Nita Shrikant Kulkarni, MD

Clinical question: Can a program of education, feedback, and proper training reduce catheter-associated urinary tract infections in hospitalized patients?

Bottom line: The Comprehensive Unit-based Safety Program, or CUSP, is a national program in the United States that aims to reduce catheter-associated urinary tract infections (CAUTIs) by focusing on proper technical skills, behavioral changes, education, and feedback. Implementation of the CUSP recommendations was effective in reducing catheter use and CAUTIs in patients in nonintensive care units (non-ICUs). The program was likely successful because it included both socioadaptive and technical changes and allowed the individual hospitals to customize interventions based on their own needs.

Reference: Saint S, Greene MT, Krein SL, et al. A program to prevent catheter-associated urinary tract infection in acute care. N Engl J Med 2016;374(22):2111-2119.

Design: Case series; LOE: 2b

Setting: Inpatient (any location)

Synopsis: This study reports the results of an 18-month program to reduce CAUTIs that was implemented in 926 inpatient units in 603 acute-care U.S. hospitals (which represents 10% of the acute care hospitals in the country). Overall, 40% of the units were ICUs while the remainder were non-ICUs.

Key recommendations of the program included the following: (1) assessing for the presence and need for a urinary catheter daily, (2) avoiding the use of a urinary catheter while emphasizing alternative urine-collection methods, and (3) promoting proper insertion and maintenance of catheters, when necessary. Hospitals were allowed to decide how best to implement these interventions in their individual units. Furthermore, participating unit teams received education on the prevention of CAUTIs as well as feedback on catheter use and the rate of CAUTIs on their individual units.

Data were collected over a 3-month baseline phase, a 2-month implementation phase, and a 12-month sustainability phase. After adjusting for hospital characteristics, the rate of CAUTIs decreased from 2.40 infections per 1000 catheter-days at the end of the baseline phase to 2.05 infections per 1000 catheter-days at the end of the sustainability phase. The reduction was statistically significant only in non-ICUs where CAUTIs decreased from 2.28 to 1.54 infections per 1000 catheter-days while catheter use decreased from 20.1% to 18.8%. This was not a randomized controlled trial, so confounding variables including secular trends may have affected the findings in this study.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Can a program of education, feedback, and proper training reduce catheter-associated urinary tract infections in hospitalized patients?

Bottom line: The Comprehensive Unit-based Safety Program, or CUSP, is a national program in the United States that aims to reduce catheter-associated urinary tract infections (CAUTIs) by focusing on proper technical skills, behavioral changes, education, and feedback. Implementation of the CUSP recommendations was effective in reducing catheter use and CAUTIs in patients in nonintensive care units (non-ICUs). The program was likely successful because it included both socioadaptive and technical changes and allowed the individual hospitals to customize interventions based on their own needs.

Reference: Saint S, Greene MT, Krein SL, et al. A program to prevent catheter-associated urinary tract infection in acute care. N Engl J Med 2016;374(22):2111-2119.

Design: Case series; LOE: 2b

Setting: Inpatient (any location)

Synopsis: This study reports the results of an 18-month program to reduce CAUTIs that was implemented in 926 inpatient units in 603 acute-care U.S. hospitals (which represents 10% of the acute care hospitals in the country). Overall, 40% of the units were ICUs while the remainder were non-ICUs.

Key recommendations of the program included the following: (1) assessing for the presence and need for a urinary catheter daily, (2) avoiding the use of a urinary catheter while emphasizing alternative urine-collection methods, and (3) promoting proper insertion and maintenance of catheters, when necessary. Hospitals were allowed to decide how best to implement these interventions in their individual units. Furthermore, participating unit teams received education on the prevention of CAUTIs as well as feedback on catheter use and the rate of CAUTIs on their individual units.

Data were collected over a 3-month baseline phase, a 2-month implementation phase, and a 12-month sustainability phase. After adjusting for hospital characteristics, the rate of CAUTIs decreased from 2.40 infections per 1000 catheter-days at the end of the baseline phase to 2.05 infections per 1000 catheter-days at the end of the sustainability phase. The reduction was statistically significant only in non-ICUs where CAUTIs decreased from 2.28 to 1.54 infections per 1000 catheter-days while catheter use decreased from 20.1% to 18.8%. This was not a randomized controlled trial, so confounding variables including secular trends may have affected the findings in this study.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Can a program of education, feedback, and proper training reduce catheter-associated urinary tract infections in hospitalized patients?

Bottom line: The Comprehensive Unit-based Safety Program, or CUSP, is a national program in the United States that aims to reduce catheter-associated urinary tract infections (CAUTIs) by focusing on proper technical skills, behavioral changes, education, and feedback. Implementation of the CUSP recommendations was effective in reducing catheter use and CAUTIs in patients in nonintensive care units (non-ICUs). The program was likely successful because it included both socioadaptive and technical changes and allowed the individual hospitals to customize interventions based on their own needs.

Reference: Saint S, Greene MT, Krein SL, et al. A program to prevent catheter-associated urinary tract infection in acute care. N Engl J Med 2016;374(22):2111-2119.

Design: Case series; LOE: 2b

Setting: Inpatient (any location)

Synopsis: This study reports the results of an 18-month program to reduce CAUTIs that was implemented in 926 inpatient units in 603 acute-care U.S. hospitals (which represents 10% of the acute care hospitals in the country). Overall, 40% of the units were ICUs while the remainder were non-ICUs.

Key recommendations of the program included the following: (1) assessing for the presence and need for a urinary catheter daily, (2) avoiding the use of a urinary catheter while emphasizing alternative urine-collection methods, and (3) promoting proper insertion and maintenance of catheters, when necessary. Hospitals were allowed to decide how best to implement these interventions in their individual units. Furthermore, participating unit teams received education on the prevention of CAUTIs as well as feedback on catheter use and the rate of CAUTIs on their individual units.

Data were collected over a 3-month baseline phase, a 2-month implementation phase, and a 12-month sustainability phase. After adjusting for hospital characteristics, the rate of CAUTIs decreased from 2.40 infections per 1000 catheter-days at the end of the baseline phase to 2.05 infections per 1000 catheter-days at the end of the sustainability phase. The reduction was statistically significant only in non-ICUs where CAUTIs decreased from 2.28 to 1.54 infections per 1000 catheter-days while catheter use decreased from 20.1% to 18.8%. This was not a randomized controlled trial, so confounding variables including secular trends may have affected the findings in this study.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Can the use of procalcitonin levels to determine when to discontinue antibiotic therapy safely reduce the duration of antibiotic use in critically ill patients?

Bottom line: For patients in the intensive care unit (ICU) who receive antibiotics for presumed or proven bacterial infections, the use of procalcitonin levels to determine when to stop antibiotic therapy results in decreased duration and consumption of antibiotics without increasing mortality.

Reference: De Jong E, Van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016;16(7):819-827.

Design: Randomized controlled trial (nonblinded); LOE: 1b

Setting: Inpatient (ICU only)

Synopsis: To test the efficacy and safety of procalcitonin-guided antibiotic therapy, these investigators recruited patients in the ICU who had received their first doses of antibiotics for a presumed or proven bacterial infection within 24 hours of enrollment. Patients who were severely immunosuppressed and patients requiring prolonged courses of antibiotics (such as those with endocarditis) were excluded.

Using concealed allocation, patients were assigned to procalcitonin-guided treatment (n = 761) or to usual care (n = 785). The usual care group did not have procalcitonin levels drawn. In the procalcitonin group, patients had a procalcitonin level drawn close to the start of antibiotic therapy and daily thereafter until discharge from the ICU or 3 days after stopping antibiotic use. These levels were provided to the attending physician who could then decide whether to stop giving antibiotics.

Although the study protocol recommended that antibiotics be discontinued if the procalcitonin level had decreased by more than 80% of its peak value or reached a level of 0.5 mcg/L, the ultimate decision to do so was at the discretion of the attending physician. Overall, fewer than half the physicians actually discontinued antibiotics within 24 hours of reaching either of these goals. Despite this, the procalcitonin group had decreased number of days of antibiotic treatment (5 days vs 7 days; between group absolute difference = 1.22; 95% CI 0.65-1.78; P < .0001) and decreased consumption of antibiotics (7.5 daily defined doses vs 9.3 daily defined doses; between group absolute difference = 2.69; 1.26-4.12; P < .0001). Additionally, when examining 28-day mortality rates, the procalcitonin group was noninferior to the standard group, and ultimately, had fewer deaths than the standard group (20% vs 25%; between group absolute difference = 5.4%;1.2-9.5; P = .012). This mortality benefit persisted at 1 year.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Can the use of procalcitonin levels to determine when to discontinue antibiotic therapy safely reduce the duration of antibiotic use in critically ill patients?

Bottom line: For patients in the intensive care unit (ICU) who receive antibiotics for presumed or proven bacterial infections, the use of procalcitonin levels to determine when to stop antibiotic therapy results in decreased duration and consumption of antibiotics without increasing mortality.

Reference: De Jong E, Van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016;16(7):819-827.

Design: Randomized controlled trial (nonblinded); LOE: 1b

Setting: Inpatient (ICU only)

Synopsis: To test the efficacy and safety of procalcitonin-guided antibiotic therapy, these investigators recruited patients in the ICU who had received their first doses of antibiotics for a presumed or proven bacterial infection within 24 hours of enrollment. Patients who were severely immunosuppressed and patients requiring prolonged courses of antibiotics (such as those with endocarditis) were excluded.

Using concealed allocation, patients were assigned to procalcitonin-guided treatment (n = 761) or to usual care (n = 785). The usual care group did not have procalcitonin levels drawn. In the procalcitonin group, patients had a procalcitonin level drawn close to the start of antibiotic therapy and daily thereafter until discharge from the ICU or 3 days after stopping antibiotic use. These levels were provided to the attending physician who could then decide whether to stop giving antibiotics.

Although the study protocol recommended that antibiotics be discontinued if the procalcitonin level had decreased by more than 80% of its peak value or reached a level of 0.5 mcg/L, the ultimate decision to do so was at the discretion of the attending physician. Overall, fewer than half the physicians actually discontinued antibiotics within 24 hours of reaching either of these goals. Despite this, the procalcitonin group had decreased number of days of antibiotic treatment (5 days vs 7 days; between group absolute difference = 1.22; 95% CI 0.65-1.78; P < .0001) and decreased consumption of antibiotics (7.5 daily defined doses vs 9.3 daily defined doses; between group absolute difference = 2.69; 1.26-4.12; P < .0001). Additionally, when examining 28-day mortality rates, the procalcitonin group was noninferior to the standard group, and ultimately, had fewer deaths than the standard group (20% vs 25%; between group absolute difference = 5.4%;1.2-9.5; P = .012). This mortality benefit persisted at 1 year.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Can the use of procalcitonin levels to determine when to discontinue antibiotic therapy safely reduce the duration of antibiotic use in critically ill patients?

Bottom line: For patients in the intensive care unit (ICU) who receive antibiotics for presumed or proven bacterial infections, the use of procalcitonin levels to determine when to stop antibiotic therapy results in decreased duration and consumption of antibiotics without increasing mortality.

Reference: De Jong E, Van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016;16(7):819-827.

Design: Randomized controlled trial (nonblinded); LOE: 1b

Setting: Inpatient (ICU only)

Synopsis: To test the efficacy and safety of procalcitonin-guided antibiotic therapy, these investigators recruited patients in the ICU who had received their first doses of antibiotics for a presumed or proven bacterial infection within 24 hours of enrollment. Patients who were severely immunosuppressed and patients requiring prolonged courses of antibiotics (such as those with endocarditis) were excluded.

Using concealed allocation, patients were assigned to procalcitonin-guided treatment (n = 761) or to usual care (n = 785). The usual care group did not have procalcitonin levels drawn. In the procalcitonin group, patients had a procalcitonin level drawn close to the start of antibiotic therapy and daily thereafter until discharge from the ICU or 3 days after stopping antibiotic use. These levels were provided to the attending physician who could then decide whether to stop giving antibiotics.

Although the study protocol recommended that antibiotics be discontinued if the procalcitonin level had decreased by more than 80% of its peak value or reached a level of 0.5 mcg/L, the ultimate decision to do so was at the discretion of the attending physician. Overall, fewer than half the physicians actually discontinued antibiotics within 24 hours of reaching either of these goals. Despite this, the procalcitonin group had decreased number of days of antibiotic treatment (5 days vs 7 days; between group absolute difference = 1.22; 95% CI 0.65-1.78; P < .0001) and decreased consumption of antibiotics (7.5 daily defined doses vs 9.3 daily defined doses; between group absolute difference = 2.69; 1.26-4.12; P < .0001). Additionally, when examining 28-day mortality rates, the procalcitonin group was noninferior to the standard group, and ultimately, had fewer deaths than the standard group (20% vs 25%; between group absolute difference = 5.4%;1.2-9.5; P = .012). This mortality benefit persisted at 1 year.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: What is the best management strategy for postoperative atrial fibrillation?

Bottom line: For new-onset atrial fibrillation (AF) following cardiac surgery, both rate control and rhythm control are reasonable strategies. There is no a clear advantage of one over the other. (LOE = 1b)

Reference: Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate control versus rhythm control for atrial fibrillation after cardiac surgery. N Engl J Med 2016;374(20):1911–1921.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

Postoperative AF is a common complication of cardiac surgery. In this trial, investigators identified more than 2000 patients who were undergoing coronary-artery bypass grafting and/or cardiac valve surgery. Of these patients, one-third developed new-onset AF and were randomized to receive either rate control or rhythm control.

In the rate-control group, patients received medications to slow heart rate to less than 100 beats per minute. If sinus rhythm was not achieved, these patients could then receive rhythm control per their physician's discretion. In the rhythm-control group, patients received amiodarone with or without rate-lowering medication, followed by cardioversion if AF persisted for 24 to 48 hours. The crossover rate in both groups was approximately 25% due to either drug ineffectiveness in the rate-control group or drug side effects in the rhythm-control group. All patients who remained in AF after 48 hours received anticoagulation.

The 2 groups were similar at baseline: mean age was 69 years, 75% were male, and 94% were white. Intention-to-treat analysis was used to test the primary endpoint of number of days in the emergency department or hospital within 60 days after randomization. There was no significant difference detected in this outcome between the 2 groups, even when the initial length of stay was adjusted for discharge readiness from an AF perspective. A sensitivity analysis accounting for the large number of crossovers also confirmed this finding. More than 90% of patients in both groups had a stable heart rhythm at the 60-day follow-up. Complication rates and 30-day readmission rates were also similar in the 2 groups.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: What is the best management strategy for postoperative atrial fibrillation?

Bottom line: For new-onset atrial fibrillation (AF) following cardiac surgery, both rate control and rhythm control are reasonable strategies. There is no a clear advantage of one over the other. (LOE = 1b)

Reference: Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate control versus rhythm control for atrial fibrillation after cardiac surgery. N Engl J Med 2016;374(20):1911–1921.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

Postoperative AF is a common complication of cardiac surgery. In this trial, investigators identified more than 2000 patients who were undergoing coronary-artery bypass grafting and/or cardiac valve surgery. Of these patients, one-third developed new-onset AF and were randomized to receive either rate control or rhythm control.

In the rate-control group, patients received medications to slow heart rate to less than 100 beats per minute. If sinus rhythm was not achieved, these patients could then receive rhythm control per their physician's discretion. In the rhythm-control group, patients received amiodarone with or without rate-lowering medication, followed by cardioversion if AF persisted for 24 to 48 hours. The crossover rate in both groups was approximately 25% due to either drug ineffectiveness in the rate-control group or drug side effects in the rhythm-control group. All patients who remained in AF after 48 hours received anticoagulation.

The 2 groups were similar at baseline: mean age was 69 years, 75% were male, and 94% were white. Intention-to-treat analysis was used to test the primary endpoint of number of days in the emergency department or hospital within 60 days after randomization. There was no significant difference detected in this outcome between the 2 groups, even when the initial length of stay was adjusted for discharge readiness from an AF perspective. A sensitivity analysis accounting for the large number of crossovers also confirmed this finding. More than 90% of patients in both groups had a stable heart rhythm at the 60-day follow-up. Complication rates and 30-day readmission rates were also similar in the 2 groups.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: What is the best management strategy for postoperative atrial fibrillation?

Bottom line: For new-onset atrial fibrillation (AF) following cardiac surgery, both rate control and rhythm control are reasonable strategies. There is no a clear advantage of one over the other. (LOE = 1b)

Reference: Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate control versus rhythm control for atrial fibrillation after cardiac surgery. N Engl J Med 2016;374(20):1911–1921.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

Postoperative AF is a common complication of cardiac surgery. In this trial, investigators identified more than 2000 patients who were undergoing coronary-artery bypass grafting and/or cardiac valve surgery. Of these patients, one-third developed new-onset AF and were randomized to receive either rate control or rhythm control.

In the rate-control group, patients received medications to slow heart rate to less than 100 beats per minute. If sinus rhythm was not achieved, these patients could then receive rhythm control per their physician's discretion. In the rhythm-control group, patients received amiodarone with or without rate-lowering medication, followed by cardioversion if AF persisted for 24 to 48 hours. The crossover rate in both groups was approximately 25% due to either drug ineffectiveness in the rate-control group or drug side effects in the rhythm-control group. All patients who remained in AF after 48 hours received anticoagulation.

The 2 groups were similar at baseline: mean age was 69 years, 75% were male, and 94% were white. Intention-to-treat analysis was used to test the primary endpoint of number of days in the emergency department or hospital within 60 days after randomization. There was no significant difference detected in this outcome between the 2 groups, even when the initial length of stay was adjusted for discharge readiness from an AF perspective. A sensitivity analysis accounting for the large number of crossovers also confirmed this finding. More than 90% of patients in both groups had a stable heart rhythm at the 60-day follow-up. Complication rates and 30-day readmission rates were also similar in the 2 groups.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: For critically ill patients with acute kidney injury, does early initiation of renal replacement therapy improve mortality?

Bottom line: In this single-center study, early initiation of renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI) decreased the number of deaths at 90 days. Larger studies are required to confirm this finding. Although some patients may prefer to avoid dialysis and its inherent risks, this preference must be balanced with the greater risk of mortality that may occur by not undergoing this treatment early on. (LOE = 1b)

Reference: Zarbock A, Kellum JA, Schmidt C, et al. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury. JAMA 2016;315(20):2190–2199.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

To study the optimal time for initiation of RRT for critically ill patients with AKI, these authors recruited patients with severe sepsis, pressor requirements, refractory fluid overload, or nonrenal organ dysfunction who developed stage 2 AKI (urine output < 0.5 mL/kg/h for more than 12 hours or a 2-fold increase in serum creatinine from baseline). Patients with chronic kidney disease, glomerulonephritis, interstitial nephritis, vasculitis, and postrenal obstruction were excluded, among others.

Overall, 231 patients were randomized to receive either early RRT or delayed RRT. RRT was delivered initially as continuous venovenous hemodiafiltration and could be changed to an intermittent procedure such as intermittent hemodialysis or sustained low-efficiency daily dialysis if renal recovery did not occur after 7 days. Early RRT was initiated within 8 hours of diagnosis of stage 2 AKI while delayed RRT was initiated within 12 hours after patients had developed stage 3 AKI (urine output < 0.3mL/kg/h for more than 24 hours or a 3-fold increase in serum creatinine from baseline) or if patients had an absolute indication for RRT. Patients in the 2 groups had similar baseline Sequential Organ Failure Assessment scores and almost all were surgical patients. Although all patients in the early group received RRT, 9% of patients in the delayed group did not, mostly because they did not progress to stage 3 AKI.

Early RRT resulted in a significantly decreased 90-day mortality rate as compared with delayed RRT (39% vs 55%; P = .03). Patients in the early group also had a decreased duration of RRT (9 days vs 25 days; P = .04), decreased length of hospital stay (51 days vs 82 days; P < .001), and greater recovery of renal function at 90 days (54% vs 39%; P = .02). The authors postulate that initiating early RRT may prevent further injury to the kidneys and other organs by reducing systemic inflammation.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: For critically ill patients with acute kidney injury, does early initiation of renal replacement therapy improve mortality?

Bottom line: In this single-center study, early initiation of renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI) decreased the number of deaths at 90 days. Larger studies are required to confirm this finding. Although some patients may prefer to avoid dialysis and its inherent risks, this preference must be balanced with the greater risk of mortality that may occur by not undergoing this treatment early on. (LOE = 1b)

Reference: Zarbock A, Kellum JA, Schmidt C, et al. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury. JAMA 2016;315(20):2190–2199.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

To study the optimal time for initiation of RRT for critically ill patients with AKI, these authors recruited patients with severe sepsis, pressor requirements, refractory fluid overload, or nonrenal organ dysfunction who developed stage 2 AKI (urine output < 0.5 mL/kg/h for more than 12 hours or a 2-fold increase in serum creatinine from baseline). Patients with chronic kidney disease, glomerulonephritis, interstitial nephritis, vasculitis, and postrenal obstruction were excluded, among others.

Overall, 231 patients were randomized to receive either early RRT or delayed RRT. RRT was delivered initially as continuous venovenous hemodiafiltration and could be changed to an intermittent procedure such as intermittent hemodialysis or sustained low-efficiency daily dialysis if renal recovery did not occur after 7 days. Early RRT was initiated within 8 hours of diagnosis of stage 2 AKI while delayed RRT was initiated within 12 hours after patients had developed stage 3 AKI (urine output < 0.3mL/kg/h for more than 24 hours or a 3-fold increase in serum creatinine from baseline) or if patients had an absolute indication for RRT. Patients in the 2 groups had similar baseline Sequential Organ Failure Assessment scores and almost all were surgical patients. Although all patients in the early group received RRT, 9% of patients in the delayed group did not, mostly because they did not progress to stage 3 AKI.

Early RRT resulted in a significantly decreased 90-day mortality rate as compared with delayed RRT (39% vs 55%; P = .03). Patients in the early group also had a decreased duration of RRT (9 days vs 25 days; P = .04), decreased length of hospital stay (51 days vs 82 days; P < .001), and greater recovery of renal function at 90 days (54% vs 39%; P = .02). The authors postulate that initiating early RRT may prevent further injury to the kidneys and other organs by reducing systemic inflammation.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: For critically ill patients with acute kidney injury, does early initiation of renal replacement therapy improve mortality?

Bottom line: In this single-center study, early initiation of renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI) decreased the number of deaths at 90 days. Larger studies are required to confirm this finding. Although some patients may prefer to avoid dialysis and its inherent risks, this preference must be balanced with the greater risk of mortality that may occur by not undergoing this treatment early on. (LOE = 1b)

Reference: Zarbock A, Kellum JA, Schmidt C, et al. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury. JAMA 2016;315(20):2190–2199.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

To study the optimal time for initiation of RRT for critically ill patients with AKI, these authors recruited patients with severe sepsis, pressor requirements, refractory fluid overload, or nonrenal organ dysfunction who developed stage 2 AKI (urine output < 0.5 mL/kg/h for more than 12 hours or a 2-fold increase in serum creatinine from baseline). Patients with chronic kidney disease, glomerulonephritis, interstitial nephritis, vasculitis, and postrenal obstruction were excluded, among others.

Overall, 231 patients were randomized to receive either early RRT or delayed RRT. RRT was delivered initially as continuous venovenous hemodiafiltration and could be changed to an intermittent procedure such as intermittent hemodialysis or sustained low-efficiency daily dialysis if renal recovery did not occur after 7 days. Early RRT was initiated within 8 hours of diagnosis of stage 2 AKI while delayed RRT was initiated within 12 hours after patients had developed stage 3 AKI (urine output < 0.3mL/kg/h for more than 24 hours or a 3-fold increase in serum creatinine from baseline) or if patients had an absolute indication for RRT. Patients in the 2 groups had similar baseline Sequential Organ Failure Assessment scores and almost all were surgical patients. Although all patients in the early group received RRT, 9% of patients in the delayed group did not, mostly because they did not progress to stage 3 AKI.

Early RRT resulted in a significantly decreased 90-day mortality rate as compared with delayed RRT (39% vs 55%; P = .03). Patients in the early group also had a decreased duration of RRT (9 days vs 25 days; P = .04), decreased length of hospital stay (51 days vs 82 days; P < .001), and greater recovery of renal function at 90 days (54% vs 39%; P = .02). The authors postulate that initiating early RRT may prevent further injury to the kidneys and other organs by reducing systemic inflammation.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does coronary artery bypass grafting added to medical therapy decrease mortality in patients with coronary artery disease and systolic heart failure?

Bottom line: Coronary artery bypass grafting (CABG) plus medical therapy decreases mortality as compared with medical therapy alone in patients with ischemic cardiomyopathy. You would need to treat 14 patients with CABG to prevent one death. (LOE = 1b)

Reference: Velazquez EJ, Lee KL, Jones RH, et al, for the STICHES Investigators. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med 2016;374(16):1511-1520.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Using concealed allocation, these investigators randomized patients with heart failure with ejection fraction of 35% or less and coronary artery disease amenable to CABG to receive either guideline-directed medical therapy plus CABG (n = 610) or guideline-directed medical therapy alone (n = 602). The 2 groups were similar at baseline and the majority was categorized as New York Heart Failure Association class II. Overall, 91% of the CABG group underwent the procedure within the first year following randomization. Notably, 20% of the medical therapy group also underwent CABG during the long-term follow-up period (11% crossed over to CABG within the first year). The medial duration for follow-up was 9.8 years and analysis was by intention to treat. CABG plus medical therapy resulted in fewer deaths over 10 years as compared with medical therapy alone (59% vs 66%; hazard ratio [HR] = 0.84; 95% CI 0.73 - 0.97; P = .02). The CABG group also had fewer deaths specifically from cardiovascular causes (40% vs 49%; P = .006). A per-protocol analysis showed an even greater benefit with CABG (HR = 0.77; 0.67 - 0.90; P = .001) suggesting that the crossovers in this trial may have diluted the observed effect of CABG.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does coronary artery bypass grafting added to medical therapy decrease mortality in patients with coronary artery disease and systolic heart failure?

Bottom line: Coronary artery bypass grafting (CABG) plus medical therapy decreases mortality as compared with medical therapy alone in patients with ischemic cardiomyopathy. You would need to treat 14 patients with CABG to prevent one death. (LOE = 1b)

Reference: Velazquez EJ, Lee KL, Jones RH, et al, for the STICHES Investigators. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med 2016;374(16):1511-1520.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Using concealed allocation, these investigators randomized patients with heart failure with ejection fraction of 35% or less and coronary artery disease amenable to CABG to receive either guideline-directed medical therapy plus CABG (n = 610) or guideline-directed medical therapy alone (n = 602). The 2 groups were similar at baseline and the majority was categorized as New York Heart Failure Association class II. Overall, 91% of the CABG group underwent the procedure within the first year following randomization. Notably, 20% of the medical therapy group also underwent CABG during the long-term follow-up period (11% crossed over to CABG within the first year). The medial duration for follow-up was 9.8 years and analysis was by intention to treat. CABG plus medical therapy resulted in fewer deaths over 10 years as compared with medical therapy alone (59% vs 66%; hazard ratio [HR] = 0.84; 95% CI 0.73 - 0.97; P = .02). The CABG group also had fewer deaths specifically from cardiovascular causes (40% vs 49%; P = .006). A per-protocol analysis showed an even greater benefit with CABG (HR = 0.77; 0.67 - 0.90; P = .001) suggesting that the crossovers in this trial may have diluted the observed effect of CABG.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does coronary artery bypass grafting added to medical therapy decrease mortality in patients with coronary artery disease and systolic heart failure?

Bottom line: Coronary artery bypass grafting (CABG) plus medical therapy decreases mortality as compared with medical therapy alone in patients with ischemic cardiomyopathy. You would need to treat 14 patients with CABG to prevent one death. (LOE = 1b)

Reference: Velazquez EJ, Lee KL, Jones RH, et al, for the STICHES Investigators. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med 2016;374(16):1511-1520.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Using concealed allocation, these investigators randomized patients with heart failure with ejection fraction of 35% or less and coronary artery disease amenable to CABG to receive either guideline-directed medical therapy plus CABG (n = 610) or guideline-directed medical therapy alone (n = 602). The 2 groups were similar at baseline and the majority was categorized as New York Heart Failure Association class II. Overall, 91% of the CABG group underwent the procedure within the first year following randomization. Notably, 20% of the medical therapy group also underwent CABG during the long-term follow-up period (11% crossed over to CABG within the first year). The medial duration for follow-up was 9.8 years and analysis was by intention to treat. CABG plus medical therapy resulted in fewer deaths over 10 years as compared with medical therapy alone (59% vs 66%; hazard ratio [HR] = 0.84; 95% CI 0.73 - 0.97; P = .02). The CABG group also had fewer deaths specifically from cardiovascular causes (40% vs 49%; P = .006). A per-protocol analysis showed an even greater benefit with CABG (HR = 0.77; 0.67 - 0.90; P = .001) suggesting that the crossovers in this trial may have diluted the observed effect of CABG.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of stent retrievers in conjunction with tissue plasminogen activator improve outcomes in patients with acute ischemic stroke?

Bottom line: The use of stent retriever devices in addition to tissue plasminogen activator (tPA) in patients with anterior circulation acute ischemic stroke results in more patients with functional independence at 90 days. Based on data from the studies included in this review, the American Heart Association/American Stroke Association guidelines now strongly recommend the use of stent retrievers with class 1a level of evidence. (LOE = 1a)

Reference: Touma L, Filion KB, Sterling LH, Atallah R, Windle SB, Eisenberg MJ. Stent retrievers for the treatment of acute ischemic stroke. JAMA Neurol 2016;73(3):275-281.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Intra-arterial therapy using stent retriever devices for thrombectomy added to standard therapy with tPA is a promising treatment for acute ischemic stroke. Four recent randomized controlled trials examining the effectiveness of stent retrievers have been terminated early because of the strong benefit seen with this therapy.

In this study, investigators searched MEDLINE, EMBASE, and the Cochrane Library, as well as trial registries and references of included studies, to find randomized controlled trials that compared stent retrievers plus tPA with tPA alone. Two authors independently extracted data from the 5 included studies (N = 1287) and assessed study quality using the Cochrane Collaboration Risk of Bias Tool.

All studies included patients with imaging-confirmed anterior circulation strokes and used the modified Rankin Scale (mRS) to assess for improvement in functional status at 90 days. Four of the 5 studies only included patients with excellent pre-stroke functional independence. Additionally, 4 of the 5 studies restricted stent retriever therapy to patients who presented within 6 hours of onset of stroke symptoms. The studies had a low risk of bias overall.

The pooled 90-day outcomes showed that patients who received stent retriever therapy plus tPA were more likely to achieve greater functional independence, defined as an mRS score of 0 to 2, than patients who received tPA alone (relative risk 1.72; 95% CI 1.38 - 1.99). You would need to treat 6 patients with stent retriever therapy to have one patient achieve functional independence. There were no significant differences detected in mortality or in the rates of intracranial bleeds or parenchymal hematomas.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of stent retrievers in conjunction with tissue plasminogen activator improve outcomes in patients with acute ischemic stroke?

Bottom line: The use of stent retriever devices in addition to tissue plasminogen activator (tPA) in patients with anterior circulation acute ischemic stroke results in more patients with functional independence at 90 days. Based on data from the studies included in this review, the American Heart Association/American Stroke Association guidelines now strongly recommend the use of stent retrievers with class 1a level of evidence. (LOE = 1a)

Reference: Touma L, Filion KB, Sterling LH, Atallah R, Windle SB, Eisenberg MJ. Stent retrievers for the treatment of acute ischemic stroke. JAMA Neurol 2016;73(3):275-281.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Intra-arterial therapy using stent retriever devices for thrombectomy added to standard therapy with tPA is a promising treatment for acute ischemic stroke. Four recent randomized controlled trials examining the effectiveness of stent retrievers have been terminated early because of the strong benefit seen with this therapy.

In this study, investigators searched MEDLINE, EMBASE, and the Cochrane Library, as well as trial registries and references of included studies, to find randomized controlled trials that compared stent retrievers plus tPA with tPA alone. Two authors independently extracted data from the 5 included studies (N = 1287) and assessed study quality using the Cochrane Collaboration Risk of Bias Tool.

All studies included patients with imaging-confirmed anterior circulation strokes and used the modified Rankin Scale (mRS) to assess for improvement in functional status at 90 days. Four of the 5 studies only included patients with excellent pre-stroke functional independence. Additionally, 4 of the 5 studies restricted stent retriever therapy to patients who presented within 6 hours of onset of stroke symptoms. The studies had a low risk of bias overall.

The pooled 90-day outcomes showed that patients who received stent retriever therapy plus tPA were more likely to achieve greater functional independence, defined as an mRS score of 0 to 2, than patients who received tPA alone (relative risk 1.72; 95% CI 1.38 - 1.99). You would need to treat 6 patients with stent retriever therapy to have one patient achieve functional independence. There were no significant differences detected in mortality or in the rates of intracranial bleeds or parenchymal hematomas.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of stent retrievers in conjunction with tissue plasminogen activator improve outcomes in patients with acute ischemic stroke?

Bottom line: The use of stent retriever devices in addition to tissue plasminogen activator (tPA) in patients with anterior circulation acute ischemic stroke results in more patients with functional independence at 90 days. Based on data from the studies included in this review, the American Heart Association/American Stroke Association guidelines now strongly recommend the use of stent retrievers with class 1a level of evidence. (LOE = 1a)

Reference: Touma L, Filion KB, Sterling LH, Atallah R, Windle SB, Eisenberg MJ. Stent retrievers for the treatment of acute ischemic stroke. JAMA Neurol 2016;73(3):275-281.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Intra-arterial therapy using stent retriever devices for thrombectomy added to standard therapy with tPA is a promising treatment for acute ischemic stroke. Four recent randomized controlled trials examining the effectiveness of stent retrievers have been terminated early because of the strong benefit seen with this therapy.

In this study, investigators searched MEDLINE, EMBASE, and the Cochrane Library, as well as trial registries and references of included studies, to find randomized controlled trials that compared stent retrievers plus tPA with tPA alone. Two authors independently extracted data from the 5 included studies (N = 1287) and assessed study quality using the Cochrane Collaboration Risk of Bias Tool.

All studies included patients with imaging-confirmed anterior circulation strokes and used the modified Rankin Scale (mRS) to assess for improvement in functional status at 90 days. Four of the 5 studies only included patients with excellent pre-stroke functional independence. Additionally, 4 of the 5 studies restricted stent retriever therapy to patients who presented within 6 hours of onset of stroke symptoms. The studies had a low risk of bias overall.

The pooled 90-day outcomes showed that patients who received stent retriever therapy plus tPA were more likely to achieve greater functional independence, defined as an mRS score of 0 to 2, than patients who received tPA alone (relative risk 1.72; 95% CI 1.38 - 1.99). You would need to treat 6 patients with stent retriever therapy to have one patient achieve functional independence. There were no significant differences detected in mortality or in the rates of intracranial bleeds or parenchymal hematomas.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: What strategies are effective in reducing contrast-induced nephropathy?

Bottom line: N-acetylcysteine plus intravenous fluids alone or in combination with a statin can prevent contrast-induced nephropathy (CIN). However, the strength of the evidence for these interventions is low. (LOE = 1b)

Reference: Subramaniam RM, Suarez-Cuervo C, Wilson RF, et al. Effectiveness of prevention strategies for contrast-induced nephropathy. Ann Intern Med 2016;164(6):406-416.

Study design: Systematic review

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis

CIN is defined as an increase in serum creatinine of more than 25% or 0.5 mg/dL (44.2 umol/L) within 3 days of intravenous contrast administration. These investigators searched MEDLINE, EMBASE, and the Cochrane Library along with reference lists of relevant articles to find studies that evaluated use of N-acetylcysteine, sodium bicarbonate, sodium chloride, statins, or ascorbic acid to prevent CIN.

Two reviewers independently screened articles for eligibility, assessed each study's risk of bias, and graded the strength of evidence (SOE) for different comparisons. A total of 86 randomized controlled trials examining different strategies for CIN prevention were included. Ultimately, only 3 strategies were shown to have both a clinically important and statistically significant benefit: (1) low-dose N-acetylcysteine plus intravenous (IV) saline versus IV saline alone (pooled relative risk [RR] 0.75; 95% CI 0.63-0.89; low SOE), (2) N-acetylcysteine plus IV saline versus IV saline alone in patients receiving low-osmolar contrast media (pooled RR 0.69; 0.58-0.84; moderate SOE), and (3) statin plus N-acetylcysteine versus N-acetylcysteine alone (pooled RR 0.52; 0.29-0.93; low SOE). There were no statistically significant benefits seen with sodium bicarbonate or ascorbic acid.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: What strategies are effective in reducing contrast-induced nephropathy?

Bottom line: N-acetylcysteine plus intravenous fluids alone or in combination with a statin can prevent contrast-induced nephropathy (CIN). However, the strength of the evidence for these interventions is low. (LOE = 1b)

Reference: Subramaniam RM, Suarez-Cuervo C, Wilson RF, et al. Effectiveness of prevention strategies for contrast-induced nephropathy. Ann Intern Med 2016;164(6):406-416.

Study design: Systematic review

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis

CIN is defined as an increase in serum creatinine of more than 25% or 0.5 mg/dL (44.2 umol/L) within 3 days of intravenous contrast administration. These investigators searched MEDLINE, EMBASE, and the Cochrane Library along with reference lists of relevant articles to find studies that evaluated use of N-acetylcysteine, sodium bicarbonate, sodium chloride, statins, or ascorbic acid to prevent CIN.

Two reviewers independently screened articles for eligibility, assessed each study's risk of bias, and graded the strength of evidence (SOE) for different comparisons. A total of 86 randomized controlled trials examining different strategies for CIN prevention were included. Ultimately, only 3 strategies were shown to have both a clinically important and statistically significant benefit: (1) low-dose N-acetylcysteine plus intravenous (IV) saline versus IV saline alone (pooled relative risk [RR] 0.75; 95% CI 0.63-0.89; low SOE), (2) N-acetylcysteine plus IV saline versus IV saline alone in patients receiving low-osmolar contrast media (pooled RR 0.69; 0.58-0.84; moderate SOE), and (3) statin plus N-acetylcysteine versus N-acetylcysteine alone (pooled RR 0.52; 0.29-0.93; low SOE). There were no statistically significant benefits seen with sodium bicarbonate or ascorbic acid.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: What strategies are effective in reducing contrast-induced nephropathy?

Bottom line: N-acetylcysteine plus intravenous fluids alone or in combination with a statin can prevent contrast-induced nephropathy (CIN). However, the strength of the evidence for these interventions is low. (LOE = 1b)

Reference: Subramaniam RM, Suarez-Cuervo C, Wilson RF, et al. Effectiveness of prevention strategies for contrast-induced nephropathy. Ann Intern Med 2016;164(6):406-416.

Study design: Systematic review

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis

CIN is defined as an increase in serum creatinine of more than 25% or 0.5 mg/dL (44.2 umol/L) within 3 days of intravenous contrast administration. These investigators searched MEDLINE, EMBASE, and the Cochrane Library along with reference lists of relevant articles to find studies that evaluated use of N-acetylcysteine, sodium bicarbonate, sodium chloride, statins, or ascorbic acid to prevent CIN.

Two reviewers independently screened articles for eligibility, assessed each study's risk of bias, and graded the strength of evidence (SOE) for different comparisons. A total of 86 randomized controlled trials examining different strategies for CIN prevention were included. Ultimately, only 3 strategies were shown to have both a clinically important and statistically significant benefit: (1) low-dose N-acetylcysteine plus intravenous (IV) saline versus IV saline alone (pooled relative risk [RR] 0.75; 95% CI 0.63-0.89; low SOE), (2) N-acetylcysteine plus IV saline versus IV saline alone in patients receiving low-osmolar contrast media (pooled RR 0.69; 0.58-0.84; moderate SOE), and (3) statin plus N-acetylcysteine versus N-acetylcysteine alone (pooled RR 0.52; 0.29-0.93; low SOE). There were no statistically significant benefits seen with sodium bicarbonate or ascorbic acid.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of high-flow oxygen therapy for 24 hours following extubation reduce the risk of reintubation in low-risk patients?

Bottom line: Using high-flow nasal cannula oxygen therapy for 24 hours following extubation of patients who are already at low risk of reintubation further reduces the risk of reintubation. You would need to treat 14 patients with high-flow therapy to prevent reintubation in one patient. (LOE = 1b)

Reference: Hernandez G, Vaquero C, Gonzalez P, et al. Effect of postextubation high-flow nasal cannula vs conventional oxygen therapy on reintubation in low-risk patients. JAMA 2016;315(13):1354-1361.

Study design: Randomized controlled trial (nonblinded)

Funding source: Self-funded or unfunded

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

These investigators recruited mechanically ventilated adult patients who were ready for extubation and who met the criteria for low risk for reintubation. Low risk was defined as: younger than 65 years; Acute Physiology and Chronic Health Evaluation (APACHE) II score of less than 12; fewer than 2 comorbidities; body mass index of less than 30; ability to manage secretions; simple weaning; and the absence of heart failure, moderate-to-severe chronic obstructive pulmonary disease, airway patency issues, and prolonged mechanical ventilation.

Using concealed allocation, these patients were randomized to receive either conventional oxygen therapy or high-flow oxygen therapy for 24 hours following extubation. Conventional oxygen therapy was continued in both groups after 24 hours as needed. The 2 groups had a mean age of 51 years and similar APACHE scores at baseline. The use of high-flow oxygen therapy reduced the rate of reintubation within 72 hours from 12.2% to 4.9% (absolute difference 7.2%; 95% CI 2.5%-12.2%; number needed to treat [NNT] = 14; P = .004). There were no significant differences detected in the 2 groups in secondary outcomes including time to reintubation or hospital length of stay. Notably, the study population had a high proportion of surgical and neurocritical patients, resulting in one-third of the reintubations occurring because of nonrespiratory causes such as repeat surgery or altered mental status. When the analysis was limited to only the respiratory-related intubations, the reduced risk of reintubation persisted in the high-flow oxygen group (1.5% vs 8.7%; NNT = 14; P = .001).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of high-flow oxygen therapy for 24 hours following extubation reduce the risk of reintubation in low-risk patients?

Bottom line: Using high-flow nasal cannula oxygen therapy for 24 hours following extubation of patients who are already at low risk of reintubation further reduces the risk of reintubation. You would need to treat 14 patients with high-flow therapy to prevent reintubation in one patient. (LOE = 1b)

Reference: Hernandez G, Vaquero C, Gonzalez P, et al. Effect of postextubation high-flow nasal cannula vs conventional oxygen therapy on reintubation in low-risk patients. JAMA 2016;315(13):1354-1361.

Study design: Randomized controlled trial (nonblinded)

Funding source: Self-funded or unfunded

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

These investigators recruited mechanically ventilated adult patients who were ready for extubation and who met the criteria for low risk for reintubation. Low risk was defined as: younger than 65 years; Acute Physiology and Chronic Health Evaluation (APACHE) II score of less than 12; fewer than 2 comorbidities; body mass index of less than 30; ability to manage secretions; simple weaning; and the absence of heart failure, moderate-to-severe chronic obstructive pulmonary disease, airway patency issues, and prolonged mechanical ventilation.

Using concealed allocation, these patients were randomized to receive either conventional oxygen therapy or high-flow oxygen therapy for 24 hours following extubation. Conventional oxygen therapy was continued in both groups after 24 hours as needed. The 2 groups had a mean age of 51 years and similar APACHE scores at baseline. The use of high-flow oxygen therapy reduced the rate of reintubation within 72 hours from 12.2% to 4.9% (absolute difference 7.2%; 95% CI 2.5%-12.2%; number needed to treat [NNT] = 14; P = .004). There were no significant differences detected in the 2 groups in secondary outcomes including time to reintubation or hospital length of stay. Notably, the study population had a high proportion of surgical and neurocritical patients, resulting in one-third of the reintubations occurring because of nonrespiratory causes such as repeat surgery or altered mental status. When the analysis was limited to only the respiratory-related intubations, the reduced risk of reintubation persisted in the high-flow oxygen group (1.5% vs 8.7%; NNT = 14; P = .001).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of high-flow oxygen therapy for 24 hours following extubation reduce the risk of reintubation in low-risk patients?

Bottom line: Using high-flow nasal cannula oxygen therapy for 24 hours following extubation of patients who are already at low risk of reintubation further reduces the risk of reintubation. You would need to treat 14 patients with high-flow therapy to prevent reintubation in one patient. (LOE = 1b)

Reference: Hernandez G, Vaquero C, Gonzalez P, et al. Effect of postextubation high-flow nasal cannula vs conventional oxygen therapy on reintubation in low-risk patients. JAMA 2016;315(13):1354-1361.

Study design: Randomized controlled trial (nonblinded)

Funding source: Self-funded or unfunded

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

These investigators recruited mechanically ventilated adult patients who were ready for extubation and who met the criteria for low risk for reintubation. Low risk was defined as: younger than 65 years; Acute Physiology and Chronic Health Evaluation (APACHE) II score of less than 12; fewer than 2 comorbidities; body mass index of less than 30; ability to manage secretions; simple weaning; and the absence of heart failure, moderate-to-severe chronic obstructive pulmonary disease, airway patency issues, and prolonged mechanical ventilation.

Using concealed allocation, these patients were randomized to receive either conventional oxygen therapy or high-flow oxygen therapy for 24 hours following extubation. Conventional oxygen therapy was continued in both groups after 24 hours as needed. The 2 groups had a mean age of 51 years and similar APACHE scores at baseline. The use of high-flow oxygen therapy reduced the rate of reintubation within 72 hours from 12.2% to 4.9% (absolute difference 7.2%; 95% CI 2.5%-12.2%; number needed to treat [NNT] = 14; P = .004). There were no significant differences detected in the 2 groups in secondary outcomes including time to reintubation or hospital length of stay. Notably, the study population had a high proportion of surgical and neurocritical patients, resulting in one-third of the reintubations occurring because of nonrespiratory causes such as repeat surgery or altered mental status. When the analysis was limited to only the respiratory-related intubations, the reduced risk of reintubation persisted in the high-flow oxygen group (1.5% vs 8.7%; NNT = 14; P = .001).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: What are the best criteria to identify sepsis and septic shock?

Bottom line: An international task force of experts has updated the definitions of sepsis and septic shock and created a new bedside scoring tool to identify patients with suspected infection who may be at high risk for poor outcomes. Based on the Sequential Organ Failure Assessment (SOFA) score, the new quickSOFA states that meeting 2 of 3 clinical criteria (respiratory rate of 22 per minute or greater, systolic blood pressure of 100 mg Hg or less, and altered mental status) identifies patients at high risk of poor outcomes from sepsis. This score will need to be validated further in multiple health care settings before it can be widely accepted in clinical practice. (LOE = 5)

References: 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.

Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of clinical criteria for sepsis (Sepsis-3). JAMA 2016;315(8):762-774.

Shankar-Hari M, Phillips GS, Levy ML, et al. Developing a new definition and assessing new clinical criteria for septic shock (Sepsis-3). JAMA 2016;315(8):775-787.

Study design: Other

Funding source: Foundation

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis: Systemic inflammatory response syndrome (SIRS) criteria are present in many hospitalized patients, even those without infections or life-threatening illnesses. The use of these criteria to identify sepsis may lead to misdiagnosis. Funded by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, an international task force consisting of 19 critical care, infectious disease, surgical, and pulmonary specialists convened to update the definitions of sepsis and septic shock and identify clinical criteria that can be used to recognize patients at high risk for mortality. Researchers conducted a systematic review and meta-analysis of observational studies followed by a Delphi consensus process to determine appropriate criteria for identifying septic shock. Furthermore, they validated and confirmed the ability of different clinical criteria, including the SIRS criteria and the SOFA score, to predict poor outcomes in patients with suspected infection.

Per the task force's recommendations, sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is a subset of sepsis in which there is an increased risk of mortality due to profound circulatory and cellular metabolism abnormalities. Sepsis can be identified by an increase in the SOFA score of 2 points or more. This is associated with an in-hospital mortality exceeding 10%. Septic shock can be identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and a serum lactate level greater than 18 mg/dL (> 2 mmol/L) after adequate fluid resuscitation. This combination of clinical criteria is associated with a hospital mortality rate of 40%.

Using a derivation and validation cohort of approximately 75,000 patients, the group also developed a new bedside clinical measure termed quickSOFA, or qSOFA, which consists of a respiratory rate of 22 per minute or greater, altered mental status, and systolic blood pressure of 100 mm Hg or less. Patients with suspected infection who are not in the intensive care unit and have at least 2 of these 3 criteria are at higher risk of poor outcomes from sepsis (area under receiver operating characteristics curve = 0.81).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: What are the best criteria to identify sepsis and septic shock?

Bottom line: An international task force of experts has updated the definitions of sepsis and septic shock and created a new bedside scoring tool to identify patients with suspected infection who may be at high risk for poor outcomes. Based on the Sequential Organ Failure Assessment (SOFA) score, the new quickSOFA states that meeting 2 of 3 clinical criteria (respiratory rate of 22 per minute or greater, systolic blood pressure of 100 mg Hg or less, and altered mental status) identifies patients at high risk of poor outcomes from sepsis. This score will need to be validated further in multiple health care settings before it can be widely accepted in clinical practice. (LOE = 5)

References: 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.

Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of clinical criteria for sepsis (Sepsis-3). JAMA 2016;315(8):762-774.

Shankar-Hari M, Phillips GS, Levy ML, et al. Developing a new definition and assessing new clinical criteria for septic shock (Sepsis-3). JAMA 2016;315(8):775-787.

Study design: Other

Funding source: Foundation

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis: Systemic inflammatory response syndrome (SIRS) criteria are present in many hospitalized patients, even those without infections or life-threatening illnesses. The use of these criteria to identify sepsis may lead to misdiagnosis. Funded by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, an international task force consisting of 19 critical care, infectious disease, surgical, and pulmonary specialists convened to update the definitions of sepsis and septic shock and identify clinical criteria that can be used to recognize patients at high risk for mortality. Researchers conducted a systematic review and meta-analysis of observational studies followed by a Delphi consensus process to determine appropriate criteria for identifying septic shock. Furthermore, they validated and confirmed the ability of different clinical criteria, including the SIRS criteria and the SOFA score, to predict poor outcomes in patients with suspected infection.

Per the task force's recommendations, sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is a subset of sepsis in which there is an increased risk of mortality due to profound circulatory and cellular metabolism abnormalities. Sepsis can be identified by an increase in the SOFA score of 2 points or more. This is associated with an in-hospital mortality exceeding 10%. Septic shock can be identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and a serum lactate level greater than 18 mg/dL (> 2 mmol/L) after adequate fluid resuscitation. This combination of clinical criteria is associated with a hospital mortality rate of 40%.

Using a derivation and validation cohort of approximately 75,000 patients, the group also developed a new bedside clinical measure termed quickSOFA, or qSOFA, which consists of a respiratory rate of 22 per minute or greater, altered mental status, and systolic blood pressure of 100 mm Hg or less. Patients with suspected infection who are not in the intensive care unit and have at least 2 of these 3 criteria are at higher risk of poor outcomes from sepsis (area under receiver operating characteristics curve = 0.81).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: What are the best criteria to identify sepsis and septic shock?

Bottom line: An international task force of experts has updated the definitions of sepsis and septic shock and created a new bedside scoring tool to identify patients with suspected infection who may be at high risk for poor outcomes. Based on the Sequential Organ Failure Assessment (SOFA) score, the new quickSOFA states that meeting 2 of 3 clinical criteria (respiratory rate of 22 per minute or greater, systolic blood pressure of 100 mg Hg or less, and altered mental status) identifies patients at high risk of poor outcomes from sepsis. This score will need to be validated further in multiple health care settings before it can be widely accepted in clinical practice. (LOE = 5)

References: 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.

Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of clinical criteria for sepsis (Sepsis-3). JAMA 2016;315(8):762-774.

Shankar-Hari M, Phillips GS, Levy ML, et al. Developing a new definition and assessing new clinical criteria for septic shock (Sepsis-3). JAMA 2016;315(8):775-787.

Study design: Other

Funding source: Foundation

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis: Systemic inflammatory response syndrome (SIRS) criteria are present in many hospitalized patients, even those without infections or life-threatening illnesses. The use of these criteria to identify sepsis may lead to misdiagnosis. Funded by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, an international task force consisting of 19 critical care, infectious disease, surgical, and pulmonary specialists convened to update the definitions of sepsis and septic shock and identify clinical criteria that can be used to recognize patients at high risk for mortality. Researchers conducted a systematic review and meta-analysis of observational studies followed by a Delphi consensus process to determine appropriate criteria for identifying septic shock. Furthermore, they validated and confirmed the ability of different clinical criteria, including the SIRS criteria and the SOFA score, to predict poor outcomes in patients with suspected infection.

Per the task force's recommendations, sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is a subset of sepsis in which there is an increased risk of mortality due to profound circulatory and cellular metabolism abnormalities. Sepsis can be identified by an increase in the SOFA score of 2 points or more. This is associated with an in-hospital mortality exceeding 10%. Septic shock can be identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and a serum lactate level greater than 18 mg/dL (> 2 mmol/L) after adequate fluid resuscitation. This combination of clinical criteria is associated with a hospital mortality rate of 40%.

Using a derivation and validation cohort of approximately 75,000 patients, the group also developed a new bedside clinical measure termed quickSOFA, or qSOFA, which consists of a respiratory rate of 22 per minute or greater, altered mental status, and systolic blood pressure of 100 mm Hg or less. Patients with suspected infection who are not in the intensive care unit and have at least 2 of these 3 criteria are at higher risk of poor outcomes from sepsis (area under receiver operating characteristics curve = 0.81).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: What is the best antibiotic strategy to improve outcomes in patients hospitalized with community-acquired pneumonia?

Bottom line: For patients hospitalized with community-acquired pneumonia (CAP), start antibiotics early, use either fluoroquinolone monotherapy or beta-lactam/macrolide combination therapy, and switch to oral antibiotics as soon as patients are hemodynamically stable and can take oral medications. Although the evidence is mostly of low quality, this review reaffirms what we already do. (LOE = 2a)

Reference: Lee JS, Giesler DL, Gellad WF, Fine MJ. Antibiotic therapy for adults hospitalized with community-acquired pneumonia. JAMA 2016;315(6):593-602.

Study design: Systematic review

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis: These investigators searched MEDLINE, EMBASE, and the Cochrane databases to identify studies that evaluated outcomes for patients hospitalized with CAP with regard to optimal timing of antibiotic initiation, initial antibiotic selection, and criteria for transition from intravenous to oral antibiotic therapy. Two authors independently reviewed studies for inclusion and assessed study quality.

Of 8 low-quality observational studies, 4 showed a significant association between initiating antibiotic therapy within 4 hours to 8 hours of hospital arrival and reduced mortality. When comparing 2 different antibiotic strategies, 6 of 8 observational studies showed mortality benefit with the use of beta-lactams plus macrolides as compared with beta-lactam monotherapy, though the 2 recent high-quality randomized trials had conflicting results. All three observational studies that compared fluoroquinolones with beta-lactam monotherapy for the treatment of CAP showed an association with fluoroquinolone use and decreased mortality.

Finally, one high-quality trial showed that transitioning patients to oral antibiotics once they meet clinical criteria for stability (stable vital signs, lack of confusion, ability to tolerate oral medications) leads to a shorter length of stay.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: What is the best antibiotic strategy to improve outcomes in patients hospitalized with community-acquired pneumonia?

Bottom line: For patients hospitalized with community-acquired pneumonia (CAP), start antibiotics early, use either fluoroquinolone monotherapy or beta-lactam/macrolide combination therapy, and switch to oral antibiotics as soon as patients are hemodynamically stable and can take oral medications. Although the evidence is mostly of low quality, this review reaffirms what we already do. (LOE = 2a)

Reference: Lee JS, Giesler DL, Gellad WF, Fine MJ. Antibiotic therapy for adults hospitalized with community-acquired pneumonia. JAMA 2016;315(6):593-602.

Study design: Systematic review

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis: These investigators searched MEDLINE, EMBASE, and the Cochrane databases to identify studies that evaluated outcomes for patients hospitalized with CAP with regard to optimal timing of antibiotic initiation, initial antibiotic selection, and criteria for transition from intravenous to oral antibiotic therapy. Two authors independently reviewed studies for inclusion and assessed study quality.

Of 8 low-quality observational studies, 4 showed a significant association between initiating antibiotic therapy within 4 hours to 8 hours of hospital arrival and reduced mortality. When comparing 2 different antibiotic strategies, 6 of 8 observational studies showed mortality benefit with the use of beta-lactams plus macrolides as compared with beta-lactam monotherapy, though the 2 recent high-quality randomized trials had conflicting results. All three observational studies that compared fluoroquinolones with beta-lactam monotherapy for the treatment of CAP showed an association with fluoroquinolone use and decreased mortality.

Finally, one high-quality trial showed that transitioning patients to oral antibiotics once they meet clinical criteria for stability (stable vital signs, lack of confusion, ability to tolerate oral medications) leads to a shorter length of stay.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: What is the best antibiotic strategy to improve outcomes in patients hospitalized with community-acquired pneumonia?

Bottom line: For patients hospitalized with community-acquired pneumonia (CAP), start antibiotics early, use either fluoroquinolone monotherapy or beta-lactam/macrolide combination therapy, and switch to oral antibiotics as soon as patients are hemodynamically stable and can take oral medications. Although the evidence is mostly of low quality, this review reaffirms what we already do. (LOE = 2a)

Reference: Lee JS, Giesler DL, Gellad WF, Fine MJ. Antibiotic therapy for adults hospitalized with community-acquired pneumonia. JAMA 2016;315(6):593-602.

Study design: Systematic review

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis: These investigators searched MEDLINE, EMBASE, and the Cochrane databases to identify studies that evaluated outcomes for patients hospitalized with CAP with regard to optimal timing of antibiotic initiation, initial antibiotic selection, and criteria for transition from intravenous to oral antibiotic therapy. Two authors independently reviewed studies for inclusion and assessed study quality.

Of 8 low-quality observational studies, 4 showed a significant association between initiating antibiotic therapy within 4 hours to 8 hours of hospital arrival and reduced mortality. When comparing 2 different antibiotic strategies, 6 of 8 observational studies showed mortality benefit with the use of beta-lactams plus macrolides as compared with beta-lactam monotherapy, though the 2 recent high-quality randomized trials had conflicting results. All three observational studies that compared fluoroquinolones with beta-lactam monotherapy for the treatment of CAP showed an association with fluoroquinolone use and decreased mortality.

Finally, one high-quality trial showed that transitioning patients to oral antibiotics once they meet clinical criteria for stability (stable vital signs, lack of confusion, ability to tolerate oral medications) leads to a shorter length of stay.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.