Clinical

Clinical question: Given advances in the understanding and treatment of sepsis, can sepsis be better defined?

Background: Definitions of sepsis and septic shock were last revised in 2001. The current definitions are based on a constellation of clinical signs and symptoms in a patient with suspected infection. Recent studies suggest that the definitions have low sensitivity and specificity, and they do not correlate well with patient outcomes.

Study design: Consensus guidelines.

Setting: Task force of 19 critical care, infectious disease, surgical, and pulmonary specialists convened in 2014 by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine.

Synopsis: The task force recommended that sepsis be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and that it be identified by a change of more than one point in the Sequential Organ Failure Assessment (SOFA) score. This score incorporates the Glasgow Coma Scale, mean arterial blood pressure (MAP), PaO2/FiO2, platelet count, creatinine, and bilirubin. Septic shock is defined as a subset of sepsis with profound circulatory, cellular, and metabolic abnormalities, and it’s identified by serum lactate level >2 mmol/L and vasopressor requirement to maintain a MAP of ≥65 mm Hg in the absence of hypovolemia. These new definitions have higher sensitivity and specificity and can predict mortality more accurately. Patients with these definitions of sepsis and septic shock have in-hospital mortality >10% and >40%, respectively. The presence of two or more quick SOFA (qSOFA) elements (altered mentation, systolic blood pressure ≤100 mm Hg, and respiratory rate ≥22/min) identifies adult patients with suspected infection who need more extensive laboratory testing to exclude sepsis.

Bottom line: Defining sepsis now requires more laboratory testing but provides more diagnostic consistency and more accurately predicts outcomes.

Citation: Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287.

Clinical question: Given advances in the understanding and treatment of sepsis, can sepsis be better defined?

Background: Definitions of sepsis and septic shock were last revised in 2001. The current definitions are based on a constellation of clinical signs and symptoms in a patient with suspected infection. Recent studies suggest that the definitions have low sensitivity and specificity, and they do not correlate well with patient outcomes.

Study design: Consensus guidelines.

Setting: Task force of 19 critical care, infectious disease, surgical, and pulmonary specialists convened in 2014 by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine.

Synopsis: The task force recommended that sepsis be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and that it be identified by a change of more than one point in the Sequential Organ Failure Assessment (SOFA) score. This score incorporates the Glasgow Coma Scale, mean arterial blood pressure (MAP), PaO2/FiO2, platelet count, creatinine, and bilirubin. Septic shock is defined as a subset of sepsis with profound circulatory, cellular, and metabolic abnormalities, and it’s identified by serum lactate level >2 mmol/L and vasopressor requirement to maintain a MAP of ≥65 mm Hg in the absence of hypovolemia. These new definitions have higher sensitivity and specificity and can predict mortality more accurately. Patients with these definitions of sepsis and septic shock have in-hospital mortality >10% and >40%, respectively. The presence of two or more quick SOFA (qSOFA) elements (altered mentation, systolic blood pressure ≤100 mm Hg, and respiratory rate ≥22/min) identifies adult patients with suspected infection who need more extensive laboratory testing to exclude sepsis.

Bottom line: Defining sepsis now requires more laboratory testing but provides more diagnostic consistency and more accurately predicts outcomes.

Citation: Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287.

Clinical question: Given advances in the understanding and treatment of sepsis, can sepsis be better defined?

Background: Definitions of sepsis and septic shock were last revised in 2001. The current definitions are based on a constellation of clinical signs and symptoms in a patient with suspected infection. Recent studies suggest that the definitions have low sensitivity and specificity, and they do not correlate well with patient outcomes.

Study design: Consensus guidelines.

Setting: Task force of 19 critical care, infectious disease, surgical, and pulmonary specialists convened in 2014 by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine.

Synopsis: The task force recommended that sepsis be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and that it be identified by a change of more than one point in the Sequential Organ Failure Assessment (SOFA) score. This score incorporates the Glasgow Coma Scale, mean arterial blood pressure (MAP), PaO2/FiO2, platelet count, creatinine, and bilirubin. Septic shock is defined as a subset of sepsis with profound circulatory, cellular, and metabolic abnormalities, and it’s identified by serum lactate level >2 mmol/L and vasopressor requirement to maintain a MAP of ≥65 mm Hg in the absence of hypovolemia. These new definitions have higher sensitivity and specificity and can predict mortality more accurately. Patients with these definitions of sepsis and septic shock have in-hospital mortality >10% and >40%, respectively. The presence of two or more quick SOFA (qSOFA) elements (altered mentation, systolic blood pressure ≤100 mm Hg, and respiratory rate ≥22/min) identifies adult patients with suspected infection who need more extensive laboratory testing to exclude sepsis.

Bottom line: Defining sepsis now requires more laboratory testing but provides more diagnostic consistency and more accurately predicts outcomes.

Citation: Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287.

Clinical question: Does the use of disinfection caps on catheter hubs on central venous catheters (CVCs) reduce central-line-associated bloodstream infection (CLABSI) and blood culture contamination (BCC) in hematology-oncology patients?

Background: CVCs have facilitated the administration of chemotherapy, blood products, and fluids in cancer patients; however, their use has also brought about risk of infections. Use of an antiseptic barrier cap may result in decreased rates of CLABSI and BCC.

Study design: Multiphase prospective study

Setting: Memorial Sloan Kettering Cancer Center, New York City.

Synopsis: Disinfection caps on CVCs were sequentially introduced on high-risk units (HRUs) followed by hospital-wide implementation. The primary outcome was hospital-wide and unit-specific rates of hospital-acquired (HA) CLABSI. In Phase 1 and 2, the CDC guidelines for catheter maintenance were followed. In Phase 3, the intervention was implemented in the HRUs. In Phase 4, the intervention extended hospital-wide. HA-CLABSI declined significantly compared to baseline only in HRUs. A possible explanation is that reduction in CLABSI on general wards was not apparent due to the short follow-up period as opposed to the longer follow-up period for the HRUs. The secondary outcome was that the rates of BCC declined significantly in Phase 3 and 4 when compared to Phase 1 and 2. As for limitations, the study is not a randomized controlled trial; variable follow-up periods may have contributed to different outcomes observed on the different units.

Bottom line: Implementation of disinfection caps significantly reduces rates of CLABSI in HRUs and reduces BCCs in both HRUs and general oncology units, with substantial clinical and cost-savings implications.

Citation: Kamboj M, Blair R, Bell N, et al. Use of disinfection cap to reduce central-line-associated bloodstream infection and blood culture contamination among hematology-oncology patients. Infect Control Hosp Epidemiol. 2015;36(12):1401-1408.

Short Take

High Workload among Attending Physicians Has Negative Outcomes

Retrospective study found associations between higher attending physician workload and lower teaching evaluation scores from residents as well as increased risks to patient safety.

Citation: Wingo MT, Halvorsen AJ, Beckman TJ, Johnson MG, Reed DA. Associations between attending physician workload, teaching effectiveness, and patient safety. J Hosp Med. 2016;11(3):169-173.

Clinical question: Does the use of disinfection caps on catheter hubs on central venous catheters (CVCs) reduce central-line-associated bloodstream infection (CLABSI) and blood culture contamination (BCC) in hematology-oncology patients?

Background: CVCs have facilitated the administration of chemotherapy, blood products, and fluids in cancer patients; however, their use has also brought about risk of infections. Use of an antiseptic barrier cap may result in decreased rates of CLABSI and BCC.

Study design: Multiphase prospective study

Setting: Memorial Sloan Kettering Cancer Center, New York City.

Synopsis: Disinfection caps on CVCs were sequentially introduced on high-risk units (HRUs) followed by hospital-wide implementation. The primary outcome was hospital-wide and unit-specific rates of hospital-acquired (HA) CLABSI. In Phase 1 and 2, the CDC guidelines for catheter maintenance were followed. In Phase 3, the intervention was implemented in the HRUs. In Phase 4, the intervention extended hospital-wide. HA-CLABSI declined significantly compared to baseline only in HRUs. A possible explanation is that reduction in CLABSI on general wards was not apparent due to the short follow-up period as opposed to the longer follow-up period for the HRUs. The secondary outcome was that the rates of BCC declined significantly in Phase 3 and 4 when compared to Phase 1 and 2. As for limitations, the study is not a randomized controlled trial; variable follow-up periods may have contributed to different outcomes observed on the different units.

Bottom line: Implementation of disinfection caps significantly reduces rates of CLABSI in HRUs and reduces BCCs in both HRUs and general oncology units, with substantial clinical and cost-savings implications.

Citation: Kamboj M, Blair R, Bell N, et al. Use of disinfection cap to reduce central-line-associated bloodstream infection and blood culture contamination among hematology-oncology patients. Infect Control Hosp Epidemiol. 2015;36(12):1401-1408.

Short Take

High Workload among Attending Physicians Has Negative Outcomes

Retrospective study found associations between higher attending physician workload and lower teaching evaluation scores from residents as well as increased risks to patient safety.

Citation: Wingo MT, Halvorsen AJ, Beckman TJ, Johnson MG, Reed DA. Associations between attending physician workload, teaching effectiveness, and patient safety. J Hosp Med. 2016;11(3):169-173.

Clinical question: Does the use of disinfection caps on catheter hubs on central venous catheters (CVCs) reduce central-line-associated bloodstream infection (CLABSI) and blood culture contamination (BCC) in hematology-oncology patients?

Background: CVCs have facilitated the administration of chemotherapy, blood products, and fluids in cancer patients; however, their use has also brought about risk of infections. Use of an antiseptic barrier cap may result in decreased rates of CLABSI and BCC.

Study design: Multiphase prospective study

Setting: Memorial Sloan Kettering Cancer Center, New York City.

Synopsis: Disinfection caps on CVCs were sequentially introduced on high-risk units (HRUs) followed by hospital-wide implementation. The primary outcome was hospital-wide and unit-specific rates of hospital-acquired (HA) CLABSI. In Phase 1 and 2, the CDC guidelines for catheter maintenance were followed. In Phase 3, the intervention was implemented in the HRUs. In Phase 4, the intervention extended hospital-wide. HA-CLABSI declined significantly compared to baseline only in HRUs. A possible explanation is that reduction in CLABSI on general wards was not apparent due to the short follow-up period as opposed to the longer follow-up period for the HRUs. The secondary outcome was that the rates of BCC declined significantly in Phase 3 and 4 when compared to Phase 1 and 2. As for limitations, the study is not a randomized controlled trial; variable follow-up periods may have contributed to different outcomes observed on the different units.

Bottom line: Implementation of disinfection caps significantly reduces rates of CLABSI in HRUs and reduces BCCs in both HRUs and general oncology units, with substantial clinical and cost-savings implications.

Citation: Kamboj M, Blair R, Bell N, et al. Use of disinfection cap to reduce central-line-associated bloodstream infection and blood culture contamination among hematology-oncology patients. Infect Control Hosp Epidemiol. 2015;36(12):1401-1408.

Short Take

High Workload among Attending Physicians Has Negative Outcomes

Retrospective study found associations between higher attending physician workload and lower teaching evaluation scores from residents as well as increased risks to patient safety.

Citation: Wingo MT, Halvorsen AJ, Beckman TJ, Johnson MG, Reed DA. Associations between attending physician workload, teaching effectiveness, and patient safety. J Hosp Med. 2016;11(3):169-173.

Clinical question: Does inhaled isopropyl alcohol alleviate nausea as compared to inhaled saline solution among patients presenting to the ED with a chief complaint of nausea?

Background: Nausea and vomiting account for 4.8 million ED visits each year; however, antiemetics have not shown superiority compared to placebo. Isopropyl alcohol nasal inhalation is more effective than saline solution in treating postoperative nausea and vomiting; however, there have been no investigations of this therapy in the ED setting.

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

Setting: Emergency department at the San Antonio Military Medical Center, Texas.

Synopsis: Investigators randomized a convenience sample of 80 patients in the ED presenting with nausea or vomiting to either inhaled isopropyl alcohol (37) or saline solution (43). Subjects would nasally inhale at 0, 2, and 4 minutes. Nausea outcomes were self-rated on a scale of 0–10, with 0 being no nausea and 10 being worst nausea imaginable. Responses were taken at 0, 2, 4, 6, and 10 minutes postintervention. Primary outcome was the score at 10 minutes postintervention. The minimally significant difference was two points.

Patients in the intervention arm reported lower scores during every study period than the patients in the placebo arm. Median nausea scores at 10 minutes postintervention were lower by three in the intervention arm compared to placebo arm (P<0.001). Limitations include the short (10-minute) evaluation period, which limits identification of any adverse events; limited information on duration of symptom relief and whether the isopropyl alcohol effect persisted; possible selection bias due to utilizing a convenience sample; and use of a subjective scale for the primary outcome.

Bottom line: Isopropyl alcohol inhalation is effective in reducing nausea 10 minutes after intervention as compared with placebo in the ED setting.

Citation: Beadle KL, Helbling AR, Love SL, April MD, Hunter CJ. Isopropyl alcohol nasal inhalation for nausea in the emergency department: a randomized controlled trial [published online ahead of print November 21, 2015]. Ann Emerg Med. doi:10.1016/j.annemergmed.2015.09.031.

Clinical question: Does inhaled isopropyl alcohol alleviate nausea as compared to inhaled saline solution among patients presenting to the ED with a chief complaint of nausea?

Background: Nausea and vomiting account for 4.8 million ED visits each year; however, antiemetics have not shown superiority compared to placebo. Isopropyl alcohol nasal inhalation is more effective than saline solution in treating postoperative nausea and vomiting; however, there have been no investigations of this therapy in the ED setting.

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

Setting: Emergency department at the San Antonio Military Medical Center, Texas.

Synopsis: Investigators randomized a convenience sample of 80 patients in the ED presenting with nausea or vomiting to either inhaled isopropyl alcohol (37) or saline solution (43). Subjects would nasally inhale at 0, 2, and 4 minutes. Nausea outcomes were self-rated on a scale of 0–10, with 0 being no nausea and 10 being worst nausea imaginable. Responses were taken at 0, 2, 4, 6, and 10 minutes postintervention. Primary outcome was the score at 10 minutes postintervention. The minimally significant difference was two points.

Patients in the intervention arm reported lower scores during every study period than the patients in the placebo arm. Median nausea scores at 10 minutes postintervention were lower by three in the intervention arm compared to placebo arm (P<0.001). Limitations include the short (10-minute) evaluation period, which limits identification of any adverse events; limited information on duration of symptom relief and whether the isopropyl alcohol effect persisted; possible selection bias due to utilizing a convenience sample; and use of a subjective scale for the primary outcome.

Bottom line: Isopropyl alcohol inhalation is effective in reducing nausea 10 minutes after intervention as compared with placebo in the ED setting.

Citation: Beadle KL, Helbling AR, Love SL, April MD, Hunter CJ. Isopropyl alcohol nasal inhalation for nausea in the emergency department: a randomized controlled trial [published online ahead of print November 21, 2015]. Ann Emerg Med. doi:10.1016/j.annemergmed.2015.09.031.

Clinical question: Does inhaled isopropyl alcohol alleviate nausea as compared to inhaled saline solution among patients presenting to the ED with a chief complaint of nausea?

Background: Nausea and vomiting account for 4.8 million ED visits each year; however, antiemetics have not shown superiority compared to placebo. Isopropyl alcohol nasal inhalation is more effective than saline solution in treating postoperative nausea and vomiting; however, there have been no investigations of this therapy in the ED setting.

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

Setting: Emergency department at the San Antonio Military Medical Center, Texas.

Synopsis: Investigators randomized a convenience sample of 80 patients in the ED presenting with nausea or vomiting to either inhaled isopropyl alcohol (37) or saline solution (43). Subjects would nasally inhale at 0, 2, and 4 minutes. Nausea outcomes were self-rated on a scale of 0–10, with 0 being no nausea and 10 being worst nausea imaginable. Responses were taken at 0, 2, 4, 6, and 10 minutes postintervention. Primary outcome was the score at 10 minutes postintervention. The minimally significant difference was two points.

Patients in the intervention arm reported lower scores during every study period than the patients in the placebo arm. Median nausea scores at 10 minutes postintervention were lower by three in the intervention arm compared to placebo arm (P<0.001). Limitations include the short (10-minute) evaluation period, which limits identification of any adverse events; limited information on duration of symptom relief and whether the isopropyl alcohol effect persisted; possible selection bias due to utilizing a convenience sample; and use of a subjective scale for the primary outcome.

Bottom line: Isopropyl alcohol inhalation is effective in reducing nausea 10 minutes after intervention as compared with placebo in the ED setting.

Citation: Beadle KL, Helbling AR, Love SL, April MD, Hunter CJ. Isopropyl alcohol nasal inhalation for nausea in the emergency department: a randomized controlled trial [published online ahead of print November 21, 2015]. Ann Emerg Med. doi:10.1016/j.annemergmed.2015.09.031.

Clinical question: What is the association between proton pump inhibitor (PPI) use and incident chronic kidney disease (CKD)?

Background: Medication use may play a potential role in the increasing prevalence of CKD. PPIs are commonly prescribed, and several observational studies have linked their use with multiple adverse outcomes, including acute interstitial nephritis. The risk for CKD with PPI use has never been evaluated.

Study design: Prospective cohort study.

Setting: U.S., multi-center.

Synopsis: Among 10,482 patients in the Atherosclerosis Risk in Communities study (ARIC) with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m2, PPI use was associated with a 1.50 times risk of incident CKD (95% CI, 1.14–1.96; P=0.003) and a 1.64 times risk of incident acute kidney injury (95% CI, 1.22–2.21; P<0.001) when compared to nonusers. PPI use continued to have an association with incident CKD even when compared directly with H2 receptor antagonist users (adjusted HR, 1.39; 95% CI, 1.01–1.91). Findings were replicated in a cohort of 248,751 patients in the Geisinger Health System, and in all analyses, PPI use was associated with CKD.

One limitation is that this was an observational study and causality between PPI use and CKD cannot be established.

Bottom line: PPIs are associated with risk for CKD, and in patients on therapy, its use should be reevaluated.

Citation: Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016;176(2):238-246.

Clinical question: What is the association between proton pump inhibitor (PPI) use and incident chronic kidney disease (CKD)?

Background: Medication use may play a potential role in the increasing prevalence of CKD. PPIs are commonly prescribed, and several observational studies have linked their use with multiple adverse outcomes, including acute interstitial nephritis. The risk for CKD with PPI use has never been evaluated.

Study design: Prospective cohort study.

Setting: U.S., multi-center.

Synopsis: Among 10,482 patients in the Atherosclerosis Risk in Communities study (ARIC) with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m2, PPI use was associated with a 1.50 times risk of incident CKD (95% CI, 1.14–1.96; P=0.003) and a 1.64 times risk of incident acute kidney injury (95% CI, 1.22–2.21; P<0.001) when compared to nonusers. PPI use continued to have an association with incident CKD even when compared directly with H2 receptor antagonist users (adjusted HR, 1.39; 95% CI, 1.01–1.91). Findings were replicated in a cohort of 248,751 patients in the Geisinger Health System, and in all analyses, PPI use was associated with CKD.

One limitation is that this was an observational study and causality between PPI use and CKD cannot be established.

Bottom line: PPIs are associated with risk for CKD, and in patients on therapy, its use should be reevaluated.

Citation: Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016;176(2):238-246.

Clinical question: What is the association between proton pump inhibitor (PPI) use and incident chronic kidney disease (CKD)?

Background: Medication use may play a potential role in the increasing prevalence of CKD. PPIs are commonly prescribed, and several observational studies have linked their use with multiple adverse outcomes, including acute interstitial nephritis. The risk for CKD with PPI use has never been evaluated.

Study design: Prospective cohort study.

Setting: U.S., multi-center.

Synopsis: Among 10,482 patients in the Atherosclerosis Risk in Communities study (ARIC) with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m2, PPI use was associated with a 1.50 times risk of incident CKD (95% CI, 1.14–1.96; P=0.003) and a 1.64 times risk of incident acute kidney injury (95% CI, 1.22–2.21; P<0.001) when compared to nonusers. PPI use continued to have an association with incident CKD even when compared directly with H2 receptor antagonist users (adjusted HR, 1.39; 95% CI, 1.01–1.91). Findings were replicated in a cohort of 248,751 patients in the Geisinger Health System, and in all analyses, PPI use was associated with CKD.

One limitation is that this was an observational study and causality between PPI use and CKD cannot be established.

Bottom line: PPIs are associated with risk for CKD, and in patients on therapy, its use should be reevaluated.

Citation: Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016;176(2):238-246.

Clinical question: What risk factors could predict the likelihood of Pseudomonas and methicillin-resistant Staphylococcus aureus (MRSA) in patients hospitalized with healthcare-associated pneumonia (HCAP)?

Background: Patients identified with HCAP have an increased risk for multi-drug-resistant pathogens, such as gram-negative (GNR) organisms and MRSA. Meeting criteria for HCAP does not discriminate between the different infections, which require different antibiotic classes for treatment. Risk factors need to be identified to determine the most likely infectious organism to help guide initial empiric antibiotic therapy.

Study design: Retrospective cohort study.

Setting: Veterans Affairs hospitals.

Synopsis: Of 61,651 veterans with HCAP diagnosis, 1,156 (1.9%) had a discharge diagnosis of Pseudomonas pneumonia and were found to be younger and more likely to be immunocompromised; have hemiplegia; have a history of chronic obstructive pulmonary disease; have had corticosteroid exposure; and have been exposed to a fluoroquinolone, β-lactam, cephalosporin, or carbapenem antiobiotic within 90 days prior to admission. Pseudomonas pneumonia was negatively associated with age >84, drug abuse, diabetes, and higher socioeconomic status. A discharge diagnosis of MRSA pneumonia was found in 641 patients (1.0%), who also were positively associated with the male gender, age >74, recent nursing home stay, and recent exposure to fluoroquinolone antibiotics within 90 days prior to admission.

MRSA pneumonia was negatively associated with complicated diabetes. Neither diagnosis was present in 59,854 patients (97.1%).

This study was limited due to its predominantly male veteran population, low incidence of Pseudomonas and MRSA pneumonia being identified, and Pseudomonas as the only GNR organism analyzed.

Bottom line: Risk factors identified for Pseudomonas and MRSA pneumonia can help guide targeted antibiotics for HCAP patients.

Citation: Metersky ML, Frei CR, Mortenson EM. Predictors of Pseudomonas and methicillin-resistant Staphylococcus aureus in hospitalized patients with healthcare-associated pneumonia. Respirology. 2016;21(1):157-163.

Short Take

Hematuria as Marker of Urologic Cancer

Narrative literature review did not demonstrate beneficial role of screening urinalysis for cancer detection in asymptomatic patients, but it did suggest including gross hematuria as part of routine review of systems.

Citation: Nielsen M, Qaseem A, High Value Care Task Force of the American College of Physicians. Hematuria as a marker of occult urinary tract cancer: advice for high-value care from the American College of Physicians. Ann Intern Med. 2016;164(7):488-497. doi:10.7326/M15-1496.

Clinical question: What risk factors could predict the likelihood of Pseudomonas and methicillin-resistant Staphylococcus aureus (MRSA) in patients hospitalized with healthcare-associated pneumonia (HCAP)?

Background: Patients identified with HCAP have an increased risk for multi-drug-resistant pathogens, such as gram-negative (GNR) organisms and MRSA. Meeting criteria for HCAP does not discriminate between the different infections, which require different antibiotic classes for treatment. Risk factors need to be identified to determine the most likely infectious organism to help guide initial empiric antibiotic therapy.

Study design: Retrospective cohort study.

Setting: Veterans Affairs hospitals.

Synopsis: Of 61,651 veterans with HCAP diagnosis, 1,156 (1.9%) had a discharge diagnosis of Pseudomonas pneumonia and were found to be younger and more likely to be immunocompromised; have hemiplegia; have a history of chronic obstructive pulmonary disease; have had corticosteroid exposure; and have been exposed to a fluoroquinolone, β-lactam, cephalosporin, or carbapenem antiobiotic within 90 days prior to admission. Pseudomonas pneumonia was negatively associated with age >84, drug abuse, diabetes, and higher socioeconomic status. A discharge diagnosis of MRSA pneumonia was found in 641 patients (1.0%), who also were positively associated with the male gender, age >74, recent nursing home stay, and recent exposure to fluoroquinolone antibiotics within 90 days prior to admission.

MRSA pneumonia was negatively associated with complicated diabetes. Neither diagnosis was present in 59,854 patients (97.1%).

This study was limited due to its predominantly male veteran population, low incidence of Pseudomonas and MRSA pneumonia being identified, and Pseudomonas as the only GNR organism analyzed.

Bottom line: Risk factors identified for Pseudomonas and MRSA pneumonia can help guide targeted antibiotics for HCAP patients.

Citation: Metersky ML, Frei CR, Mortenson EM. Predictors of Pseudomonas and methicillin-resistant Staphylococcus aureus in hospitalized patients with healthcare-associated pneumonia. Respirology. 2016;21(1):157-163.

Short Take

Hematuria as Marker of Urologic Cancer

Narrative literature review did not demonstrate beneficial role of screening urinalysis for cancer detection in asymptomatic patients, but it did suggest including gross hematuria as part of routine review of systems.

Citation: Nielsen M, Qaseem A, High Value Care Task Force of the American College of Physicians. Hematuria as a marker of occult urinary tract cancer: advice for high-value care from the American College of Physicians. Ann Intern Med. 2016;164(7):488-497. doi:10.7326/M15-1496.

Clinical question: What risk factors could predict the likelihood of Pseudomonas and methicillin-resistant Staphylococcus aureus (MRSA) in patients hospitalized with healthcare-associated pneumonia (HCAP)?

Background: Patients identified with HCAP have an increased risk for multi-drug-resistant pathogens, such as gram-negative (GNR) organisms and MRSA. Meeting criteria for HCAP does not discriminate between the different infections, which require different antibiotic classes for treatment. Risk factors need to be identified to determine the most likely infectious organism to help guide initial empiric antibiotic therapy.

Study design: Retrospective cohort study.

Setting: Veterans Affairs hospitals.

Synopsis: Of 61,651 veterans with HCAP diagnosis, 1,156 (1.9%) had a discharge diagnosis of Pseudomonas pneumonia and were found to be younger and more likely to be immunocompromised; have hemiplegia; have a history of chronic obstructive pulmonary disease; have had corticosteroid exposure; and have been exposed to a fluoroquinolone, β-lactam, cephalosporin, or carbapenem antiobiotic within 90 days prior to admission. Pseudomonas pneumonia was negatively associated with age >84, drug abuse, diabetes, and higher socioeconomic status. A discharge diagnosis of MRSA pneumonia was found in 641 patients (1.0%), who also were positively associated with the male gender, age >74, recent nursing home stay, and recent exposure to fluoroquinolone antibiotics within 90 days prior to admission.

MRSA pneumonia was negatively associated with complicated diabetes. Neither diagnosis was present in 59,854 patients (97.1%).

This study was limited due to its predominantly male veteran population, low incidence of Pseudomonas and MRSA pneumonia being identified, and Pseudomonas as the only GNR organism analyzed.

Bottom line: Risk factors identified for Pseudomonas and MRSA pneumonia can help guide targeted antibiotics for HCAP patients.

Citation: Metersky ML, Frei CR, Mortenson EM. Predictors of Pseudomonas and methicillin-resistant Staphylococcus aureus in hospitalized patients with healthcare-associated pneumonia. Respirology. 2016;21(1):157-163.

Short Take

Hematuria as Marker of Urologic Cancer

Narrative literature review did not demonstrate beneficial role of screening urinalysis for cancer detection in asymptomatic patients, but it did suggest including gross hematuria as part of routine review of systems.

Citation: Nielsen M, Qaseem A, High Value Care Task Force of the American College of Physicians. Hematuria as a marker of occult urinary tract cancer: advice for high-value care from the American College of Physicians. Ann Intern Med. 2016;164(7):488-497. doi:10.7326/M15-1496.

Clinical question: What are the current recommendations for antithrombotic therapy in various venous thromboembolism (VTE) scenarios?

Background: VTE is commonly encountered with a multitude of therapeutic options. Selecting the optimal anticoagulant is as important as making the diagnosis and requires knowledge of individual patient characteristics to initiate the correct therapy. These factors include malignancy, location of thrombus, and history of recurrent VTE despite anticoagulation.

Study design: Guideline.

Setting: Expert panel.

Synopsis: For VTE patients without cancer, non-vitamin K oral anticoagulants (NOAC) are now suggested over vitamin K antagonists (Grade 2B). However, there remains no strong evidence to favor one NOAC over another.

Better evidence now supports the prior recommendation to discourage IVC filters for VTE that is being treated with anticoagulation (Grade 1B).

In pulmonary embolism of the subsegmental type without proximal DVT, clinical surveillance is favored over anticoagulation in lower-risk patients (Grade 2C).

Low-molecular-weight heparin (LMWH) is advised in recurrent VTE treated with non-LMWH, and for recurrences on LMWH, a dose increase of LMWH is advised (Grade 2C).

Finally, routine use of compression stockings for post-thrombotic syndrome prevention is not routinely recommended (Grade 2B).

Limitations include only 20 of the 54 total recommendations being of strong Grade 1 criteria. Additionally, none of the 54 statements are drawn from high-quality evidence.

Further study is needed to continually update our practice in caring for VTE disease as more experience and comparison data are obtained with the use of NOAC drugs.

Bottom line: Anticoagulant therapy recommendations have been updated, but few are strong recommendations and none are based on high-quality evidence.

Citation: Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315-352.

Clinical question: What are the current recommendations for antithrombotic therapy in various venous thromboembolism (VTE) scenarios?

Background: VTE is commonly encountered with a multitude of therapeutic options. Selecting the optimal anticoagulant is as important as making the diagnosis and requires knowledge of individual patient characteristics to initiate the correct therapy. These factors include malignancy, location of thrombus, and history of recurrent VTE despite anticoagulation.

Study design: Guideline.

Setting: Expert panel.

Synopsis: For VTE patients without cancer, non-vitamin K oral anticoagulants (NOAC) are now suggested over vitamin K antagonists (Grade 2B). However, there remains no strong evidence to favor one NOAC over another.

Better evidence now supports the prior recommendation to discourage IVC filters for VTE that is being treated with anticoagulation (Grade 1B).

In pulmonary embolism of the subsegmental type without proximal DVT, clinical surveillance is favored over anticoagulation in lower-risk patients (Grade 2C).

Low-molecular-weight heparin (LMWH) is advised in recurrent VTE treated with non-LMWH, and for recurrences on LMWH, a dose increase of LMWH is advised (Grade 2C).

Finally, routine use of compression stockings for post-thrombotic syndrome prevention is not routinely recommended (Grade 2B).

Limitations include only 20 of the 54 total recommendations being of strong Grade 1 criteria. Additionally, none of the 54 statements are drawn from high-quality evidence.

Further study is needed to continually update our practice in caring for VTE disease as more experience and comparison data are obtained with the use of NOAC drugs.

Bottom line: Anticoagulant therapy recommendations have been updated, but few are strong recommendations and none are based on high-quality evidence.

Citation: Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315-352.

Clinical question: What are the current recommendations for antithrombotic therapy in various venous thromboembolism (VTE) scenarios?

Background: VTE is commonly encountered with a multitude of therapeutic options. Selecting the optimal anticoagulant is as important as making the diagnosis and requires knowledge of individual patient characteristics to initiate the correct therapy. These factors include malignancy, location of thrombus, and history of recurrent VTE despite anticoagulation.

Study design: Guideline.

Setting: Expert panel.

Synopsis: For VTE patients without cancer, non-vitamin K oral anticoagulants (NOAC) are now suggested over vitamin K antagonists (Grade 2B). However, there remains no strong evidence to favor one NOAC over another.

Better evidence now supports the prior recommendation to discourage IVC filters for VTE that is being treated with anticoagulation (Grade 1B).

In pulmonary embolism of the subsegmental type without proximal DVT, clinical surveillance is favored over anticoagulation in lower-risk patients (Grade 2C).

Low-molecular-weight heparin (LMWH) is advised in recurrent VTE treated with non-LMWH, and for recurrences on LMWH, a dose increase of LMWH is advised (Grade 2C).

Finally, routine use of compression stockings for post-thrombotic syndrome prevention is not routinely recommended (Grade 2B).

Limitations include only 20 of the 54 total recommendations being of strong Grade 1 criteria. Additionally, none of the 54 statements are drawn from high-quality evidence.

Further study is needed to continually update our practice in caring for VTE disease as more experience and comparison data are obtained with the use of NOAC drugs.

Bottom line: Anticoagulant therapy recommendations have been updated, but few are strong recommendations and none are based on high-quality evidence.

Citation: Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315-352.

Clinical question: Is tamsulosin efficacious as an expulsive therapy for distal ureter stones ≤10 mm in diameter?

Background: Ureteric calculi are a common reason for hospital admission, and use of medical expulsive therapy during observation periods for small caliber stones has gained much attention recently. Specifically, tamsulosin has been suggested as a medical therapy for small stones.

Study design: Randomized, double-blind, placebo-controlled study.

Setting: Five EDs in Australia.

Synopsis: A total of 403 patients participated in the study, based on inclusion criteria of age older than 18 years with symptoms and CT evidence of ureteric stones Exclusion criteria included fever, glomerular filtration rate <60, and calculi >10 mm. Patients were randomized to placebo or 0.4 mg tamsulosin daily for 28 days. The outcome was stone expulsion demonstrated by absence of calculi on repeat CT. Stone passage in the entire group occurred in 87% of the tamsulosin arm and 81.9% of the placebo, with a 95% CI of -3.0% to 13%, which was not a significant difference with P=0.22.

Interestingly, in a subgroup analysis of larger stones 5–10 mm, 83% of tamsulosin subjects compared to 61% of placebo subjects had stone passage that was significant at a 22% difference and P=.03.

Limitations included compliance in both groups, applicability to other populations given study based in Australia, and the lack of follow-through with CT scan at 28 days in 17% of the original group, resulting in missing outcome data.

Bottom line: Patients with ureteric stones 5–10 mm in size demonstrate increased spontaneous stone expulsion with the addition of tamsulosin and should thus be offered this therapy.

Citation: Furyk J, Chu K, Banks C, et al. Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial. Ann Emerg Med. 2016;67(1):86-95.e2.

Short Take

Low Diagnostic Yield of Blood Cultures in Hospitalized Medical Patients

Prospective cohort study of patients hospitalized on a medical service demonstrated a true positive rate of blood cultures that was lower than previously studied. Using objective clinical predictors may improve likelihood of true positive blood cultures.

Citation: Linsenmeyer K, Gupta K, Strymish JM, Dhanani M, Brecher SM, Breu AC. Culture if spikes? Indications and yield of blood cultures in hospitalized medical patients [published online ahead of print January 13, 2016]. J Hosp Med. doi:10.1002/jhm.2541.

Clinical question: Is tamsulosin efficacious as an expulsive therapy for distal ureter stones ≤10 mm in diameter?

Background: Ureteric calculi are a common reason for hospital admission, and use of medical expulsive therapy during observation periods for small caliber stones has gained much attention recently. Specifically, tamsulosin has been suggested as a medical therapy for small stones.

Study design: Randomized, double-blind, placebo-controlled study.

Setting: Five EDs in Australia.

Synopsis: A total of 403 patients participated in the study, based on inclusion criteria of age older than 18 years with symptoms and CT evidence of ureteric stones Exclusion criteria included fever, glomerular filtration rate <60, and calculi >10 mm. Patients were randomized to placebo or 0.4 mg tamsulosin daily for 28 days. The outcome was stone expulsion demonstrated by absence of calculi on repeat CT. Stone passage in the entire group occurred in 87% of the tamsulosin arm and 81.9% of the placebo, with a 95% CI of -3.0% to 13%, which was not a significant difference with P=0.22.

Interestingly, in a subgroup analysis of larger stones 5–10 mm, 83% of tamsulosin subjects compared to 61% of placebo subjects had stone passage that was significant at a 22% difference and P=.03.

Limitations included compliance in both groups, applicability to other populations given study based in Australia, and the lack of follow-through with CT scan at 28 days in 17% of the original group, resulting in missing outcome data.

Bottom line: Patients with ureteric stones 5–10 mm in size demonstrate increased spontaneous stone expulsion with the addition of tamsulosin and should thus be offered this therapy.

Citation: Furyk J, Chu K, Banks C, et al. Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial. Ann Emerg Med. 2016;67(1):86-95.e2.

Short Take

Low Diagnostic Yield of Blood Cultures in Hospitalized Medical Patients

Prospective cohort study of patients hospitalized on a medical service demonstrated a true positive rate of blood cultures that was lower than previously studied. Using objective clinical predictors may improve likelihood of true positive blood cultures.

Citation: Linsenmeyer K, Gupta K, Strymish JM, Dhanani M, Brecher SM, Breu AC. Culture if spikes? Indications and yield of blood cultures in hospitalized medical patients [published online ahead of print January 13, 2016]. J Hosp Med. doi:10.1002/jhm.2541.

Clinical question: Is tamsulosin efficacious as an expulsive therapy for distal ureter stones ≤10 mm in diameter?

Background: Ureteric calculi are a common reason for hospital admission, and use of medical expulsive therapy during observation periods for small caliber stones has gained much attention recently. Specifically, tamsulosin has been suggested as a medical therapy for small stones.

Study design: Randomized, double-blind, placebo-controlled study.

Setting: Five EDs in Australia.

Synopsis: A total of 403 patients participated in the study, based on inclusion criteria of age older than 18 years with symptoms and CT evidence of ureteric stones Exclusion criteria included fever, glomerular filtration rate <60, and calculi >10 mm. Patients were randomized to placebo or 0.4 mg tamsulosin daily for 28 days. The outcome was stone expulsion demonstrated by absence of calculi on repeat CT. Stone passage in the entire group occurred in 87% of the tamsulosin arm and 81.9% of the placebo, with a 95% CI of -3.0% to 13%, which was not a significant difference with P=0.22.

Interestingly, in a subgroup analysis of larger stones 5–10 mm, 83% of tamsulosin subjects compared to 61% of placebo subjects had stone passage that was significant at a 22% difference and P=.03.

Limitations included compliance in both groups, applicability to other populations given study based in Australia, and the lack of follow-through with CT scan at 28 days in 17% of the original group, resulting in missing outcome data.

Bottom line: Patients with ureteric stones 5–10 mm in size demonstrate increased spontaneous stone expulsion with the addition of tamsulosin and should thus be offered this therapy.

Citation: Furyk J, Chu K, Banks C, et al. Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial. Ann Emerg Med. 2016;67(1):86-95.e2.

Short Take

Low Diagnostic Yield of Blood Cultures in Hospitalized Medical Patients

Prospective cohort study of patients hospitalized on a medical service demonstrated a true positive rate of blood cultures that was lower than previously studied. Using objective clinical predictors may improve likelihood of true positive blood cultures.

Citation: Linsenmeyer K, Gupta K, Strymish JM, Dhanani M, Brecher SM, Breu AC. Culture if spikes? Indications and yield of blood cultures in hospitalized medical patients [published online ahead of print January 13, 2016]. J Hosp Med. doi:10.1002/jhm.2541.

Clinical question: Do claim-prone physicians account for a substantial share of all paid malpractice claims?

Background: Many studies have compared physicians who have multiple malpractice claims against them with colleagues who have few or no claims against them and have identified systemic differences in their age, sex, and specialty. However, only a few published studies have analyzed the nature of maldistribution itself.

Study design: Retrospective cohort study.

Setting: Using data from the National Practitioner Data Bank (NPDB).

Synopsis: The NPDB is a confidential data repository created by Congress in 1986. Information was obtained on all payments reported to the NPDB against physicians in the U.S. between January 1, 2005, and December 31, 2014. The study sample consisted of 66,426 paid claims against 54,099 physicians.

Physicians in four specialty groups accounted for more than half the claims: internal medicine (15%), obstetrics and gynecology (13%), general surgery (12%), and family medicine (11%). One percent of all physicians accounted for 32% of paid claims. Physicians’ risk of future paid claims increased monotonically with their number of previous paid claims. Physicians who had two paid claims had almost twice the risk of having another one (HR, 1.97; 95% CI, 1.86–2.07).

Risk also varied widely according to specialty. Compared with internal medicine physicians, neurosurgeons had approximately double the risk of recurrence (HR, 2.32; 95% CI, 1.77–3.03).

The study has some limitations. Some malpractice payments do not reach the NPDB. The study also focused on paid claims only.

Bottom line: A small group of U.S. physicians accounted for a disproportionately large share of paid malpractice claims. Several physician characteristics, most notably the number of previous claims and physician specialty, were significantly associated with recurrence of claims.

Citation: Studdert DM, Bismark MM, Mello MM, Singh H, Spittal MJ. Prevalence and characteristics of physicians prone to malpractice claims. N Engl J Med. 2016;374(4):354-362. doi:10.1056/nejmsa1506137.

Clinical question: Do claim-prone physicians account for a substantial share of all paid malpractice claims?

Background: Many studies have compared physicians who have multiple malpractice claims against them with colleagues who have few or no claims against them and have identified systemic differences in their age, sex, and specialty. However, only a few published studies have analyzed the nature of maldistribution itself.

Study design: Retrospective cohort study.

Setting: Using data from the National Practitioner Data Bank (NPDB).

Synopsis: The NPDB is a confidential data repository created by Congress in 1986. Information was obtained on all payments reported to the NPDB against physicians in the U.S. between January 1, 2005, and December 31, 2014. The study sample consisted of 66,426 paid claims against 54,099 physicians.

Physicians in four specialty groups accounted for more than half the claims: internal medicine (15%), obstetrics and gynecology (13%), general surgery (12%), and family medicine (11%). One percent of all physicians accounted for 32% of paid claims. Physicians’ risk of future paid claims increased monotonically with their number of previous paid claims. Physicians who had two paid claims had almost twice the risk of having another one (HR, 1.97; 95% CI, 1.86–2.07).

Risk also varied widely according to specialty. Compared with internal medicine physicians, neurosurgeons had approximately double the risk of recurrence (HR, 2.32; 95% CI, 1.77–3.03).

The study has some limitations. Some malpractice payments do not reach the NPDB. The study also focused on paid claims only.

Bottom line: A small group of U.S. physicians accounted for a disproportionately large share of paid malpractice claims. Several physician characteristics, most notably the number of previous claims and physician specialty, were significantly associated with recurrence of claims.

Citation: Studdert DM, Bismark MM, Mello MM, Singh H, Spittal MJ. Prevalence and characteristics of physicians prone to malpractice claims. N Engl J Med. 2016;374(4):354-362. doi:10.1056/nejmsa1506137.

Clinical question: Do claim-prone physicians account for a substantial share of all paid malpractice claims?

Background: Many studies have compared physicians who have multiple malpractice claims against them with colleagues who have few or no claims against them and have identified systemic differences in their age, sex, and specialty. However, only a few published studies have analyzed the nature of maldistribution itself.

Study design: Retrospective cohort study.

Setting: Using data from the National Practitioner Data Bank (NPDB).

Synopsis: The NPDB is a confidential data repository created by Congress in 1986. Information was obtained on all payments reported to the NPDB against physicians in the U.S. between January 1, 2005, and December 31, 2014. The study sample consisted of 66,426 paid claims against 54,099 physicians.

Physicians in four specialty groups accounted for more than half the claims: internal medicine (15%), obstetrics and gynecology (13%), general surgery (12%), and family medicine (11%). One percent of all physicians accounted for 32% of paid claims. Physicians’ risk of future paid claims increased monotonically with their number of previous paid claims. Physicians who had two paid claims had almost twice the risk of having another one (HR, 1.97; 95% CI, 1.86–2.07).

Risk also varied widely according to specialty. Compared with internal medicine physicians, neurosurgeons had approximately double the risk of recurrence (HR, 2.32; 95% CI, 1.77–3.03).

The study has some limitations. Some malpractice payments do not reach the NPDB. The study also focused on paid claims only.

Bottom line: A small group of U.S. physicians accounted for a disproportionately large share of paid malpractice claims. Several physician characteristics, most notably the number of previous claims and physician specialty, were significantly associated with recurrence of claims.

Citation: Studdert DM, Bismark MM, Mello MM, Singh H, Spittal MJ. Prevalence and characteristics of physicians prone to malpractice claims. N Engl J Med. 2016;374(4):354-362. doi:10.1056/nejmsa1506137.

Clinical question: What is the association of preoperative frailty on one-year postoperative mortality?

Background: Frailty is an aggregate expression of susceptibility to poor outcomes owing to age and disease-related deficits that accumulate with multiple domains. Frailty in this study was defined by the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining diagnoses indicator. It is a binary variable that uses 12 clusters of frailty-defining diagnoses.

Study design: Population-based retrospective cohort study.

Setting: All hospital and physician services funded through the public health care system in Toronto.

Synopsis: The study had 202,980 patients who underwent major elective non-cardiac surgery. Frailty-defining diagnoses were present in 6,289 patients (3.1%). Mean age for the frail population was about 77 years. Joint replacements were the most common procedures for the frail and non-frail groups. Knee replacements were more prevalent in the non-frail group. One year after surgery, 855 frail patients (13.6%) and 9,433 non-frail patients (4.8%) died (unadjusted hazard ratio [HR], 2.98; 95% CI, 2.78–3.20). When adjusted for age, sex, neighborhood income quintile, and procedure, one-year mortality risk remained significantly higher in the frail group. One-year risk of death was significantly higher in frail patients for all surgical procedures, especially with total joint arthroplasty.

The relative hazard ratio of mortality in frail versus non-frail was extremely high in the early postoperative period, most notably at postoperative day three.

One major weakness of the study is that there is no universal definition of frailty, plus the results are difficult to generalize across populations.

Bottom line: Presence of preoperative frailty-defining diagnoses is associated with increased risk for one-year postoperative mortality; the risk appears to be very high in the early postoperative period.

Citation: McIsaac D, Bryson G, van Walraven C. Association of frailty and 1-year postoperative mortality following major elective noncardiac surgery: a population-based cohort study [published online ahead of print January 20, 2016]. JAMA Surg. doi:10.1001/jamasurg.2015.5085.

Short Take

Early Discharge Associated with Longer Length of Stay

Retrospective analysis showed early discharge before noon was associated with longer length of stay, especially among emergent admissions. However, multiple metrics should be used to measure true effectiveness of an early discharge program.

Citation: Rajkomar A, Valencia V, Novelero M, Mourad M, Auerbach A. The association between discharge before noon and length of stay in medical and surgical patients [published online ahead of print December 30, 2015]. J Hosp Med. doi:10.1002/jhm.2529.

Clinical question: What is the association of preoperative frailty on one-year postoperative mortality?

Background: Frailty is an aggregate expression of susceptibility to poor outcomes owing to age and disease-related deficits that accumulate with multiple domains. Frailty in this study was defined by the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining diagnoses indicator. It is a binary variable that uses 12 clusters of frailty-defining diagnoses.

Study design: Population-based retrospective cohort study.

Setting: All hospital and physician services funded through the public health care system in Toronto.

Synopsis: The study had 202,980 patients who underwent major elective non-cardiac surgery. Frailty-defining diagnoses were present in 6,289 patients (3.1%). Mean age for the frail population was about 77 years. Joint replacements were the most common procedures for the frail and non-frail groups. Knee replacements were more prevalent in the non-frail group. One year after surgery, 855 frail patients (13.6%) and 9,433 non-frail patients (4.8%) died (unadjusted hazard ratio [HR], 2.98; 95% CI, 2.78–3.20). When adjusted for age, sex, neighborhood income quintile, and procedure, one-year mortality risk remained significantly higher in the frail group. One-year risk of death was significantly higher in frail patients for all surgical procedures, especially with total joint arthroplasty.

The relative hazard ratio of mortality in frail versus non-frail was extremely high in the early postoperative period, most notably at postoperative day three.

One major weakness of the study is that there is no universal definition of frailty, plus the results are difficult to generalize across populations.

Bottom line: Presence of preoperative frailty-defining diagnoses is associated with increased risk for one-year postoperative mortality; the risk appears to be very high in the early postoperative period.

Citation: McIsaac D, Bryson G, van Walraven C. Association of frailty and 1-year postoperative mortality following major elective noncardiac surgery: a population-based cohort study [published online ahead of print January 20, 2016]. JAMA Surg. doi:10.1001/jamasurg.2015.5085.

Short Take

Early Discharge Associated with Longer Length of Stay

Retrospective analysis showed early discharge before noon was associated with longer length of stay, especially among emergent admissions. However, multiple metrics should be used to measure true effectiveness of an early discharge program.

Citation: Rajkomar A, Valencia V, Novelero M, Mourad M, Auerbach A. The association between discharge before noon and length of stay in medical and surgical patients [published online ahead of print December 30, 2015]. J Hosp Med. doi:10.1002/jhm.2529.

Clinical question: What is the association of preoperative frailty on one-year postoperative mortality?

Background: Frailty is an aggregate expression of susceptibility to poor outcomes owing to age and disease-related deficits that accumulate with multiple domains. Frailty in this study was defined by the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining diagnoses indicator. It is a binary variable that uses 12 clusters of frailty-defining diagnoses.

Study design: Population-based retrospective cohort study.

Setting: All hospital and physician services funded through the public health care system in Toronto.

Synopsis: The study had 202,980 patients who underwent major elective non-cardiac surgery. Frailty-defining diagnoses were present in 6,289 patients (3.1%). Mean age for the frail population was about 77 years. Joint replacements were the most common procedures for the frail and non-frail groups. Knee replacements were more prevalent in the non-frail group. One year after surgery, 855 frail patients (13.6%) and 9,433 non-frail patients (4.8%) died (unadjusted hazard ratio [HR], 2.98; 95% CI, 2.78–3.20). When adjusted for age, sex, neighborhood income quintile, and procedure, one-year mortality risk remained significantly higher in the frail group. One-year risk of death was significantly higher in frail patients for all surgical procedures, especially with total joint arthroplasty.

The relative hazard ratio of mortality in frail versus non-frail was extremely high in the early postoperative period, most notably at postoperative day three.

One major weakness of the study is that there is no universal definition of frailty, plus the results are difficult to generalize across populations.

Bottom line: Presence of preoperative frailty-defining diagnoses is associated with increased risk for one-year postoperative mortality; the risk appears to be very high in the early postoperative period.

Citation: McIsaac D, Bryson G, van Walraven C. Association of frailty and 1-year postoperative mortality following major elective noncardiac surgery: a population-based cohort study [published online ahead of print January 20, 2016]. JAMA Surg. doi:10.1001/jamasurg.2015.5085.

Short Take

Early Discharge Associated with Longer Length of Stay

Retrospective analysis showed early discharge before noon was associated with longer length of stay, especially among emergent admissions. However, multiple metrics should be used to measure true effectiveness of an early discharge program.

Citation: Rajkomar A, Valencia V, Novelero M, Mourad M, Auerbach A. The association between discharge before noon and length of stay in medical and surgical patients [published online ahead of print December 30, 2015]. J Hosp Med. doi:10.1002/jhm.2529.

Case

A 66-year-old man with diabetes mellitus type 2 and hypertension underwent left total knee replacement. Several hours after surgery, the patient developed atrial fibrillation (AF). He was asymptomatic, and reversible causes of AF were ruled out. Approximately 18 hours later, he spontaneously reverted back to sinus rhythm. Should this patient, who has no known prior history of AF and a CHA2DS2-VASc score of 3, be started on anticoagulation?

Background

Hospitalists are commonly consulted for evaluation and management of postoperative atrial fibrillation (POAF). The incidence of new-onset AF associated with non-cardiac surgery is approximately 2% and may be more frequent in an elderly population.1 The increased adrenergic tone associated with surgery is thought to elicit AF in some patients. POAF has also been associated with positive fluid balance, electrolyte abnormalities, and hypoxemia.2 Some of these patients will spontaneously revert back to sinus rhythm after these issues are reversed. Others will go on to develop chronic or paroxysmal AF that persists indefinitely. It is also likely that some patients with POAF, in fact, already had asymptomatic AF that was simply undetected prior to hospitalization.

Hospitalists are faced with the difficult task of determining which patients with POAF will benefit from either short-term or long-term anticoagulation. This has not been well studied in postsurgical patients, in contrast to medical patients in whom stroke risk from AF has been very well-characterized. The decision may be further complicated by bleeding risk (associated with either some surgeries or with patient-dependent factors).3

It is worth noting that following major cardiac or thoracic surgery, POAF is common; the incidence ranges from 10% to 60%. In these cases, POAF may be triggered by transient atrial ischemia or by postoperative inflammation and may have a different natural history from POAF in non-cardiac surgery patients in terms of both reversibility and stroke risk. More retrospective data are available regarding cardiothoracic surgery patients.

Previous American Heart Association (AHA) and American College of Cardiology (ACC) guidelines stated that POAF lasting longer than 48 hours warranted anticoagulation. This recommendation was removed from the newest update. The 2014 updated AHA/ACC guidelines are less absolute and now state only that “it is reasonable to administer antithrombotic medication in patients who developed postoperative AF, as recommended for nonsurgical patients” (Level of Evidence: B) in regard to cardiothoracic surgery.4

There is no specific recommendation regarding POAF for non-cardiac surgery patients. The current guidelines are likely purposefully vague due to the lack of direct evidence. The following is a review of the existing literature and a suggested approach to anticoagulation in POAF.

Review

How common is postoperative atrial fibrillation? New-onset AF during hospitalization is known to occur in association with many acute conditions including surgery, infection, and myocardial infarction. About half of the cases of in-hospital new-onset AF are associated with surgery. AF is more commonly seen in surgery that involves the thoracic cavity and cardiac structures. In a cross-sectional epidemiologic study of 22 million patients in California, 20.8% of patients undergoing cardiac surgery developed POAF compared with only 1.3% of patients undergoing non-cardiac surgery.5 A smaller study of non-cardiac surgery patients found a 30-day POAF incidence of 0.37%.2

Does postoperative atrial fibrillation increase the short-term risk of stroke? A major concern in AF is the risk of stroke. It is well-established that prolonged or recurrent AF increases the risk for stroke over months or years, but do short episodes of POAF increase stroke risk to a significant degree? Most of the studies in the literature focus on perioperative stroke risk specifically in cardiothoracic surgery. A prospective study of 4,000 patients undergoing cardiac surgery found that the in-hospital postoperative stroke risk was 3.3% in patients with POAF compared to 1.4% in patients without POAF (P<0.01).6 Similar outcomes were seen in a VA study looking at patients who underwent open heart surgery: Stroke risk was 5.3% at six months in POAF patients compared to 2.4% in those without POAF.7 Another study of coronary artery bypass graft (CABG) patients with a follow-up of almost six years showed a stroke risk of 12.1% in POAF patients compared to 8.4% in those without POAF.8

 

It is not clear that all of the increase in stroke risk is a direct effect of POAF. Indeed, in a retrospective analysis of almost 3,000 CABG patients, 1.1% suffered a stroke during their hospital stay. Fewer than half of those had a cardiac rhythm other than sinus rhythm. In the 15 stroke patients who developed POAF, nine presented with stroke symptoms prior to the first episode of AF.9 The authors suggest that aggressive anticoagulation for POAF would not have prevented most of these events.

Furthermore, the rate of in-hospital stroke after non-cardiac surgery is probably much lower, though it has not been as well studied. These data raise some questions as to the benefit of anticoagulation in the immediate postoperative period, though it is difficult to draw firm conclusions without randomized data.

What about non-cardiac surgery? There is less evidence available for patients undergoing non-cardiac surgery, but the few studies that do exist also point to higher stroke risk in patients with POAF. A large population-based study using ICD codes found that the one-year risk of stroke for patients with POAF after non-cardiac surgery was 1.47% compared to 0.36% in non-cardiac surgery patients without POAF (P<0.001). Based on these data, the long-term stroke risk after POAF in non-cardiac surgery patients is similar to that of medical AF patients with a CHA2DS2-VASc score of 2. The authors of this study suggest that transient POAF after non-cardiac surgery may carry a long-term stroke risk similar to any other AF diagnosis.10 However, this study design is subject to significant ascertainment bias (i.e., they may have unintentionally captured some patients with preexisting or prolonged AF), and further research is needed to better delineate this risk.

Does increased stroke risk translate into increased mortality? In a retrospective study of 17,000 patients, El-Chami et al found that POAF after CABG was associated with decreased survival after one year (90% versus 96%) and 10 years (55% versus 70%).11 However, those patients who develop POAF may be sicker overall.

Another study showed that death due to stroke occurred in 4.2% of POAF patients compared to 0.2% of non-POAF patients in a five-year period.12 Based on these studies, POAF is likely associated with increased mortality, but there may be other unaccounted variables. Nevertheless, the increased mortality associated with POAF in these populations is similar to that seen for non-surgical population-based studies13 and provides support that those with newly diagnosed AF in the post-surgical setting should at least be followed closely to assess for recurrence.

What is a patient’s risk of developing atrial fibrillation later in life? When we choose to anticoagulate patients with POAF, we then have to determine whether they should be committed to long-term anticoagulation. It is thought that many cases of POAF are transient; however, some patients will go on to have persistent or paroxysmal AF after discharge.

A retrospective study examined 571 patients who underwent CABG, 30% of whom had POAF during the index admission. After five years of follow-up, 25% of those with POAF were diagnosed with paroxysmal or persistent AF after discharge compared to only 3% of patients without POAF. Researchers did this by looking at the most recent ECG, if done in the last year, or by obtaining a new ECG at the five-year point.12 By this method, it is probable that some diagnoses of paroxysmal AF were missed.

In another study of about 300 CABG patients, about 20% of patients with POAF also went on to develop post-discharge AF, defined as symptomatic AF that led to medical evaluation. As in the previous study, it is likely that there were undetected episodes of AF.14 Thus, in cardiothoracic surgery patients, some but not all of whom develop POAF have recurrent or ongoing AF. For this reason, if anticoagulation is started, it may be reasonable to stop anticoagulation after weeks or months if ongoing AF is not apparent.

 

What is the risk of postoperative bleeding if anticoagulation is started? Any decision about the benefits of anticoagulation must be weighed against the risks, most notably the risk of serious or life-threatening bleeding. This risk may be heightened in the immediate perioperative period. Discussions should always take place with our surgical colleagues about type of surgery, intraoperative complications, and postoperative risk of bleeding.

Anticoagulation, if indicated, should not be started until postoperative bleeding risk is deemed appropriately low. That said, the 2015 BRIDGE trial (looking at the benefits and risks of “bridging” patients before surgery) provides some peripheral but meaningful information about postoperative bleeding risk. In this study, patients with preexisting AF who underwent low-bleeding-risk surgery and were bridged on day one after surgery with therapeutic doses of unfractionated or low-molecular-weight heparin had a significantly higher risk of postoperative bleeding compared to non-bridged patients, with a number needed to harm of 50.15 It may be reasonable—and likely safer—to wait a couple days to start anticoagulation for patients with POAF.

What is the expert’s opinion? We asked one of our cardiac electrophysiologists what her approach is to this situation. In general, if a patient has a low stroke risk and is in AF for fewer than 24 hours, it is reasonable to defer anticoagulation and follow as an outpatient. Regardless of risk, if AF is sustained for more than 24 hours, we recommend at least four weeks of anticoagulation and close outpatient follow-up, which should include a period of ambulatory monitoring to determine the need for continued anticoagulation. We also recommend considering what comprises the patient’s stroke risk.

For example, if the CHA2DS2-VASc score is 2 but the points come from being a female with coronary artery disease, we would consider forgoing anticoagulation but arranging for an outpatient cardiac monitor with cardiology follow-up. If the patient has a history of stroke or TIA, we recommend continuing anticoagulation indefinitely.

Back to the Case

Given our patient’s episode of POAF lasted fewer than 24 hours, it would be reasonable to hold off starting anticoagulation, but he should be followed as an outpatient with ambulatory monitoring at a minimum, monitoring for recurrence. If he were to develop recurrent AF, then he would warrant anticoagulation based on an annual stroke risk of 3.2% as determined by a CHA2DS2-VASc score of 3.

Bottom Line

Our strategy is as follows: If a patient has a low stroke risk (i.e., CHA2DS2-VASc score <2) and is in AF for fewer than 24 hours, anticoagulation is not started, but outpatient follow-up is arranged to monitor symptoms. Regardless of stroke risk, if a patient is in AF for more than 24 hours, we initiate and continue anticoagulation for a minimum of four weeks and arrange outpatient follow-up with a period of ambulatory monitoring to determine need for continued anticoagulation. If a patient has a high stroke risk (CHA2DS2-VASc >2) or if their risk factors include a history of stroke or TIA, anticoagulation is started and continued indefinitely. Risk-benefit discussion is held with the patient, especially with regard to bleeding risk, prior to anticoagulation initiation. If the individual patient’s situation presents further nuance, we ask for the assistance of our cardiology or cardiac electrophysiology colleagues.

Final Thought

None of the mentioned studies investigated or included newer oral anticoagulants. Risk-benefit ratios may change (potentially considerably) with these agents. Further study is needed. We expect, in due time, studies will look at the question of POAF in regard to newer anticoagulant agents, and perhaps then our decision making will change. TH

---

 

Dr. Evavold is a resident in the hospitalist training program, while Dr. Lessing and Dr. Merritt are hospitalists in the Department of Internal Medicine at the University of Colorado. Dr. Tzou is a cardiologist in the section of electrophysiology at the University of Colorado.

References:

1. POISE Study Group, Devereaux PJ, Yang H, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371(9627):1839-1847. doi:10.1016/s0140-6736(08)60601-7.
2. Christians K, Wu B, Quebbeman E, Brasel K. Postoperative atrial fibrillation in noncardiothoracic surgical patients. Am J Surg. 2001;182(6):713-715. doi:10.1016/s0002-9610(01)00799-1.
3. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-1100. doi:10.1378/chest.10-0134.
4. Fleisher L, Beckman J, Brown K, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 2002 guidelines on perioperative cardiovascular evaluation for noncardiac surgery). Circulation. 2007;116(17):e418-e500. doi:10.1161/circulationaha.107.185699.
5. Walkey A, Benjamin E, Lubitz S. New-onset atrial fibrillation during hospitalization. J Am Coll Cardiol. 2014;64(22):2432-2433. doi:10.1016/j.jacc.2014.09.034.
6. Creswell L, Schuessler R, Rosenbloom M, Cox J. Hazards of postoperative atrial arrhythmias. Ann Thorac Surg. 1993;56(3):539-549. doi:10.1016/0003-4975(93)90894-n.
7. Almassi G, Schowalter T, Nicolosi A, et al. Atrial fibrillation after cardiac surgery: a major morbid event? Ann Surg. 1997;226(4):501-513.
8. Horwich P, Buth K, Légaré J. New onset postoperative atrial fibrillation is associated with a long-term risk for stroke and death following cardiac surgery. J Card Surg. 2013;28(1):8-13. doi:10.1111/jocs.12033.
9. Kollar A, Lick S, Vasquez K, Conti V. Relationship of atrial fibrillation and stroke after coronary artery bypass graft surgery: when is anticoagulation indicated? Ann Thorac Surg. 2006;82(2):515-523. doi:10.1016/j.athoracsur.2006.03.037.
10. Gialdini G, Nearing K, Bhave P, et al. Perioperative atrial fibrillation and the long-term risk of ischemic stroke. JAMA. 2014;312(6):616. doi:10.1001/jama.2014.9143.
11. El-Chami M, Kilgo P, Thourani V, et al. New-onset atrial fibrillation predicts long-term mortality after coronary artery bypass graft. J Am Coll Cardiol. 2010;55(13):1370-1376. doi:10.1016/j.jacc.2009.10.058.
12. Ahlsson A, Fengsrud E, Bodin L, Englund A. Postoperative atrial fibrillation in patients undergoing aortocoronary bypass surgery carries an eightfold risk of future atrial fibrillation and a doubled cardiovascular mortality. Euro J Cardiothorac Surg. 2010;37(6):1353-1359. doi:10.1016/j.ejcts.2009.12.033.
13. Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98(10):946-952.
14. Antonelli D, Peres D, Freedberg N, Feldman A, Rosenfeld T. Incidence of postdischarge symptomatic paroxysmal atrial fibrillation in patients who underwent coronary artery bypass graft: long-term follow-up. Pacing Clin Electrophysiol. 2004;27(3):365-367. doi:10.1111/j.1540-8159.2004.00443.x.
15. Douketis J, Spyropoulos A, Kaatz S, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015;373(9):823-833. doi:10.1056/nejmoa1501035.

Case

A 66-year-old man with diabetes mellitus type 2 and hypertension underwent left total knee replacement. Several hours after surgery, the patient developed atrial fibrillation (AF). He was asymptomatic, and reversible causes of AF were ruled out. Approximately 18 hours later, he spontaneously reverted back to sinus rhythm. Should this patient, who has no known prior history of AF and a CHA2DS2-VASc score of 3, be started on anticoagulation?

Background

Hospitalists are commonly consulted for evaluation and management of postoperative atrial fibrillation (POAF). The incidence of new-onset AF associated with non-cardiac surgery is approximately 2% and may be more frequent in an elderly population.1 The increased adrenergic tone associated with surgery is thought to elicit AF in some patients. POAF has also been associated with positive fluid balance, electrolyte abnormalities, and hypoxemia.2 Some of these patients will spontaneously revert back to sinus rhythm after these issues are reversed. Others will go on to develop chronic or paroxysmal AF that persists indefinitely. It is also likely that some patients with POAF, in fact, already had asymptomatic AF that was simply undetected prior to hospitalization.

Hospitalists are faced with the difficult task of determining which patients with POAF will benefit from either short-term or long-term anticoagulation. This has not been well studied in postsurgical patients, in contrast to medical patients in whom stroke risk from AF has been very well-characterized. The decision may be further complicated by bleeding risk (associated with either some surgeries or with patient-dependent factors).3

It is worth noting that following major cardiac or thoracic surgery, POAF is common; the incidence ranges from 10% to 60%. In these cases, POAF may be triggered by transient atrial ischemia or by postoperative inflammation and may have a different natural history from POAF in non-cardiac surgery patients in terms of both reversibility and stroke risk. More retrospective data are available regarding cardiothoracic surgery patients.

Previous American Heart Association (AHA) and American College of Cardiology (ACC) guidelines stated that POAF lasting longer than 48 hours warranted anticoagulation. This recommendation was removed from the newest update. The 2014 updated AHA/ACC guidelines are less absolute and now state only that “it is reasonable to administer antithrombotic medication in patients who developed postoperative AF, as recommended for nonsurgical patients” (Level of Evidence: B) in regard to cardiothoracic surgery.4

There is no specific recommendation regarding POAF for non-cardiac surgery patients. The current guidelines are likely purposefully vague due to the lack of direct evidence. The following is a review of the existing literature and a suggested approach to anticoagulation in POAF.

Review

How common is postoperative atrial fibrillation? New-onset AF during hospitalization is known to occur in association with many acute conditions including surgery, infection, and myocardial infarction. About half of the cases of in-hospital new-onset AF are associated with surgery. AF is more commonly seen in surgery that involves the thoracic cavity and cardiac structures. In a cross-sectional epidemiologic study of 22 million patients in California, 20.8% of patients undergoing cardiac surgery developed POAF compared with only 1.3% of patients undergoing non-cardiac surgery.5 A smaller study of non-cardiac surgery patients found a 30-day POAF incidence of 0.37%.2

Does postoperative atrial fibrillation increase the short-term risk of stroke? A major concern in AF is the risk of stroke. It is well-established that prolonged or recurrent AF increases the risk for stroke over months or years, but do short episodes of POAF increase stroke risk to a significant degree? Most of the studies in the literature focus on perioperative stroke risk specifically in cardiothoracic surgery. A prospective study of 4,000 patients undergoing cardiac surgery found that the in-hospital postoperative stroke risk was 3.3% in patients with POAF compared to 1.4% in patients without POAF (P<0.01).6 Similar outcomes were seen in a VA study looking at patients who underwent open heart surgery: Stroke risk was 5.3% at six months in POAF patients compared to 2.4% in those without POAF.7 Another study of coronary artery bypass graft (CABG) patients with a follow-up of almost six years showed a stroke risk of 12.1% in POAF patients compared to 8.4% in those without POAF.8

 

It is not clear that all of the increase in stroke risk is a direct effect of POAF. Indeed, in a retrospective analysis of almost 3,000 CABG patients, 1.1% suffered a stroke during their hospital stay. Fewer than half of those had a cardiac rhythm other than sinus rhythm. In the 15 stroke patients who developed POAF, nine presented with stroke symptoms prior to the first episode of AF.9 The authors suggest that aggressive anticoagulation for POAF would not have prevented most of these events.

Furthermore, the rate of in-hospital stroke after non-cardiac surgery is probably much lower, though it has not been as well studied. These data raise some questions as to the benefit of anticoagulation in the immediate postoperative period, though it is difficult to draw firm conclusions without randomized data.

What about non-cardiac surgery? There is less evidence available for patients undergoing non-cardiac surgery, but the few studies that do exist also point to higher stroke risk in patients with POAF. A large population-based study using ICD codes found that the one-year risk of stroke for patients with POAF after non-cardiac surgery was 1.47% compared to 0.36% in non-cardiac surgery patients without POAF (P<0.001). Based on these data, the long-term stroke risk after POAF in non-cardiac surgery patients is similar to that of medical AF patients with a CHA2DS2-VASc score of 2. The authors of this study suggest that transient POAF after non-cardiac surgery may carry a long-term stroke risk similar to any other AF diagnosis.10 However, this study design is subject to significant ascertainment bias (i.e., they may have unintentionally captured some patients with preexisting or prolonged AF), and further research is needed to better delineate this risk.

Does increased stroke risk translate into increased mortality? In a retrospective study of 17,000 patients, El-Chami et al found that POAF after CABG was associated with decreased survival after one year (90% versus 96%) and 10 years (55% versus 70%).11 However, those patients who develop POAF may be sicker overall.

Another study showed that death due to stroke occurred in 4.2% of POAF patients compared to 0.2% of non-POAF patients in a five-year period.12 Based on these studies, POAF is likely associated with increased mortality, but there may be other unaccounted variables. Nevertheless, the increased mortality associated with POAF in these populations is similar to that seen for non-surgical population-based studies13 and provides support that those with newly diagnosed AF in the post-surgical setting should at least be followed closely to assess for recurrence.

What is a patient’s risk of developing atrial fibrillation later in life? When we choose to anticoagulate patients with POAF, we then have to determine whether they should be committed to long-term anticoagulation. It is thought that many cases of POAF are transient; however, some patients will go on to have persistent or paroxysmal AF after discharge.

A retrospective study examined 571 patients who underwent CABG, 30% of whom had POAF during the index admission. After five years of follow-up, 25% of those with POAF were diagnosed with paroxysmal or persistent AF after discharge compared to only 3% of patients without POAF. Researchers did this by looking at the most recent ECG, if done in the last year, or by obtaining a new ECG at the five-year point.12 By this method, it is probable that some diagnoses of paroxysmal AF were missed.

In another study of about 300 CABG patients, about 20% of patients with POAF also went on to develop post-discharge AF, defined as symptomatic AF that led to medical evaluation. As in the previous study, it is likely that there were undetected episodes of AF.14 Thus, in cardiothoracic surgery patients, some but not all of whom develop POAF have recurrent or ongoing AF. For this reason, if anticoagulation is started, it may be reasonable to stop anticoagulation after weeks or months if ongoing AF is not apparent.

 

What is the risk of postoperative bleeding if anticoagulation is started? Any decision about the benefits of anticoagulation must be weighed against the risks, most notably the risk of serious or life-threatening bleeding. This risk may be heightened in the immediate perioperative period. Discussions should always take place with our surgical colleagues about type of surgery, intraoperative complications, and postoperative risk of bleeding.

Anticoagulation, if indicated, should not be started until postoperative bleeding risk is deemed appropriately low. That said, the 2015 BRIDGE trial (looking at the benefits and risks of “bridging” patients before surgery) provides some peripheral but meaningful information about postoperative bleeding risk. In this study, patients with preexisting AF who underwent low-bleeding-risk surgery and were bridged on day one after surgery with therapeutic doses of unfractionated or low-molecular-weight heparin had a significantly higher risk of postoperative bleeding compared to non-bridged patients, with a number needed to harm of 50.15 It may be reasonable—and likely safer—to wait a couple days to start anticoagulation for patients with POAF.

What is the expert’s opinion? We asked one of our cardiac electrophysiologists what her approach is to this situation. In general, if a patient has a low stroke risk and is in AF for fewer than 24 hours, it is reasonable to defer anticoagulation and follow as an outpatient. Regardless of risk, if AF is sustained for more than 24 hours, we recommend at least four weeks of anticoagulation and close outpatient follow-up, which should include a period of ambulatory monitoring to determine the need for continued anticoagulation. We also recommend considering what comprises the patient’s stroke risk.

For example, if the CHA2DS2-VASc score is 2 but the points come from being a female with coronary artery disease, we would consider forgoing anticoagulation but arranging for an outpatient cardiac monitor with cardiology follow-up. If the patient has a history of stroke or TIA, we recommend continuing anticoagulation indefinitely.

Back to the Case

Given our patient’s episode of POAF lasted fewer than 24 hours, it would be reasonable to hold off starting anticoagulation, but he should be followed as an outpatient with ambulatory monitoring at a minimum, monitoring for recurrence. If he were to develop recurrent AF, then he would warrant anticoagulation based on an annual stroke risk of 3.2% as determined by a CHA2DS2-VASc score of 3.

Bottom Line

Our strategy is as follows: If a patient has a low stroke risk (i.e., CHA2DS2-VASc score <2) and is in AF for fewer than 24 hours, anticoagulation is not started, but outpatient follow-up is arranged to monitor symptoms. Regardless of stroke risk, if a patient is in AF for more than 24 hours, we initiate and continue anticoagulation for a minimum of four weeks and arrange outpatient follow-up with a period of ambulatory monitoring to determine need for continued anticoagulation. If a patient has a high stroke risk (CHA2DS2-VASc >2) or if their risk factors include a history of stroke or TIA, anticoagulation is started and continued indefinitely. Risk-benefit discussion is held with the patient, especially with regard to bleeding risk, prior to anticoagulation initiation. If the individual patient’s situation presents further nuance, we ask for the assistance of our cardiology or cardiac electrophysiology colleagues.

Final Thought

None of the mentioned studies investigated or included newer oral anticoagulants. Risk-benefit ratios may change (potentially considerably) with these agents. Further study is needed. We expect, in due time, studies will look at the question of POAF in regard to newer anticoagulant agents, and perhaps then our decision making will change. TH

---

 

Dr. Evavold is a resident in the hospitalist training program, while Dr. Lessing and Dr. Merritt are hospitalists in the Department of Internal Medicine at the University of Colorado. Dr. Tzou is a cardiologist in the section of electrophysiology at the University of Colorado.

References:

1. POISE Study Group, Devereaux PJ, Yang H, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371(9627):1839-1847. doi:10.1016/s0140-6736(08)60601-7.
2. Christians K, Wu B, Quebbeman E, Brasel K. Postoperative atrial fibrillation in noncardiothoracic surgical patients. Am J Surg. 2001;182(6):713-715. doi:10.1016/s0002-9610(01)00799-1.
3. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-1100. doi:10.1378/chest.10-0134.
4. Fleisher L, Beckman J, Brown K, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 2002 guidelines on perioperative cardiovascular evaluation for noncardiac surgery). Circulation. 2007;116(17):e418-e500. doi:10.1161/circulationaha.107.185699.
5. Walkey A, Benjamin E, Lubitz S. New-onset atrial fibrillation during hospitalization. J Am Coll Cardiol. 2014;64(22):2432-2433. doi:10.1016/j.jacc.2014.09.034.
6. Creswell L, Schuessler R, Rosenbloom M, Cox J. Hazards of postoperative atrial arrhythmias. Ann Thorac Surg. 1993;56(3):539-549. doi:10.1016/0003-4975(93)90894-n.
7. Almassi G, Schowalter T, Nicolosi A, et al. Atrial fibrillation after cardiac surgery: a major morbid event? Ann Surg. 1997;226(4):501-513.
8. Horwich P, Buth K, Légaré J. New onset postoperative atrial fibrillation is associated with a long-term risk for stroke and death following cardiac surgery. J Card Surg. 2013;28(1):8-13. doi:10.1111/jocs.12033.
9. Kollar A, Lick S, Vasquez K, Conti V. Relationship of atrial fibrillation and stroke after coronary artery bypass graft surgery: when is anticoagulation indicated? Ann Thorac Surg. 2006;82(2):515-523. doi:10.1016/j.athoracsur.2006.03.037.
10. Gialdini G, Nearing K, Bhave P, et al. Perioperative atrial fibrillation and the long-term risk of ischemic stroke. JAMA. 2014;312(6):616. doi:10.1001/jama.2014.9143.
11. El-Chami M, Kilgo P, Thourani V, et al. New-onset atrial fibrillation predicts long-term mortality after coronary artery bypass graft. J Am Coll Cardiol. 2010;55(13):1370-1376. doi:10.1016/j.jacc.2009.10.058.
12. Ahlsson A, Fengsrud E, Bodin L, Englund A. Postoperative atrial fibrillation in patients undergoing aortocoronary bypass surgery carries an eightfold risk of future atrial fibrillation and a doubled cardiovascular mortality. Euro J Cardiothorac Surg. 2010;37(6):1353-1359. doi:10.1016/j.ejcts.2009.12.033.
13. Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98(10):946-952.
14. Antonelli D, Peres D, Freedberg N, Feldman A, Rosenfeld T. Incidence of postdischarge symptomatic paroxysmal atrial fibrillation in patients who underwent coronary artery bypass graft: long-term follow-up. Pacing Clin Electrophysiol. 2004;27(3):365-367. doi:10.1111/j.1540-8159.2004.00443.x.
15. Douketis J, Spyropoulos A, Kaatz S, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015;373(9):823-833. doi:10.1056/nejmoa1501035.

Case

A 66-year-old man with diabetes mellitus type 2 and hypertension underwent left total knee replacement. Several hours after surgery, the patient developed atrial fibrillation (AF). He was asymptomatic, and reversible causes of AF were ruled out. Approximately 18 hours later, he spontaneously reverted back to sinus rhythm. Should this patient, who has no known prior history of AF and a CHA2DS2-VASc score of 3, be started on anticoagulation?

Background

Hospitalists are commonly consulted for evaluation and management of postoperative atrial fibrillation (POAF). The incidence of new-onset AF associated with non-cardiac surgery is approximately 2% and may be more frequent in an elderly population.1 The increased adrenergic tone associated with surgery is thought to elicit AF in some patients. POAF has also been associated with positive fluid balance, electrolyte abnormalities, and hypoxemia.2 Some of these patients will spontaneously revert back to sinus rhythm after these issues are reversed. Others will go on to develop chronic or paroxysmal AF that persists indefinitely. It is also likely that some patients with POAF, in fact, already had asymptomatic AF that was simply undetected prior to hospitalization.

Hospitalists are faced with the difficult task of determining which patients with POAF will benefit from either short-term or long-term anticoagulation. This has not been well studied in postsurgical patients, in contrast to medical patients in whom stroke risk from AF has been very well-characterized. The decision may be further complicated by bleeding risk (associated with either some surgeries or with patient-dependent factors).3

It is worth noting that following major cardiac or thoracic surgery, POAF is common; the incidence ranges from 10% to 60%. In these cases, POAF may be triggered by transient atrial ischemia or by postoperative inflammation and may have a different natural history from POAF in non-cardiac surgery patients in terms of both reversibility and stroke risk. More retrospective data are available regarding cardiothoracic surgery patients.

Previous American Heart Association (AHA) and American College of Cardiology (ACC) guidelines stated that POAF lasting longer than 48 hours warranted anticoagulation. This recommendation was removed from the newest update. The 2014 updated AHA/ACC guidelines are less absolute and now state only that “it is reasonable to administer antithrombotic medication in patients who developed postoperative AF, as recommended for nonsurgical patients” (Level of Evidence: B) in regard to cardiothoracic surgery.4

There is no specific recommendation regarding POAF for non-cardiac surgery patients. The current guidelines are likely purposefully vague due to the lack of direct evidence. The following is a review of the existing literature and a suggested approach to anticoagulation in POAF.

Review

How common is postoperative atrial fibrillation? New-onset AF during hospitalization is known to occur in association with many acute conditions including surgery, infection, and myocardial infarction. About half of the cases of in-hospital new-onset AF are associated with surgery. AF is more commonly seen in surgery that involves the thoracic cavity and cardiac structures. In a cross-sectional epidemiologic study of 22 million patients in California, 20.8% of patients undergoing cardiac surgery developed POAF compared with only 1.3% of patients undergoing non-cardiac surgery.5 A smaller study of non-cardiac surgery patients found a 30-day POAF incidence of 0.37%.2

Does postoperative atrial fibrillation increase the short-term risk of stroke? A major concern in AF is the risk of stroke. It is well-established that prolonged or recurrent AF increases the risk for stroke over months or years, but do short episodes of POAF increase stroke risk to a significant degree? Most of the studies in the literature focus on perioperative stroke risk specifically in cardiothoracic surgery. A prospective study of 4,000 patients undergoing cardiac surgery found that the in-hospital postoperative stroke risk was 3.3% in patients with POAF compared to 1.4% in patients without POAF (P<0.01).6 Similar outcomes were seen in a VA study looking at patients who underwent open heart surgery: Stroke risk was 5.3% at six months in POAF patients compared to 2.4% in those without POAF.7 Another study of coronary artery bypass graft (CABG) patients with a follow-up of almost six years showed a stroke risk of 12.1% in POAF patients compared to 8.4% in those without POAF.8

 

It is not clear that all of the increase in stroke risk is a direct effect of POAF. Indeed, in a retrospective analysis of almost 3,000 CABG patients, 1.1% suffered a stroke during their hospital stay. Fewer than half of those had a cardiac rhythm other than sinus rhythm. In the 15 stroke patients who developed POAF, nine presented with stroke symptoms prior to the first episode of AF.9 The authors suggest that aggressive anticoagulation for POAF would not have prevented most of these events.

Furthermore, the rate of in-hospital stroke after non-cardiac surgery is probably much lower, though it has not been as well studied. These data raise some questions as to the benefit of anticoagulation in the immediate postoperative period, though it is difficult to draw firm conclusions without randomized data.

What about non-cardiac surgery? There is less evidence available for patients undergoing non-cardiac surgery, but the few studies that do exist also point to higher stroke risk in patients with POAF. A large population-based study using ICD codes found that the one-year risk of stroke for patients with POAF after non-cardiac surgery was 1.47% compared to 0.36% in non-cardiac surgery patients without POAF (P<0.001). Based on these data, the long-term stroke risk after POAF in non-cardiac surgery patients is similar to that of medical AF patients with a CHA2DS2-VASc score of 2. The authors of this study suggest that transient POAF after non-cardiac surgery may carry a long-term stroke risk similar to any other AF diagnosis.10 However, this study design is subject to significant ascertainment bias (i.e., they may have unintentionally captured some patients with preexisting or prolonged AF), and further research is needed to better delineate this risk.

Does increased stroke risk translate into increased mortality? In a retrospective study of 17,000 patients, El-Chami et al found that POAF after CABG was associated with decreased survival after one year (90% versus 96%) and 10 years (55% versus 70%).11 However, those patients who develop POAF may be sicker overall.

Another study showed that death due to stroke occurred in 4.2% of POAF patients compared to 0.2% of non-POAF patients in a five-year period.12 Based on these studies, POAF is likely associated with increased mortality, but there may be other unaccounted variables. Nevertheless, the increased mortality associated with POAF in these populations is similar to that seen for non-surgical population-based studies13 and provides support that those with newly diagnosed AF in the post-surgical setting should at least be followed closely to assess for recurrence.

What is a patient’s risk of developing atrial fibrillation later in life? When we choose to anticoagulate patients with POAF, we then have to determine whether they should be committed to long-term anticoagulation. It is thought that many cases of POAF are transient; however, some patients will go on to have persistent or paroxysmal AF after discharge.

A retrospective study examined 571 patients who underwent CABG, 30% of whom had POAF during the index admission. After five years of follow-up, 25% of those with POAF were diagnosed with paroxysmal or persistent AF after discharge compared to only 3% of patients without POAF. Researchers did this by looking at the most recent ECG, if done in the last year, or by obtaining a new ECG at the five-year point.12 By this method, it is probable that some diagnoses of paroxysmal AF were missed.

In another study of about 300 CABG patients, about 20% of patients with POAF also went on to develop post-discharge AF, defined as symptomatic AF that led to medical evaluation. As in the previous study, it is likely that there were undetected episodes of AF.14 Thus, in cardiothoracic surgery patients, some but not all of whom develop POAF have recurrent or ongoing AF. For this reason, if anticoagulation is started, it may be reasonable to stop anticoagulation after weeks or months if ongoing AF is not apparent.

 

What is the risk of postoperative bleeding if anticoagulation is started? Any decision about the benefits of anticoagulation must be weighed against the risks, most notably the risk of serious or life-threatening bleeding. This risk may be heightened in the immediate perioperative period. Discussions should always take place with our surgical colleagues about type of surgery, intraoperative complications, and postoperative risk of bleeding.

Anticoagulation, if indicated, should not be started until postoperative bleeding risk is deemed appropriately low. That said, the 2015 BRIDGE trial (looking at the benefits and risks of “bridging” patients before surgery) provides some peripheral but meaningful information about postoperative bleeding risk. In this study, patients with preexisting AF who underwent low-bleeding-risk surgery and were bridged on day one after surgery with therapeutic doses of unfractionated or low-molecular-weight heparin had a significantly higher risk of postoperative bleeding compared to non-bridged patients, with a number needed to harm of 50.15 It may be reasonable—and likely safer—to wait a couple days to start anticoagulation for patients with POAF.

What is the expert’s opinion? We asked one of our cardiac electrophysiologists what her approach is to this situation. In general, if a patient has a low stroke risk and is in AF for fewer than 24 hours, it is reasonable to defer anticoagulation and follow as an outpatient. Regardless of risk, if AF is sustained for more than 24 hours, we recommend at least four weeks of anticoagulation and close outpatient follow-up, which should include a period of ambulatory monitoring to determine the need for continued anticoagulation. We also recommend considering what comprises the patient’s stroke risk.

For example, if the CHA2DS2-VASc score is 2 but the points come from being a female with coronary artery disease, we would consider forgoing anticoagulation but arranging for an outpatient cardiac monitor with cardiology follow-up. If the patient has a history of stroke or TIA, we recommend continuing anticoagulation indefinitely.

Back to the Case

Given our patient’s episode of POAF lasted fewer than 24 hours, it would be reasonable to hold off starting anticoagulation, but he should be followed as an outpatient with ambulatory monitoring at a minimum, monitoring for recurrence. If he were to develop recurrent AF, then he would warrant anticoagulation based on an annual stroke risk of 3.2% as determined by a CHA2DS2-VASc score of 3.

Bottom Line

Our strategy is as follows: If a patient has a low stroke risk (i.e., CHA2DS2-VASc score <2) and is in AF for fewer than 24 hours, anticoagulation is not started, but outpatient follow-up is arranged to monitor symptoms. Regardless of stroke risk, if a patient is in AF for more than 24 hours, we initiate and continue anticoagulation for a minimum of four weeks and arrange outpatient follow-up with a period of ambulatory monitoring to determine need for continued anticoagulation. If a patient has a high stroke risk (CHA2DS2-VASc >2) or if their risk factors include a history of stroke or TIA, anticoagulation is started and continued indefinitely. Risk-benefit discussion is held with the patient, especially with regard to bleeding risk, prior to anticoagulation initiation. If the individual patient’s situation presents further nuance, we ask for the assistance of our cardiology or cardiac electrophysiology colleagues.

Final Thought

None of the mentioned studies investigated or included newer oral anticoagulants. Risk-benefit ratios may change (potentially considerably) with these agents. Further study is needed. We expect, in due time, studies will look at the question of POAF in regard to newer anticoagulant agents, and perhaps then our decision making will change. TH

---

 

Dr. Evavold is a resident in the hospitalist training program, while Dr. Lessing and Dr. Merritt are hospitalists in the Department of Internal Medicine at the University of Colorado. Dr. Tzou is a cardiologist in the section of electrophysiology at the University of Colorado.

References:

1. POISE Study Group, Devereaux PJ, Yang H, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371(9627):1839-1847. doi:10.1016/s0140-6736(08)60601-7.
2. Christians K, Wu B, Quebbeman E, Brasel K. Postoperative atrial fibrillation in noncardiothoracic surgical patients. Am J Surg. 2001;182(6):713-715. doi:10.1016/s0002-9610(01)00799-1.
3. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-1100. doi:10.1378/chest.10-0134.
4. Fleisher L, Beckman J, Brown K, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 2002 guidelines on perioperative cardiovascular evaluation for noncardiac surgery). Circulation. 2007;116(17):e418-e500. doi:10.1161/circulationaha.107.185699.
5. Walkey A, Benjamin E, Lubitz S. New-onset atrial fibrillation during hospitalization. J Am Coll Cardiol. 2014;64(22):2432-2433. doi:10.1016/j.jacc.2014.09.034.
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