, and the new therapy regimen brought adequate progress in ROM. Four months after the second surgery, the patient had full extension and 135° of flexion and was transitioned into wearing the PCL Rebound brace.

Discussion

This case was unique because of the midsubstance ITB tear and simultaneous multiligament injury caused by a KD-IIIL, a KD involving the ACL, the PCL, and the PLC with the medial side intact. There is limited research on ITB repair generally, with or without KD involvement. In a retrospective review of acute knee trauma cases, ITB pathologies were seen on 45% of reviewed MRI scans, and only 3% of the injuries were grade III; in addition, only 9 (5%) of the 200 cases involved both ITB and multiligament (ACL, PCL) knee injuries.⁶

After our patient’s ACL, PCL, and PLC were reconstructed, a fan piece of the Achilles tendon allograft from the PLC reconstruction was used to repair the ITB. The graft was used to reconstitute the torn gapped portion of the band in multiple locations, and this repair helped restore stability. The literature has reported numerous surgical uses for a portion of the ITB but few studies on repairing this anatomical structure. Preservation of the ITB is important to restoration of native anatomy and function. The ITB helps with anterolateral stabilization of the knee and with resistance of varus stress and internal tibial rotation.

The PLC reconstruction used in this case has been biomechanically validated as restoring the knee to near native stability through anatomical reconstruction of the PLC’s 3 main static stabilizers: the FCL, the PLT, and the popliteofibular ligament.^7-9 First described in 2004,⁷ this anatomical PLC reconstruction technique has improved subjective and objective patient outcomes.^10,11 For combined PLC injuries (eg, our patient’s injuries), Geeslin and LaPrade¹⁰ recommended concurrent reconstruction of the cruciate ligaments. In addition to the PLC reconstruction, the anatomical double-bundle PCL reconstruction used in this case has demonstrated significant improvements in subjective and objective outcome scores and objective knee stability.¹²

Although the stability and anatomy of this patient’s injured knee were reestablished, his development of arthrofibrosis is important. Many have discussed the commonality of arthrofibrosis or decreased ROM after extensive multiligament reconstruction surgeries.^13,14 One study involving surgical management and outcomes of multiligament knee injuries found that, in more than half of its cases, restoration of full ROM required at least one operation after the initial one.¹³ Therefore, it is not unusual that our patient required a second operation for decreased ROM.

Conclusion

After surgery, excellent stabilization was achieved. Although the patient had setbacks related to pain and decreased ROM, his second surgery and continued physical therapy likely will help him return to his preoperative recreational activity levels.

Take-Home Points

• Reconstruction of a torn ITB is important in restoration of native anatomy and function given its properties in anterolateral stabilization and resistance to varus stress and internal tibial rotation.
• Restoration of posterolateral instability primarily involves reconstructing the FCL, PLT, and popliteofibular ligament.
• For combined PLC injuries, concurrent reconstruction of the cruciate ligaments in one stage is highly recommended.
• Post-surgery, a 6-week non-weight-bearing, limited flexion rehab protocol utilizing a dynamic PCL brace, such as the PCL Rebound brace, is recommended to prevent posterior tibial sag.
• Arthrofibrosis and decreased ROM can be seen following a violent knee injury which requires extensive multiligament reconstruction surgeries, occasionally requiring a secondary surgery for further restoration of knee motion.

Tibiofemoral knee dislocations are uncommon injuries that have devastating complications and potentially result in complex surgeries.¹ Knee dislocations (KDs) can be classified with the Schenck system.² KD-I is a multiligament injury involving the anterior cruciate ligament (ACL) or the posterior cruciate ligament (PCL), and the scale increases in severity/number of ligaments involved, with KD-V being a multiligament injury with periarticular fracture.²

In this article, we report the case of a complex multiligament knee reconstruction performed with a midsubstance iliotibial band (ITB) repair. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 27-year-old man presented 12 days after a paraskiing crash in which he collided with a tree at 45 mph and fell 40 feet before hitting snow. Physical examination revealed a large hemarthrosis of the left lower extremity and ecchymosis about the posterolateral aspect of the knee and popliteal fossa. Range of motion (ROM) was limited from 5° of hyperextension to 90° of flexion. Additional motion was deferred secondary to pain. Varus stress testing at 0° and 30° of knee flexion demonstrated significant side-to-side differences. The Lachman test, posterior drawer test, and posterolateral drawer test were all 3+. The dial test was 3 to 4+ compared with the contralateral knee. Valgus stress testing at 0° and 30° of flexion did not reveal any side-to-side laxity. The calf was nontender, and all compartments were soft. The patient reported no neurovascular symptoms and had no neuromotor deficits other than mild common peroneal nerve dysesthesias.

Varus stress radiographs showed increased side-to-side gapping (8 mm) of the lateral compartment of the injured knee. Kneeling posterior stress radiographs, limited because of the patient’s inability to apply full stress on the injured knee secondary to pain, showed a difference of 6 mm in increased posterior translation on the uninjured leg (Figures 1A-1D).

First Surgery

1. PLC Approach. A lateral hockey-stick skin incision was made along the ITB and extended distally between the fibular head and the Gerdy tubercle. The subcutaneous tissue was then dissected, and a posteriorly based flap was developed for preservation of vascular support to the superficial tissues. The ITB and the lateral capsule had completely torn off of the femur, allowing exposure directly into the joint. The long and short heads of the biceps femoris were exposed, with about 50% of the biceps attachment torn. The FCL was torn midsubstance, and the PLT had no remnant attachment left on the femur.

2. ITB and Lateral Capsule Tag Stitched. The torn ends of the ITB were dissected and tag stitches placed in each end. Tag stitches were also placed in the lateral capsule in preparation for a direct repair.

3. Neurolysis. The common peroneal nerve was found encased in a significant amount of scar tissue, and extensive neurolysis was required. Slow, methodical dissection was performed under the partially torn long head of the biceps femoris and was continued through the scar tissue and adhesions. Distally, 5 mm to 7 mm of the peroneus longus fascia was incised as part of the neurolysis in order to prevent nerve irritation or foot drop caused by postoperative swelling.

4. PLC Tunnels. The margin between the lateral gastrocnemius tendon and the soleus muscle was identified by blunt dissection that allowed palpation of the posteromedial aspect of the fibular styloid and the popliteus musculotendinous junction. The underlying biceps bursa was incised in order to locate the midportion of the FCL remnant, which typically is tag-stitched with No. 2 FiberWire to help identify the femoral attachment (this was not done because of the complete tear at the midsubstance of the FCL).
Subperiosteal dissection of the lateral aspect of the fibular head was performed anterior to posterior and distally extended to the champagne-glass drop-off of the fibular head. Continuing the dissection distally beyond this point can endanger the common peroneal nerve. A small sulcus can be palpated where the distal FCL inserts on the fibular head. Posteriorly, a small elevator was used to dissect the soleus muscle off of the posteromedial aspect of the fibular head, where the fibular tunnel would later be created.

A Chandler retractor was placed posterior to the fibular head to protect the neurovascular bundle. With the aid of a collateral ligament aiming device, a guide pin was drilled from the lateral aspect of the fibular head (FCL attachment) to the posteromedial downslope of the fibular styloid (popliteofibular ligament attachment). The entry point of the guide pin was immediately above the champagne- glass drop-off, at the distal insertion site of the FCL, which was described as being 28.4 mm from the styloid tip and 8.2 mm posterior to the anterior margin of the fibular head.3 Care should be taken not to ream the tunnel too proximal, as doing so increases the risk of iatrogenic fracture. A 7-mm reamer was then used to drill the fibular tunnel. To facilitate later passage of the graft, a passing suture was placed through the tunnel, leaving the loop anterolateral.

Next, the starting point for the tibial tunnel was located on the flat spot of the anterolateral tibia distal and medial to the Gerdy tubercle, just lateral to the tibial tubercle. The tibial popliteal sulcus was identified by palpation of the posterolateral tibial plateau to localize the site of the popliteus musculotendinous junction, which is the ideal location of the posterior aperture of the tibial tunnel. This point is 1 cm proximal and 1 cm medial to the posteromedial exit of the fibular tunnel. A Chandler retractor was placed anterior to the lateral gastrocnemius to protect the neurovascular bundle. In the locations described earlier, a cruciate aiming device was used to place a guide pin anterior to posterior. A 9-mm tunnel was overreamed and a passing suture placed, leaving the loop posterior to facilitate graft passage.

The femoral insertions of the FCL and the PLT were then identified. ITB splitting was not necessary, given the complete midsubstance tear of this structure. The FCL attachment was identified 1.4 mm proximal and 3.1 mm posterior to the lateral epicondyle.3 Sharp dissection was performed in this location, proximal to distal, exposing the lateral epicondyle and the small sulcus at the FCL attachment site. A collateral ligament reconstruction aiming sleeve was used to drill a guide pin over the FCL femoral attachment site and out the medial aspect of the distal thigh, about 5 cm proximal and anterior to the adductor tubercle.

The femoral attachment of the PLT was reported located 18.5 mm anterior to the FCL insertion, in the anterior fifth of the popliteal sulcus.³ Although arthrotomy is usually required in order to access the PLT attachment, it was not necessary in this case, given the lateral capsule tear. A guide pin was inserted at the PLT attachment site, parallel to the FCL pin. After proper placement was verified, a 9-mm reamer was used to drill the FCL and PLT tunnels to a depth of 25 mm (socket), and a passing suture was placed into each tunnel to facilitate graft passage.

5. ACL Graft Harvest. The central third of the ipsilateral patellar tendon was harvested for use in the ACL reconstruction. Included were a 10-mm × 20-mm bone plug from the patella and a 10-mm × 25-mm bone plug from the tibial tubercle. The patella defect was then bone-grafted, and the patellar tendon closed side-to-side.

6. Graft Preparation. For the PLC, we used a split Achilles tendon allograft that had two 9-mm × 25-mm bone plugs proximally and were tubularized distally. For the PCL, we used an anterolateral bundle (ALB), which consisted of an Achilles tendon allograft that had an 11-mm × 25-mm bone plug proximally and was tubularized distally, and a posteromedial bundle (PMB), which consisted of a tibialis anterior allograft that was tubularized at both ends. For the ACL, we used a bone–patellar tendon–bone autograft 10 mm in diameter with a 20-mm femoral bone plug and a 25-mm tibial bone plug distally.

7. Arthroscopy. We created standard anterolateral and anteromedial parapatellar portals and performed arthroscopy, including lysis of adhesions. Cartilage and menisci were lesion-free.

8. PCL Femoral Tunnels. The ALB attachment was identified and outlined with a coagulator between the trochlear point and the medial arch point, adjacent to the edge of the articular cartilage. Similarly, the PMB attachment was marked about 8 mm or 9 mm posterior to the edge of the articular cartilage of the medial femoral condyle and slightly posterior to the ALB tunnel.⁴

In the anterolateral tunnel, an acorn reamer 11 mm in diameter was used to score the entry point of the ALB femoral tunnel. An eyelet pin was then drilled through the reamer anteromedially out the knee. Then a closed socket tunnel was reamed over the eyelet pin to a depth of 25 mm. A passing suture was pulled through the tunnel in preparation for graft passage. 

With use of the same technique, a 7-mm reamer was placed against the outline of the PMB attachment site, and an eyelet pin was drilled through this reamer and out the anteromedial aspect of the knee. Again, a 25-mm deep closed socket was reamed. A bone bridge distance of 2 mm was maintained between the 2 femoral PCL bundle tunnels.

9. ACL Femoral Tunnel. The femoral ACL attachment was identified and outlined. An over-the-top guide was used to determine proper placement of the 10-mm low-profile reamer. A guide pin was drilled through the center of the reamer. The reamer was used to create a 25-mm deep closed socket tunnel, and a passing stitch was placed. 

10. PCL Tibial Tunnel. With use of a 70° arthroscope for visualization, a posteromedial arthroscopic portal was created, and a shaver and a coagulator were used to identify the tibial PCL attachment, located distally along the PCL facet, until the proximal aspect of the popliteus muscle fibers were visualized. A guide pin was drilled starting at the anteromedial aspect of the tibia, about 6 cm distal to the joint line and centered between the anterior tibial crest and the medial tibial border. The pin exited posteriorly at the center of the PCL tibial attachment along the PCL bundle ridge, which was reported located between the ALB and the PMB on the tibia.5 Pin placement was verified with intraoperative lateral and anteroposterior radiographs. On the lateral radiograph, the pin should be about 6 mm or 7 mm proximal to the champagne-glass drop-off at the PCL facet on the posterior aspect of the tibia. On the anteroposterior radiograph, the pin should be 1 mm to 2 mm distal to the joint line and at the medial aspect of the lateral tibial eminence. A large curette was passed through the posteromedial arthroscopic portal both to retract the posterior tissues away from the reamer and to protect against guide-pin protrusion The guide pin was then overreamed with a 12-mm acorn reamer.

A large smoother was passed proximally up the tibial tunnel and then pulled out the anteromedial portal with a grasper. The smoother was gently cycled to smooth the intra-articular tibial tunnel aperture to remove any bony spicules that could interfere with graft passage. The smoother was then pulled back into the joint, passed out the anterolateral arthroscopic portal, and secured with a small clamp.⁴

11. ACL Tibial Tunnel. The ACL tibial attachment site was identified and cleaned of soft tissue. A guide pin was placed and then overreamed with a 10-mm acorn reamer.

12. PCL Femoral Fixation. The PMB graft was passed into its tunnel and secured with a 7-mm × 23-mm titanium screw. Next, the ALB was secured to the femur with a 7-mm × 20-mm titanium screw. The smoother was used to pull both grafts down through the tibial tunnel.

13. ACL Femoral Fixation. A 7-mm × 20-mm titanium screw was then used to fix the ACL autograft inside the femur. Traction was applied to the 3 cruciate grafts. There was no sign of impingement.

14. PLC Femoral Fixation. The FCL and the popliteus bone plugs were passed into their respective femoral sockets and secured with 7-mm × 20-mm titanium screws.

15. Lateral Capsule Femoral Anchors. Two suture anchors were placed into the femur, and the sutures were passed through the femoral portion of the lateral capsule for later repair.

16. PCL Tibial Fixation. Both grafts were fixed with a fully threaded bicortical 6.5-mm × 40-mm cannulated cancellous screw and an 18-mm spiked washer. The ALB was fixed first, with the knee flexed to 90°, traction on the graft, and the tibia in neutral rotation. Restoration of the normal tibiofemoral step-off was verified. The PMB was then fixed with the knee in full extension. A posterior drawer test was performed to verify restoration of stability.

17. PLC Fibula Fixation. The PLT graft was passed down the popliteal hiatus, and the FCL graft was passed under the remnant of the biceps bursa on the fibular head and then through the fibular head, anterolateral to posteromedial. The FCL graft was fixed in the fibular tunnel with the knee in 20° of flexion, a slight valgus reduction force, the tibia in neutral rotation, and traction on the graft. A 7-mm × 23-mm bioabsorbable screw was used.

18. Lateral Capsular Repair. The lateral capsule was directly repaired with the previously placed sutures. The sutures were tied with the knee in 20° of flexion.

19. PLC Tibial Fixation. The grafts were passed together, posterior to anterior, through the tibial tunnel. The knee was cycled several times through complete flexion/extension ROM. A 9-mm × 23-mm bioabsorbable screw was then used to fix the grafts to the tibia. During this fixation, the knee was kept in 60° of flexion and neutral rotation while traction was being applied to the distal end of both grafts.

20. ACL Tibial Fixation. A 9-mm × 20-mm titanium screw was used to fix the ACL graft with the knee in full extension. The graft was then viewed intra-articularly to confirm there was no impingement. The Lachman, posterior drawer, posterolateral drawer, dial, and varus stress tests were performed to ensure restoration of stability.

21. ITB Repair. A portion of the remaining Achilles tendon allograft was used to perform ITB reconstruction (reconstitution of the gaped portion of the ITB). Orthocord (DePuy Synthes) and Vicryl (Ethicon) sutures were used for this reconstruction. Knee stability was deemed restored, and the incisions were closed in standard layered fashion.

First Surgery: Postoperative Management

The patient remained non-weight-bearing the first 6 weeks after surgery, with prone knee flexion limited (0°-90°) the first 2 weeks. In addition, a PCL Jack brace (Albrecht) was placed 1 week after surgery and was to be worn at all times to decrease stress on the PCL grafts.

As ROM was not progressing as expected, the patient was instructed to use a continuous passive motion (CPM) machine 2 hours 3 times a day. About 4 weeks after surgery, with ROM still not progressing, the frequency of use of this machine was increased.

Despite continued physical therapy, use of the CPM machine, and pain management, ROM was limited (11°-90° of flexion) 5.5 months after left knee multiligament reconstruction. However, stress radiographs showed excellent stability. Varus stress radiographs showed a side-to-side difference of 0.3 mm less on the left (injured) knee, and kneeling PCL stress radiographs showed a side-to-side difference of 1.3 mm more on the left knee (Figures 3A-3D).

Second Surgery and Postoperative Management

As gentle manipulation under anesthesia was unsuccessful, the patient underwent knee arthroscopy, including 4-compartment lysis of adhesions, arthroscopically assisted posteromedial capsular release, and post-débridement manipulation under anesthesia. During manipulation, full extension and knee flexion up to 135° were achieved. ACL, PCL, and popliteus grafts were visualized and confirmed to be intact. 

After this second surgery, the patient was to resume physical therapy and begin weight- bearing as tolerated. Active ROM was prioritized in an attempt to reach full ROM. In addition, a CPM machine was to be used from 0° to 135° of knee flexion 4 hours 3 times a day for 6 weeks.

Two weeks after surgery, the patient had continued pain, and extracapsular swelling in the left knee. However, ROM (0°-115° of flexion) was improved relative to before surgery (11°-90° of flexion), though it remained below the range on the contralateral side. Of note, the patient reported having a flexion contracture (~10°) in the immediate postoperative period. He had woken up with it after sleeping with the CPM machine the night before. The contracture delayed his physical therapy for several hours and resulted in a redesign of his therapy protocol to emphasize full, active knee extension and patellar mobilization, as well as discontinuation of use of the CPM machine. Corticosteroids were initiated to help with the extracapsular swelling, and the new therapy regimen brought adequate progress in ROM. Four months after the second surgery, the patient had full extension and 135° of flexion and was transitioned into wearing the PCL Rebound brace.

Discussion

This case was unique because of the midsubstance ITB tear and simultaneous multiligament injury caused by a KD-IIIL, a KD involving the ACL, the PCL, and the PLC with the medial side intact. There is limited research on ITB repair generally, with or without KD involvement. In a retrospective review of acute knee trauma cases, ITB pathologies were seen on 45% of reviewed MRI scans, and only 3% of the injuries were grade III; in addition, only 9 (5%) of the 200 cases involved both ITB and multiligament (ACL, PCL) knee injuries.⁶

After our patient’s ACL, PCL, and PLC were reconstructed, a fan piece of the Achilles tendon allograft from the PLC reconstruction was used to repair the ITB. The graft was used to reconstitute the torn gapped portion of the band in multiple locations, and this repair helped restore stability. The literature has reported numerous surgical uses for a portion of the ITB but few studies on repairing this anatomical structure. Preservation of the ITB is important to restoration of native anatomy and function. The ITB helps with anterolateral stabilization of the knee and with resistance of varus stress and internal tibial rotation.

The PLC reconstruction used in this case has been biomechanically validated as restoring the knee to near native stability through anatomical reconstruction of the PLC’s 3 main static stabilizers: the FCL, the PLT, and the popliteofibular ligament.^7-9 First described in 2004,⁷ this anatomical PLC reconstruction technique has improved subjective and objective patient outcomes.^10,11 For combined PLC injuries (eg, our patient’s injuries), Geeslin and LaPrade¹⁰ recommended concurrent reconstruction of the cruciate ligaments. In addition to the PLC reconstruction, the anatomical double-bundle PCL reconstruction used in this case has demonstrated significant improvements in subjective and objective outcome scores and objective knee stability.¹²

Although the stability and anatomy of this patient’s injured knee were reestablished, his development of arthrofibrosis is important. Many have discussed the commonality of arthrofibrosis or decreased ROM after extensive multiligament reconstruction surgeries.^13,14 One study involving surgical management and outcomes of multiligament knee injuries found that, in more than half of its cases, restoration of full ROM required at least one operation after the initial one.¹³ Therefore, it is not unusual that our patient required a second operation for decreased ROM.

Conclusion

After surgery, excellent stabilization was achieved. Although the patient had setbacks related to pain and decreased ROM, his second surgery and continued physical therapy likely will help him return to his preoperative recreational activity levels.

An 83-year-old man presented to the emergency department with acute, painless loss of vision in his left eye. His vision in that eye had been normal in the middle of the night when he woke to use the restroom, but on awakening 6 hours later he could perceive only light or darkness.

He denied headache, scalp tenderness, jaw claudication, fever, weight loss, myalgia, or other neurologic symptoms. He had not experienced any recent change in his vision before this presentation, including halos around lights, floaters, eye pain, or redness. However, 6 months ago he had undergone left cataract surgery (left phacoemulsification with intraocular implant) without complications. And he said that when he was 3 years old, he had sustained a serious injury to his right eye.

His medical history included ischemic heart disease and hypertension. His medications included losartan, furosemide, amlodi­pine, atorvastatin, and aspirin.

CAUSES OF ACUTE MONOCULAR VISION LOSS

1. Which of the following is the least likely cause of this patient’s acute monocular vision loss?

• Optic neuritis
• Retinal vein occlusion
• Retinal artery occlusion
• Pituitary apoplexy
• Retinal detachment

Acute vision loss is often so distressing to the patient that the emergency department may be the first step in evaluation. While its diagnosis and management often require an interdisciplinary effort, early evaluation and triage of this potential medical emergency is often done by clinicians without specialized training in ophthalmology.

The physiology of vision is complex and the list of possible causes of vision loss is long, but the differential diagnosis can be narrowed quickly by considering the time course of vision loss and the anatomic localization.¹

The time course (including onset and tempo) of vision loss can classified as:

• Transient (ie, vision returned to normal by the time seen by clinician)
• Acute (instantaneous onset, ie, within seconds to minutes)
• Subacute (progression over days to weeks)
• Chronic (insidious progression over months to years).

Although acute vision loss is usually dramatic, insidious vision loss may occasionally be unnoticed for a surprisingly long time until the normal eye is inadvertently shielded.

Anatomic localization. Lesions anterior to the optic chiasm cause monocular vision loss, whereas lesions at or posterior to the chiasm lead to bilateral visual field defects. Problems leading to monocular blindness can be broadly divided into 3 anatomic categories (Figure 1):

• Ocular medial (including the cornea, anterior chamber, and lens)
• Retinal
• Neurologic (including the optic nerve and chiasm).

Clues from the history

A careful ophthalmic history is an essential initial step in the evaluation (Table 1). In addition, nonvisual symptoms can help narrow the differential diagnosis.

Nausea and vomiting often accompany acute elevation of intraocular pressure.

Focal neurologic deficits or other neurologic symptoms can point to a demyelinating disease such as multiple sclerosis.

Risk factors for vascular atherosclerotic disease such as diabetes, hypertension, and coronary artery disease raise concern for retinal, optic nerve, or cerebral ischemia.

Medications with anticholinergic and adrenergic properties can also precipitate monocular vision loss with acute angle-closure glaucoma.

Can we rule out anything yet?

Our patient presented with painless monocular vision loss. As discussed, causes of monocular vision loss can be localized to ocular abnormalities and prechiasmatic neurologic ones. Retinal detachment, occlusion of a retinal artery or vein, and optic neuritis are all important potential causes of acute monocular vision loss.

Pituitary apoplexy, on the other hand, is characterized by an acute increase in pituitary volume, often leading to compression of the optic chiasm resulting in a visual-field defect. It is most often characterized by binocular deficits (eg, bitemporal hemianopia) but is less likely to cause monocular vision loss.¹

CASE CONTINUED: EXAMINATION

On examination, the patient appeared comfortable. His temperature was 97.6°F (36.4°C), pulse 59 beats per minute, respiratory rate 18 per minute, and blood pressure 153/56 mm Hg.

Heart and lung examinations were notable for a grade 3 of 6 midsystolic, low-pitched murmur in the aortic area radiating to the neck, bilateral carotid bruits, and clear lungs. The cardiac impulse was normal in location and character. There was no evidence of aortic insufficiency (including auscultation during exhalation phase while sitting upright).

Eye examination. Visual acuity in the right eye was 20/200 with correction (owing to his eye injury at age 3). With the left eye, he could see only light or darkness. The conjunctiva and sclera were normal.

The right pupil was irregular and measured 3 mm (baseline from his previous eye injury). The left pupil was 3.5 mm. The direct pupillary response was preserved, but a relative afferent pupillary defect was present: on the swinging flashlight test, the left pupil dilated when the flashlight was passed from the right to the left pupil. Extraocular movements were full and intact bilaterally. The rest of the neurologic examination was normal.

An ophthalmologist was urgently consulted. A dilated funduscopic examination of the left eye revealed peripapillary atrophy, tortuous vessels, a cherry red macular spot, and flame hemorrhages, but no disc edema or pallor (Figure 2).

FURTHER WORKUP

2. Which of the following investigations would be least useful and not indicated at this point for this patient?

• Carotid ultrasonography
• Electrocardiography and echocardiography
• Magnetic resonance angiography of the brain
• Computed tomographic (CT) angiography of the head and neck
• Testing for the factor V Leiden and prothrombin gene mutations

A systematic ocular physical examination can offer important diagnostic information (Table 2). Ophthalmoscopy directly examines the optic disc, macula, and retinal vasculature. To interpret the funduscopic examination, we need a basic understanding of the vascular supply to the eye (Figure 3).

Information from references 4 and 5.

For example, the cherry red spot within the macula in our patient is characteristic of central retinal artery occlusion and highlights the relationship between anatomy and pathophysiology. The retina’s blood supply is compromised, leading to an ischemic, white background (secondary to edema of the inner third of the retina), but the macula continues to be nourished by the posterior ciliary arteries. This contrast in color is accentuated by the underlying structures composing the fovea, which lacks the nerve fiber layer and ganglion cell layer, making the vascular bed more visible.^2,3

Also in our patient, the marked reduction in visual acuity and relative afferent pupillary defect in the left eye point to unilateral optic nerve (or retinal ganglion cell) dysfunction. The findings on direct funduscopy were consistent with acute central retinal artery ischemia or occlusion. Central retinal artery occlusion can be either arteritic (due to inflammation, most often giant cell arteritis) or nonarteritic (due to atherosclerotic vascular disease).

Thus, carotid ultrasonography, electrocardiography, and transthoracic and transesophageal echocardiography are important components of the further workup. In addition, urgent brain imaging including either CT angiography or magnetic resonance angiography of the head and neck is indicated in all patients with central retinal artery occlusion.

Thrombophilia testing, including tests for the factor V Leiden and prothrombin gene mutations, is indicated in specific cases when a hypercoagulable state is suggested by components of the history, physical examination, and laboratory and radiologic testing. Thrombophilia testing would be low-yield and should not be part of the first-line testing in elderly patients with several atherosclerotic risk factors, such as our patient.

CASE CONTINUED: LABORATORY AND IMAGING EVIDENCE

Initial laboratory work showed:

• Mild microcytic anemia
• Erythrocyte sedimentation rate 77 mm/hour (reference range 1–10)
• C-reactive protein 4.0 mg/dL (reference range < 0.9).

The rest of the complete blood cell count and metabolic profile were unremarkable. His hemoglobin A_1c value was 5.3% (reference range 4.8%–6.2%).

A neurologist was urgently consulted.

Magnetic resonance imaging of the brain without contrast revealed nonspecific white-matter disease with no evidence of ischemic stroke.

Magnetic resonance angiography of the head and neck with contrast demonstrated 20% to 40% stenosis in both carotid arteries with otherwise patent anterior and posterior circulation.

Continuous monitoring of the left carotid artery with transcranial Doppler ultrasonography was also ordered, and the study concluded there were no undetected microembolic events.

Transthoracic echocardiography showed aortic sclerosis with no other abnormalities.

Ophthalmic fluorescein angiography was performed and showed patchy choroidal hypoperfusion, severe delayed filling, and extensive pruning of the arterial circulation with no  involvement of the posterior ciliary arteries.

Given the elevated inflammatory markers, pulse-dose intravenous methylprednisolone was started, and a temporal artery biopsy was planned.

CENTRAL RETINAL ARTERY OCCLUSION: NONARTERITIC VS ARTERITIC CAUSES

3. Which of the following is least useful to differentiate arteritic from nonarteritic causes of central retinal artery occlusion?

• Finding emboli in the retinal vasculature on funduscopy
• Temporal artery biopsy
• Measuring the C-reactive protein level and the erythrocyte sedimentation rate
• Echocardiography
• Positron-emission tomography (PET)
• Retinal fluorescein angiography

In patients diagnosed with central retinal artery occlusion, the next step is to differentiate between nonarteritic and arteritic causes, since separating them has therapeutic relevance.

The carotid artery is the main culprit for embolic disease affecting the central retinal artery, leading to the nonarteritic subtype. Thus, evaluation of acute retinal ischemia secondary to nonarteritic central retinal artery occlusion is similar to the evaluation of patients with an acute cerebral stroke.⁴ Studies have shown that 25% of patients diagnosed with central retinal artery occlusion have an additional ischemic insult in the cerebrovascular system, and these patients are at high risk of recurrent ocular or cerebral infarction. Workup includes diffusion-weighted MRI, angiography, echocardiography, and telemetry.⁵

Arteritic central retinal artery occlusion is most often caused by giant cell arteritis. The American College of Rheumatology classification criteria for giant cell arteritis include 3 of the following 5:

• Age 50 or older
• New onset of localized headache
• Temporal artery tenderness or decreased temporal artery pulse
• Erythrocyte sedimentation rate 50 mm/hour or greater
• Positive biopsy findings.⁶  

Temporal artery biopsy is the gold standard for the diagnosis of giant cell arteritis and should be done whenever the disease is suspected.^7,8 However, the test is invasive and imperfect, as a negative result does not completely rule out giant cell arteritis.⁹

Although a unilateral temporal artery biopsy can be falsely negative, several studies evaluating the efficacy of bilateral biopsies did not show significant improvement in the diagnostic yield.^10,11

Ophthalmic fluorescein angiography is another helpful test for distinguishing nonarteritic from arteritic central retinal artery occlusion.¹² Involvement of the posterior ciliary arteries usually occurs in giant cell arteritis, and this leads to choroidal malperfusion with or without retinal involvement. The optic nerve may also be infarcted by closure of the paraoptic vessels fed by the posterior ciliary vessels.^12,13 Such involvement of multiple vessels would not be typical with nonarteritic central retinal artery occlusion. Thus, this finding is helpful in making the final diagnosis along with supplying possible prognostic information.¹³

PET-CT is emerging as a test for early inflammation in extracranial disease, but its utility for diagnosing intracranial disease is limited by high uptake of the tracer fluoro­deoxyglucose by the brain and low resolution.¹⁴ Currently, it has no established role in the evaluation of patients with central retinal artery occlusion and would have no utility in differentiating arteritic vs nonarteritic causes of central retinal artery occlusion.

If giant cell arteritis is suspected, it is essential to start intravenous pulse-dose methyl­prednisolone early to prevent further vision loss in the contralateral eye. Treatment should not be delayed for invasive testing or temporal artery biopsy. Improvement in headache, jaw claudication, or scalp tenderness once steroids are initiated also helps support the diagnosis of giant cell arteritis.⁷

Unfortunately, visual symptoms may be irreversible despite treatment.

Our patient’s central retinal artery occlusion

This case highlights how difficult it is in practice to distinguish nonarteritic from arteritic central retinal artery occlusion.

Our patient had numerous cardiovascular risk factors, including known carotid and coronary artery disease, favoring a nonarteritic diagnosis.

On the other hand, his elevated inflammatory markers suggested an underlying inflammatory response. He lacked the characteristic headache and other systemic signs of giant cell arteritis, but this has been described in about 25% of patients.¹⁵ If emboli are seen on funduscopy, further workup for arteritic central retinal artery occlusion is not warranted, but emboli are not always present. Then again, absence of posterior ciliary artery involvement on fluorescein angiography pointed away from giant cell arteritis.

CASE CONTINUED: FINAL DIAGNOSIS

Biopsy of the left temporal artery showed intimal thickening with focal destruction of the internal elastic lamina by dystrophic calcification with no evidence of inflammatory infiltrates, giant cells, or granulomata in the adventitia, media, or intima. Based on the results of biopsy study and fluorescein angiography, we concluded that this was nonarteritic central retinal artery occlusion related to atherosclerotic disease.

Methylprednisolone was discontinued. The patient was discharged on aspirin, losartan, furosemide, amlodipine, and high-dose atorvastatin for standard stroke prevention. He was followed by the medical team and the ophthalmology department. At 6 weeks, there was only marginal improvement in the visual acuity of the left eye.

 

 

MANAGEMENT

4. Management of nonarteritic central retinal artery occlusion could include all of the following except which one?

• Ocular massage
• Intravenous thrombolysis
• Intra-arterial thrombolysis
• Risk-factor modification
• Intraocular steroid injection

In patients with acute vision loss from nonarteritic central retinal artery occlusion, acute strategies to restore retinal perfusion include noninvasive “standard” therapies and thrombolysis (intravenous or intra-arterial). Unfortunately, consensus and guidelines are lacking.

Traditional therapies include sublingual isosorbide dinitrate, systemic pentoxifylline, inhalation of a carbogen, hyperbaric oxygen, ocular massage, intravenous acetazolamide and mannitol, anterior chamber paracentesis, and systemic steroids. However, none of these have been shown to be more effective than placebo.¹⁶

Thrombolytic therapy, analogous to the treatment of patients with ischemic stroke or myocardial infarction, is more controversial in acute central retinal artery occlusion.¹³ Data from small case-series suggested that intra-arterial or intravenous thrombolysis might improve visual acuity with reasonable safety.¹⁷ On the other hand, a randomized study from the United Kingdom that compared intra-arterial thrombolysis within a 24-hour window and conservative measures concluded that thrombolysis should not be used.¹⁸

Thrombolysis is thus used only in selected patients on a case-specific basis with involvement of a multispecialty team including stroke neurologists, especially if patients present within hours of onset and have concomitant neurologic symptoms.

Treatment beyond the acute phase focuses on preventing complications of the eye ischemia and aggressively managing systemic atherosclerotic risk factors to decrease the incidence of further ischemic events. Other interventions  include endarterectomy for significant carotid stenosis and anticoagulation to prevent cardioembolic embolization (such as atrial fibrillation). Most experts agree on the addition of an antiplatelet agent.^13,19

Intraocular steroid injection can be used in the management of some retinal disorders but has no value in nonarteritic central retinal artery occlusion.

Vision recovery in nonarteritic central retinal artery occlusion is variable, but the prognosis is generally poor. The visual acuity on presentation, the onset of the symptoms, and collateral vessels are major factors influencing long-term recovery. Most of the recovery occurs within 7 days and involves peripheral vision rather than central vision. Several studies report some recovery in peripheral vision in approximately 30% to 35% of affected eyes.^20–22

PROMPT ACTION MAY SAVE SIGHT

Vision loss is a common presenting symptom in the emergency setting. A meticulous history and systematic physical examination can narrow the differential diagnosis of this neuro-ophthalmologic emergency. Acute retinal ischemia from central retinal artery occlusion is the ocular equivalent of an ischemic stroke, and they share risk factors, diagnostic workup, and management approaches.

Both etiologic subtypes (ie, arteritic and nonarteritic) require prompt intervention by front-line physicians. If giant cell arteritis is suspected, corticosteroid therapy must be initiated to save the contralateral retina from ischemia. Suspicion of central retinal artery occlusion warrants immediate evaluation by a neurologist to consider thrombolysis. Prompt action and interdisciplinary care involving an ophthalmologist, neurologist, and emergency or internal medicine physician may save a patient from permanent visual disability.

KEY POINTS

• Monocular vision loss requires urgent evaluation with a multidisciplinary management approach.
• There are no consensus treatment guidelines for nonarteritic central retinal artery occlusion, but the workup includes a comprehensive stroke evaluation.
• Arteritic central retinal artery occlusion is most often due to giant cell arteritis, and when it is suspected, the patient should be empirically treated with steroids.

An 83-year-old man presented to the emergency department with acute, painless loss of vision in his left eye. His vision in that eye had been normal in the middle of the night when he woke to use the restroom, but on awakening 6 hours later he could perceive only light or darkness.

He denied headache, scalp tenderness, jaw claudication, fever, weight loss, myalgia, or other neurologic symptoms. He had not experienced any recent change in his vision before this presentation, including halos around lights, floaters, eye pain, or redness. However, 6 months ago he had undergone left cataract surgery (left phacoemulsification with intraocular implant) without complications. And he said that when he was 3 years old, he had sustained a serious injury to his right eye.

His medical history included ischemic heart disease and hypertension. His medications included losartan, furosemide, amlodi­pine, atorvastatin, and aspirin.

CAUSES OF ACUTE MONOCULAR VISION LOSS

1. Which of the following is the least likely cause of this patient’s acute monocular vision loss?

• Optic neuritis
• Retinal vein occlusion
• Retinal artery occlusion
• Pituitary apoplexy
• Retinal detachment

Acute vision loss is often so distressing to the patient that the emergency department may be the first step in evaluation. While its diagnosis and management often require an interdisciplinary effort, early evaluation and triage of this potential medical emergency is often done by clinicians without specialized training in ophthalmology.

The physiology of vision is complex and the list of possible causes of vision loss is long, but the differential diagnosis can be narrowed quickly by considering the time course of vision loss and the anatomic localization.¹

The time course (including onset and tempo) of vision loss can classified as:

• Transient (ie, vision returned to normal by the time seen by clinician)
• Acute (instantaneous onset, ie, within seconds to minutes)
• Subacute (progression over days to weeks)
• Chronic (insidious progression over months to years).

Although acute vision loss is usually dramatic, insidious vision loss may occasionally be unnoticed for a surprisingly long time until the normal eye is inadvertently shielded.

Anatomic localization. Lesions anterior to the optic chiasm cause monocular vision loss, whereas lesions at or posterior to the chiasm lead to bilateral visual field defects. Problems leading to monocular blindness can be broadly divided into 3 anatomic categories (Figure 1):

• Ocular medial (including the cornea, anterior chamber, and lens)
• Retinal
• Neurologic (including the optic nerve and chiasm).

Clues from the history

A careful ophthalmic history is an essential initial step in the evaluation (Table 1). In addition, nonvisual symptoms can help narrow the differential diagnosis.

Nausea and vomiting often accompany acute elevation of intraocular pressure.

Focal neurologic deficits or other neurologic symptoms can point to a demyelinating disease such as multiple sclerosis.

Risk factors for vascular atherosclerotic disease such as diabetes, hypertension, and coronary artery disease raise concern for retinal, optic nerve, or cerebral ischemia.

Medications with anticholinergic and adrenergic properties can also precipitate monocular vision loss with acute angle-closure glaucoma.

Can we rule out anything yet?

Our patient presented with painless monocular vision loss. As discussed, causes of monocular vision loss can be localized to ocular abnormalities and prechiasmatic neurologic ones. Retinal detachment, occlusion of a retinal artery or vein, and optic neuritis are all important potential causes of acute monocular vision loss.

Pituitary apoplexy, on the other hand, is characterized by an acute increase in pituitary volume, often leading to compression of the optic chiasm resulting in a visual-field defect. It is most often characterized by binocular deficits (eg, bitemporal hemianopia) but is less likely to cause monocular vision loss.¹

CASE CONTINUED: EXAMINATION

On examination, the patient appeared comfortable. His temperature was 97.6°F (36.4°C), pulse 59 beats per minute, respiratory rate 18 per minute, and blood pressure 153/56 mm Hg.

Heart and lung examinations were notable for a grade 3 of 6 midsystolic, low-pitched murmur in the aortic area radiating to the neck, bilateral carotid bruits, and clear lungs. The cardiac impulse was normal in location and character. There was no evidence of aortic insufficiency (including auscultation during exhalation phase while sitting upright).

Eye examination. Visual acuity in the right eye was 20/200 with correction (owing to his eye injury at age 3). With the left eye, he could see only light or darkness. The conjunctiva and sclera were normal.

The right pupil was irregular and measured 3 mm (baseline from his previous eye injury). The left pupil was 3.5 mm. The direct pupillary response was preserved, but a relative afferent pupillary defect was present: on the swinging flashlight test, the left pupil dilated when the flashlight was passed from the right to the left pupil. Extraocular movements were full and intact bilaterally. The rest of the neurologic examination was normal.

An ophthalmologist was urgently consulted. A dilated funduscopic examination of the left eye revealed peripapillary atrophy, tortuous vessels, a cherry red macular spot, and flame hemorrhages, but no disc edema or pallor (Figure 2).

FURTHER WORKUP

2. Which of the following investigations would be least useful and not indicated at this point for this patient?

• Carotid ultrasonography
• Electrocardiography and echocardiography
• Magnetic resonance angiography of the brain
• Computed tomographic (CT) angiography of the head and neck
• Testing for the factor V Leiden and prothrombin gene mutations

A systematic ocular physical examination can offer important diagnostic information (Table 2). Ophthalmoscopy directly examines the optic disc, macula, and retinal vasculature. To interpret the funduscopic examination, we need a basic understanding of the vascular supply to the eye (Figure 3).

Information from references 4 and 5.

For example, the cherry red spot within the macula in our patient is characteristic of central retinal artery occlusion and highlights the relationship between anatomy and pathophysiology. The retina’s blood supply is compromised, leading to an ischemic, white background (secondary to edema of the inner third of the retina), but the macula continues to be nourished by the posterior ciliary arteries. This contrast in color is accentuated by the underlying structures composing the fovea, which lacks the nerve fiber layer and ganglion cell layer, making the vascular bed more visible.^2,3

Also in our patient, the marked reduction in visual acuity and relative afferent pupillary defect in the left eye point to unilateral optic nerve (or retinal ganglion cell) dysfunction. The findings on direct funduscopy were consistent with acute central retinal artery ischemia or occlusion. Central retinal artery occlusion can be either arteritic (due to inflammation, most often giant cell arteritis) or nonarteritic (due to atherosclerotic vascular disease).

Thus, carotid ultrasonography, electrocardiography, and transthoracic and transesophageal echocardiography are important components of the further workup. In addition, urgent brain imaging including either CT angiography or magnetic resonance angiography of the head and neck is indicated in all patients with central retinal artery occlusion.

Thrombophilia testing, including tests for the factor V Leiden and prothrombin gene mutations, is indicated in specific cases when a hypercoagulable state is suggested by components of the history, physical examination, and laboratory and radiologic testing. Thrombophilia testing would be low-yield and should not be part of the first-line testing in elderly patients with several atherosclerotic risk factors, such as our patient.

CASE CONTINUED: LABORATORY AND IMAGING EVIDENCE

Initial laboratory work showed:

• Mild microcytic anemia
• Erythrocyte sedimentation rate 77 mm/hour (reference range 1–10)
• C-reactive protein 4.0 mg/dL (reference range < 0.9).

The rest of the complete blood cell count and metabolic profile were unremarkable. His hemoglobin A_1c value was 5.3% (reference range 4.8%–6.2%).

A neurologist was urgently consulted.

Magnetic resonance imaging of the brain without contrast revealed nonspecific white-matter disease with no evidence of ischemic stroke.

Magnetic resonance angiography of the head and neck with contrast demonstrated 20% to 40% stenosis in both carotid arteries with otherwise patent anterior and posterior circulation.

Continuous monitoring of the left carotid artery with transcranial Doppler ultrasonography was also ordered, and the study concluded there were no undetected microembolic events.

Transthoracic echocardiography showed aortic sclerosis with no other abnormalities.

Ophthalmic fluorescein angiography was performed and showed patchy choroidal hypoperfusion, severe delayed filling, and extensive pruning of the arterial circulation with no  involvement of the posterior ciliary arteries.

Given the elevated inflammatory markers, pulse-dose intravenous methylprednisolone was started, and a temporal artery biopsy was planned.

CENTRAL RETINAL ARTERY OCCLUSION: NONARTERITIC VS ARTERITIC CAUSES

3. Which of the following is least useful to differentiate arteritic from nonarteritic causes of central retinal artery occlusion?

• Finding emboli in the retinal vasculature on funduscopy
• Temporal artery biopsy
• Measuring the C-reactive protein level and the erythrocyte sedimentation rate
• Echocardiography
• Positron-emission tomography (PET)
• Retinal fluorescein angiography

In patients diagnosed with central retinal artery occlusion, the next step is to differentiate between nonarteritic and arteritic causes, since separating them has therapeutic relevance.

The carotid artery is the main culprit for embolic disease affecting the central retinal artery, leading to the nonarteritic subtype. Thus, evaluation of acute retinal ischemia secondary to nonarteritic central retinal artery occlusion is similar to the evaluation of patients with an acute cerebral stroke.⁴ Studies have shown that 25% of patients diagnosed with central retinal artery occlusion have an additional ischemic insult in the cerebrovascular system, and these patients are at high risk of recurrent ocular or cerebral infarction. Workup includes diffusion-weighted MRI, angiography, echocardiography, and telemetry.⁵

Arteritic central retinal artery occlusion is most often caused by giant cell arteritis. The American College of Rheumatology classification criteria for giant cell arteritis include 3 of the following 5:

• Age 50 or older
• New onset of localized headache
• Temporal artery tenderness or decreased temporal artery pulse
• Erythrocyte sedimentation rate 50 mm/hour or greater
• Positive biopsy findings.⁶  

Temporal artery biopsy is the gold standard for the diagnosis of giant cell arteritis and should be done whenever the disease is suspected.^7,8 However, the test is invasive and imperfect, as a negative result does not completely rule out giant cell arteritis.⁹

Although a unilateral temporal artery biopsy can be falsely negative, several studies evaluating the efficacy of bilateral biopsies did not show significant improvement in the diagnostic yield.^10,11

Ophthalmic fluorescein angiography is another helpful test for distinguishing nonarteritic from arteritic central retinal artery occlusion.¹² Involvement of the posterior ciliary arteries usually occurs in giant cell arteritis, and this leads to choroidal malperfusion with or without retinal involvement. The optic nerve may also be infarcted by closure of the paraoptic vessels fed by the posterior ciliary vessels.^12,13 Such involvement of multiple vessels would not be typical with nonarteritic central retinal artery occlusion. Thus, this finding is helpful in making the final diagnosis along with supplying possible prognostic information.¹³

PET-CT is emerging as a test for early inflammation in extracranial disease, but its utility for diagnosing intracranial disease is limited by high uptake of the tracer fluoro­deoxyglucose by the brain and low resolution.¹⁴ Currently, it has no established role in the evaluation of patients with central retinal artery occlusion and would have no utility in differentiating arteritic vs nonarteritic causes of central retinal artery occlusion.

If giant cell arteritis is suspected, it is essential to start intravenous pulse-dose methyl­prednisolone early to prevent further vision loss in the contralateral eye. Treatment should not be delayed for invasive testing or temporal artery biopsy. Improvement in headache, jaw claudication, or scalp tenderness once steroids are initiated also helps support the diagnosis of giant cell arteritis.⁷

Unfortunately, visual symptoms may be irreversible despite treatment.

Our patient’s central retinal artery occlusion

This case highlights how difficult it is in practice to distinguish nonarteritic from arteritic central retinal artery occlusion.

Our patient had numerous cardiovascular risk factors, including known carotid and coronary artery disease, favoring a nonarteritic diagnosis.

On the other hand, his elevated inflammatory markers suggested an underlying inflammatory response. He lacked the characteristic headache and other systemic signs of giant cell arteritis, but this has been described in about 25% of patients.¹⁵ If emboli are seen on funduscopy, further workup for arteritic central retinal artery occlusion is not warranted, but emboli are not always present. Then again, absence of posterior ciliary artery involvement on fluorescein angiography pointed away from giant cell arteritis.

CASE CONTINUED: FINAL DIAGNOSIS

Biopsy of the left temporal artery showed intimal thickening with focal destruction of the internal elastic lamina by dystrophic calcification with no evidence of inflammatory infiltrates, giant cells, or granulomata in the adventitia, media, or intima. Based on the results of biopsy study and fluorescein angiography, we concluded that this was nonarteritic central retinal artery occlusion related to atherosclerotic disease.

Methylprednisolone was discontinued. The patient was discharged on aspirin, losartan, furosemide, amlodipine, and high-dose atorvastatin for standard stroke prevention. He was followed by the medical team and the ophthalmology department. At 6 weeks, there was only marginal improvement in the visual acuity of the left eye.

 

 

MANAGEMENT

4. Management of nonarteritic central retinal artery occlusion could include all of the following except which one?

• Ocular massage
• Intravenous thrombolysis
• Intra-arterial thrombolysis
• Risk-factor modification
• Intraocular steroid injection

In patients with acute vision loss from nonarteritic central retinal artery occlusion, acute strategies to restore retinal perfusion include noninvasive “standard” therapies and thrombolysis (intravenous or intra-arterial). Unfortunately, consensus and guidelines are lacking.

Traditional therapies include sublingual isosorbide dinitrate, systemic pentoxifylline, inhalation of a carbogen, hyperbaric oxygen, ocular massage, intravenous acetazolamide and mannitol, anterior chamber paracentesis, and systemic steroids. However, none of these have been shown to be more effective than placebo.¹⁶

Thrombolytic therapy, analogous to the treatment of patients with ischemic stroke or myocardial infarction, is more controversial in acute central retinal artery occlusion.¹³ Data from small case-series suggested that intra-arterial or intravenous thrombolysis might improve visual acuity with reasonable safety.¹⁷ On the other hand, a randomized study from the United Kingdom that compared intra-arterial thrombolysis within a 24-hour window and conservative measures concluded that thrombolysis should not be used.¹⁸

Thrombolysis is thus used only in selected patients on a case-specific basis with involvement of a multispecialty team including stroke neurologists, especially if patients present within hours of onset and have concomitant neurologic symptoms.

Treatment beyond the acute phase focuses on preventing complications of the eye ischemia and aggressively managing systemic atherosclerotic risk factors to decrease the incidence of further ischemic events. Other interventions  include endarterectomy for significant carotid stenosis and anticoagulation to prevent cardioembolic embolization (such as atrial fibrillation). Most experts agree on the addition of an antiplatelet agent.^13,19

Intraocular steroid injection can be used in the management of some retinal disorders but has no value in nonarteritic central retinal artery occlusion.

Vision recovery in nonarteritic central retinal artery occlusion is variable, but the prognosis is generally poor. The visual acuity on presentation, the onset of the symptoms, and collateral vessels are major factors influencing long-term recovery. Most of the recovery occurs within 7 days and involves peripheral vision rather than central vision. Several studies report some recovery in peripheral vision in approximately 30% to 35% of affected eyes.^20–22

PROMPT ACTION MAY SAVE SIGHT

Vision loss is a common presenting symptom in the emergency setting. A meticulous history and systematic physical examination can narrow the differential diagnosis of this neuro-ophthalmologic emergency. Acute retinal ischemia from central retinal artery occlusion is the ocular equivalent of an ischemic stroke, and they share risk factors, diagnostic workup, and management approaches.

Both etiologic subtypes (ie, arteritic and nonarteritic) require prompt intervention by front-line physicians. If giant cell arteritis is suspected, corticosteroid therapy must be initiated to save the contralateral retina from ischemia. Suspicion of central retinal artery occlusion warrants immediate evaluation by a neurologist to consider thrombolysis. Prompt action and interdisciplinary care involving an ophthalmologist, neurologist, and emergency or internal medicine physician may save a patient from permanent visual disability.

KEY POINTS

• Monocular vision loss requires urgent evaluation with a multidisciplinary management approach.
• There are no consensus treatment guidelines for nonarteritic central retinal artery occlusion, but the workup includes a comprehensive stroke evaluation.
• Arteritic central retinal artery occlusion is most often due to giant cell arteritis, and when it is suspected, the patient should be empirically treated with steroids.

An 83-year-old man presented to the emergency department with acute, painless loss of vision in his left eye. His vision in that eye had been normal in the middle of the night when he woke to use the restroom, but on awakening 6 hours later he could perceive only light or darkness.

He denied headache, scalp tenderness, jaw claudication, fever, weight loss, myalgia, or other neurologic symptoms. He had not experienced any recent change in his vision before this presentation, including halos around lights, floaters, eye pain, or redness. However, 6 months ago he had undergone left cataract surgery (left phacoemulsification with intraocular implant) without complications. And he said that when he was 3 years old, he had sustained a serious injury to his right eye.

His medical history included ischemic heart disease and hypertension. His medications included losartan, furosemide, amlodi­pine, atorvastatin, and aspirin.

CAUSES OF ACUTE MONOCULAR VISION LOSS

1. Which of the following is the least likely cause of this patient’s acute monocular vision loss?

• Optic neuritis
• Retinal vein occlusion
• Retinal artery occlusion
• Pituitary apoplexy
• Retinal detachment

Acute vision loss is often so distressing to the patient that the emergency department may be the first step in evaluation. While its diagnosis and management often require an interdisciplinary effort, early evaluation and triage of this potential medical emergency is often done by clinicians without specialized training in ophthalmology.

The physiology of vision is complex and the list of possible causes of vision loss is long, but the differential diagnosis can be narrowed quickly by considering the time course of vision loss and the anatomic localization.¹

The time course (including onset and tempo) of vision loss can classified as:

• Transient (ie, vision returned to normal by the time seen by clinician)
• Acute (instantaneous onset, ie, within seconds to minutes)
• Subacute (progression over days to weeks)
• Chronic (insidious progression over months to years).

Although acute vision loss is usually dramatic, insidious vision loss may occasionally be unnoticed for a surprisingly long time until the normal eye is inadvertently shielded.

Anatomic localization. Lesions anterior to the optic chiasm cause monocular vision loss, whereas lesions at or posterior to the chiasm lead to bilateral visual field defects. Problems leading to monocular blindness can be broadly divided into 3 anatomic categories (Figure 1):

• Ocular medial (including the cornea, anterior chamber, and lens)
• Retinal
• Neurologic (including the optic nerve and chiasm).

Clues from the history

A careful ophthalmic history is an essential initial step in the evaluation (Table 1). In addition, nonvisual symptoms can help narrow the differential diagnosis.

Nausea and vomiting often accompany acute elevation of intraocular pressure.

Focal neurologic deficits or other neurologic symptoms can point to a demyelinating disease such as multiple sclerosis.

Risk factors for vascular atherosclerotic disease such as diabetes, hypertension, and coronary artery disease raise concern for retinal, optic nerve, or cerebral ischemia.

Medications with anticholinergic and adrenergic properties can also precipitate monocular vision loss with acute angle-closure glaucoma.

Can we rule out anything yet?

Our patient presented with painless monocular vision loss. As discussed, causes of monocular vision loss can be localized to ocular abnormalities and prechiasmatic neurologic ones. Retinal detachment, occlusion of a retinal artery or vein, and optic neuritis are all important potential causes of acute monocular vision loss.

Pituitary apoplexy, on the other hand, is characterized by an acute increase in pituitary volume, often leading to compression of the optic chiasm resulting in a visual-field defect. It is most often characterized by binocular deficits (eg, bitemporal hemianopia) but is less likely to cause monocular vision loss.¹

CASE CONTINUED: EXAMINATION

On examination, the patient appeared comfortable. His temperature was 97.6°F (36.4°C), pulse 59 beats per minute, respiratory rate 18 per minute, and blood pressure 153/56 mm Hg.

Heart and lung examinations were notable for a grade 3 of 6 midsystolic, low-pitched murmur in the aortic area radiating to the neck, bilateral carotid bruits, and clear lungs. The cardiac impulse was normal in location and character. There was no evidence of aortic insufficiency (including auscultation during exhalation phase while sitting upright).

Eye examination. Visual acuity in the right eye was 20/200 with correction (owing to his eye injury at age 3). With the left eye, he could see only light or darkness. The conjunctiva and sclera were normal.

The right pupil was irregular and measured 3 mm (baseline from his previous eye injury). The left pupil was 3.5 mm. The direct pupillary response was preserved, but a relative afferent pupillary defect was present: on the swinging flashlight test, the left pupil dilated when the flashlight was passed from the right to the left pupil. Extraocular movements were full and intact bilaterally. The rest of the neurologic examination was normal.

An ophthalmologist was urgently consulted. A dilated funduscopic examination of the left eye revealed peripapillary atrophy, tortuous vessels, a cherry red macular spot, and flame hemorrhages, but no disc edema or pallor (Figure 2).

FURTHER WORKUP

2. Which of the following investigations would be least useful and not indicated at this point for this patient?

• Carotid ultrasonography
• Electrocardiography and echocardiography
• Magnetic resonance angiography of the brain
• Computed tomographic (CT) angiography of the head and neck
• Testing for the factor V Leiden and prothrombin gene mutations

A systematic ocular physical examination can offer important diagnostic information (Table 2). Ophthalmoscopy directly examines the optic disc, macula, and retinal vasculature. To interpret the funduscopic examination, we need a basic understanding of the vascular supply to the eye (Figure 3).

Information from references 4 and 5.

For example, the cherry red spot within the macula in our patient is characteristic of central retinal artery occlusion and highlights the relationship between anatomy and pathophysiology. The retina’s blood supply is compromised, leading to an ischemic, white background (secondary to edema of the inner third of the retina), but the macula continues to be nourished by the posterior ciliary arteries. This contrast in color is accentuated by the underlying structures composing the fovea, which lacks the nerve fiber layer and ganglion cell layer, making the vascular bed more visible.^2,3

Also in our patient, the marked reduction in visual acuity and relative afferent pupillary defect in the left eye point to unilateral optic nerve (or retinal ganglion cell) dysfunction. The findings on direct funduscopy were consistent with acute central retinal artery ischemia or occlusion. Central retinal artery occlusion can be either arteritic (due to inflammation, most often giant cell arteritis) or nonarteritic (due to atherosclerotic vascular disease).

Thus, carotid ultrasonography, electrocardiography, and transthoracic and transesophageal echocardiography are important components of the further workup. In addition, urgent brain imaging including either CT angiography or magnetic resonance angiography of the head and neck is indicated in all patients with central retinal artery occlusion.

Thrombophilia testing, including tests for the factor V Leiden and prothrombin gene mutations, is indicated in specific cases when a hypercoagulable state is suggested by components of the history, physical examination, and laboratory and radiologic testing. Thrombophilia testing would be low-yield and should not be part of the first-line testing in elderly patients with several atherosclerotic risk factors, such as our patient.

CASE CONTINUED: LABORATORY AND IMAGING EVIDENCE

Initial laboratory work showed:

• Mild microcytic anemia
• Erythrocyte sedimentation rate 77 mm/hour (reference range 1–10)
• C-reactive protein 4.0 mg/dL (reference range < 0.9).

The rest of the complete blood cell count and metabolic profile were unremarkable. His hemoglobin A_1c value was 5.3% (reference range 4.8%–6.2%).

A neurologist was urgently consulted.

Magnetic resonance imaging of the brain without contrast revealed nonspecific white-matter disease with no evidence of ischemic stroke.

Magnetic resonance angiography of the head and neck with contrast demonstrated 20% to 40% stenosis in both carotid arteries with otherwise patent anterior and posterior circulation.

Continuous monitoring of the left carotid artery with transcranial Doppler ultrasonography was also ordered, and the study concluded there were no undetected microembolic events.

Transthoracic echocardiography showed aortic sclerosis with no other abnormalities.

Ophthalmic fluorescein angiography was performed and showed patchy choroidal hypoperfusion, severe delayed filling, and extensive pruning of the arterial circulation with no  involvement of the posterior ciliary arteries.

Given the elevated inflammatory markers, pulse-dose intravenous methylprednisolone was started, and a temporal artery biopsy was planned.

CENTRAL RETINAL ARTERY OCCLUSION: NONARTERITIC VS ARTERITIC CAUSES

3. Which of the following is least useful to differentiate arteritic from nonarteritic causes of central retinal artery occlusion?

• Finding emboli in the retinal vasculature on funduscopy
• Temporal artery biopsy
• Measuring the C-reactive protein level and the erythrocyte sedimentation rate
• Echocardiography
• Positron-emission tomography (PET)
• Retinal fluorescein angiography

In patients diagnosed with central retinal artery occlusion, the next step is to differentiate between nonarteritic and arteritic causes, since separating them has therapeutic relevance.

The carotid artery is the main culprit for embolic disease affecting the central retinal artery, leading to the nonarteritic subtype. Thus, evaluation of acute retinal ischemia secondary to nonarteritic central retinal artery occlusion is similar to the evaluation of patients with an acute cerebral stroke.⁴ Studies have shown that 25% of patients diagnosed with central retinal artery occlusion have an additional ischemic insult in the cerebrovascular system, and these patients are at high risk of recurrent ocular or cerebral infarction. Workup includes diffusion-weighted MRI, angiography, echocardiography, and telemetry.⁵

Arteritic central retinal artery occlusion is most often caused by giant cell arteritis. The American College of Rheumatology classification criteria for giant cell arteritis include 3 of the following 5:

• Age 50 or older
• New onset of localized headache
• Temporal artery tenderness or decreased temporal artery pulse
• Erythrocyte sedimentation rate 50 mm/hour or greater
• Positive biopsy findings.⁶  

Temporal artery biopsy is the gold standard for the diagnosis of giant cell arteritis and should be done whenever the disease is suspected.^7,8 However, the test is invasive and imperfect, as a negative result does not completely rule out giant cell arteritis.⁹

Although a unilateral temporal artery biopsy can be falsely negative, several studies evaluating the efficacy of bilateral biopsies did not show significant improvement in the diagnostic yield.^10,11

Ophthalmic fluorescein angiography is another helpful test for distinguishing nonarteritic from arteritic central retinal artery occlusion.¹² Involvement of the posterior ciliary arteries usually occurs in giant cell arteritis, and this leads to choroidal malperfusion with or without retinal involvement. The optic nerve may also be infarcted by closure of the paraoptic vessels fed by the posterior ciliary vessels.^12,13 Such involvement of multiple vessels would not be typical with nonarteritic central retinal artery occlusion. Thus, this finding is helpful in making the final diagnosis along with supplying possible prognostic information.¹³

PET-CT is emerging as a test for early inflammation in extracranial disease, but its utility for diagnosing intracranial disease is limited by high uptake of the tracer fluoro­deoxyglucose by the brain and low resolution.¹⁴ Currently, it has no established role in the evaluation of patients with central retinal artery occlusion and would have no utility in differentiating arteritic vs nonarteritic causes of central retinal artery occlusion.

If giant cell arteritis is suspected, it is essential to start intravenous pulse-dose methyl­prednisolone early to prevent further vision loss in the contralateral eye. Treatment should not be delayed for invasive testing or temporal artery biopsy. Improvement in headache, jaw claudication, or scalp tenderness once steroids are initiated also helps support the diagnosis of giant cell arteritis.⁷

Unfortunately, visual symptoms may be irreversible despite treatment.

Our patient’s central retinal artery occlusion

This case highlights how difficult it is in practice to distinguish nonarteritic from arteritic central retinal artery occlusion.

Our patient had numerous cardiovascular risk factors, including known carotid and coronary artery disease, favoring a nonarteritic diagnosis.

On the other hand, his elevated inflammatory markers suggested an underlying inflammatory response. He lacked the characteristic headache and other systemic signs of giant cell arteritis, but this has been described in about 25% of patients.¹⁵ If emboli are seen on funduscopy, further workup for arteritic central retinal artery occlusion is not warranted, but emboli are not always present. Then again, absence of posterior ciliary artery involvement on fluorescein angiography pointed away from giant cell arteritis.

CASE CONTINUED: FINAL DIAGNOSIS

Biopsy of the left temporal artery showed intimal thickening with focal destruction of the internal elastic lamina by dystrophic calcification with no evidence of inflammatory infiltrates, giant cells, or granulomata in the adventitia, media, or intima. Based on the results of biopsy study and fluorescein angiography, we concluded that this was nonarteritic central retinal artery occlusion related to atherosclerotic disease.

Methylprednisolone was discontinued. The patient was discharged on aspirin, losartan, furosemide, amlodipine, and high-dose atorvastatin for standard stroke prevention. He was followed by the medical team and the ophthalmology department. At 6 weeks, there was only marginal improvement in the visual acuity of the left eye.

 

 

MANAGEMENT

4. Management of nonarteritic central retinal artery occlusion could include all of the following except which one?

• Ocular massage
• Intravenous thrombolysis
• Intra-arterial thrombolysis
• Risk-factor modification
• Intraocular steroid injection

In patients with acute vision loss from nonarteritic central retinal artery occlusion, acute strategies to restore retinal perfusion include noninvasive “standard” therapies and thrombolysis (intravenous or intra-arterial). Unfortunately, consensus and guidelines are lacking.

Traditional therapies include sublingual isosorbide dinitrate, systemic pentoxifylline, inhalation of a carbogen, hyperbaric oxygen, ocular massage, intravenous acetazolamide and mannitol, anterior chamber paracentesis, and systemic steroids. However, none of these have been shown to be more effective than placebo.¹⁶

Thrombolytic therapy, analogous to the treatment of patients with ischemic stroke or myocardial infarction, is more controversial in acute central retinal artery occlusion.¹³ Data from small case-series suggested that intra-arterial or intravenous thrombolysis might improve visual acuity with reasonable safety.¹⁷ On the other hand, a randomized study from the United Kingdom that compared intra-arterial thrombolysis within a 24-hour window and conservative measures concluded that thrombolysis should not be used.¹⁸

Thrombolysis is thus used only in selected patients on a case-specific basis with involvement of a multispecialty team including stroke neurologists, especially if patients present within hours of onset and have concomitant neurologic symptoms.

Treatment beyond the acute phase focuses on preventing complications of the eye ischemia and aggressively managing systemic atherosclerotic risk factors to decrease the incidence of further ischemic events. Other interventions  include endarterectomy for significant carotid stenosis and anticoagulation to prevent cardioembolic embolization (such as atrial fibrillation). Most experts agree on the addition of an antiplatelet agent.^13,19

Intraocular steroid injection can be used in the management of some retinal disorders but has no value in nonarteritic central retinal artery occlusion.

Vision recovery in nonarteritic central retinal artery occlusion is variable, but the prognosis is generally poor. The visual acuity on presentation, the onset of the symptoms, and collateral vessels are major factors influencing long-term recovery. Most of the recovery occurs within 7 days and involves peripheral vision rather than central vision. Several studies report some recovery in peripheral vision in approximately 30% to 35% of affected eyes.^20–22

PROMPT ACTION MAY SAVE SIGHT

Vision loss is a common presenting symptom in the emergency setting. A meticulous history and systematic physical examination can narrow the differential diagnosis of this neuro-ophthalmologic emergency. Acute retinal ischemia from central retinal artery occlusion is the ocular equivalent of an ischemic stroke, and they share risk factors, diagnostic workup, and management approaches.

Both etiologic subtypes (ie, arteritic and nonarteritic) require prompt intervention by front-line physicians. If giant cell arteritis is suspected, corticosteroid therapy must be initiated to save the contralateral retina from ischemia. Suspicion of central retinal artery occlusion warrants immediate evaluation by a neurologist to consider thrombolysis. Prompt action and interdisciplinary care involving an ophthalmologist, neurologist, and emergency or internal medicine physician may save a patient from permanent visual disability.

KEY POINTS

• Monocular vision loss requires urgent evaluation with a multidisciplinary management approach.
• There are no consensus treatment guidelines for nonarteritic central retinal artery occlusion, but the workup includes a comprehensive stroke evaluation.
• Arteritic central retinal artery occlusion is most often due to giant cell arteritis, and when it is suspected, the patient should be empirically treated with steroids.

Enterotomy can be a serious complication in abdominopelvic surgery, particularly if it is not immediately recognized and treated. Risk of visceral injury increases when complex dissection is required for treatment of cancer, resection of endometriosis, and extensive lysis of adhesions.

In a retrospective review from 1984 to 2003, investigators assessed intestinal injuries at the time of gynecologic operations. Of the 110 cases reported, about 37% occurred during the opening of the peritoneal cavity, 38% during adhesiolysis and pelvic dissection, 9% during laparoscopy, 9% during vaginal surgery, and 8% during dilation and curettage. Of the bowel injuries, more than 75% were minor.¹ Mortality from unrecognized bowel injury is significant, and as such, appropriate recognition and management of these injuries is critical.²

Methods of repair

The two main methods of bowel repair are primary closure and resection with re-anastamosis. The decision to employ each is influenced by multiple factors. Primary closure is best suited to small lesions (1 cm or less) that are a result of cold or sharp injury. However, thermal injury sustained via electrosurgical devices induces delayed tissue damage beyond the visible edges of the immediate defect, and surgeons should consider a resection of bowel to at least 1 cm beyond the immediately apparent injury site. Additionally, resection and re-anastamosis should also be considered if the damaged segment of bowel has poor blood supply, integrity, or the repair would result in tension along the suture/staple line or luminal narrowing.

Simple small bowel closures

Serosal abrasions need not be repaired; however, small tears of the serosa and muscularis can be managed with a single layer of interrupted 3-0 absorbable or permanent silk suture on a tapered needle. The suture line should be perpendicular to the longitudinal axis of the bowel at 2-mm to 3-mm intervals in order to prevent narrowing of the lumen. The suture should pass through serosal and muscular layers in an imbricating (Lembert) stitch. For smaller defects of less than 6 mm, a single layer closure is typically adequate.

Small bowel resection

Some larger defects, thermal injuries, and segments with multiple enterotomies may be best repaired with resection and re-anastamosis technique. A segment of resectable bowel is chosen such that the afferent and efferent limbs to be re-anastamosed can be reapproximated in a tension-free fashion. A mesenterotomy is made at the proximal and distal portions of the involved bowel. A gastrointestinal anastomotic stapler is then inserted perpendicularly across the bowel. The remaining wedge of connected mesentery can then be efficiently excised with an electrothermal bipolar coagulator device ensuring that maximal mesentery and blood supply are preserved to the remaining limbs of intestine. The proximal and distal segments are then aligned at the antimesenteric sides.

Large bowel repair

Defects in the serosa and small lacerations can be managed with a primary closure, similar to the small intestine. For more extensive injuries that may require resection, diversion, or complicated repair, consultation with a gynecologic oncologist or general or colorectal surgeon may be indicated as colotomy repairs are associated with higher rates of breakdown and fistula. If fecal contamination is present, copious irrigation should be performed and placement of a peritoneal drain to reduce the likelihood of abscess formation should be considered. If appropriate antibiotic prophylaxis for colonic surgery has not been given prior to skin incision, it should be administered once the colotomy is identified.

Standard prophylaxis for hysterectomy (such as a first-generation cephalosporin like cefazolin) is not adequate for large bowel surgery, and either metronidazole should be added or a second-generation cephalosporin such as cefoxitin should be given. For patients with penicillin allergy, clindamycin or vancomycin with either gentamicin or a fluoroquinolone should be administered.⁶

Postoperative management

The potential for postoperative morbidity must be understood for appropriate management following bowel surgery. Ileus is common and the clinician should understand how to diagnose and manage it. Additionally, intra-abdominal abscess, anastomotic leak, fistula formation, and mechanical obstruction are complications that may require surgical intervention and must be vigilantly managed.

The routine use of postoperative nasogastric tube (NGT) does not hasten return of bowel function or prevent leak from sites of gastrointestinal repair. In fact, early feeding has been associated with reduced perioperative complications and earlier return of bowel function has been observed without the use of NGT.⁷ In general, for small and large intestinal injuries, early feeding is considered acceptable.⁸

Prolonged antibiotic prophylaxis, beyond 24 hours, is not recommended.⁶

Avoiding injury

Gynecologic surgeons should adhere to surgical principles with sharp dissection for adhesions, gentle tissue handling, adequate exposure, and light retraction to prevent bowel injury or minimize their extent. Laparoscopic entry sites should be chosen based on the likelihood of abdominal adhesions. When the patient’s history predicts a high likelihood of intraperitoneal adhesions, the left upper quadrant site should be strongly considered as the entry site. The likelihood of gastrointestinal injury is not influenced by open versus closed laparoscopic entry and surgeons should use the technique with which they have the greatest experience and skill.⁹ However, in patients who have had prior laparotomies, there is an increased risk of periumbilical adhesions, and consideration should be made for a nonumbilical entry site.¹⁰ Methodical sharp dissection and sparing use of thermal energy should be used with adhesiolysis. When injury occurs, prompt recognition, preparation, and methodical management can mitigate the impact.

Dr. Staley is a gynecologic oncology fellow at the University of North Carolina, Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures.

References

1. Int Surg. 2006 Nov-Dec;91(6):336-40.

2. J Am Coll Surg. 2001 Jun;192(6):677-83.

3. Doherty, G. Current Diagnosis and Treatment: Surgery. Thirteenth Edition. New York: McGraw Hill, 2010.

4. Hoffman B. Williams Gynecology. Third Edition. New York: McGraw Hill, 2016.

5. Berek J, Hacker N. Berek & Hacker’s Gynecologic Oncology. Sixth Edition. Philadelphia: Wolters Kluwer, 2015.

6. Surg Infect (Larchmt). 2013 Feb;14(1):73-156.

7. Br J Surg. 2005 Jun;92(6):673-80.

8. Am J Obstet Gynecol. 2001 Jul;185(1):1-4.

9. Cochrane Database Syst Rev. 2015 Aug 31;8:CD006583.

10. Br J Obstet Gynaecol. 1997 May;104(5):595-600.


 

Enterotomy can be a serious complication in abdominopelvic surgery, particularly if it is not immediately recognized and treated. Risk of visceral injury increases when complex dissection is required for treatment of cancer, resection of endometriosis, and extensive lysis of adhesions.

In a retrospective review from 1984 to 2003, investigators assessed intestinal injuries at the time of gynecologic operations. Of the 110 cases reported, about 37% occurred during the opening of the peritoneal cavity, 38% during adhesiolysis and pelvic dissection, 9% during laparoscopy, 9% during vaginal surgery, and 8% during dilation and curettage. Of the bowel injuries, more than 75% were minor.¹ Mortality from unrecognized bowel injury is significant, and as such, appropriate recognition and management of these injuries is critical.²

Methods of repair

The two main methods of bowel repair are primary closure and resection with re-anastamosis. The decision to employ each is influenced by multiple factors. Primary closure is best suited to small lesions (1 cm or less) that are a result of cold or sharp injury. However, thermal injury sustained via electrosurgical devices induces delayed tissue damage beyond the visible edges of the immediate defect, and surgeons should consider a resection of bowel to at least 1 cm beyond the immediately apparent injury site. Additionally, resection and re-anastamosis should also be considered if the damaged segment of bowel has poor blood supply, integrity, or the repair would result in tension along the suture/staple line or luminal narrowing.

Simple small bowel closures

Serosal abrasions need not be repaired; however, small tears of the serosa and muscularis can be managed with a single layer of interrupted 3-0 absorbable or permanent silk suture on a tapered needle. The suture line should be perpendicular to the longitudinal axis of the bowel at 2-mm to 3-mm intervals in order to prevent narrowing of the lumen. The suture should pass through serosal and muscular layers in an imbricating (Lembert) stitch. For smaller defects of less than 6 mm, a single layer closure is typically adequate.

Small bowel resection

Some larger defects, thermal injuries, and segments with multiple enterotomies may be best repaired with resection and re-anastamosis technique. A segment of resectable bowel is chosen such that the afferent and efferent limbs to be re-anastamosed can be reapproximated in a tension-free fashion. A mesenterotomy is made at the proximal and distal portions of the involved bowel. A gastrointestinal anastomotic stapler is then inserted perpendicularly across the bowel. The remaining wedge of connected mesentery can then be efficiently excised with an electrothermal bipolar coagulator device ensuring that maximal mesentery and blood supply are preserved to the remaining limbs of intestine. The proximal and distal segments are then aligned at the antimesenteric sides.

Large bowel repair

Defects in the serosa and small lacerations can be managed with a primary closure, similar to the small intestine. For more extensive injuries that may require resection, diversion, or complicated repair, consultation with a gynecologic oncologist or general or colorectal surgeon may be indicated as colotomy repairs are associated with higher rates of breakdown and fistula. If fecal contamination is present, copious irrigation should be performed and placement of a peritoneal drain to reduce the likelihood of abscess formation should be considered. If appropriate antibiotic prophylaxis for colonic surgery has not been given prior to skin incision, it should be administered once the colotomy is identified.

Standard prophylaxis for hysterectomy (such as a first-generation cephalosporin like cefazolin) is not adequate for large bowel surgery, and either metronidazole should be added or a second-generation cephalosporin such as cefoxitin should be given. For patients with penicillin allergy, clindamycin or vancomycin with either gentamicin or a fluoroquinolone should be administered.⁶

Postoperative management

The potential for postoperative morbidity must be understood for appropriate management following bowel surgery. Ileus is common and the clinician should understand how to diagnose and manage it. Additionally, intra-abdominal abscess, anastomotic leak, fistula formation, and mechanical obstruction are complications that may require surgical intervention and must be vigilantly managed.

The routine use of postoperative nasogastric tube (NGT) does not hasten return of bowel function or prevent leak from sites of gastrointestinal repair. In fact, early feeding has been associated with reduced perioperative complications and earlier return of bowel function has been observed without the use of NGT.⁷ In general, for small and large intestinal injuries, early feeding is considered acceptable.⁸

Prolonged antibiotic prophylaxis, beyond 24 hours, is not recommended.⁶

Avoiding injury

Gynecologic surgeons should adhere to surgical principles with sharp dissection for adhesions, gentle tissue handling, adequate exposure, and light retraction to prevent bowel injury or minimize their extent. Laparoscopic entry sites should be chosen based on the likelihood of abdominal adhesions. When the patient’s history predicts a high likelihood of intraperitoneal adhesions, the left upper quadrant site should be strongly considered as the entry site. The likelihood of gastrointestinal injury is not influenced by open versus closed laparoscopic entry and surgeons should use the technique with which they have the greatest experience and skill.⁹ However, in patients who have had prior laparotomies, there is an increased risk of periumbilical adhesions, and consideration should be made for a nonumbilical entry site.¹⁰ Methodical sharp dissection and sparing use of thermal energy should be used with adhesiolysis. When injury occurs, prompt recognition, preparation, and methodical management can mitigate the impact.

Dr. Staley is a gynecologic oncology fellow at the University of North Carolina, Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures.

References

1. Int Surg. 2006 Nov-Dec;91(6):336-40.

2. J Am Coll Surg. 2001 Jun;192(6):677-83.

3. Doherty, G. Current Diagnosis and Treatment: Surgery. Thirteenth Edition. New York: McGraw Hill, 2010.

4. Hoffman B. Williams Gynecology. Third Edition. New York: McGraw Hill, 2016.

5. Berek J, Hacker N. Berek & Hacker’s Gynecologic Oncology. Sixth Edition. Philadelphia: Wolters Kluwer, 2015.

6. Surg Infect (Larchmt). 2013 Feb;14(1):73-156.

7. Br J Surg. 2005 Jun;92(6):673-80.

8. Am J Obstet Gynecol. 2001 Jul;185(1):1-4.

9. Cochrane Database Syst Rev. 2015 Aug 31;8:CD006583.

10. Br J Obstet Gynaecol. 1997 May;104(5):595-600.


 

Enterotomy can be a serious complication in abdominopelvic surgery, particularly if it is not immediately recognized and treated. Risk of visceral injury increases when complex dissection is required for treatment of cancer, resection of endometriosis, and extensive lysis of adhesions.

In a retrospective review from 1984 to 2003, investigators assessed intestinal injuries at the time of gynecologic operations. Of the 110 cases reported, about 37% occurred during the opening of the peritoneal cavity, 38% during adhesiolysis and pelvic dissection, 9% during laparoscopy, 9% during vaginal surgery, and 8% during dilation and curettage. Of the bowel injuries, more than 75% were minor.¹ Mortality from unrecognized bowel injury is significant, and as such, appropriate recognition and management of these injuries is critical.²

Methods of repair

The two main methods of bowel repair are primary closure and resection with re-anastamosis. The decision to employ each is influenced by multiple factors. Primary closure is best suited to small lesions (1 cm or less) that are a result of cold or sharp injury. However, thermal injury sustained via electrosurgical devices induces delayed tissue damage beyond the visible edges of the immediate defect, and surgeons should consider a resection of bowel to at least 1 cm beyond the immediately apparent injury site. Additionally, resection and re-anastamosis should also be considered if the damaged segment of bowel has poor blood supply, integrity, or the repair would result in tension along the suture/staple line or luminal narrowing.

Simple small bowel closures

Serosal abrasions need not be repaired; however, small tears of the serosa and muscularis can be managed with a single layer of interrupted 3-0 absorbable or permanent silk suture on a tapered needle. The suture line should be perpendicular to the longitudinal axis of the bowel at 2-mm to 3-mm intervals in order to prevent narrowing of the lumen. The suture should pass through serosal and muscular layers in an imbricating (Lembert) stitch. For smaller defects of less than 6 mm, a single layer closure is typically adequate.

Small bowel resection

Some larger defects, thermal injuries, and segments with multiple enterotomies may be best repaired with resection and re-anastamosis technique. A segment of resectable bowel is chosen such that the afferent and efferent limbs to be re-anastamosed can be reapproximated in a tension-free fashion. A mesenterotomy is made at the proximal and distal portions of the involved bowel. A gastrointestinal anastomotic stapler is then inserted perpendicularly across the bowel. The remaining wedge of connected mesentery can then be efficiently excised with an electrothermal bipolar coagulator device ensuring that maximal mesentery and blood supply are preserved to the remaining limbs of intestine. The proximal and distal segments are then aligned at the antimesenteric sides.

Large bowel repair

Defects in the serosa and small lacerations can be managed with a primary closure, similar to the small intestine. For more extensive injuries that may require resection, diversion, or complicated repair, consultation with a gynecologic oncologist or general or colorectal surgeon may be indicated as colotomy repairs are associated with higher rates of breakdown and fistula. If fecal contamination is present, copious irrigation should be performed and placement of a peritoneal drain to reduce the likelihood of abscess formation should be considered. If appropriate antibiotic prophylaxis for colonic surgery has not been given prior to skin incision, it should be administered once the colotomy is identified.

Standard prophylaxis for hysterectomy (such as a first-generation cephalosporin like cefazolin) is not adequate for large bowel surgery, and either metronidazole should be added or a second-generation cephalosporin such as cefoxitin should be given. For patients with penicillin allergy, clindamycin or vancomycin with either gentamicin or a fluoroquinolone should be administered.⁶

Postoperative management

The potential for postoperative morbidity must be understood for appropriate management following bowel surgery. Ileus is common and the clinician should understand how to diagnose and manage it. Additionally, intra-abdominal abscess, anastomotic leak, fistula formation, and mechanical obstruction are complications that may require surgical intervention and must be vigilantly managed.

The routine use of postoperative nasogastric tube (NGT) does not hasten return of bowel function or prevent leak from sites of gastrointestinal repair. In fact, early feeding has been associated with reduced perioperative complications and earlier return of bowel function has been observed without the use of NGT.⁷ In general, for small and large intestinal injuries, early feeding is considered acceptable.⁸

Prolonged antibiotic prophylaxis, beyond 24 hours, is not recommended.⁶

Avoiding injury

Gynecologic surgeons should adhere to surgical principles with sharp dissection for adhesions, gentle tissue handling, adequate exposure, and light retraction to prevent bowel injury or minimize their extent. Laparoscopic entry sites should be chosen based on the likelihood of abdominal adhesions. When the patient’s history predicts a high likelihood of intraperitoneal adhesions, the left upper quadrant site should be strongly considered as the entry site. The likelihood of gastrointestinal injury is not influenced by open versus closed laparoscopic entry and surgeons should use the technique with which they have the greatest experience and skill.⁹ However, in patients who have had prior laparotomies, there is an increased risk of periumbilical adhesions, and consideration should be made for a nonumbilical entry site.¹⁰ Methodical sharp dissection and sparing use of thermal energy should be used with adhesiolysis. When injury occurs, prompt recognition, preparation, and methodical management can mitigate the impact.

Dr. Staley is a gynecologic oncology fellow at the University of North Carolina, Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures.

References

1. Int Surg. 2006 Nov-Dec;91(6):336-40.

2. J Am Coll Surg. 2001 Jun;192(6):677-83.

3. Doherty, G. Current Diagnosis and Treatment: Surgery. Thirteenth Edition. New York: McGraw Hill, 2010.

4. Hoffman B. Williams Gynecology. Third Edition. New York: McGraw Hill, 2016.

5. Berek J, Hacker N. Berek & Hacker’s Gynecologic Oncology. Sixth Edition. Philadelphia: Wolters Kluwer, 2015.

6. Surg Infect (Larchmt). 2013 Feb;14(1):73-156.

7. Br J Surg. 2005 Jun;92(6):673-80.

8. Am J Obstet Gynecol. 2001 Jul;185(1):1-4.

9. Cochrane Database Syst Rev. 2015 Aug 31;8:CD006583.

10. Br J Obstet Gynaecol. 1997 May;104(5):595-600.


 

Endometriosis affects approximately 11% of women; the disease can be categorized as pelvic endometriosis and extrapelvic endometriosis, based on anatomic presentation. It is estimated that about 12% of extrapelvic disease involves the diaphragm or thoracic cavity.

While diaphragmatic endometriosis often is asymptomatic, patients who are symptomatic can experience progressive and incapacitating pain. A significant number of patients with diaphragmatic endometriosis can go undiagnosed for long periods of time because of a traditional focus on the lower pelvic region. Some cases are misdiagnosed as other conditions involving the gastrointestinal tract or of cardiothoracic origin, because of the propensity of diaphragmatic disease to occur posteriorly and hide behind the liver. The variable appearance of endometriotic lesions and the lack of reliable diagnostic or imaging tests also can contribute to delayed diagnosis.

Pathophysiology

In addition to retrograde menstruation, there are two other common theories regarding the pathophysiology of thoracic endometriosis. First, high prostaglandin F2-alpha at ovulation may result in vasospasm and ischemia of the lungs (resulting, in turn, in alveolar rupture and subsequent pneumothorax). Second, the loss of a mucus plug during menses may result in communication between the environment and peritoneal cavity.

Courtesy Dr. Ceana Nezhat

A multidisciplinary approach

Since the introduction of video laparoscopy and ease of evaluation of the upper abdomen, more extrapelvic endometriosis – including disease in the upper abdomen and diaphragm – is being diagnosed. The thoracic and visceral diaphragm are the most commonly described sites of thoracic endometriosis, and disease is often right sided, with parenchymal involvement less commonly reported.

Courtesy Dr. Ceana Nezhat

Watch a video from Dr. Ceana Nezhat demonstrating a step wise vaporization and excision of diaphragmatic endometriosis utilizing different techniques.
(Courtesy Dr. Ceana Nezhat)

Plasma jet energy and ultrasonic energy are good alternatives when a CO₂ laser is not available and are preferable to the use of cold scissors because of subsequent bleeding, which requires bipolar hemostasis.

Monopolar electrocautery is not as good a choice for treating diaphragmatic endometriosis because of higher depth of penetration, which may cause tissue necrosis and subsequent delayed diaphragmatic fenestrations. It also may cause unpredictable diaphragmatic muscular contractions and electrical conduction transmitted to the heart, inducing arrhythmia.

For patients treated via combined VALS and VATS procedures, endometriotic lesions involving the entire thickness of the diaphragm should be completely resected, and the defect can be repaired with either sutures or staples.

In all cases, special anesthesia considerations must be made given the inability to completely ventilate the lung. In our practice, we use a double-lumen endotracheal tube for single lung ventilation, if needed. A bronchial blocker is used to isolate the lung when the double-lumen endotracheal tube cannot be inserted.

It is important to note that we do not recommend VATS with VALS in all suspicious cases. We reserve VATS only for patients with catamenial pneumothorax, catamenial hemothorax, hemoptysis, and pulmonary nodules, defined as Thoracic Endometriosis Syndrome. We usually start with medical management first, then proceed to VALS, and finally, VATS, with the intention to treat if the patient fails nonsurgical treatments. It is better to avoid VATS, if possible, because it is associated with longer recovery and more pain; it should be done if all else fails.

If the patient has completed childbearing or passed reproductive age, bilateral salpingectomy, or hysterectomy with or without bilateral salpingo-oophorectomy, may be considered as the first step prior to more aggressive excisional procedures. This is especially true for widespread lesions, as branches of the phrenic nerve are difficult to see and injury could result in paralysis of the diaphragm. It’s important to appreciate that if estrogen stimulation to the diaphragmatic lesions is to cease for the long term, hormonal suppression or surgical treatment including bilateral oophorectomy should be utilized.

My colleagues and I have reported on our experience with a multidisciplinary approach in the treatment of diaphragmatic endometriosis in 25 patients. All had both pelvic and thoracic symptoms, and the majority had endometrial implants on both the thoracic and visceral sides of the diaphragm.

There were two postoperative complications: a diaphragmatic hernia and a vaginal cuff hematoma. Over a follow-up period of 3-18 months, all 25 patients had significant improvement or resolution of their chest complaints, and most remained asymptomatic for more than 6 months (JSLS. 2014 Jul-Sep;18[3]. pii: e2014.00312. doi: 10.4293/JSLS.2014.00312).

Dr. Ceana Nezhat is the fellowship director of Nezhat Medical Center, the medical director of training and education at Northside Hospital, and an adjunct clinical professor of gynecology and obstetrics at Emory University, all in Atlanta. He is president of SRS (Society of Reproductive Surgeons) and past president of AAGL (American Association of Gynecologic Laparoscopists). Dr. Nezhat is a consultant for Novuson Surgical, Karl Storz Endoscopy, Lumenis, and AbbVie; a medical advisor for Plasma Surgical, and a member of the scientific advisory board for SurgiQuest.

Suggested readings

1. Nezhat C, Nezhat F, Nezhat C. Nezhat’s Operative Gynecologic Laparoscopy with Hysteroscopy. Fourth Edition. Cambridge University Press. 2013.

2. Am J Med. 1996 Feb;100(2):164-70.

3. Fertil Steril. 1998 Jun;69(6):1048-55.

4. Clin Obstet Gynecol. 1999 Sep;42(3):699-711.

5. JSLS. 2012 Jan-Mar; 16(1):140-2.

Endometriosis affects approximately 11% of women; the disease can be categorized as pelvic endometriosis and extrapelvic endometriosis, based on anatomic presentation. It is estimated that about 12% of extrapelvic disease involves the diaphragm or thoracic cavity.

While diaphragmatic endometriosis often is asymptomatic, patients who are symptomatic can experience progressive and incapacitating pain. A significant number of patients with diaphragmatic endometriosis can go undiagnosed for long periods of time because of a traditional focus on the lower pelvic region. Some cases are misdiagnosed as other conditions involving the gastrointestinal tract or of cardiothoracic origin, because of the propensity of diaphragmatic disease to occur posteriorly and hide behind the liver. The variable appearance of endometriotic lesions and the lack of reliable diagnostic or imaging tests also can contribute to delayed diagnosis.

Pathophysiology

In addition to retrograde menstruation, there are two other common theories regarding the pathophysiology of thoracic endometriosis. First, high prostaglandin F2-alpha at ovulation may result in vasospasm and ischemia of the lungs (resulting, in turn, in alveolar rupture and subsequent pneumothorax). Second, the loss of a mucus plug during menses may result in communication between the environment and peritoneal cavity.

Courtesy Dr. Ceana Nezhat

A multidisciplinary approach

Since the introduction of video laparoscopy and ease of evaluation of the upper abdomen, more extrapelvic endometriosis – including disease in the upper abdomen and diaphragm – is being diagnosed. The thoracic and visceral diaphragm are the most commonly described sites of thoracic endometriosis, and disease is often right sided, with parenchymal involvement less commonly reported.

Courtesy Dr. Ceana Nezhat

Watch a video from Dr. Ceana Nezhat demonstrating a step wise vaporization and excision of diaphragmatic endometriosis utilizing different techniques.
(Courtesy Dr. Ceana Nezhat)

Plasma jet energy and ultrasonic energy are good alternatives when a CO₂ laser is not available and are preferable to the use of cold scissors because of subsequent bleeding, which requires bipolar hemostasis.

Monopolar electrocautery is not as good a choice for treating diaphragmatic endometriosis because of higher depth of penetration, which may cause tissue necrosis and subsequent delayed diaphragmatic fenestrations. It also may cause unpredictable diaphragmatic muscular contractions and electrical conduction transmitted to the heart, inducing arrhythmia.

For patients treated via combined VALS and VATS procedures, endometriotic lesions involving the entire thickness of the diaphragm should be completely resected, and the defect can be repaired with either sutures or staples.

In all cases, special anesthesia considerations must be made given the inability to completely ventilate the lung. In our practice, we use a double-lumen endotracheal tube for single lung ventilation, if needed. A bronchial blocker is used to isolate the lung when the double-lumen endotracheal tube cannot be inserted.

It is important to note that we do not recommend VATS with VALS in all suspicious cases. We reserve VATS only for patients with catamenial pneumothorax, catamenial hemothorax, hemoptysis, and pulmonary nodules, defined as Thoracic Endometriosis Syndrome. We usually start with medical management first, then proceed to VALS, and finally, VATS, with the intention to treat if the patient fails nonsurgical treatments. It is better to avoid VATS, if possible, because it is associated with longer recovery and more pain; it should be done if all else fails.

If the patient has completed childbearing or passed reproductive age, bilateral salpingectomy, or hysterectomy with or without bilateral salpingo-oophorectomy, may be considered as the first step prior to more aggressive excisional procedures. This is especially true for widespread lesions, as branches of the phrenic nerve are difficult to see and injury could result in paralysis of the diaphragm. It’s important to appreciate that if estrogen stimulation to the diaphragmatic lesions is to cease for the long term, hormonal suppression or surgical treatment including bilateral oophorectomy should be utilized.

My colleagues and I have reported on our experience with a multidisciplinary approach in the treatment of diaphragmatic endometriosis in 25 patients. All had both pelvic and thoracic symptoms, and the majority had endometrial implants on both the thoracic and visceral sides of the diaphragm.

There were two postoperative complications: a diaphragmatic hernia and a vaginal cuff hematoma. Over a follow-up period of 3-18 months, all 25 patients had significant improvement or resolution of their chest complaints, and most remained asymptomatic for more than 6 months (JSLS. 2014 Jul-Sep;18[3]. pii: e2014.00312. doi: 10.4293/JSLS.2014.00312).

Dr. Ceana Nezhat is the fellowship director of Nezhat Medical Center, the medical director of training and education at Northside Hospital, and an adjunct clinical professor of gynecology and obstetrics at Emory University, all in Atlanta. He is president of SRS (Society of Reproductive Surgeons) and past president of AAGL (American Association of Gynecologic Laparoscopists). Dr. Nezhat is a consultant for Novuson Surgical, Karl Storz Endoscopy, Lumenis, and AbbVie; a medical advisor for Plasma Surgical, and a member of the scientific advisory board for SurgiQuest.

Suggested readings

1. Nezhat C, Nezhat F, Nezhat C. Nezhat’s Operative Gynecologic Laparoscopy with Hysteroscopy. Fourth Edition. Cambridge University Press. 2013.

2. Am J Med. 1996 Feb;100(2):164-70.

3. Fertil Steril. 1998 Jun;69(6):1048-55.

4. Clin Obstet Gynecol. 1999 Sep;42(3):699-711.

5. JSLS. 2012 Jan-Mar; 16(1):140-2.

Endometriosis affects approximately 11% of women; the disease can be categorized as pelvic endometriosis and extrapelvic endometriosis, based on anatomic presentation. It is estimated that about 12% of extrapelvic disease involves the diaphragm or thoracic cavity.

While diaphragmatic endometriosis often is asymptomatic, patients who are symptomatic can experience progressive and incapacitating pain. A significant number of patients with diaphragmatic endometriosis can go undiagnosed for long periods of time because of a traditional focus on the lower pelvic region. Some cases are misdiagnosed as other conditions involving the gastrointestinal tract or of cardiothoracic origin, because of the propensity of diaphragmatic disease to occur posteriorly and hide behind the liver. The variable appearance of endometriotic lesions and the lack of reliable diagnostic or imaging tests also can contribute to delayed diagnosis.

Pathophysiology

In addition to retrograde menstruation, there are two other common theories regarding the pathophysiology of thoracic endometriosis. First, high prostaglandin F2-alpha at ovulation may result in vasospasm and ischemia of the lungs (resulting, in turn, in alveolar rupture and subsequent pneumothorax). Second, the loss of a mucus plug during menses may result in communication between the environment and peritoneal cavity.

Courtesy Dr. Ceana Nezhat

A multidisciplinary approach

Since the introduction of video laparoscopy and ease of evaluation of the upper abdomen, more extrapelvic endometriosis – including disease in the upper abdomen and diaphragm – is being diagnosed. The thoracic and visceral diaphragm are the most commonly described sites of thoracic endometriosis, and disease is often right sided, with parenchymal involvement less commonly reported.

Courtesy Dr. Ceana Nezhat

Watch a video from Dr. Ceana Nezhat demonstrating a step wise vaporization and excision of diaphragmatic endometriosis utilizing different techniques.
(Courtesy Dr. Ceana Nezhat)

Plasma jet energy and ultrasonic energy are good alternatives when a CO₂ laser is not available and are preferable to the use of cold scissors because of subsequent bleeding, which requires bipolar hemostasis.

Monopolar electrocautery is not as good a choice for treating diaphragmatic endometriosis because of higher depth of penetration, which may cause tissue necrosis and subsequent delayed diaphragmatic fenestrations. It also may cause unpredictable diaphragmatic muscular contractions and electrical conduction transmitted to the heart, inducing arrhythmia.

For patients treated via combined VALS and VATS procedures, endometriotic lesions involving the entire thickness of the diaphragm should be completely resected, and the defect can be repaired with either sutures or staples.

In all cases, special anesthesia considerations must be made given the inability to completely ventilate the lung. In our practice, we use a double-lumen endotracheal tube for single lung ventilation, if needed. A bronchial blocker is used to isolate the lung when the double-lumen endotracheal tube cannot be inserted.

It is important to note that we do not recommend VATS with VALS in all suspicious cases. We reserve VATS only for patients with catamenial pneumothorax, catamenial hemothorax, hemoptysis, and pulmonary nodules, defined as Thoracic Endometriosis Syndrome. We usually start with medical management first, then proceed to VALS, and finally, VATS, with the intention to treat if the patient fails nonsurgical treatments. It is better to avoid VATS, if possible, because it is associated with longer recovery and more pain; it should be done if all else fails.

If the patient has completed childbearing or passed reproductive age, bilateral salpingectomy, or hysterectomy with or without bilateral salpingo-oophorectomy, may be considered as the first step prior to more aggressive excisional procedures. This is especially true for widespread lesions, as branches of the phrenic nerve are difficult to see and injury could result in paralysis of the diaphragm. It’s important to appreciate that if estrogen stimulation to the diaphragmatic lesions is to cease for the long term, hormonal suppression or surgical treatment including bilateral oophorectomy should be utilized.

My colleagues and I have reported on our experience with a multidisciplinary approach in the treatment of diaphragmatic endometriosis in 25 patients. All had both pelvic and thoracic symptoms, and the majority had endometrial implants on both the thoracic and visceral sides of the diaphragm.

There were two postoperative complications: a diaphragmatic hernia and a vaginal cuff hematoma. Over a follow-up period of 3-18 months, all 25 patients had significant improvement or resolution of their chest complaints, and most remained asymptomatic for more than 6 months (JSLS. 2014 Jul-Sep;18[3]. pii: e2014.00312. doi: 10.4293/JSLS.2014.00312).

Dr. Ceana Nezhat is the fellowship director of Nezhat Medical Center, the medical director of training and education at Northside Hospital, and an adjunct clinical professor of gynecology and obstetrics at Emory University, all in Atlanta. He is president of SRS (Society of Reproductive Surgeons) and past president of AAGL (American Association of Gynecologic Laparoscopists). Dr. Nezhat is a consultant for Novuson Surgical, Karl Storz Endoscopy, Lumenis, and AbbVie; a medical advisor for Plasma Surgical, and a member of the scientific advisory board for SurgiQuest.

Suggested readings

1. Nezhat C, Nezhat F, Nezhat C. Nezhat’s Operative Gynecologic Laparoscopy with Hysteroscopy. Fourth Edition. Cambridge University Press. 2013.

2. Am J Med. 1996 Feb;100(2):164-70.

3. Fertil Steril. 1998 Jun;69(6):1048-55.

4. Clin Obstet Gynecol. 1999 Sep;42(3):699-711.

5. JSLS. 2012 Jan-Mar; 16(1):140-2.

The first case of diaphragmatic endometriosis was reported by Alan Brews in 1954¹. Unfortunately, no guidelines exist to enhance the recognition and treatment.

Diaphragmatic and thoracic endometriosis often is overlooked by the gynecologist, not only because of lack of appreciation of the symptoms but also because of the failure to properly work-up the patient and evaluate the diaphragm at time of surgery. In a retrospective review of 3,008 patients with pelvic endometriosis published in Surgical Endoscopy in 2013, Marcello Ceccaroni, MD, PhD, and his colleagues found 46 cases (1.53%) with the intraoperative diagnosis of diaphragmatic endometriosis, six with liver involvement. Multiple diaphragmatic endometriosis lesions were seen in 70% of patients and, the vast majority being right-sided lesions (87%), with 11% of cases having bilateral lesions.² While in the study, superficial lesions were generally vaporized using the argon beam coagulator, deep lesions were removed by sharp dissection, highlighting the need to have adequately trained minimally invasive surgeons treating diaphragmatic lesions via incision. If a pneumothorax occurred, and reabsorbable suture was placed after adequate expansion of the lung via positive pressure ventilation and progressive air suctioning with complete evacuation of the pneumothorax prior to the final closure (i.e., a purse string around the suction device), then the integrity of the closure could be proven using a bubble test with 500cc of saline placed at the diaphragm.

Dr. Miller is clinical associate professor at the University of Illinois at Chicago and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago; director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column. He reported having no financial disclosures related to this column.

References

1. Proc R Soc Med. 1954 Jun; 47(6):461-8.

2. Surg Endosc. 2013 Feb;27(2):625-32.

The first case of diaphragmatic endometriosis was reported by Alan Brews in 1954¹. Unfortunately, no guidelines exist to enhance the recognition and treatment.

Diaphragmatic and thoracic endometriosis often is overlooked by the gynecologist, not only because of lack of appreciation of the symptoms but also because of the failure to properly work-up the patient and evaluate the diaphragm at time of surgery. In a retrospective review of 3,008 patients with pelvic endometriosis published in Surgical Endoscopy in 2013, Marcello Ceccaroni, MD, PhD, and his colleagues found 46 cases (1.53%) with the intraoperative diagnosis of diaphragmatic endometriosis, six with liver involvement. Multiple diaphragmatic endometriosis lesions were seen in 70% of patients and, the vast majority being right-sided lesions (87%), with 11% of cases having bilateral lesions.² While in the study, superficial lesions were generally vaporized using the argon beam coagulator, deep lesions were removed by sharp dissection, highlighting the need to have adequately trained minimally invasive surgeons treating diaphragmatic lesions via incision. If a pneumothorax occurred, and reabsorbable suture was placed after adequate expansion of the lung via positive pressure ventilation and progressive air suctioning with complete evacuation of the pneumothorax prior to the final closure (i.e., a purse string around the suction device), then the integrity of the closure could be proven using a bubble test with 500cc of saline placed at the diaphragm.

Dr. Miller is clinical associate professor at the University of Illinois at Chicago and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago; director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column. He reported having no financial disclosures related to this column.

References

1. Proc R Soc Med. 1954 Jun; 47(6):461-8.

2. Surg Endosc. 2013 Feb;27(2):625-32.

The first case of diaphragmatic endometriosis was reported by Alan Brews in 1954¹. Unfortunately, no guidelines exist to enhance the recognition and treatment.

Diaphragmatic and thoracic endometriosis often is overlooked by the gynecologist, not only because of lack of appreciation of the symptoms but also because of the failure to properly work-up the patient and evaluate the diaphragm at time of surgery. In a retrospective review of 3,008 patients with pelvic endometriosis published in Surgical Endoscopy in 2013, Marcello Ceccaroni, MD, PhD, and his colleagues found 46 cases (1.53%) with the intraoperative diagnosis of diaphragmatic endometriosis, six with liver involvement. Multiple diaphragmatic endometriosis lesions were seen in 70% of patients and, the vast majority being right-sided lesions (87%), with 11% of cases having bilateral lesions.² While in the study, superficial lesions were generally vaporized using the argon beam coagulator, deep lesions were removed by sharp dissection, highlighting the need to have adequately trained minimally invasive surgeons treating diaphragmatic lesions via incision. If a pneumothorax occurred, and reabsorbable suture was placed after adequate expansion of the lung via positive pressure ventilation and progressive air suctioning with complete evacuation of the pneumothorax prior to the final closure (i.e., a purse string around the suction device), then the integrity of the closure could be proven using a bubble test with 500cc of saline placed at the diaphragm.

Dr. Miller is clinical associate professor at the University of Illinois at Chicago and past president of the AAGL. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in metropolitan Chicago; director of minimally invasive gynecologic surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column. He reported having no financial disclosures related to this column.

References

1. Proc R Soc Med. 1954 Jun; 47(6):461-8.

2. Surg Endosc. 2013 Feb;27(2):625-32.

Click here to access Optimal Treatment of Patients With Diabetes

Table of Contents

• Overview of the 2017 VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes
• Roundtable Discussion: Implementing the 2017 VA/DoD Diabetes Clinical Practice Guideline
• Bolus Insulin Prescribing Recommendations for Patients With Type 2 Diabetes Mellitus
• Serious Mental Illness and Its Impact on Diabetes Care in a VA Nurse/Pharmacist-Managed Population
• Concentrated Insulins: A Review and Recommendations
• Glycemic Control After Discontinuation of Metformin in Patients With Elevated Serum Creatinine

Click here to access Optimal Treatment of Patients With Diabetes

Table of Contents

• Overview of the 2017 VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes
• Roundtable Discussion: Implementing the 2017 VA/DoD Diabetes Clinical Practice Guideline
• Bolus Insulin Prescribing Recommendations for Patients With Type 2 Diabetes Mellitus
• Serious Mental Illness and Its Impact on Diabetes Care in a VA Nurse/Pharmacist-Managed Population
• Concentrated Insulins: A Review and Recommendations
• Glycemic Control After Discontinuation of Metformin in Patients With Elevated Serum Creatinine

Click here to access Optimal Treatment of Patients With Diabetes

Table of Contents

• Overview of the 2017 VA/DoD Clinical Practice Guideline for the Management of Type 2 Diabetes
• Roundtable Discussion: Implementing the 2017 VA/DoD Diabetes Clinical Practice Guideline
• Bolus Insulin Prescribing Recommendations for Patients With Type 2 Diabetes Mellitus
• Serious Mental Illness and Its Impact on Diabetes Care in a VA Nurse/Pharmacist-Managed Population
• Concentrated Insulins: A Review and Recommendations
• Glycemic Control After Discontinuation of Metformin in Patients With Elevated Serum Creatinine

This article reviews recommendations and evidence concerning current anticoagulant management for venous thromboembolism and perioperative care, with an emphasis on individualizing treatment for real-world patients.

TREATING ACUTE VENOUS THROMBOEMBOLISM

Case 1: Deep vein thrombosis in an otherwise healthy man

A 40-year-old man presents with 7 days of progressive right leg swelling. He has no antecedent risk factors for deep vein thrombosis or other medical problems. Venous ultrasonography reveals an iliofemoral deep vein thrombosis. How should he be managed?

• Outpatient treatment with low-molecular-weight heparin for 4 to 6 days plus warfarin
• Outpatient treatment with a direct oral anticoagulant, ie, apixaban, dabigatran (which requires 4 to 6 days of initial treatment with low-molecular-weight heparin), or rivaroxaban
• Catheter-directed thrombolysis followed by low-molecular-weight heparin, then warfarin or a direct oral anticoagulant
• Inpatient intravenous heparin for 7 to 10 days, then warfarin or a direct oral anticoagulant

All of these are acceptable for managing acute venous thromboembolism, but the clinician’s role is to identify which treatment is most appropriate for an individual patient.

Deep vein thrombosis is not a single condition

Multiple guidelines exist to help decide on a management strategy. Those of the American College of Chest Physicians (ACCP)¹ are used most often.

That said, guidelines are established for “average” patients, so it is important to look beyond guidelines and individualize management. Venous thromboembolism is not a single entity; it has a myriad of clinical presentations that could call for different treatments. Most patients have submassive deep vein thrombosis or pulmonary embolism, which is not limb-threatening nor associated with hemodynamic instability. It can also differ in terms of etiology and can be unprovoked (or idiopathic), cancer-related, catheter-associated, or provoked by surgery or immobility.

Deep vein thrombosis has a wide spectrum of presentations. It can involve the veins of the calf only, or it can involve the femoral and iliac veins and other locations including the splanchnic veins, the cerebral sinuses, and upper extremities. Pulmonary embolism can be massive (defined as being associated with hemodynamic instability or impending respiratory failure) or submassive. Similarly, patients differ in terms of baseline medical conditions, mobility, and lifestyle. Anticoagulant management decisions should take all these factors into account.

Consider clot location

Our patient with iliofemoral deep vein thrombosis is best managed differently than a more typical patient with less extensive thrombosis that would involve the popliteal or femoral vein segments, or both. A clot that involves the iliac vein is more likely to lead to postthrombotic chronic pain and swelling as the lack of venous outflow bypass channels to circumvent the clot location creates higher venous pressure within the affected leg. Therefore, for our patient, catheter-directed thrombolysis is an option that should be considered.

Catheter-directed thrombolysis trials

According to the “open-vein hypothesis,” quickly eliminating the thrombus and restoring unobstructed venous flow may mitigate the risk not only of recurrent thrombosis, but also of postthrombotic syndrome, which is often not given much consideration acutely but can cause significant, life-altering chronic disability.

The “valve-integrity hypothesis” is also important; it considers whether lytic therapy may help prevent damage to such valves in an attempt to mitigate the amount of venous hypertension.

Thus, catheter-directed thrombolysis offers theoretical benefits, and recent trials have assessed it against standard anticoagulation treatments.

The CaVenT trial (Catheter-Directed Venous Thrombolysis),² conducted in Norway, randomized 209 patients with midfemoral to iliac deep vein thrombosis to conventional treatment (anticoagulation alone) or anticoagulation plus catheter-directed thrombolysis. At 2 years, postthrombotic syndrome had occurred in 41% of the catheter-directed thrombolysis group compared with 56% of the conventional treatment group (P = .047). At 5 years, the difference widened to 43% vs 71% (P < .01, number needed to treat = 4).³ Despite the superiority of lytic therapy, the incidence of postthrombotic syndrome remained high in patients who received this treatment. 

The ATTRACT trial (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis),⁴ a US multicenter, open-label, assessor-blind study, randomized 698 patients with femoral or more-proximal deep vein thrombosis to either standard care (anticoagulant therapy and graduated elastic compression stockings) or standard care plus catheter-directed thrombolysis. In preliminary results presented at the Society of Interventional Radiology meeting in March 2017, although no difference was found in the primary outcome (postthrombotic syndrome at 24 months), catheter-directed thrombolysis for iliofemoral deep vein thrombosis led to a 25% reduction in moderate to severe postthrombotic syndrome.

Although it is too early to draw conclusions before publication of the ATTRACT study, the preliminary results highlight the need to individualize treatment and to be selective about using catheter-directed thrombolysis. The trials provide reassurance that catheter-directed lysis is a reasonable and safe intervention when performed by physicians experienced in the procedure. The risk of major bleeding appears to be low (about 2%) and that for intracranial hemorrhage even lower (< 0.5%).

Catheter-directed thrombolysis is appropriate in some cases

The 2016 ACCP guidelines¹ recommend anticoagulant therapy alone over catheter-directed thrombolysis for patients with acute proximal deep vein thrombosis of the leg. However, it is a grade 2C (weak) recommendation.

They provide no specific recommendation as to the clinical indications for catheter-directed thrombolysis, but identify patients who would be most likely to benefit, ie, those who have: 

• Iliofemoral deep vein thrombosis
• Symptoms for less than 14 days
• Good functional status
• Life expectancy of more than 1 year
• Low risk of bleeding.

Our patient satisfies these criteria, suggesting that catheter-directed thrombolysis is a reasonable option for him. 

Timing is important. Catheter-directed lysis is more likely to be beneficial if used before fibrin deposits form and stiffen the venous valves, causing irreversible damage that leads to postthrombotic syndrome. 

 

 

Role of direct oral anticoagulants

The availability of direct oral anticoagulants has generated interest in defining their therapeutic role in patients with venous thromboembolism.

In a meta-analysis⁵ of major trials comparing direct oral anticoagulants and vitamin K antagonists such as warfarin, no significant difference was found for the risk of recurrent venous thromboembolism or venous thromboembolism-related deaths. However, fewer patients experienced major bleeding with direct oral anticoagulants (relative risk 0.61, P = .002). Although significant, the absolute risk reduction was small; the incidence of major bleeding was 1.1% with direct oral anticoagulants vs 1.8% with vitamin K antagonists.

The main advantage of direct oral anticoagulants is greater convenience for the patient.

WHICH PATIENTS ON WARFARIN NEED BRIDGING PREOPERATIVELY?

Many patients still take warfarin, particularly those with atrial fibrillation, a mechanical heart valve, or venous thromboembolism. In many countries, warfarin remains the dominant anticoagulant for stroke prevention. Whether these patients need heparin during the period of perioperative warfarin interruption is a frequently encountered scenario that, until recently, was controversial. Recent studies have helped to inform the need for heparin bridging in many of these patients.

Case 2: An elderly woman on warfarin facing cancer surgery

A 75-year-old woman weighing 65 kg is scheduled for elective colon resection for incidentally found colon cancer. She is taking warfarin for atrial fibrillation. She also has hypertension and diabetes and had a transient ischemic attack 10 years ago.

One doctor told her she needs to be assessed for heparin bridging, but another told her she does not need bridging.

The default management should be not to bridge patients who have atrial fibrillation, but to consider bridging in selected patients, such as those with recent stroke or transient ischemic attack or a prior thromboembolic event during warfarin interruption. However, decisions about bridging should not be made on the basis of the CHADS₂ score alone. For the patient described here, I would recommend not bridging.

Complex factors contribute to stroke risk

Stroke risk for patients with atrial fibrillation can be quickly estimated with the CHADS₂ score, based on: 

• Congestive heart failure (1 point)
• Hypertension (1 point)
• Age at least 75 (1 point)
• Diabetes (1 point)
• Stroke or transient ischemic attack (2 points).

Our patient has a score of 5, corresponding to an annual adjusted stroke risk of 12.5%. Whether her transient ischemic attack of 10 years ago is comparable in significance to a recent stroke is debatable and highlights a weakness of clinical prediction rules. Moreover, such prediction scores were developed to estimate the long-term risk of stroke if anticoagulants are not given, and they have not been assessed in a perioperative setting where there is short-term interruption of anticoagulants. Also, the perioperative milieu is associated with additional factors not captured in these clinical prediction rules that may affect the risk of stroke.

Thus, the risk of perioperative stroke likely involves the interplay of multiple factors, including the type of surgery the patient is undergoing. Some factors may be mitigated:

• Rebound hypercoagulability after stopping an oral anticoagulant can be prevented by intraoperative blood pressure and volume control
• Elevated biochemical factors (eg, D-dimer, B-type natriuretic peptide, troponin) may be lowered with perioperative aspirin therapy
• Lipid and genetic factors may be mitigated with perioperative statin use.

Can heparin bridging also mitigate the risk?

Bridging in patients with atrial fibrillation

Most patients who are taking warfarin are doing so because of atrial fibrillation, so most evidence about perioperative bridging was developed in such patients.

The BRIDGE trial (Bridging Anticoagulation in Patients Who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery)⁶ was the first randomized controlled trial to compare a bridging and no-bridging strategy for patients with atrial fibrillation who required warfarin interruption for elective surgery. Nearly 2,000 patients were given either low-molecular-weight heparin or placebo starting 3 days before until 24 hours before a procedure, and then for 5 to 10 days afterwards. For all patients, warfarin was stopped 5 days before the procedure and was resumed within 24 hours afterwards.

A no-bridging strategy was noninferior to bridging: the risk of perioperative arterial thromboembolism was 0.4% without bridging vs 0.3% with bridging (P = .01 for noninferiority). In addition, a no-bridging strategy conferred a lower risk of major bleeding than bridging: 1.3% vs 3.2% (relative risk 0.41, P = .005 for superiority).

Although the difference in absolute bleeding risk was small, bleeding rates were lower than those seen outside of clinical trials, as the bridging protocol used in BRIDGE was designed to minimize the risk of bleeding. Also, although only 5% of patients had a CHADS₂ score of 5 or 6, such patients are infrequent in clinical practice, and BRIDGE did include a considerable proportion (17%) of patients with a prior stroke or transient ischemic attack who would be considered at high risk.

Other evidence about heparin bridging is derived from observational studies, more than 10 of which have been conducted. In general, they have found that not bridging is associated with low rates of arterial thromboembolism (< 0.5%) and that bridging is associated with high rates of major bleeding (4%–7%).^7–12

Bridging in patients with a mechanical heart valve

Warfarin is the only anticoagulant option for patients who have a mechanical heart valve. No randomized controlled trials have evaluated the benefits of perioperative bridging vs no bridging in this setting.

Observational (cohort) studies suggest that the risk of perioperative arterial thromboembolism is similar with or without bridging anticoagulation, although most patients studied were bridged and those not bridged were considered at low risk (eg, with a bileaflet aortic valve and no additional risk factors).¹³ However, without stronger evidence from randomized controlled trials, bridging should be the default management for patients with a mechanical heart valve. In our practice, we bridge most patients who have a mechanical heart valve unless they are considered to be at low risk, such as those who have a bileaflet aortic valve.

 

 

Bridging in patients with prior venous thromboembolism

Even less evidence is available for periprocedural management of patients who have a history of venous thromboembolism. No randomized controlled trials exist evaluating bridging vs no bridging. In 1 cohort study in which more than 90% of patients had had thromboembolism more than 3 months before the procedure, the rate of recurrent venous thromboembolism without bridging was less than 0.5%.¹⁴

It is reasonable to bridge patients who need anticoagulant interruption within 3 months of diagnosis of a deep vein thrombosis or pulmonary embolism, and to consider using a temporary inferior vena cava filter for patients who have had a clot who need treatment interruption during the initial 3 to 4 weeks after diagnosis.

Practice guidelines: Perioperative anticoagulation

Guidance for preoperative and postoperative bridging for patients taking warfarin is summarized in Table 2.

CARDIAC PROCEDURES

For patients facing a procedure to implant an implantable cardioverter-defibrillator (ICD) or pacemaker, a procedure-specific concern is the avoidance of pocket hematoma.

Patients on warfarin: Do not bridge

The BRUISE CONTROL-1 trial (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial)¹⁹ randomized patients undergoing pacemaker or ICD implantation to either continued anticoagulation therapy and not bridging (ie, continued warfarin so long as the international normalized ratio was < 3) vs conventional bridging treatment (ie, stopping warfarin and bridging with low-molecular-weight heparin). A clinically significant device-pocket hematoma occurred in 3.5% of the continued-warfarin group vs 16.0% in the heparin-bridging group (P < .001). Thromboembolic complications were rare, and rates did not differ between the 2 groups.

Results of the BRUISE CONTROL-1 trial serve as a caution to at least not be too aggressive with bridging. The study design involved resuming heparin 24 hours after surgery, which is perhaps more aggressive than standard practice. In our practice, we wait at least 24 hours to reinstate heparin after minor surgery, and 48 to 72 hours after surgery with higher bleeding risk.

These results are perhaps not surprising if one considers how carefully surgeons try to control bleeding during surgery for patients taking anticoagulants. For patients who are not on an anticoagulant, small bleeding may be less of a concern during a procedure. When high doses of heparin are introduced soon after surgery, small concerns during surgery may become big problems afterward.

Based on these results, it is reasonable to undertake device implantation without interruption of a vitamin K antagonist such as warfarin.

Patients on direct oral anticoagulants: The jury is still out

The similar BRUISE CONTROL-2 trial is currently under way, comparing interruption vs continuation of dabigatran for patients undergoing cardiac device surgery.

In Europe, surgeons are less concerned than those in the United States about operating while a patient is on anticoagulant therapy. But the safety of this practice is not backed by strong evidence.

Direct oral anticoagulants: Consider pharmacokinetics

Direct oral anticoagulants are potent and fast-acting, with a peak effect 1 to 3 hours after intake. This rapid anticoagulant action is similar to that of bridging with low-molecular-weight heparin, and caution is needed when administering direct oral anticoagulants, especially after major surgery or surgery with a high bleeding risk.

Frost et al²⁰ compared the pharmacokinetics of apixaban (with twice-daily dosing) and rivaroxaban (once-daily dosing) and found that peak anticoagulant activity is faster and higher with rivaroxaban. This is important, because many patients will take their anticoagulant first thing in the morning. Consequently, if patients require any kind of procedure (including dental), they should skip the morning dose of the direct oral anticoagulant to avoid having the procedure done during the peak anticoagulant effect, and they should either not take that day’s dose or defer the dose until the evening after the procedure. 

MANAGING SURGERY FOR PATIENTS ON A DIRECT ORAL ANTICOAGULANT

Case 3: An elderly woman on apixaban facing surgery

Let us imagine that our previous patient takes apixaban instead of warfarin. She is 75 years old, has atrial fibrillation, and is about to undergo elective colon resection for cancer. One doctor advises her to simply stop apixaban for 2 days, while another says she should go off apixaban for 5 days and will need bridging. Which plan is best?

In the perioperative setting, our goal is to interrupt patients’ anticoagulant therapy for the shortest time that results in no residual anticoagulant effect at the time of the procedure. 

They further recommend that if the risk of venous thromboembolism is high, low-molecular-weight heparin bridging should be done while stopping the direct oral anticoagulant, with the heparin discontinued 24 hours before the procedure. This recommendation seems counterintuitive, as it is advising replacing a short-acting anticoagulant with low-molecular-weight heparin, another short-acting anticoagulant.

The guidelines committee was unable to provide strength and grading of their recommendations, as too few well-designed studies are available to support them. The doctor in case 3 who advised stopping apixaban for 5 days and bridging is following the guidelines, but without much evidence to support this strategy.

 

 

Is bridging needed during interruption of a direct oral anticoagulant?

There are no randomized, controlled trials of bridging vs no bridging in patients taking direct oral anticoagulants. Substudies exist of patients taking these drugs for atrial fibrillation who had treatment interrupted for procedures, but the studies did not randomize bridging vs no bridging, nor were bridging regimens standardized. Three of the four atrial fibrillation trials had a blinded design (warfarin vs direct oral anticoagulants), making perioperative management difficult, as physicians did not know the pharmacokinetics of the drugs their patients were taking.^22–24

We used the database from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial²² to evaluate bridging in patients taking either warfarin or dabigatran. With an open-label study design (the blinding was only for the 110 mg and 150 mg dabigatran doses), clinicians were aware of whether patients were receiving warfarin or dabigatran, thereby facilitating perioperative management. Among dabigatran-treated patients, those who were bridged had significantly more major bleeding than those not bridged (6.5% vs 1.8%, P < .001), with no difference between the groups for stroke or systemic embolism. Although it is not a randomized controlled trial, it does provide evidence that bridging may not be advisable for patients taking a direct oral anticoagulant.

The 2017 American College of Cardiology guidelines²⁵ conclude that parenteral bridging is not indicated for direct oral anticoagulants. Although this is not based on strong evidence, the guidance appears reasonable according to the evidence at hand.

The 2017 American Heart Association Guidelines¹⁶ recommend a somewhat complex approach based on periprocedural bleeding risk and thromboembolic risk.

How long to interrupt direct oral anticoagulants?

Evidence for this approach comes from a prospective cohort study²⁷ of 541 patients being treated with dabigatran who were having an elective surgery or invasive procedure. Patients received standard perioperative management, with the timing of the last dabigatran dose before the procedure (24 hours, 48 hours, or 96 hours) based on the bleeding risk of surgery and the patient’s creatinine clearance. Dabigatran was resumed 24 to 72 hours after the procedure. No heparin bridging was done. Patients were followed for up to 30 days postoperatively. The results were favorable with few complications: one transient ischemic attack (0.2%), 10 major bleeding episodes (1.8%), and 28 minor bleeding episodes (5.2%).

A subgroup of 181 patients in this study²⁸ had a plasma sample drawn just before surgery, allowing the investigators to assess the level of coagulation factors after dabigatran interruption. Results were as follows:

• 93% had a normal prothrombin time 
• 80% had a normal activated partial thromboplastin time
• 33% had a normal thrombin time
• 81% had a normal dilute thrombin time.

The dilute thrombin time is considered the most reliable test of the anticoagulant effect of dabigatran but is not widely available. The activated partial thromboplastin time can provide a more widely used coagulation test to assess (in a less precise manner) whether there is an anticoagulant effect of dabigatran present, and more sensitive activated partial thromboplastin time assays can be used to better detect any residual dabigatran effect.

Dabigatran levels were also measured. Although 66% of patients had low drug levels just before surgery, the others still had substantial dabigatran on board. The fact that bleeding event rates were so low in this study despite the presence of dabigatran in many patients raises the question of whether having some drug on board is a good predictor of bleeding risk.

An interruption protocol with a longer interruption interval—12 to 14 hours longer than in the previous study (3 days for high-bleed risk procedures, 2 days for low-bleed risk procedures)—brought the activated partial thromboplastin time and dilute thrombin time to normal levels for 100% of patients with the protocol for high-bleeding-risk surgery. This study was based on small numbers and its interruption strategy needs further investigation.²⁹

Case 3 continued

The PAUSE study (NCT02228798), a multicenter, prospective cohort study, is designed to establish a safe, standardized protocol for the perioperative management of patients with atrial fibrillation taking dabigatran, rivaroxaban, or apixaban and will include 3,300 patients.

PATIENTS WITH A CORONARY STENT WHO NEED SURGERY

Case 4: A woman with a stent facing surgery

A 70-year-old woman needs breast cancer resection. She has coronary artery disease and had a drug-eluting stent placed 5 months ago after elective cardiac catheterization. She also has hypertension, obesity, and type 2 diabetes. Her medications include an angiotensin II receptor blocker, hydrochlorothiazide, insulin, and an oral hypoglycemic. She is also taking aspirin 81 mg daily and ticagrelor (a P2Y₁₂ receptor antagonist) 90 mg twice daily.

Her cardiologist is concerned that stopping antiplatelet therapy could trigger acute stent thrombosis, which has a 50% or higher mortality rate.

Should she stop taking aspirin before surgery? What about the ticagrelor?

 

 

Is aspirin safe during surgery?

Evidence concerning aspirin during surgery comes from Perioperative Ischemic Evaluation 2 (POISE-2), a double-blind, randomized controlled trial.³⁰ Patients who had known cardiovascular disease or risk factors for cardiovascular disease and were about to undergo noncardiac surgery were stratified according to whether they had been taking aspirin before the study (patients taking aspirin within 72 hours of the surgery were excluded from randomization). Participants in each group were randomized to take either aspirin or placebo just before surgery. The primary outcome was the combined rate of death or nonfatal myocardial infarction 30 days after randomization.

The study found no differences in the primary end point between the two groups. However, major bleeding occurred significantly more often in the aspirin group (4.6% vs 3.8%, hazard ratio 1.2, 95% confidence interval 1.0–1.5).

Moreover, only 4% of the patients in this trial had a cardiac stent. The trial excluded patients who had had a bare-metal stent placed within 6 weeks or a drug-eluting stent placed within 1 year, so it does not help us answer whether aspirin should be stopped for our current patient.

Is surgery safe for patients with stents?

The safety of undergoing surgery with a stent was investigated in a large US Veterans Administration retrospective cohort study.³¹ More than 20,000 patients with stents who underwent noncardiac surgery within 2 years of stent placement were compared with a control group of more than 41,000 patients with stents who did not undergo surgery. Patients were matched by stent type and cardiac risk factors at the time of stent placement.

The risk of an adverse cardiac event in both the surgical and nonsurgical cohorts was highest in the initial 6 weeks after stent placement and plateaued 6 months after stent placement, when the risk difference between the surgical and nonsurgical groups leveled off to 1%.

The risk of a major adverse cardiac event postoperatively was much more dependent on the timing of stent placement in complex and inpatient surgeries. For outpatient surgeries, the risk of a major cardiac event was very low and the timing of stent placement did not matter.

A Danish observational study³² compared more than 4,000 patients with drug-eluting stents having surgery to more than 20,000 matched controls without coronary heart disease having similar surgery. The risk of myocardial infarction or cardiac death was much higher for patients undergoing surgery within 1 month after drug-eluting stent placement compared with controls without heart disease and patients with stent placement longer than 1 month before surgery.

Our practice is to continue aspirin for surgery in patients with coronary stents regardless of the timing of placement. Although there is a small increased risk of bleeding, this must be balanced against thrombotic risk. We typically stop clopidogrel 5 to 7 days before surgery and ticagrelor 3 to 5 days before surgery. We may decide to give platelets before very-high-risk surgery (eg, intracranial, spinal) if there is a decision to continue both antiplatelet drugs—for example, in a patient who recently received a drug-eluting stent (ie, within 3 months). It is essential to involve the cardiologist and surgeon in these decisions.

BOTTOM LINE

This article reviews recommendations and evidence concerning current anticoagulant management for venous thromboembolism and perioperative care, with an emphasis on individualizing treatment for real-world patients.

TREATING ACUTE VENOUS THROMBOEMBOLISM

Case 1: Deep vein thrombosis in an otherwise healthy man

A 40-year-old man presents with 7 days of progressive right leg swelling. He has no antecedent risk factors for deep vein thrombosis or other medical problems. Venous ultrasonography reveals an iliofemoral deep vein thrombosis. How should he be managed?

• Outpatient treatment with low-molecular-weight heparin for 4 to 6 days plus warfarin
• Outpatient treatment with a direct oral anticoagulant, ie, apixaban, dabigatran (which requires 4 to 6 days of initial treatment with low-molecular-weight heparin), or rivaroxaban
• Catheter-directed thrombolysis followed by low-molecular-weight heparin, then warfarin or a direct oral anticoagulant
• Inpatient intravenous heparin for 7 to 10 days, then warfarin or a direct oral anticoagulant

All of these are acceptable for managing acute venous thromboembolism, but the clinician’s role is to identify which treatment is most appropriate for an individual patient.

Deep vein thrombosis is not a single condition

Multiple guidelines exist to help decide on a management strategy. Those of the American College of Chest Physicians (ACCP)¹ are used most often.

That said, guidelines are established for “average” patients, so it is important to look beyond guidelines and individualize management. Venous thromboembolism is not a single entity; it has a myriad of clinical presentations that could call for different treatments. Most patients have submassive deep vein thrombosis or pulmonary embolism, which is not limb-threatening nor associated with hemodynamic instability. It can also differ in terms of etiology and can be unprovoked (or idiopathic), cancer-related, catheter-associated, or provoked by surgery or immobility.

Deep vein thrombosis has a wide spectrum of presentations. It can involve the veins of the calf only, or it can involve the femoral and iliac veins and other locations including the splanchnic veins, the cerebral sinuses, and upper extremities. Pulmonary embolism can be massive (defined as being associated with hemodynamic instability or impending respiratory failure) or submassive. Similarly, patients differ in terms of baseline medical conditions, mobility, and lifestyle. Anticoagulant management decisions should take all these factors into account.

Consider clot location

Our patient with iliofemoral deep vein thrombosis is best managed differently than a more typical patient with less extensive thrombosis that would involve the popliteal or femoral vein segments, or both. A clot that involves the iliac vein is more likely to lead to postthrombotic chronic pain and swelling as the lack of venous outflow bypass channels to circumvent the clot location creates higher venous pressure within the affected leg. Therefore, for our patient, catheter-directed thrombolysis is an option that should be considered.

Catheter-directed thrombolysis trials

According to the “open-vein hypothesis,” quickly eliminating the thrombus and restoring unobstructed venous flow may mitigate the risk not only of recurrent thrombosis, but also of postthrombotic syndrome, which is often not given much consideration acutely but can cause significant, life-altering chronic disability.

The “valve-integrity hypothesis” is also important; it considers whether lytic therapy may help prevent damage to such valves in an attempt to mitigate the amount of venous hypertension.

Thus, catheter-directed thrombolysis offers theoretical benefits, and recent trials have assessed it against standard anticoagulation treatments.

The CaVenT trial (Catheter-Directed Venous Thrombolysis),² conducted in Norway, randomized 209 patients with midfemoral to iliac deep vein thrombosis to conventional treatment (anticoagulation alone) or anticoagulation plus catheter-directed thrombolysis. At 2 years, postthrombotic syndrome had occurred in 41% of the catheter-directed thrombolysis group compared with 56% of the conventional treatment group (P = .047). At 5 years, the difference widened to 43% vs 71% (P < .01, number needed to treat = 4).³ Despite the superiority of lytic therapy, the incidence of postthrombotic syndrome remained high in patients who received this treatment. 

The ATTRACT trial (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis),⁴ a US multicenter, open-label, assessor-blind study, randomized 698 patients with femoral or more-proximal deep vein thrombosis to either standard care (anticoagulant therapy and graduated elastic compression stockings) or standard care plus catheter-directed thrombolysis. In preliminary results presented at the Society of Interventional Radiology meeting in March 2017, although no difference was found in the primary outcome (postthrombotic syndrome at 24 months), catheter-directed thrombolysis for iliofemoral deep vein thrombosis led to a 25% reduction in moderate to severe postthrombotic syndrome.

Although it is too early to draw conclusions before publication of the ATTRACT study, the preliminary results highlight the need to individualize treatment and to be selective about using catheter-directed thrombolysis. The trials provide reassurance that catheter-directed lysis is a reasonable and safe intervention when performed by physicians experienced in the procedure. The risk of major bleeding appears to be low (about 2%) and that for intracranial hemorrhage even lower (< 0.5%).

Catheter-directed thrombolysis is appropriate in some cases

The 2016 ACCP guidelines¹ recommend anticoagulant therapy alone over catheter-directed thrombolysis for patients with acute proximal deep vein thrombosis of the leg. However, it is a grade 2C (weak) recommendation.

They provide no specific recommendation as to the clinical indications for catheter-directed thrombolysis, but identify patients who would be most likely to benefit, ie, those who have: 

• Iliofemoral deep vein thrombosis
• Symptoms for less than 14 days
• Good functional status
• Life expectancy of more than 1 year
• Low risk of bleeding.

Our patient satisfies these criteria, suggesting that catheter-directed thrombolysis is a reasonable option for him. 

Timing is important. Catheter-directed lysis is more likely to be beneficial if used before fibrin deposits form and stiffen the venous valves, causing irreversible damage that leads to postthrombotic syndrome. 

 

 

Role of direct oral anticoagulants

The availability of direct oral anticoagulants has generated interest in defining their therapeutic role in patients with venous thromboembolism.

In a meta-analysis⁵ of major trials comparing direct oral anticoagulants and vitamin K antagonists such as warfarin, no significant difference was found for the risk of recurrent venous thromboembolism or venous thromboembolism-related deaths. However, fewer patients experienced major bleeding with direct oral anticoagulants (relative risk 0.61, P = .002). Although significant, the absolute risk reduction was small; the incidence of major bleeding was 1.1% with direct oral anticoagulants vs 1.8% with vitamin K antagonists.

The main advantage of direct oral anticoagulants is greater convenience for the patient.

WHICH PATIENTS ON WARFARIN NEED BRIDGING PREOPERATIVELY?

Many patients still take warfarin, particularly those with atrial fibrillation, a mechanical heart valve, or venous thromboembolism. In many countries, warfarin remains the dominant anticoagulant for stroke prevention. Whether these patients need heparin during the period of perioperative warfarin interruption is a frequently encountered scenario that, until recently, was controversial. Recent studies have helped to inform the need for heparin bridging in many of these patients.

Case 2: An elderly woman on warfarin facing cancer surgery

A 75-year-old woman weighing 65 kg is scheduled for elective colon resection for incidentally found colon cancer. She is taking warfarin for atrial fibrillation. She also has hypertension and diabetes and had a transient ischemic attack 10 years ago.

One doctor told her she needs to be assessed for heparin bridging, but another told her she does not need bridging.

The default management should be not to bridge patients who have atrial fibrillation, but to consider bridging in selected patients, such as those with recent stroke or transient ischemic attack or a prior thromboembolic event during warfarin interruption. However, decisions about bridging should not be made on the basis of the CHADS₂ score alone. For the patient described here, I would recommend not bridging.

Complex factors contribute to stroke risk

Stroke risk for patients with atrial fibrillation can be quickly estimated with the CHADS₂ score, based on: 

• Congestive heart failure (1 point)
• Hypertension (1 point)
• Age at least 75 (1 point)
• Diabetes (1 point)
• Stroke or transient ischemic attack (2 points).

Our patient has a score of 5, corresponding to an annual adjusted stroke risk of 12.5%. Whether her transient ischemic attack of 10 years ago is comparable in significance to a recent stroke is debatable and highlights a weakness of clinical prediction rules. Moreover, such prediction scores were developed to estimate the long-term risk of stroke if anticoagulants are not given, and they have not been assessed in a perioperative setting where there is short-term interruption of anticoagulants. Also, the perioperative milieu is associated with additional factors not captured in these clinical prediction rules that may affect the risk of stroke.

Thus, the risk of perioperative stroke likely involves the interplay of multiple factors, including the type of surgery the patient is undergoing. Some factors may be mitigated:

• Rebound hypercoagulability after stopping an oral anticoagulant can be prevented by intraoperative blood pressure and volume control
• Elevated biochemical factors (eg, D-dimer, B-type natriuretic peptide, troponin) may be lowered with perioperative aspirin therapy
• Lipid and genetic factors may be mitigated with perioperative statin use.

Can heparin bridging also mitigate the risk?

Bridging in patients with atrial fibrillation

Most patients who are taking warfarin are doing so because of atrial fibrillation, so most evidence about perioperative bridging was developed in such patients.

The BRIDGE trial (Bridging Anticoagulation in Patients Who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery)⁶ was the first randomized controlled trial to compare a bridging and no-bridging strategy for patients with atrial fibrillation who required warfarin interruption for elective surgery. Nearly 2,000 patients were given either low-molecular-weight heparin or placebo starting 3 days before until 24 hours before a procedure, and then for 5 to 10 days afterwards. For all patients, warfarin was stopped 5 days before the procedure and was resumed within 24 hours afterwards.

A no-bridging strategy was noninferior to bridging: the risk of perioperative arterial thromboembolism was 0.4% without bridging vs 0.3% with bridging (P = .01 for noninferiority). In addition, a no-bridging strategy conferred a lower risk of major bleeding than bridging: 1.3% vs 3.2% (relative risk 0.41, P = .005 for superiority).

Although the difference in absolute bleeding risk was small, bleeding rates were lower than those seen outside of clinical trials, as the bridging protocol used in BRIDGE was designed to minimize the risk of bleeding. Also, although only 5% of patients had a CHADS₂ score of 5 or 6, such patients are infrequent in clinical practice, and BRIDGE did include a considerable proportion (17%) of patients with a prior stroke or transient ischemic attack who would be considered at high risk.

Other evidence about heparin bridging is derived from observational studies, more than 10 of which have been conducted. In general, they have found that not bridging is associated with low rates of arterial thromboembolism (< 0.5%) and that bridging is associated with high rates of major bleeding (4%–7%).^7–12

Bridging in patients with a mechanical heart valve

Warfarin is the only anticoagulant option for patients who have a mechanical heart valve. No randomized controlled trials have evaluated the benefits of perioperative bridging vs no bridging in this setting.

Observational (cohort) studies suggest that the risk of perioperative arterial thromboembolism is similar with or without bridging anticoagulation, although most patients studied were bridged and those not bridged were considered at low risk (eg, with a bileaflet aortic valve and no additional risk factors).¹³ However, without stronger evidence from randomized controlled trials, bridging should be the default management for patients with a mechanical heart valve. In our practice, we bridge most patients who have a mechanical heart valve unless they are considered to be at low risk, such as those who have a bileaflet aortic valve.

 

 

Bridging in patients with prior venous thromboembolism

Even less evidence is available for periprocedural management of patients who have a history of venous thromboembolism. No randomized controlled trials exist evaluating bridging vs no bridging. In 1 cohort study in which more than 90% of patients had had thromboembolism more than 3 months before the procedure, the rate of recurrent venous thromboembolism without bridging was less than 0.5%.¹⁴

It is reasonable to bridge patients who need anticoagulant interruption within 3 months of diagnosis of a deep vein thrombosis or pulmonary embolism, and to consider using a temporary inferior vena cava filter for patients who have had a clot who need treatment interruption during the initial 3 to 4 weeks after diagnosis.

Practice guidelines: Perioperative anticoagulation

Guidance for preoperative and postoperative bridging for patients taking warfarin is summarized in Table 2.

CARDIAC PROCEDURES

For patients facing a procedure to implant an implantable cardioverter-defibrillator (ICD) or pacemaker, a procedure-specific concern is the avoidance of pocket hematoma.

Patients on warfarin: Do not bridge

The BRUISE CONTROL-1 trial (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial)¹⁹ randomized patients undergoing pacemaker or ICD implantation to either continued anticoagulation therapy and not bridging (ie, continued warfarin so long as the international normalized ratio was < 3) vs conventional bridging treatment (ie, stopping warfarin and bridging with low-molecular-weight heparin). A clinically significant device-pocket hematoma occurred in 3.5% of the continued-warfarin group vs 16.0% in the heparin-bridging group (P < .001). Thromboembolic complications were rare, and rates did not differ between the 2 groups.

Results of the BRUISE CONTROL-1 trial serve as a caution to at least not be too aggressive with bridging. The study design involved resuming heparin 24 hours after surgery, which is perhaps more aggressive than standard practice. In our practice, we wait at least 24 hours to reinstate heparin after minor surgery, and 48 to 72 hours after surgery with higher bleeding risk.

These results are perhaps not surprising if one considers how carefully surgeons try to control bleeding during surgery for patients taking anticoagulants. For patients who are not on an anticoagulant, small bleeding may be less of a concern during a procedure. When high doses of heparin are introduced soon after surgery, small concerns during surgery may become big problems afterward.

Based on these results, it is reasonable to undertake device implantation without interruption of a vitamin K antagonist such as warfarin.

Patients on direct oral anticoagulants: The jury is still out

The similar BRUISE CONTROL-2 trial is currently under way, comparing interruption vs continuation of dabigatran for patients undergoing cardiac device surgery.

In Europe, surgeons are less concerned than those in the United States about operating while a patient is on anticoagulant therapy. But the safety of this practice is not backed by strong evidence.

Direct oral anticoagulants: Consider pharmacokinetics

Direct oral anticoagulants are potent and fast-acting, with a peak effect 1 to 3 hours after intake. This rapid anticoagulant action is similar to that of bridging with low-molecular-weight heparin, and caution is needed when administering direct oral anticoagulants, especially after major surgery or surgery with a high bleeding risk.

Frost et al²⁰ compared the pharmacokinetics of apixaban (with twice-daily dosing) and rivaroxaban (once-daily dosing) and found that peak anticoagulant activity is faster and higher with rivaroxaban. This is important, because many patients will take their anticoagulant first thing in the morning. Consequently, if patients require any kind of procedure (including dental), they should skip the morning dose of the direct oral anticoagulant to avoid having the procedure done during the peak anticoagulant effect, and they should either not take that day’s dose or defer the dose until the evening after the procedure. 

MANAGING SURGERY FOR PATIENTS ON A DIRECT ORAL ANTICOAGULANT

Case 3: An elderly woman on apixaban facing surgery

Let us imagine that our previous patient takes apixaban instead of warfarin. She is 75 years old, has atrial fibrillation, and is about to undergo elective colon resection for cancer. One doctor advises her to simply stop apixaban for 2 days, while another says she should go off apixaban for 5 days and will need bridging. Which plan is best?

In the perioperative setting, our goal is to interrupt patients’ anticoagulant therapy for the shortest time that results in no residual anticoagulant effect at the time of the procedure. 

They further recommend that if the risk of venous thromboembolism is high, low-molecular-weight heparin bridging should be done while stopping the direct oral anticoagulant, with the heparin discontinued 24 hours before the procedure. This recommendation seems counterintuitive, as it is advising replacing a short-acting anticoagulant with low-molecular-weight heparin, another short-acting anticoagulant.

The guidelines committee was unable to provide strength and grading of their recommendations, as too few well-designed studies are available to support them. The doctor in case 3 who advised stopping apixaban for 5 days and bridging is following the guidelines, but without much evidence to support this strategy.

 

 

Is bridging needed during interruption of a direct oral anticoagulant?

There are no randomized, controlled trials of bridging vs no bridging in patients taking direct oral anticoagulants. Substudies exist of patients taking these drugs for atrial fibrillation who had treatment interrupted for procedures, but the studies did not randomize bridging vs no bridging, nor were bridging regimens standardized. Three of the four atrial fibrillation trials had a blinded design (warfarin vs direct oral anticoagulants), making perioperative management difficult, as physicians did not know the pharmacokinetics of the drugs their patients were taking.^22–24

We used the database from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial²² to evaluate bridging in patients taking either warfarin or dabigatran. With an open-label study design (the blinding was only for the 110 mg and 150 mg dabigatran doses), clinicians were aware of whether patients were receiving warfarin or dabigatran, thereby facilitating perioperative management. Among dabigatran-treated patients, those who were bridged had significantly more major bleeding than those not bridged (6.5% vs 1.8%, P < .001), with no difference between the groups for stroke or systemic embolism. Although it is not a randomized controlled trial, it does provide evidence that bridging may not be advisable for patients taking a direct oral anticoagulant.

The 2017 American College of Cardiology guidelines²⁵ conclude that parenteral bridging is not indicated for direct oral anticoagulants. Although this is not based on strong evidence, the guidance appears reasonable according to the evidence at hand.

The 2017 American Heart Association Guidelines¹⁶ recommend a somewhat complex approach based on periprocedural bleeding risk and thromboembolic risk.

How long to interrupt direct oral anticoagulants?

Evidence for this approach comes from a prospective cohort study²⁷ of 541 patients being treated with dabigatran who were having an elective surgery or invasive procedure. Patients received standard perioperative management, with the timing of the last dabigatran dose before the procedure (24 hours, 48 hours, or 96 hours) based on the bleeding risk of surgery and the patient’s creatinine clearance. Dabigatran was resumed 24 to 72 hours after the procedure. No heparin bridging was done. Patients were followed for up to 30 days postoperatively. The results were favorable with few complications: one transient ischemic attack (0.2%), 10 major bleeding episodes (1.8%), and 28 minor bleeding episodes (5.2%).

A subgroup of 181 patients in this study²⁸ had a plasma sample drawn just before surgery, allowing the investigators to assess the level of coagulation factors after dabigatran interruption. Results were as follows:

• 93% had a normal prothrombin time 
• 80% had a normal activated partial thromboplastin time
• 33% had a normal thrombin time
• 81% had a normal dilute thrombin time.

The dilute thrombin time is considered the most reliable test of the anticoagulant effect of dabigatran but is not widely available. The activated partial thromboplastin time can provide a more widely used coagulation test to assess (in a less precise manner) whether there is an anticoagulant effect of dabigatran present, and more sensitive activated partial thromboplastin time assays can be used to better detect any residual dabigatran effect.

Dabigatran levels were also measured. Although 66% of patients had low drug levels just before surgery, the others still had substantial dabigatran on board. The fact that bleeding event rates were so low in this study despite the presence of dabigatran in many patients raises the question of whether having some drug on board is a good predictor of bleeding risk.

An interruption protocol with a longer interruption interval—12 to 14 hours longer than in the previous study (3 days for high-bleed risk procedures, 2 days for low-bleed risk procedures)—brought the activated partial thromboplastin time and dilute thrombin time to normal levels for 100% of patients with the protocol for high-bleeding-risk surgery. This study was based on small numbers and its interruption strategy needs further investigation.²⁹

Case 3 continued

The PAUSE study (NCT02228798), a multicenter, prospective cohort study, is designed to establish a safe, standardized protocol for the perioperative management of patients with atrial fibrillation taking dabigatran, rivaroxaban, or apixaban and will include 3,300 patients.

PATIENTS WITH A CORONARY STENT WHO NEED SURGERY

Case 4: A woman with a stent facing surgery

A 70-year-old woman needs breast cancer resection. She has coronary artery disease and had a drug-eluting stent placed 5 months ago after elective cardiac catheterization. She also has hypertension, obesity, and type 2 diabetes. Her medications include an angiotensin II receptor blocker, hydrochlorothiazide, insulin, and an oral hypoglycemic. She is also taking aspirin 81 mg daily and ticagrelor (a P2Y₁₂ receptor antagonist) 90 mg twice daily.

Her cardiologist is concerned that stopping antiplatelet therapy could trigger acute stent thrombosis, which has a 50% or higher mortality rate.

Should she stop taking aspirin before surgery? What about the ticagrelor?

 

 

Is aspirin safe during surgery?

Evidence concerning aspirin during surgery comes from Perioperative Ischemic Evaluation 2 (POISE-2), a double-blind, randomized controlled trial.³⁰ Patients who had known cardiovascular disease or risk factors for cardiovascular disease and were about to undergo noncardiac surgery were stratified according to whether they had been taking aspirin before the study (patients taking aspirin within 72 hours of the surgery were excluded from randomization). Participants in each group were randomized to take either aspirin or placebo just before surgery. The primary outcome was the combined rate of death or nonfatal myocardial infarction 30 days after randomization.

The study found no differences in the primary end point between the two groups. However, major bleeding occurred significantly more often in the aspirin group (4.6% vs 3.8%, hazard ratio 1.2, 95% confidence interval 1.0–1.5).

Moreover, only 4% of the patients in this trial had a cardiac stent. The trial excluded patients who had had a bare-metal stent placed within 6 weeks or a drug-eluting stent placed within 1 year, so it does not help us answer whether aspirin should be stopped for our current patient.

Is surgery safe for patients with stents?

The safety of undergoing surgery with a stent was investigated in a large US Veterans Administration retrospective cohort study.³¹ More than 20,000 patients with stents who underwent noncardiac surgery within 2 years of stent placement were compared with a control group of more than 41,000 patients with stents who did not undergo surgery. Patients were matched by stent type and cardiac risk factors at the time of stent placement.

The risk of an adverse cardiac event in both the surgical and nonsurgical cohorts was highest in the initial 6 weeks after stent placement and plateaued 6 months after stent placement, when the risk difference between the surgical and nonsurgical groups leveled off to 1%.

The risk of a major adverse cardiac event postoperatively was much more dependent on the timing of stent placement in complex and inpatient surgeries. For outpatient surgeries, the risk of a major cardiac event was very low and the timing of stent placement did not matter.

A Danish observational study³² compared more than 4,000 patients with drug-eluting stents having surgery to more than 20,000 matched controls without coronary heart disease having similar surgery. The risk of myocardial infarction or cardiac death was much higher for patients undergoing surgery within 1 month after drug-eluting stent placement compared with controls without heart disease and patients with stent placement longer than 1 month before surgery.

Our practice is to continue aspirin for surgery in patients with coronary stents regardless of the timing of placement. Although there is a small increased risk of bleeding, this must be balanced against thrombotic risk. We typically stop clopidogrel 5 to 7 days before surgery and ticagrelor 3 to 5 days before surgery. We may decide to give platelets before very-high-risk surgery (eg, intracranial, spinal) if there is a decision to continue both antiplatelet drugs—for example, in a patient who recently received a drug-eluting stent (ie, within 3 months). It is essential to involve the cardiologist and surgeon in these decisions.

BOTTOM LINE

This article reviews recommendations and evidence concerning current anticoagulant management for venous thromboembolism and perioperative care, with an emphasis on individualizing treatment for real-world patients.

TREATING ACUTE VENOUS THROMBOEMBOLISM

Case 1: Deep vein thrombosis in an otherwise healthy man

A 40-year-old man presents with 7 days of progressive right leg swelling. He has no antecedent risk factors for deep vein thrombosis or other medical problems. Venous ultrasonography reveals an iliofemoral deep vein thrombosis. How should he be managed?

• Outpatient treatment with low-molecular-weight heparin for 4 to 6 days plus warfarin
• Outpatient treatment with a direct oral anticoagulant, ie, apixaban, dabigatran (which requires 4 to 6 days of initial treatment with low-molecular-weight heparin), or rivaroxaban
• Catheter-directed thrombolysis followed by low-molecular-weight heparin, then warfarin or a direct oral anticoagulant
• Inpatient intravenous heparin for 7 to 10 days, then warfarin or a direct oral anticoagulant

All of these are acceptable for managing acute venous thromboembolism, but the clinician’s role is to identify which treatment is most appropriate for an individual patient.

Deep vein thrombosis is not a single condition

Multiple guidelines exist to help decide on a management strategy. Those of the American College of Chest Physicians (ACCP)¹ are used most often.

That said, guidelines are established for “average” patients, so it is important to look beyond guidelines and individualize management. Venous thromboembolism is not a single entity; it has a myriad of clinical presentations that could call for different treatments. Most patients have submassive deep vein thrombosis or pulmonary embolism, which is not limb-threatening nor associated with hemodynamic instability. It can also differ in terms of etiology and can be unprovoked (or idiopathic), cancer-related, catheter-associated, or provoked by surgery or immobility.

Deep vein thrombosis has a wide spectrum of presentations. It can involve the veins of the calf only, or it can involve the femoral and iliac veins and other locations including the splanchnic veins, the cerebral sinuses, and upper extremities. Pulmonary embolism can be massive (defined as being associated with hemodynamic instability or impending respiratory failure) or submassive. Similarly, patients differ in terms of baseline medical conditions, mobility, and lifestyle. Anticoagulant management decisions should take all these factors into account.

Consider clot location

Our patient with iliofemoral deep vein thrombosis is best managed differently than a more typical patient with less extensive thrombosis that would involve the popliteal or femoral vein segments, or both. A clot that involves the iliac vein is more likely to lead to postthrombotic chronic pain and swelling as the lack of venous outflow bypass channels to circumvent the clot location creates higher venous pressure within the affected leg. Therefore, for our patient, catheter-directed thrombolysis is an option that should be considered.

Catheter-directed thrombolysis trials

According to the “open-vein hypothesis,” quickly eliminating the thrombus and restoring unobstructed venous flow may mitigate the risk not only of recurrent thrombosis, but also of postthrombotic syndrome, which is often not given much consideration acutely but can cause significant, life-altering chronic disability.

The “valve-integrity hypothesis” is also important; it considers whether lytic therapy may help prevent damage to such valves in an attempt to mitigate the amount of venous hypertension.

Thus, catheter-directed thrombolysis offers theoretical benefits, and recent trials have assessed it against standard anticoagulation treatments.

The CaVenT trial (Catheter-Directed Venous Thrombolysis),² conducted in Norway, randomized 209 patients with midfemoral to iliac deep vein thrombosis to conventional treatment (anticoagulation alone) or anticoagulation plus catheter-directed thrombolysis. At 2 years, postthrombotic syndrome had occurred in 41% of the catheter-directed thrombolysis group compared with 56% of the conventional treatment group (P = .047). At 5 years, the difference widened to 43% vs 71% (P < .01, number needed to treat = 4).³ Despite the superiority of lytic therapy, the incidence of postthrombotic syndrome remained high in patients who received this treatment. 

The ATTRACT trial (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis),⁴ a US multicenter, open-label, assessor-blind study, randomized 698 patients with femoral or more-proximal deep vein thrombosis to either standard care (anticoagulant therapy and graduated elastic compression stockings) or standard care plus catheter-directed thrombolysis. In preliminary results presented at the Society of Interventional Radiology meeting in March 2017, although no difference was found in the primary outcome (postthrombotic syndrome at 24 months), catheter-directed thrombolysis for iliofemoral deep vein thrombosis led to a 25% reduction in moderate to severe postthrombotic syndrome.

Although it is too early to draw conclusions before publication of the ATTRACT study, the preliminary results highlight the need to individualize treatment and to be selective about using catheter-directed thrombolysis. The trials provide reassurance that catheter-directed lysis is a reasonable and safe intervention when performed by physicians experienced in the procedure. The risk of major bleeding appears to be low (about 2%) and that for intracranial hemorrhage even lower (< 0.5%).

Catheter-directed thrombolysis is appropriate in some cases

The 2016 ACCP guidelines¹ recommend anticoagulant therapy alone over catheter-directed thrombolysis for patients with acute proximal deep vein thrombosis of the leg. However, it is a grade 2C (weak) recommendation.

They provide no specific recommendation as to the clinical indications for catheter-directed thrombolysis, but identify patients who would be most likely to benefit, ie, those who have: 

• Iliofemoral deep vein thrombosis
• Symptoms for less than 14 days
• Good functional status
• Life expectancy of more than 1 year
• Low risk of bleeding.

Our patient satisfies these criteria, suggesting that catheter-directed thrombolysis is a reasonable option for him. 

Timing is important. Catheter-directed lysis is more likely to be beneficial if used before fibrin deposits form and stiffen the venous valves, causing irreversible damage that leads to postthrombotic syndrome. 

 

 

Role of direct oral anticoagulants

The availability of direct oral anticoagulants has generated interest in defining their therapeutic role in patients with venous thromboembolism.

In a meta-analysis⁵ of major trials comparing direct oral anticoagulants and vitamin K antagonists such as warfarin, no significant difference was found for the risk of recurrent venous thromboembolism or venous thromboembolism-related deaths. However, fewer patients experienced major bleeding with direct oral anticoagulants (relative risk 0.61, P = .002). Although significant, the absolute risk reduction was small; the incidence of major bleeding was 1.1% with direct oral anticoagulants vs 1.8% with vitamin K antagonists.

The main advantage of direct oral anticoagulants is greater convenience for the patient.

WHICH PATIENTS ON WARFARIN NEED BRIDGING PREOPERATIVELY?

Many patients still take warfarin, particularly those with atrial fibrillation, a mechanical heart valve, or venous thromboembolism. In many countries, warfarin remains the dominant anticoagulant for stroke prevention. Whether these patients need heparin during the period of perioperative warfarin interruption is a frequently encountered scenario that, until recently, was controversial. Recent studies have helped to inform the need for heparin bridging in many of these patients.

Case 2: An elderly woman on warfarin facing cancer surgery

A 75-year-old woman weighing 65 kg is scheduled for elective colon resection for incidentally found colon cancer. She is taking warfarin for atrial fibrillation. She also has hypertension and diabetes and had a transient ischemic attack 10 years ago.

One doctor told her she needs to be assessed for heparin bridging, but another told her she does not need bridging.

The default management should be not to bridge patients who have atrial fibrillation, but to consider bridging in selected patients, such as those with recent stroke or transient ischemic attack or a prior thromboembolic event during warfarin interruption. However, decisions about bridging should not be made on the basis of the CHADS₂ score alone. For the patient described here, I would recommend not bridging.

Complex factors contribute to stroke risk

Stroke risk for patients with atrial fibrillation can be quickly estimated with the CHADS₂ score, based on: 

• Congestive heart failure (1 point)
• Hypertension (1 point)
• Age at least 75 (1 point)
• Diabetes (1 point)
• Stroke or transient ischemic attack (2 points).

Our patient has a score of 5, corresponding to an annual adjusted stroke risk of 12.5%. Whether her transient ischemic attack of 10 years ago is comparable in significance to a recent stroke is debatable and highlights a weakness of clinical prediction rules. Moreover, such prediction scores were developed to estimate the long-term risk of stroke if anticoagulants are not given, and they have not been assessed in a perioperative setting where there is short-term interruption of anticoagulants. Also, the perioperative milieu is associated with additional factors not captured in these clinical prediction rules that may affect the risk of stroke.

Thus, the risk of perioperative stroke likely involves the interplay of multiple factors, including the type of surgery the patient is undergoing. Some factors may be mitigated:

• Rebound hypercoagulability after stopping an oral anticoagulant can be prevented by intraoperative blood pressure and volume control
• Elevated biochemical factors (eg, D-dimer, B-type natriuretic peptide, troponin) may be lowered with perioperative aspirin therapy
• Lipid and genetic factors may be mitigated with perioperative statin use.

Can heparin bridging also mitigate the risk?

Bridging in patients with atrial fibrillation

Most patients who are taking warfarin are doing so because of atrial fibrillation, so most evidence about perioperative bridging was developed in such patients.

The BRIDGE trial (Bridging Anticoagulation in Patients Who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery)⁶ was the first randomized controlled trial to compare a bridging and no-bridging strategy for patients with atrial fibrillation who required warfarin interruption for elective surgery. Nearly 2,000 patients were given either low-molecular-weight heparin or placebo starting 3 days before until 24 hours before a procedure, and then for 5 to 10 days afterwards. For all patients, warfarin was stopped 5 days before the procedure and was resumed within 24 hours afterwards.

A no-bridging strategy was noninferior to bridging: the risk of perioperative arterial thromboembolism was 0.4% without bridging vs 0.3% with bridging (P = .01 for noninferiority). In addition, a no-bridging strategy conferred a lower risk of major bleeding than bridging: 1.3% vs 3.2% (relative risk 0.41, P = .005 for superiority).

Although the difference in absolute bleeding risk was small, bleeding rates were lower than those seen outside of clinical trials, as the bridging protocol used in BRIDGE was designed to minimize the risk of bleeding. Also, although only 5% of patients had a CHADS₂ score of 5 or 6, such patients are infrequent in clinical practice, and BRIDGE did include a considerable proportion (17%) of patients with a prior stroke or transient ischemic attack who would be considered at high risk.

Other evidence about heparin bridging is derived from observational studies, more than 10 of which have been conducted. In general, they have found that not bridging is associated with low rates of arterial thromboembolism (< 0.5%) and that bridging is associated with high rates of major bleeding (4%–7%).^7–12

Bridging in patients with a mechanical heart valve

Warfarin is the only anticoagulant option for patients who have a mechanical heart valve. No randomized controlled trials have evaluated the benefits of perioperative bridging vs no bridging in this setting.

Observational (cohort) studies suggest that the risk of perioperative arterial thromboembolism is similar with or without bridging anticoagulation, although most patients studied were bridged and those not bridged were considered at low risk (eg, with a bileaflet aortic valve and no additional risk factors).¹³ However, without stronger evidence from randomized controlled trials, bridging should be the default management for patients with a mechanical heart valve. In our practice, we bridge most patients who have a mechanical heart valve unless they are considered to be at low risk, such as those who have a bileaflet aortic valve.

 

 

Bridging in patients with prior venous thromboembolism

Even less evidence is available for periprocedural management of patients who have a history of venous thromboembolism. No randomized controlled trials exist evaluating bridging vs no bridging. In 1 cohort study in which more than 90% of patients had had thromboembolism more than 3 months before the procedure, the rate of recurrent venous thromboembolism without bridging was less than 0.5%.¹⁴

It is reasonable to bridge patients who need anticoagulant interruption within 3 months of diagnosis of a deep vein thrombosis or pulmonary embolism, and to consider using a temporary inferior vena cava filter for patients who have had a clot who need treatment interruption during the initial 3 to 4 weeks after diagnosis.

Practice guidelines: Perioperative anticoagulation

Guidance for preoperative and postoperative bridging for patients taking warfarin is summarized in Table 2.

CARDIAC PROCEDURES

For patients facing a procedure to implant an implantable cardioverter-defibrillator (ICD) or pacemaker, a procedure-specific concern is the avoidance of pocket hematoma.

Patients on warfarin: Do not bridge

The BRUISE CONTROL-1 trial (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial)¹⁹ randomized patients undergoing pacemaker or ICD implantation to either continued anticoagulation therapy and not bridging (ie, continued warfarin so long as the international normalized ratio was < 3) vs conventional bridging treatment (ie, stopping warfarin and bridging with low-molecular-weight heparin). A clinically significant device-pocket hematoma occurred in 3.5% of the continued-warfarin group vs 16.0% in the heparin-bridging group (P < .001). Thromboembolic complications were rare, and rates did not differ between the 2 groups.

Results of the BRUISE CONTROL-1 trial serve as a caution to at least not be too aggressive with bridging. The study design involved resuming heparin 24 hours after surgery, which is perhaps more aggressive than standard practice. In our practice, we wait at least 24 hours to reinstate heparin after minor surgery, and 48 to 72 hours after surgery with higher bleeding risk.

These results are perhaps not surprising if one considers how carefully surgeons try to control bleeding during surgery for patients taking anticoagulants. For patients who are not on an anticoagulant, small bleeding may be less of a concern during a procedure. When high doses of heparin are introduced soon after surgery, small concerns during surgery may become big problems afterward.

Based on these results, it is reasonable to undertake device implantation without interruption of a vitamin K antagonist such as warfarin.

Patients on direct oral anticoagulants: The jury is still out

The similar BRUISE CONTROL-2 trial is currently under way, comparing interruption vs continuation of dabigatran for patients undergoing cardiac device surgery.

In Europe, surgeons are less concerned than those in the United States about operating while a patient is on anticoagulant therapy. But the safety of this practice is not backed by strong evidence.

Direct oral anticoagulants: Consider pharmacokinetics

Direct oral anticoagulants are potent and fast-acting, with a peak effect 1 to 3 hours after intake. This rapid anticoagulant action is similar to that of bridging with low-molecular-weight heparin, and caution is needed when administering direct oral anticoagulants, especially after major surgery or surgery with a high bleeding risk.

Frost et al²⁰ compared the pharmacokinetics of apixaban (with twice-daily dosing) and rivaroxaban (once-daily dosing) and found that peak anticoagulant activity is faster and higher with rivaroxaban. This is important, because many patients will take their anticoagulant first thing in the morning. Consequently, if patients require any kind of procedure (including dental), they should skip the morning dose of the direct oral anticoagulant to avoid having the procedure done during the peak anticoagulant effect, and they should either not take that day’s dose or defer the dose until the evening after the procedure. 

MANAGING SURGERY FOR PATIENTS ON A DIRECT ORAL ANTICOAGULANT

Case 3: An elderly woman on apixaban facing surgery

Let us imagine that our previous patient takes apixaban instead of warfarin. She is 75 years old, has atrial fibrillation, and is about to undergo elective colon resection for cancer. One doctor advises her to simply stop apixaban for 2 days, while another says she should go off apixaban for 5 days and will need bridging. Which plan is best?

In the perioperative setting, our goal is to interrupt patients’ anticoagulant therapy for the shortest time that results in no residual anticoagulant effect at the time of the procedure. 

They further recommend that if the risk of venous thromboembolism is high, low-molecular-weight heparin bridging should be done while stopping the direct oral anticoagulant, with the heparin discontinued 24 hours before the procedure. This recommendation seems counterintuitive, as it is advising replacing a short-acting anticoagulant with low-molecular-weight heparin, another short-acting anticoagulant.

The guidelines committee was unable to provide strength and grading of their recommendations, as too few well-designed studies are available to support them. The doctor in case 3 who advised stopping apixaban for 5 days and bridging is following the guidelines, but without much evidence to support this strategy.

 

 

Is bridging needed during interruption of a direct oral anticoagulant?

There are no randomized, controlled trials of bridging vs no bridging in patients taking direct oral anticoagulants. Substudies exist of patients taking these drugs for atrial fibrillation who had treatment interrupted for procedures, but the studies did not randomize bridging vs no bridging, nor were bridging regimens standardized. Three of the four atrial fibrillation trials had a blinded design (warfarin vs direct oral anticoagulants), making perioperative management difficult, as physicians did not know the pharmacokinetics of the drugs their patients were taking.^22–24

We used the database from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial²² to evaluate bridging in patients taking either warfarin or dabigatran. With an open-label study design (the blinding was only for the 110 mg and 150 mg dabigatran doses), clinicians were aware of whether patients were receiving warfarin or dabigatran, thereby facilitating perioperative management. Among dabigatran-treated patients, those who were bridged had significantly more major bleeding than those not bridged (6.5% vs 1.8%, P < .001), with no difference between the groups for stroke or systemic embolism. Although it is not a randomized controlled trial, it does provide evidence that bridging may not be advisable for patients taking a direct oral anticoagulant.

The 2017 American College of Cardiology guidelines²⁵ conclude that parenteral bridging is not indicated for direct oral anticoagulants. Although this is not based on strong evidence, the guidance appears reasonable according to the evidence at hand.

The 2017 American Heart Association Guidelines¹⁶ recommend a somewhat complex approach based on periprocedural bleeding risk and thromboembolic risk.

How long to interrupt direct oral anticoagulants?

Evidence for this approach comes from a prospective cohort study²⁷ of 541 patients being treated with dabigatran who were having an elective surgery or invasive procedure. Patients received standard perioperative management, with the timing of the last dabigatran dose before the procedure (24 hours, 48 hours, or 96 hours) based on the bleeding risk of surgery and the patient’s creatinine clearance. Dabigatran was resumed 24 to 72 hours after the procedure. No heparin bridging was done. Patients were followed for up to 30 days postoperatively. The results were favorable with few complications: one transient ischemic attack (0.2%), 10 major bleeding episodes (1.8%), and 28 minor bleeding episodes (5.2%).

A subgroup of 181 patients in this study²⁸ had a plasma sample drawn just before surgery, allowing the investigators to assess the level of coagulation factors after dabigatran interruption. Results were as follows:

• 93% had a normal prothrombin time 
• 80% had a normal activated partial thromboplastin time
• 33% had a normal thrombin time
• 81% had a normal dilute thrombin time.

The dilute thrombin time is considered the most reliable test of the anticoagulant effect of dabigatran but is not widely available. The activated partial thromboplastin time can provide a more widely used coagulation test to assess (in a less precise manner) whether there is an anticoagulant effect of dabigatran present, and more sensitive activated partial thromboplastin time assays can be used to better detect any residual dabigatran effect.

Dabigatran levels were also measured. Although 66% of patients had low drug levels just before surgery, the others still had substantial dabigatran on board. The fact that bleeding event rates were so low in this study despite the presence of dabigatran in many patients raises the question of whether having some drug on board is a good predictor of bleeding risk.

An interruption protocol with a longer interruption interval—12 to 14 hours longer than in the previous study (3 days for high-bleed risk procedures, 2 days for low-bleed risk procedures)—brought the activated partial thromboplastin time and dilute thrombin time to normal levels for 100% of patients with the protocol for high-bleeding-risk surgery. This study was based on small numbers and its interruption strategy needs further investigation.²⁹

Case 3 continued

The PAUSE study (NCT02228798), a multicenter, prospective cohort study, is designed to establish a safe, standardized protocol for the perioperative management of patients with atrial fibrillation taking dabigatran, rivaroxaban, or apixaban and will include 3,300 patients.

PATIENTS WITH A CORONARY STENT WHO NEED SURGERY

Case 4: A woman with a stent facing surgery

A 70-year-old woman needs breast cancer resection. She has coronary artery disease and had a drug-eluting stent placed 5 months ago after elective cardiac catheterization. She also has hypertension, obesity, and type 2 diabetes. Her medications include an angiotensin II receptor blocker, hydrochlorothiazide, insulin, and an oral hypoglycemic. She is also taking aspirin 81 mg daily and ticagrelor (a P2Y₁₂ receptor antagonist) 90 mg twice daily.

Her cardiologist is concerned that stopping antiplatelet therapy could trigger acute stent thrombosis, which has a 50% or higher mortality rate.

Should she stop taking aspirin before surgery? What about the ticagrelor?

 

 

Is aspirin safe during surgery?

Evidence concerning aspirin during surgery comes from Perioperative Ischemic Evaluation 2 (POISE-2), a double-blind, randomized controlled trial.³⁰ Patients who had known cardiovascular disease or risk factors for cardiovascular disease and were about to undergo noncardiac surgery were stratified according to whether they had been taking aspirin before the study (patients taking aspirin within 72 hours of the surgery were excluded from randomization). Participants in each group were randomized to take either aspirin or placebo just before surgery. The primary outcome was the combined rate of death or nonfatal myocardial infarction 30 days after randomization.

The study found no differences in the primary end point between the two groups. However, major bleeding occurred significantly more often in the aspirin group (4.6% vs 3.8%, hazard ratio 1.2, 95% confidence interval 1.0–1.5).

Moreover, only 4% of the patients in this trial had a cardiac stent. The trial excluded patients who had had a bare-metal stent placed within 6 weeks or a drug-eluting stent placed within 1 year, so it does not help us answer whether aspirin should be stopped for our current patient.

Is surgery safe for patients with stents?

The safety of undergoing surgery with a stent was investigated in a large US Veterans Administration retrospective cohort study.³¹ More than 20,000 patients with stents who underwent noncardiac surgery within 2 years of stent placement were compared with a control group of more than 41,000 patients with stents who did not undergo surgery. Patients were matched by stent type and cardiac risk factors at the time of stent placement.

The risk of an adverse cardiac event in both the surgical and nonsurgical cohorts was highest in the initial 6 weeks after stent placement and plateaued 6 months after stent placement, when the risk difference between the surgical and nonsurgical groups leveled off to 1%.

The risk of a major adverse cardiac event postoperatively was much more dependent on the timing of stent placement in complex and inpatient surgeries. For outpatient surgeries, the risk of a major cardiac event was very low and the timing of stent placement did not matter.

A Danish observational study³² compared more than 4,000 patients with drug-eluting stents having surgery to more than 20,000 matched controls without coronary heart disease having similar surgery. The risk of myocardial infarction or cardiac death was much higher for patients undergoing surgery within 1 month after drug-eluting stent placement compared with controls without heart disease and patients with stent placement longer than 1 month before surgery.

Our practice is to continue aspirin for surgery in patients with coronary stents regardless of the timing of placement. Although there is a small increased risk of bleeding, this must be balanced against thrombotic risk. We typically stop clopidogrel 5 to 7 days before surgery and ticagrelor 3 to 5 days before surgery. We may decide to give platelets before very-high-risk surgery (eg, intracranial, spinal) if there is a decision to continue both antiplatelet drugs—for example, in a patient who recently received a drug-eluting stent (ie, within 3 months). It is essential to involve the cardiologist and surgeon in these decisions.

BOTTOM LINE