Mortality Risk in Patients Older than 75 Presenting with Non-ST-Elevation Acute Coronary Syndrome

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Mortality Risk in Patients Older than 75 Presenting with Non-ST-Elevation Acute Coronary Syndrome

Clinical question: Is there a score that will predict the mortality rate in elderly patients presenting with a non-ST-elevation myocardial infarction (NSTEMI)?

Background: Although they represent only 9% of patients in clinical trials, patients over the age of 75 make up one third of patients with NSTEMI, accounting for more than half of NSTEMI-related mortality.

Study design: Retrospective cohort analysis for score calculator design, with prospective cohort validation.

Setting: The retrospective cohort was derived from a meta-analysis of 55 papers. The prospective validation arm used a cohort of patients from a randomized multicenter Italian trial.

Synopsis: The authors developed and validated a mortality predictor for patients 75 and older who present with an NSTEMI. The calculator: hemoglobin less than 10 g/dl (two points), elevated troponin levels, ECG ischemic changes, estimated glomerular filtration rate (eGFR) less than 45, previous vascular event (one point each two). The calculator predicted probabilities of death in one year ranging from 2% (score of zero) to 75% (score of six). The calculator allowed stratification into low (score: zero to one), intermediate (score: two), or high (score: three or greater) risk. High-risk patients appeared to benefit from intervention with significantly reduced risk for mortality (odds ratio 0.44).

Bottom line: A simple risk calculator stratifies elderly patients into low, intermediate, or high risk to predict mortality from NSTEMI. High-risk patients appear to achieve a mortality benefit from intervention.

Citation: Angeli F, Cavallini C, Verdecchia P, et al. A risk score for predicting 1-year mortality in patients ≥75 years of age presenting with non-ST-elevation acute coronary syndrome. Am J Cardiol. 2015;116(2):208-213.

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Clinical question: Is there a score that will predict the mortality rate in elderly patients presenting with a non-ST-elevation myocardial infarction (NSTEMI)?

Background: Although they represent only 9% of patients in clinical trials, patients over the age of 75 make up one third of patients with NSTEMI, accounting for more than half of NSTEMI-related mortality.

Study design: Retrospective cohort analysis for score calculator design, with prospective cohort validation.

Setting: The retrospective cohort was derived from a meta-analysis of 55 papers. The prospective validation arm used a cohort of patients from a randomized multicenter Italian trial.

Synopsis: The authors developed and validated a mortality predictor for patients 75 and older who present with an NSTEMI. The calculator: hemoglobin less than 10 g/dl (two points), elevated troponin levels, ECG ischemic changes, estimated glomerular filtration rate (eGFR) less than 45, previous vascular event (one point each two). The calculator predicted probabilities of death in one year ranging from 2% (score of zero) to 75% (score of six). The calculator allowed stratification into low (score: zero to one), intermediate (score: two), or high (score: three or greater) risk. High-risk patients appeared to benefit from intervention with significantly reduced risk for mortality (odds ratio 0.44).

Bottom line: A simple risk calculator stratifies elderly patients into low, intermediate, or high risk to predict mortality from NSTEMI. High-risk patients appear to achieve a mortality benefit from intervention.

Citation: Angeli F, Cavallini C, Verdecchia P, et al. A risk score for predicting 1-year mortality in patients ≥75 years of age presenting with non-ST-elevation acute coronary syndrome. Am J Cardiol. 2015;116(2):208-213.

Clinical question: Is there a score that will predict the mortality rate in elderly patients presenting with a non-ST-elevation myocardial infarction (NSTEMI)?

Background: Although they represent only 9% of patients in clinical trials, patients over the age of 75 make up one third of patients with NSTEMI, accounting for more than half of NSTEMI-related mortality.

Study design: Retrospective cohort analysis for score calculator design, with prospective cohort validation.

Setting: The retrospective cohort was derived from a meta-analysis of 55 papers. The prospective validation arm used a cohort of patients from a randomized multicenter Italian trial.

Synopsis: The authors developed and validated a mortality predictor for patients 75 and older who present with an NSTEMI. The calculator: hemoglobin less than 10 g/dl (two points), elevated troponin levels, ECG ischemic changes, estimated glomerular filtration rate (eGFR) less than 45, previous vascular event (one point each two). The calculator predicted probabilities of death in one year ranging from 2% (score of zero) to 75% (score of six). The calculator allowed stratification into low (score: zero to one), intermediate (score: two), or high (score: three or greater) risk. High-risk patients appeared to benefit from intervention with significantly reduced risk for mortality (odds ratio 0.44).

Bottom line: A simple risk calculator stratifies elderly patients into low, intermediate, or high risk to predict mortality from NSTEMI. High-risk patients appear to achieve a mortality benefit from intervention.

Citation: Angeli F, Cavallini C, Verdecchia P, et al. A risk score for predicting 1-year mortality in patients ≥75 years of age presenting with non-ST-elevation acute coronary syndrome. Am J Cardiol. 2015;116(2):208-213.

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Risk-Prediction Model Effective for Recurrent Clostridium Difficile Infection

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Risk-Prediction Model Effective for Recurrent Clostridium Difficile Infection

Clinical question: What risk factors identified at the onset of illness are associated with recurrent C. diff infection (CDI)?

Background: After initial infection, 10%–25% of patients experience recurrent CDI. The identification of patients at high risk of recurrence would be beneficial for therapeutic decision-making.

Study design: Retrospective cohort study.

Setting: Large, urban, academic medical center.

Synopsis: Authors included 4,196 patients with an initial infection defined by a positive C. diff toxin assay and unformed stools. A repeat positive toxin within 42 days of completing treatment for the initial infection represented recurrent CDI. Multiple characteristics were examined to identify risks of recurrent infection, including demographics and those related to acute and chronic disease. A logistic regression model was used to identify risk factors for recurrence. Recurrent CDI occurred in 425 patients (10.1%). Age, fluoroquinolone and high-risk antibiotic use, community-acquired healthcare-associated infection, multiple hospitalizations, and gastric acid suppression were found to predict recurrent infection through multivariate analysis. Limitations of the study included potential confounding, use of observational data, and generalizability given the urban academic medical center setting. This prediction model differs from previously developed models in that it identifies factors present at the onset of infection.

Bottom line: Multiple factors identified at the onset of illness can predict CDI recurrence.

Citation: Zilberberg MD, Reske K, Olsen M, Yan Y, Dubberke ER. Development and validation of a recurrent Clostridium difficile risk-prediction model. J Hosp Med. 2014;9(7):418-423. TH

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Clinical question: What risk factors identified at the onset of illness are associated with recurrent C. diff infection (CDI)?

Background: After initial infection, 10%–25% of patients experience recurrent CDI. The identification of patients at high risk of recurrence would be beneficial for therapeutic decision-making.

Study design: Retrospective cohort study.

Setting: Large, urban, academic medical center.

Synopsis: Authors included 4,196 patients with an initial infection defined by a positive C. diff toxin assay and unformed stools. A repeat positive toxin within 42 days of completing treatment for the initial infection represented recurrent CDI. Multiple characteristics were examined to identify risks of recurrent infection, including demographics and those related to acute and chronic disease. A logistic regression model was used to identify risk factors for recurrence. Recurrent CDI occurred in 425 patients (10.1%). Age, fluoroquinolone and high-risk antibiotic use, community-acquired healthcare-associated infection, multiple hospitalizations, and gastric acid suppression were found to predict recurrent infection through multivariate analysis. Limitations of the study included potential confounding, use of observational data, and generalizability given the urban academic medical center setting. This prediction model differs from previously developed models in that it identifies factors present at the onset of infection.

Bottom line: Multiple factors identified at the onset of illness can predict CDI recurrence.

Citation: Zilberberg MD, Reske K, Olsen M, Yan Y, Dubberke ER. Development and validation of a recurrent Clostridium difficile risk-prediction model. J Hosp Med. 2014;9(7):418-423. TH

Clinical question: What risk factors identified at the onset of illness are associated with recurrent C. diff infection (CDI)?

Background: After initial infection, 10%–25% of patients experience recurrent CDI. The identification of patients at high risk of recurrence would be beneficial for therapeutic decision-making.

Study design: Retrospective cohort study.

Setting: Large, urban, academic medical center.

Synopsis: Authors included 4,196 patients with an initial infection defined by a positive C. diff toxin assay and unformed stools. A repeat positive toxin within 42 days of completing treatment for the initial infection represented recurrent CDI. Multiple characteristics were examined to identify risks of recurrent infection, including demographics and those related to acute and chronic disease. A logistic regression model was used to identify risk factors for recurrence. Recurrent CDI occurred in 425 patients (10.1%). Age, fluoroquinolone and high-risk antibiotic use, community-acquired healthcare-associated infection, multiple hospitalizations, and gastric acid suppression were found to predict recurrent infection through multivariate analysis. Limitations of the study included potential confounding, use of observational data, and generalizability given the urban academic medical center setting. This prediction model differs from previously developed models in that it identifies factors present at the onset of infection.

Bottom line: Multiple factors identified at the onset of illness can predict CDI recurrence.

Citation: Zilberberg MD, Reske K, Olsen M, Yan Y, Dubberke ER. Development and validation of a recurrent Clostridium difficile risk-prediction model. J Hosp Med. 2014;9(7):418-423. TH

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Higher Mean Arterial Pressure in Septic Shock Patients Doesn’t Decrease Mortality

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Higher Mean Arterial Pressure in Septic Shock Patients Doesn’t Decrease Mortality

Clinical question: Does targeting a higher mean arterial pressure (MAP) in patients with septic shock lead to decreased mortality compared with targeting a more typical MAP range?

Background: The ideal blood pressure target for patients with septic shock is not currently known. There is some clinical evidence that patients with chronic arterial hypertension may require higher blood pressure to sustain kidney function.

Study design: Multicenter, randomized, stratified, open-label clinical trial.

Setting: ICUs at 29 centers in France

Synopsis: Researchers randomized 776 patients with septic shock to receive vasopressor treatment to maintain a MAP of 80-85 mmHg (high-target group) or 65-70 mmHg (low-target group). There was no significant difference between groups in the primary outcome of death at 28 days (HR in the high target group 1.07; 95% CI 0.84-1.38; P=0.57).

In patients with chronic arterial hypertension, those who were randomized to the high-target group had a reduced risk of doubling of plasma creatinine or need for renal-replacement therapy from days one to seven. Patients in the high-target group received larger amounts of vasopressors and for a longer period of time. There was no difference between the groups in the overall incidence of serious adverse events, though significantly more patients in the high-target group (6.7%) developed new onset atrial fibrillation compared with those in the low-target group (2.8%).

Bottom line: Mortality at 28 days was not significantly different in patients with septic shock who were randomized to a higher MAP target compared to patients who had a lower MAP target; this lower target encompasses the 65 mmHg target that is listed in the Surviving Sepsis Campaign guidelines.

Citation: Asfar P, Meziani F, Hamel JF, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370(17):1583-1593.

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Clinical question: Does targeting a higher mean arterial pressure (MAP) in patients with septic shock lead to decreased mortality compared with targeting a more typical MAP range?

Background: The ideal blood pressure target for patients with septic shock is not currently known. There is some clinical evidence that patients with chronic arterial hypertension may require higher blood pressure to sustain kidney function.

Study design: Multicenter, randomized, stratified, open-label clinical trial.

Setting: ICUs at 29 centers in France

Synopsis: Researchers randomized 776 patients with septic shock to receive vasopressor treatment to maintain a MAP of 80-85 mmHg (high-target group) or 65-70 mmHg (low-target group). There was no significant difference between groups in the primary outcome of death at 28 days (HR in the high target group 1.07; 95% CI 0.84-1.38; P=0.57).

In patients with chronic arterial hypertension, those who were randomized to the high-target group had a reduced risk of doubling of plasma creatinine or need for renal-replacement therapy from days one to seven. Patients in the high-target group received larger amounts of vasopressors and for a longer period of time. There was no difference between the groups in the overall incidence of serious adverse events, though significantly more patients in the high-target group (6.7%) developed new onset atrial fibrillation compared with those in the low-target group (2.8%).

Bottom line: Mortality at 28 days was not significantly different in patients with septic shock who were randomized to a higher MAP target compared to patients who had a lower MAP target; this lower target encompasses the 65 mmHg target that is listed in the Surviving Sepsis Campaign guidelines.

Citation: Asfar P, Meziani F, Hamel JF, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370(17):1583-1593.

Clinical question: Does targeting a higher mean arterial pressure (MAP) in patients with septic shock lead to decreased mortality compared with targeting a more typical MAP range?

Background: The ideal blood pressure target for patients with septic shock is not currently known. There is some clinical evidence that patients with chronic arterial hypertension may require higher blood pressure to sustain kidney function.

Study design: Multicenter, randomized, stratified, open-label clinical trial.

Setting: ICUs at 29 centers in France

Synopsis: Researchers randomized 776 patients with septic shock to receive vasopressor treatment to maintain a MAP of 80-85 mmHg (high-target group) or 65-70 mmHg (low-target group). There was no significant difference between groups in the primary outcome of death at 28 days (HR in the high target group 1.07; 95% CI 0.84-1.38; P=0.57).

In patients with chronic arterial hypertension, those who were randomized to the high-target group had a reduced risk of doubling of plasma creatinine or need for renal-replacement therapy from days one to seven. Patients in the high-target group received larger amounts of vasopressors and for a longer period of time. There was no difference between the groups in the overall incidence of serious adverse events, though significantly more patients in the high-target group (6.7%) developed new onset atrial fibrillation compared with those in the low-target group (2.8%).

Bottom line: Mortality at 28 days was not significantly different in patients with septic shock who were randomized to a higher MAP target compared to patients who had a lower MAP target; this lower target encompasses the 65 mmHg target that is listed in the Surviving Sepsis Campaign guidelines.

Citation: Asfar P, Meziani F, Hamel JF, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370(17):1583-1593.

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Infection Risk Decreases With Lower Red Blood Cell Transfusion Thresholds

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Infection Risk Decreases With Lower Red Blood Cell Transfusion Thresholds

Clinical question: Do different thresholds for red blood cell (RBC) transfusion influence the risk of infection, and does leukocyte reduction also influence the risk of infection?

Background: RBC transfusion is a common and costly medical intervention performed across U.S. hospitals. Scientists suspect that RBC transfusion may have immunomodulatory properties and may affect a patient’s risk of acquiring various infections.

Study design: Meta-analysis and systematic review.

Setting: International adult, pediatric, obstetric medical and surgical wards, and ICUs.

Synopsis: Eighteen studies performed were included in the meta-analysis of published randomized trials comparing restrictive to liberal RBC transfusion strategies in which infectious outcomes were reported. Patient enrollment spanned from 1994 to 2012. Six of the trials included pediatric patients. For adult patients, the restrictive RBC transfusion threshold ranged from 6.4–9.7 g/dL, while the liberal target ranged from 9-11.3 g/dL in included trials.

The overall pooled risk ratio for the association of restrictive vs. liberal transfusion threshold with infection was 0.99 (95% CI, 0.78-0.99; P=0.033). A decreased risk of infection with the use of a restrictive transfusion compared with a liberal threshold persisted in studies of leukocyte-reduced blood products.

Bottom line: Restrictive RBC transfusion thresholds are associated with a decreased risk of acquiring healthcare-associated infections compared with liberal transfusion thresholds.

Citation: Rohde JM, Dimcheff DE, Blumberg N, et al. Health care-associated infection after red blood cell transfusion: A systematic review and meta-analysis. JAMA. 2014;311(13):1317-1326.

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Clinical question: Do different thresholds for red blood cell (RBC) transfusion influence the risk of infection, and does leukocyte reduction also influence the risk of infection?

Background: RBC transfusion is a common and costly medical intervention performed across U.S. hospitals. Scientists suspect that RBC transfusion may have immunomodulatory properties and may affect a patient’s risk of acquiring various infections.

Study design: Meta-analysis and systematic review.

Setting: International adult, pediatric, obstetric medical and surgical wards, and ICUs.

Synopsis: Eighteen studies performed were included in the meta-analysis of published randomized trials comparing restrictive to liberal RBC transfusion strategies in which infectious outcomes were reported. Patient enrollment spanned from 1994 to 2012. Six of the trials included pediatric patients. For adult patients, the restrictive RBC transfusion threshold ranged from 6.4–9.7 g/dL, while the liberal target ranged from 9-11.3 g/dL in included trials.

The overall pooled risk ratio for the association of restrictive vs. liberal transfusion threshold with infection was 0.99 (95% CI, 0.78-0.99; P=0.033). A decreased risk of infection with the use of a restrictive transfusion compared with a liberal threshold persisted in studies of leukocyte-reduced blood products.

Bottom line: Restrictive RBC transfusion thresholds are associated with a decreased risk of acquiring healthcare-associated infections compared with liberal transfusion thresholds.

Citation: Rohde JM, Dimcheff DE, Blumberg N, et al. Health care-associated infection after red blood cell transfusion: A systematic review and meta-analysis. JAMA. 2014;311(13):1317-1326.

Clinical question: Do different thresholds for red blood cell (RBC) transfusion influence the risk of infection, and does leukocyte reduction also influence the risk of infection?

Background: RBC transfusion is a common and costly medical intervention performed across U.S. hospitals. Scientists suspect that RBC transfusion may have immunomodulatory properties and may affect a patient’s risk of acquiring various infections.

Study design: Meta-analysis and systematic review.

Setting: International adult, pediatric, obstetric medical and surgical wards, and ICUs.

Synopsis: Eighteen studies performed were included in the meta-analysis of published randomized trials comparing restrictive to liberal RBC transfusion strategies in which infectious outcomes were reported. Patient enrollment spanned from 1994 to 2012. Six of the trials included pediatric patients. For adult patients, the restrictive RBC transfusion threshold ranged from 6.4–9.7 g/dL, while the liberal target ranged from 9-11.3 g/dL in included trials.

The overall pooled risk ratio for the association of restrictive vs. liberal transfusion threshold with infection was 0.99 (95% CI, 0.78-0.99; P=0.033). A decreased risk of infection with the use of a restrictive transfusion compared with a liberal threshold persisted in studies of leukocyte-reduced blood products.

Bottom line: Restrictive RBC transfusion thresholds are associated with a decreased risk of acquiring healthcare-associated infections compared with liberal transfusion thresholds.

Citation: Rohde JM, Dimcheff DE, Blumberg N, et al. Health care-associated infection after red blood cell transfusion: A systematic review and meta-analysis. JAMA. 2014;311(13):1317-1326.

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Head Computed Tomography Scans Not Needed for Most Delirium Inpatients

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Head Computed Tomography Scans Not Needed for Most Delirium Inpatients

Clinical question: Are CT scans of the head diagnostically helpful in hospitalized patients with delirium?

Background: Studies have investigated the use of head CT scans for the evaluation of delirium in the ED, but there is scant information about the utility of head CT scans in the assessment of the hospitalized patient with delirium.

Study design: Retrospective medical record review.

Setting: Large academic medical center in Massachusetts.

Synopsis: This study was designed to assess whether head CT scans obtained on patients without a history of head trauma, fall, known intracranial process, or new neurologic deficit were useful in the workup of delirium. During a two-year period, 1,714 CT scans of the head were performed, and 398 listed the indication for the scan as “delirium, altered mental status, confusion, encephalopathy, somnolence, or unresponsiveness.” Patients with the risk factors of trauma, fall, new neurologic deficit, and known intracranial process were excluded, and 220 patients’ records were reviewed.

Only six head CT scans (2.7%) revealed an acute intracranial process. Many chronic findings were noted, such as atrophy, small vessel ischemic disease, and old stroke. The authors found that the diagnostic utility was low for a head CT scan in a patient with delirium but noted no risk factors. There may be a subset of patients in whom the diagnostic yield is higher, such as those on anticoagulation or more obtunded patients.

Bottom line: In delirious inpatients without a history of head trauma, fall, known intracranial process, or new neurologic deficit, head CT scan has low diagnostic utility.

Citation: Theisen-Toupal J, Breu AC, Mattison ML, Arnaout R. Diagnostic yield of head computed tomography for the hospitalized medical patient with delirium [published online ahead of print April 15, 2014]. J Hosp Med.

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Clinical question: Are CT scans of the head diagnostically helpful in hospitalized patients with delirium?

Background: Studies have investigated the use of head CT scans for the evaluation of delirium in the ED, but there is scant information about the utility of head CT scans in the assessment of the hospitalized patient with delirium.

Study design: Retrospective medical record review.

Setting: Large academic medical center in Massachusetts.

Synopsis: This study was designed to assess whether head CT scans obtained on patients without a history of head trauma, fall, known intracranial process, or new neurologic deficit were useful in the workup of delirium. During a two-year period, 1,714 CT scans of the head were performed, and 398 listed the indication for the scan as “delirium, altered mental status, confusion, encephalopathy, somnolence, or unresponsiveness.” Patients with the risk factors of trauma, fall, new neurologic deficit, and known intracranial process were excluded, and 220 patients’ records were reviewed.

Only six head CT scans (2.7%) revealed an acute intracranial process. Many chronic findings were noted, such as atrophy, small vessel ischemic disease, and old stroke. The authors found that the diagnostic utility was low for a head CT scan in a patient with delirium but noted no risk factors. There may be a subset of patients in whom the diagnostic yield is higher, such as those on anticoagulation or more obtunded patients.

Bottom line: In delirious inpatients without a history of head trauma, fall, known intracranial process, or new neurologic deficit, head CT scan has low diagnostic utility.

Citation: Theisen-Toupal J, Breu AC, Mattison ML, Arnaout R. Diagnostic yield of head computed tomography for the hospitalized medical patient with delirium [published online ahead of print April 15, 2014]. J Hosp Med.

Clinical question: Are CT scans of the head diagnostically helpful in hospitalized patients with delirium?

Background: Studies have investigated the use of head CT scans for the evaluation of delirium in the ED, but there is scant information about the utility of head CT scans in the assessment of the hospitalized patient with delirium.

Study design: Retrospective medical record review.

Setting: Large academic medical center in Massachusetts.

Synopsis: This study was designed to assess whether head CT scans obtained on patients without a history of head trauma, fall, known intracranial process, or new neurologic deficit were useful in the workup of delirium. During a two-year period, 1,714 CT scans of the head were performed, and 398 listed the indication for the scan as “delirium, altered mental status, confusion, encephalopathy, somnolence, or unresponsiveness.” Patients with the risk factors of trauma, fall, new neurologic deficit, and known intracranial process were excluded, and 220 patients’ records were reviewed.

Only six head CT scans (2.7%) revealed an acute intracranial process. Many chronic findings were noted, such as atrophy, small vessel ischemic disease, and old stroke. The authors found that the diagnostic utility was low for a head CT scan in a patient with delirium but noted no risk factors. There may be a subset of patients in whom the diagnostic yield is higher, such as those on anticoagulation or more obtunded patients.

Bottom line: In delirious inpatients without a history of head trauma, fall, known intracranial process, or new neurologic deficit, head CT scan has low diagnostic utility.

Citation: Theisen-Toupal J, Breu AC, Mattison ML, Arnaout R. Diagnostic yield of head computed tomography for the hospitalized medical patient with delirium [published online ahead of print April 15, 2014]. J Hosp Med.

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Hospitalist Efficiency Impacted by Increased Workloads

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Hospitalist Efficiency Impacted by Increased Workloads

Clinical question: Does an increased hospitalist workload lead to increased costs, longer lengths of stay, and worse medical outcomes?

Background: There is evidence that increased resident physician workloads contribute to adverse medical outcomes, but this has not been assessed in the hospital medicine setting. In a recent national survey of hospitalists, almost half reported that they had managed workloads that felt “unsafe.”

Study design: Retrospective cohort study.

Setting: Academic community health system in Delaware.

Synopsis: This study examined the effect of hospital occupancy and hospitalist workloads, using both daily relative value units (RVUs) and hospitalists’ daily patient census, on length of stay (LOS), hospital costs, inpatient mortality, activation of rapid response system (a proxy measure for decompensation), and 30-day readmission rates. Authors reviewed 20,241 hospitalizations and found that when hospitalist daily censuses exceeded 15 patients (or RVU of 25), length of stay increased “exponentially.” Increased workloads were not associated with worsening medical outcomes or diminished patient satisfaction scores.

The authors caution that the significantly increased costs and LOS at higher patient censuses raise concerns that hospital policies that incentivize productivity may “undermine larger system efforts targeting efficiency and costs of care.” They also suggest that hospitalist groups’ staffing approaches need to accommodate fluctuations in hospital occupancy.

Bottom line: When a hospitalist’s workload exceeds a census of 15 patients, the length of stay and cost may increase dramatically.

Article Reference: Elliott DJ, Young RS, Brice J, Aguiar R, Kolm P. Effect of hospitalist workload on the quality and efficiency of care. JAMA Intern Med. 2014;174(5):786-793.

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Clinical question: Does an increased hospitalist workload lead to increased costs, longer lengths of stay, and worse medical outcomes?

Background: There is evidence that increased resident physician workloads contribute to adverse medical outcomes, but this has not been assessed in the hospital medicine setting. In a recent national survey of hospitalists, almost half reported that they had managed workloads that felt “unsafe.”

Study design: Retrospective cohort study.

Setting: Academic community health system in Delaware.

Synopsis: This study examined the effect of hospital occupancy and hospitalist workloads, using both daily relative value units (RVUs) and hospitalists’ daily patient census, on length of stay (LOS), hospital costs, inpatient mortality, activation of rapid response system (a proxy measure for decompensation), and 30-day readmission rates. Authors reviewed 20,241 hospitalizations and found that when hospitalist daily censuses exceeded 15 patients (or RVU of 25), length of stay increased “exponentially.” Increased workloads were not associated with worsening medical outcomes or diminished patient satisfaction scores.

The authors caution that the significantly increased costs and LOS at higher patient censuses raise concerns that hospital policies that incentivize productivity may “undermine larger system efforts targeting efficiency and costs of care.” They also suggest that hospitalist groups’ staffing approaches need to accommodate fluctuations in hospital occupancy.

Bottom line: When a hospitalist’s workload exceeds a census of 15 patients, the length of stay and cost may increase dramatically.

Article Reference: Elliott DJ, Young RS, Brice J, Aguiar R, Kolm P. Effect of hospitalist workload on the quality and efficiency of care. JAMA Intern Med. 2014;174(5):786-793.

Clinical question: Does an increased hospitalist workload lead to increased costs, longer lengths of stay, and worse medical outcomes?

Background: There is evidence that increased resident physician workloads contribute to adverse medical outcomes, but this has not been assessed in the hospital medicine setting. In a recent national survey of hospitalists, almost half reported that they had managed workloads that felt “unsafe.”

Study design: Retrospective cohort study.

Setting: Academic community health system in Delaware.

Synopsis: This study examined the effect of hospital occupancy and hospitalist workloads, using both daily relative value units (RVUs) and hospitalists’ daily patient census, on length of stay (LOS), hospital costs, inpatient mortality, activation of rapid response system (a proxy measure for decompensation), and 30-day readmission rates. Authors reviewed 20,241 hospitalizations and found that when hospitalist daily censuses exceeded 15 patients (or RVU of 25), length of stay increased “exponentially.” Increased workloads were not associated with worsening medical outcomes or diminished patient satisfaction scores.

The authors caution that the significantly increased costs and LOS at higher patient censuses raise concerns that hospital policies that incentivize productivity may “undermine larger system efforts targeting efficiency and costs of care.” They also suggest that hospitalist groups’ staffing approaches need to accommodate fluctuations in hospital occupancy.

Bottom line: When a hospitalist’s workload exceeds a census of 15 patients, the length of stay and cost may increase dramatically.

Article Reference: Elliott DJ, Young RS, Brice J, Aguiar R, Kolm P. Effect of hospitalist workload on the quality and efficiency of care. JAMA Intern Med. 2014;174(5):786-793.

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Peri-Operative Clonidine Increases Hypotension, Bradycardia, Nonfatal Cardiac Arrest

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Peri-Operative Clonidine Increases Hypotension, Bradycardia, Nonfatal Cardiac Arrest

Clinical question: In patients at risk for vascular complications undergoing noncardiac surgery, do the benefits of aspirin outweigh the risks?

Background: Aspirin has been shown to reduce the rate of myocardial infarction (MI) and major vascular events in patients not undergoing surgery. The benefits of initiating or continuing aspirin in patients undergoing surgery, balanced by the potential increase in bleeding risk, have not been widely studied.

Study design: International randomized placebo-controlled trial with a 2-by-2 factorial design.

Setting: One hundred thirty-five hospitals in 23 countries, from 2010-2013.

Synopsis: The study enrolled 10,010 patients, with a mean age of 68.6 years. Inclusion criteria were age >45 years old and risk for vascular complications, defined as a history of coronary artery disease, peripheral vascular disease, or cerebrovascular accident; major vascular surgery; or at least three of the following: age >70, congestive heart failure, transient ischemic attack, hypertension, diabetes mellitus type 2, creatinine >2 mg/dL, recent smoking, undergoing major surgery, or urgent/emergent surgery.

Groups were stratified by current use of aspirin and then assigned to aspirin or placebo; patients on aspirin held it a median of seven days before surgery. Those in the active group received 200 mg of aspirin pre-operatively. Patients not previously on aspirin then continued aspirin at 100 mg/day for 30 days; those on aspirin previously received 100 mg/day for seven days and then resumed their prior dose.

No difference was found in the primary outcome of death or non-fatal MI at 30 days, but aspirin was noted to increase the risk of major bleeding (4.6% vs. 3.8%, P=0.04), most commonly occurring at the surgical site (78.3%) and the GI tract (9.3%). Because major bleeding can be associated with peri-operative MI, this may have counteracted the cardiovascular benefits of aspirin.

Bottom line: Peri-operative administration of aspirin to patients at risk for vascular complications undergoing noncardiac surgery does not decrease the risk of peri-operative death or MI and may increase the risk of post-operative bleeding.

Citation: Devereaux PJ, Mrkobrada M, Sessler DI, et al. POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014;370(16):1494-1503.

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Clinical question: In patients at risk for vascular complications undergoing noncardiac surgery, do the benefits of aspirin outweigh the risks?

Background: Aspirin has been shown to reduce the rate of myocardial infarction (MI) and major vascular events in patients not undergoing surgery. The benefits of initiating or continuing aspirin in patients undergoing surgery, balanced by the potential increase in bleeding risk, have not been widely studied.

Study design: International randomized placebo-controlled trial with a 2-by-2 factorial design.

Setting: One hundred thirty-five hospitals in 23 countries, from 2010-2013.

Synopsis: The study enrolled 10,010 patients, with a mean age of 68.6 years. Inclusion criteria were age >45 years old and risk for vascular complications, defined as a history of coronary artery disease, peripheral vascular disease, or cerebrovascular accident; major vascular surgery; or at least three of the following: age >70, congestive heart failure, transient ischemic attack, hypertension, diabetes mellitus type 2, creatinine >2 mg/dL, recent smoking, undergoing major surgery, or urgent/emergent surgery.

Groups were stratified by current use of aspirin and then assigned to aspirin or placebo; patients on aspirin held it a median of seven days before surgery. Those in the active group received 200 mg of aspirin pre-operatively. Patients not previously on aspirin then continued aspirin at 100 mg/day for 30 days; those on aspirin previously received 100 mg/day for seven days and then resumed their prior dose.

No difference was found in the primary outcome of death or non-fatal MI at 30 days, but aspirin was noted to increase the risk of major bleeding (4.6% vs. 3.8%, P=0.04), most commonly occurring at the surgical site (78.3%) and the GI tract (9.3%). Because major bleeding can be associated with peri-operative MI, this may have counteracted the cardiovascular benefits of aspirin.

Bottom line: Peri-operative administration of aspirin to patients at risk for vascular complications undergoing noncardiac surgery does not decrease the risk of peri-operative death or MI and may increase the risk of post-operative bleeding.

Citation: Devereaux PJ, Mrkobrada M, Sessler DI, et al. POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014;370(16):1494-1503.

Clinical question: In patients at risk for vascular complications undergoing noncardiac surgery, do the benefits of aspirin outweigh the risks?

Background: Aspirin has been shown to reduce the rate of myocardial infarction (MI) and major vascular events in patients not undergoing surgery. The benefits of initiating or continuing aspirin in patients undergoing surgery, balanced by the potential increase in bleeding risk, have not been widely studied.

Study design: International randomized placebo-controlled trial with a 2-by-2 factorial design.

Setting: One hundred thirty-five hospitals in 23 countries, from 2010-2013.

Synopsis: The study enrolled 10,010 patients, with a mean age of 68.6 years. Inclusion criteria were age >45 years old and risk for vascular complications, defined as a history of coronary artery disease, peripheral vascular disease, or cerebrovascular accident; major vascular surgery; or at least three of the following: age >70, congestive heart failure, transient ischemic attack, hypertension, diabetes mellitus type 2, creatinine >2 mg/dL, recent smoking, undergoing major surgery, or urgent/emergent surgery.

Groups were stratified by current use of aspirin and then assigned to aspirin or placebo; patients on aspirin held it a median of seven days before surgery. Those in the active group received 200 mg of aspirin pre-operatively. Patients not previously on aspirin then continued aspirin at 100 mg/day for 30 days; those on aspirin previously received 100 mg/day for seven days and then resumed their prior dose.

No difference was found in the primary outcome of death or non-fatal MI at 30 days, but aspirin was noted to increase the risk of major bleeding (4.6% vs. 3.8%, P=0.04), most commonly occurring at the surgical site (78.3%) and the GI tract (9.3%). Because major bleeding can be associated with peri-operative MI, this may have counteracted the cardiovascular benefits of aspirin.

Bottom line: Peri-operative administration of aspirin to patients at risk for vascular complications undergoing noncardiac surgery does not decrease the risk of peri-operative death or MI and may increase the risk of post-operative bleeding.

Citation: Devereaux PJ, Mrkobrada M, Sessler DI, et al. POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014;370(16):1494-1503.

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Fibrinolytics Increase Stroke Risk, Hemorrhage in Intermediate-Risk Pulmonary Emboli

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Fibrinolytics Increase Stroke Risk, Hemorrhage in Intermediate-Risk Pulmonary Emboli

Clinical question: Do fibrinolytics decrease mortality rates in intermediate-risk pulmonary emboli?

Background: Over the past 40 years, fibrinolytics have been studied in fewer than 1,000 patients with pulmonary emboli. Previous studies have shown improvement in hemodynamic response, though the evidence for clinical outcomes such as death and hemodynamic collapse have not been studied adequately in intermediate-risk pulmonary emboli.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Seventy-six sites in 13 countries.

Synopsis: The PEITHO [Pulmonary EmbolIsm THrOmbolysis] trial randomized 1,006 patients in a double-blind fashion. All patients had acute pulmonary emboli with evidence of right ventricular dysfunction on computed tomography scan or echocardiogram, as well as an elevated troponin, in the absence of hemodynamic compromise. Patients received tenecteplase and heparin or placebo and heparin. The primary outcome was death and hemodynamic decompensation.

The primary outcome was found in 2.6% of the treatment group and 5.6% in the placebo group (P=0.02), favoring the treatment group; however, there was no difference in death at seven days (1.2% vs. 1.8%; P=0.42) and 30 days (2.4% vs. 3.2%; P=0.42). Additionally, there were higher rates of extracranial bleeding (6.3% vs. 1.2%; P=<0.001) and stroke (2.4% vs. 0.2%; P=0.003) in the tenecteplase group than in the placebo group. Of the 12 strokes in the treatment group, 11 were hemorrhagic.

Bottom line: Treatment of intermediate-risk pulmonary emboli with fibrinolytics may improve hemodynamics; however, there is no mortality benefit, and fibrinolytic therapy carries an increased risk of bleeding and stroke.

Citation: Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411.

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Clinical question: Do fibrinolytics decrease mortality rates in intermediate-risk pulmonary emboli?

Background: Over the past 40 years, fibrinolytics have been studied in fewer than 1,000 patients with pulmonary emboli. Previous studies have shown improvement in hemodynamic response, though the evidence for clinical outcomes such as death and hemodynamic collapse have not been studied adequately in intermediate-risk pulmonary emboli.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Seventy-six sites in 13 countries.

Synopsis: The PEITHO [Pulmonary EmbolIsm THrOmbolysis] trial randomized 1,006 patients in a double-blind fashion. All patients had acute pulmonary emboli with evidence of right ventricular dysfunction on computed tomography scan or echocardiogram, as well as an elevated troponin, in the absence of hemodynamic compromise. Patients received tenecteplase and heparin or placebo and heparin. The primary outcome was death and hemodynamic decompensation.

The primary outcome was found in 2.6% of the treatment group and 5.6% in the placebo group (P=0.02), favoring the treatment group; however, there was no difference in death at seven days (1.2% vs. 1.8%; P=0.42) and 30 days (2.4% vs. 3.2%; P=0.42). Additionally, there were higher rates of extracranial bleeding (6.3% vs. 1.2%; P=<0.001) and stroke (2.4% vs. 0.2%; P=0.003) in the tenecteplase group than in the placebo group. Of the 12 strokes in the treatment group, 11 were hemorrhagic.

Bottom line: Treatment of intermediate-risk pulmonary emboli with fibrinolytics may improve hemodynamics; however, there is no mortality benefit, and fibrinolytic therapy carries an increased risk of bleeding and stroke.

Citation: Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411.

Clinical question: Do fibrinolytics decrease mortality rates in intermediate-risk pulmonary emboli?

Background: Over the past 40 years, fibrinolytics have been studied in fewer than 1,000 patients with pulmonary emboli. Previous studies have shown improvement in hemodynamic response, though the evidence for clinical outcomes such as death and hemodynamic collapse have not been studied adequately in intermediate-risk pulmonary emboli.

Study design: Randomized, double-blinded, placebo-controlled trial.

Setting: Seventy-six sites in 13 countries.

Synopsis: The PEITHO [Pulmonary EmbolIsm THrOmbolysis] trial randomized 1,006 patients in a double-blind fashion. All patients had acute pulmonary emboli with evidence of right ventricular dysfunction on computed tomography scan or echocardiogram, as well as an elevated troponin, in the absence of hemodynamic compromise. Patients received tenecteplase and heparin or placebo and heparin. The primary outcome was death and hemodynamic decompensation.

The primary outcome was found in 2.6% of the treatment group and 5.6% in the placebo group (P=0.02), favoring the treatment group; however, there was no difference in death at seven days (1.2% vs. 1.8%; P=0.42) and 30 days (2.4% vs. 3.2%; P=0.42). Additionally, there were higher rates of extracranial bleeding (6.3% vs. 1.2%; P=<0.001) and stroke (2.4% vs. 0.2%; P=0.003) in the tenecteplase group than in the placebo group. Of the 12 strokes in the treatment group, 11 were hemorrhagic.

Bottom line: Treatment of intermediate-risk pulmonary emboli with fibrinolytics may improve hemodynamics; however, there is no mortality benefit, and fibrinolytic therapy carries an increased risk of bleeding and stroke.

Citation: Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411.

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AHA/ACC Atrial Fibrillation Guidelines Updated

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AHA/ACC Atrial Fibrillation Guidelines Updated

Clinical question: What new recommendations are made in the AHA/ACC/HRS atrial fibrillation guidelines?

Background: This is the AHA’s first comprehensive update on atrial fibrillation since 2006; there were two intervening focused updates in 2011.

Synopsis: The majority of the new recommendations center on patient selection for anticoagulation and the role of the new oral anticoagulants.

CHA2DS2-VASc is now recommended over CHADS2 for evaluation of stroke risk, with anticoagulation recommended for a score of two or greater, or for a patient with any prior history of stroke or transient ischemic attack.

Warfarin, direct thrombin inhibitors, or factor Xa inhibitors may be considered in patients with normal renal function. Reduced doses of these medications may be considered in patients with moderate to severe renal dysfunction but have not been studied in clinical trials.

Warfarin remains the drug of choice for patients on hemodialysis and those with hemodynamically significant mitral stenosis or aortic valve replacement.

The clinical utility of bleeding risk scores remains insufficient for formal recommendations. There is sparse evidence on which to base recommendations for bridging, but additional studies, such as the BRIDGE trial, are ongoing. A liberal rate control strategy targeting heart rates <110 in asymptomatic patients with preserved systolic function is reasonable; ideal rate control targets remain controversial.

Citation: January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society [published online ahead of print April 10, 2014]. Circulation.

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Clinical question: What new recommendations are made in the AHA/ACC/HRS atrial fibrillation guidelines?

Background: This is the AHA’s first comprehensive update on atrial fibrillation since 2006; there were two intervening focused updates in 2011.

Synopsis: The majority of the new recommendations center on patient selection for anticoagulation and the role of the new oral anticoagulants.

CHA2DS2-VASc is now recommended over CHADS2 for evaluation of stroke risk, with anticoagulation recommended for a score of two or greater, or for a patient with any prior history of stroke or transient ischemic attack.

Warfarin, direct thrombin inhibitors, or factor Xa inhibitors may be considered in patients with normal renal function. Reduced doses of these medications may be considered in patients with moderate to severe renal dysfunction but have not been studied in clinical trials.

Warfarin remains the drug of choice for patients on hemodialysis and those with hemodynamically significant mitral stenosis or aortic valve replacement.

The clinical utility of bleeding risk scores remains insufficient for formal recommendations. There is sparse evidence on which to base recommendations for bridging, but additional studies, such as the BRIDGE trial, are ongoing. A liberal rate control strategy targeting heart rates <110 in asymptomatic patients with preserved systolic function is reasonable; ideal rate control targets remain controversial.

Citation: January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society [published online ahead of print April 10, 2014]. Circulation.

Clinical question: What new recommendations are made in the AHA/ACC/HRS atrial fibrillation guidelines?

Background: This is the AHA’s first comprehensive update on atrial fibrillation since 2006; there were two intervening focused updates in 2011.

Synopsis: The majority of the new recommendations center on patient selection for anticoagulation and the role of the new oral anticoagulants.

CHA2DS2-VASc is now recommended over CHADS2 for evaluation of stroke risk, with anticoagulation recommended for a score of two or greater, or for a patient with any prior history of stroke or transient ischemic attack.

Warfarin, direct thrombin inhibitors, or factor Xa inhibitors may be considered in patients with normal renal function. Reduced doses of these medications may be considered in patients with moderate to severe renal dysfunction but have not been studied in clinical trials.

Warfarin remains the drug of choice for patients on hemodialysis and those with hemodynamically significant mitral stenosis or aortic valve replacement.

The clinical utility of bleeding risk scores remains insufficient for formal recommendations. There is sparse evidence on which to base recommendations for bridging, but additional studies, such as the BRIDGE trial, are ongoing. A liberal rate control strategy targeting heart rates <110 in asymptomatic patients with preserved systolic function is reasonable; ideal rate control targets remain controversial.

Citation: January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society [published online ahead of print April 10, 2014]. Circulation.

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Peri-Operative Aspirin Impact on Risk of Bleeding, Death, Myocardial Infarction Examined

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Peri-Operative Aspirin Impact on Risk of Bleeding, Death, Myocardial Infarction Examined

Clinical question: Does peri-operative clonidine prevent myocardial infarction (MI)?

Background: A meta-analysis showed that peri-operative clonidine decreased death and MI compared to placebo in patients undergoing vascular surgery. It also showed that rates of death and MI were the same for patients taking clonidine vs. placebo undergoing nonvascular surgery without significant effects on hemodynamics.

Study design: Randomized controlled trial.

Setting: One hundred thirty-five centers across 23 countries.

Synopsis: The POISE-II [PeriOperative Ischemic Evaluation-II] study randomized 10,010 patients in a 1:1:1:1 fashion to analyze peri-operative clonidine and aspirin against placebo. This paper specifically examined the effects of peri-operative clonidine vs. placebo. The average age of the population was 69 years old. The most common comorbidities were diabetes (38%) and coronary artery disease (23%).

The outcomes showed that clonidine vs. placebo yielded insignificant results with respect to the primary endpoints (death, MI, or stroke: 7.6% vs. 7.0%; P=0.30); however, there were significantly higher rates of clinically significant hypotension (47.6% vs. 37.1%; P<0.001), bradycardia (12.0% vs. 8.1%; P<0.001), and nonfatal cardiac arrest (0.3% vs. 0.1%; P=0.02) in the clonidine group.

These results differ from previous, smaller studies, which suggested that there were no significant hemodynamic changes when patients received peri-operative clonidine.

Bottom line: Peri-operative clonidine does not affect the rate of MI but increases clinically significant hypotension, bradycardia, and nonfatal cardiac arrest.

Citation: Devereaux PJ, Sessler DI, Leslie K, et al. Clonidine in patients undergoing noncardiac surgery. N Engl J Med. 2014;370(16):1504-1513.

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Clinical question: Does peri-operative clonidine prevent myocardial infarction (MI)?

Background: A meta-analysis showed that peri-operative clonidine decreased death and MI compared to placebo in patients undergoing vascular surgery. It also showed that rates of death and MI were the same for patients taking clonidine vs. placebo undergoing nonvascular surgery without significant effects on hemodynamics.

Study design: Randomized controlled trial.

Setting: One hundred thirty-five centers across 23 countries.

Synopsis: The POISE-II [PeriOperative Ischemic Evaluation-II] study randomized 10,010 patients in a 1:1:1:1 fashion to analyze peri-operative clonidine and aspirin against placebo. This paper specifically examined the effects of peri-operative clonidine vs. placebo. The average age of the population was 69 years old. The most common comorbidities were diabetes (38%) and coronary artery disease (23%).

The outcomes showed that clonidine vs. placebo yielded insignificant results with respect to the primary endpoints (death, MI, or stroke: 7.6% vs. 7.0%; P=0.30); however, there were significantly higher rates of clinically significant hypotension (47.6% vs. 37.1%; P<0.001), bradycardia (12.0% vs. 8.1%; P<0.001), and nonfatal cardiac arrest (0.3% vs. 0.1%; P=0.02) in the clonidine group.

These results differ from previous, smaller studies, which suggested that there were no significant hemodynamic changes when patients received peri-operative clonidine.

Bottom line: Peri-operative clonidine does not affect the rate of MI but increases clinically significant hypotension, bradycardia, and nonfatal cardiac arrest.

Citation: Devereaux PJ, Sessler DI, Leslie K, et al. Clonidine in patients undergoing noncardiac surgery. N Engl J Med. 2014;370(16):1504-1513.

Clinical question: Does peri-operative clonidine prevent myocardial infarction (MI)?

Background: A meta-analysis showed that peri-operative clonidine decreased death and MI compared to placebo in patients undergoing vascular surgery. It also showed that rates of death and MI were the same for patients taking clonidine vs. placebo undergoing nonvascular surgery without significant effects on hemodynamics.

Study design: Randomized controlled trial.

Setting: One hundred thirty-five centers across 23 countries.

Synopsis: The POISE-II [PeriOperative Ischemic Evaluation-II] study randomized 10,010 patients in a 1:1:1:1 fashion to analyze peri-operative clonidine and aspirin against placebo. This paper specifically examined the effects of peri-operative clonidine vs. placebo. The average age of the population was 69 years old. The most common comorbidities were diabetes (38%) and coronary artery disease (23%).

The outcomes showed that clonidine vs. placebo yielded insignificant results with respect to the primary endpoints (death, MI, or stroke: 7.6% vs. 7.0%; P=0.30); however, there were significantly higher rates of clinically significant hypotension (47.6% vs. 37.1%; P<0.001), bradycardia (12.0% vs. 8.1%; P<0.001), and nonfatal cardiac arrest (0.3% vs. 0.1%; P=0.02) in the clonidine group.

These results differ from previous, smaller studies, which suggested that there were no significant hemodynamic changes when patients received peri-operative clonidine.

Bottom line: Peri-operative clonidine does not affect the rate of MI but increases clinically significant hypotension, bradycardia, and nonfatal cardiac arrest.

Citation: Devereaux PJ, Sessler DI, Leslie K, et al. Clonidine in patients undergoing noncardiac surgery. N Engl J Med. 2014;370(16):1504-1513.

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