Nita Shrikant Kulkarni, MD

Clinical question

Does barium impaction therapy using high-dose barium enemas prevent recurrent diverticular bleeding?

Bottom line

This small study demonstrates that barium impaction therapy using high-dose barium enemas is safe and effective at reducing the rate of recurrent diverticular bleeding. Note that this study was conducted in Japan, where the rate of rebleeding for patients with diverticulosis is much higher than in Western populations. (LOE = 1b-)

Reference: Nagata N, Niikura R, Shimbo T, et al. High-dose barium impaction therapy for the recurrence of colonic diverticular bleeding. Ann Surg 2015;261(2):269-275.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis

A high-dose barium enema is thought to prevent recurrent diverticular bleeding through a physical tamponade of bleeding vessels, as well as by a direct hemostatic effect of the barium itself. Retained barium in colonic diverticula over time has previously been shown to be safe.

In this trial, patients hospitalized with diverticular bleeding who had spontaneous cessation of bleeding were randomized, using concealed allocation, to receive either barium impaction therapy (n = 27) or conservative treatment (n = 27). In the barium impaction therapy group, barium sulfate was administered by gastroenterologists via an enema bag at a concentration of 200 g barium per 100 mL tap water for a total volume of 400 mL. X-ray imaging confirmed filling of multiple colonic diverticula with barium and the patient was asked to rotate positions to ensure filling of all diverticula.

Baseline characteristics were similar in the 2 groups: the majority of patients were male, the average age was 70 years, and half had a prior history of diverticular bleeding. The severity of initial bleeding was also similar, as measured by number of units of blood transfused prior to randomization and the number of days until spontaneous cessation of bleeding.

For the primary outcome of recurrence of bleeding at the 1-year follow-up, the barium group fared better than the conservative treatment group (15% vs 43%; P = .04). You would have to treat 4 patients with barium impaction therapy to prevent 1 episode of recurrent bleeding. After adjusting for factors associated with recurrent bleeding, including hypertension, nonsteroidal anti-inflammatory drug use, and chronic renal failure, the risk of bleeding was decreased in the barium group (hazard ratio = 0.34, 95% CI 0.12-0.97). Barium impaction therapy did not result in any complications. Furthermore, over the course of the follow-up period, the barium group had a decreased number of re-hospitalizations, transfusions, and repeat colonoscopies.

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

Clinical question

Does barium impaction therapy using high-dose barium enemas prevent recurrent diverticular bleeding?

Bottom line

This small study demonstrates that barium impaction therapy using high-dose barium enemas is safe and effective at reducing the rate of recurrent diverticular bleeding. Note that this study was conducted in Japan, where the rate of rebleeding for patients with diverticulosis is much higher than in Western populations. (LOE = 1b-)

Reference: Nagata N, Niikura R, Shimbo T, et al. High-dose barium impaction therapy for the recurrence of colonic diverticular bleeding. Ann Surg 2015;261(2):269-275.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis

A high-dose barium enema is thought to prevent recurrent diverticular bleeding through a physical tamponade of bleeding vessels, as well as by a direct hemostatic effect of the barium itself. Retained barium in colonic diverticula over time has previously been shown to be safe.

In this trial, patients hospitalized with diverticular bleeding who had spontaneous cessation of bleeding were randomized, using concealed allocation, to receive either barium impaction therapy (n = 27) or conservative treatment (n = 27). In the barium impaction therapy group, barium sulfate was administered by gastroenterologists via an enema bag at a concentration of 200 g barium per 100 mL tap water for a total volume of 400 mL. X-ray imaging confirmed filling of multiple colonic diverticula with barium and the patient was asked to rotate positions to ensure filling of all diverticula.

Baseline characteristics were similar in the 2 groups: the majority of patients were male, the average age was 70 years, and half had a prior history of diverticular bleeding. The severity of initial bleeding was also similar, as measured by number of units of blood transfused prior to randomization and the number of days until spontaneous cessation of bleeding.

For the primary outcome of recurrence of bleeding at the 1-year follow-up, the barium group fared better than the conservative treatment group (15% vs 43%; P = .04). You would have to treat 4 patients with barium impaction therapy to prevent 1 episode of recurrent bleeding. After adjusting for factors associated with recurrent bleeding, including hypertension, nonsteroidal anti-inflammatory drug use, and chronic renal failure, the risk of bleeding was decreased in the barium group (hazard ratio = 0.34, 95% CI 0.12-0.97). Barium impaction therapy did not result in any complications. Furthermore, over the course of the follow-up period, the barium group had a decreased number of re-hospitalizations, transfusions, and repeat colonoscopies.

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

Clinical question

Does barium impaction therapy using high-dose barium enemas prevent recurrent diverticular bleeding?

Bottom line

This small study demonstrates that barium impaction therapy using high-dose barium enemas is safe and effective at reducing the rate of recurrent diverticular bleeding. Note that this study was conducted in Japan, where the rate of rebleeding for patients with diverticulosis is much higher than in Western populations. (LOE = 1b-)

Reference: Nagata N, Niikura R, Shimbo T, et al. High-dose barium impaction therapy for the recurrence of colonic diverticular bleeding. Ann Surg 2015;261(2):269-275.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis

A high-dose barium enema is thought to prevent recurrent diverticular bleeding through a physical tamponade of bleeding vessels, as well as by a direct hemostatic effect of the barium itself. Retained barium in colonic diverticula over time has previously been shown to be safe.

In this trial, patients hospitalized with diverticular bleeding who had spontaneous cessation of bleeding were randomized, using concealed allocation, to receive either barium impaction therapy (n = 27) or conservative treatment (n = 27). In the barium impaction therapy group, barium sulfate was administered by gastroenterologists via an enema bag at a concentration of 200 g barium per 100 mL tap water for a total volume of 400 mL. X-ray imaging confirmed filling of multiple colonic diverticula with barium and the patient was asked to rotate positions to ensure filling of all diverticula.

Baseline characteristics were similar in the 2 groups: the majority of patients were male, the average age was 70 years, and half had a prior history of diverticular bleeding. The severity of initial bleeding was also similar, as measured by number of units of blood transfused prior to randomization and the number of days until spontaneous cessation of bleeding.

For the primary outcome of recurrence of bleeding at the 1-year follow-up, the barium group fared better than the conservative treatment group (15% vs 43%; P = .04). You would have to treat 4 patients with barium impaction therapy to prevent 1 episode of recurrent bleeding. After adjusting for factors associated with recurrent bleeding, including hypertension, nonsteroidal anti-inflammatory drug use, and chronic renal failure, the risk of bleeding was decreased in the barium group (hazard ratio = 0.34, 95% CI 0.12-0.97). Barium impaction therapy did not result in any complications. Furthermore, over the course of the follow-up period, the barium group had a decreased number of re-hospitalizations, transfusions, and repeat colonoscopies.

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

Clinical question: Do steroids improve outcomes in patients with severe community-acquired pneumonia and a high inflammatory response?

Bottom line

In patients with severe community-acquired pneumonia (CAP) who have elevated levels of C-reactive protein (CRP), a short course of methylprednisolone decreases treatment failure, mainly by reducing radiographic progression of pulmonary infiltrates within 3 days to 5 days of treatment initiation. The patient population studied here represents a fraction of the patients with severe CAP, so this finding cannot be generalized. Moreover, this study was small and the findings require replication before they can be applied to this population.

Reference: Torres A, Sibila O, Ferrer M, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response. JAMA 2015;313(7):677-686.

Design: Randomized controlled trial (double-blinded); LOE: 1b

Setting: Inpatient (any location)

Synopsis

A previous meta-analysis of randomized controlled trials showed that the addition of steroids for treatment of community-acquired pneumonia decreases hospital length of stay but does not affect other clinical outcomes such as mortality or need for mechanical ventilation (J Hosp Med 2013;8:68-75).

In this study, investigators enrolled patients hospitalized with severe CAP (either risk class V by the Pneumonia Severity Index or as defined by American Thoracic Society) and a CRP level of greater than 15 mg/dL. Immunosuppressed patients or those with diabetes or recent major gastrointestinal bleeding were excluded.

Patients were randomized, using concealed allocation, to receive either methylprednisolone (0.5 mg per kg) every 12 hours (n = 61) or matching placebo (n = 59) for 5 days. The primary outcome was treatment failure. Early treatment failure was defined as clinical deterioration within 72 hours of treatment, whereas late failure was defined as radiographic progression of pulmonary infiltrates by more than 50%, respiratory failure, shock, or death between 3 days and 5 days.

Baseline characteristics were similar in the 2 groups, except for lower procalcitonin levels and less septic shock in the steroid group. Antibiotic treatment on admission was similar in both groups (most commonly ceftriaxone combined with either levofloxacin or azithromycin). The majority of patients were initially admitted to the intensive care unit. In the intention-to-treat analysis, the steroid group had less treatment failure than the placebo group (13% vs 31%; P = .02). This was driven by a higher rate of late treatment failure in the placebo group, primarily due to a greater incidence of radiographic progression of infiltrates. Results were similar after adjusting for potential confounders and imbalances in baseline characteristics (hazard ratio = 0.33, 95% CI 0.12 - 0.90; P = .03). There were no significant differences in length of stay, in-hospital mortality, or adverse events between the 2 groups.

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

Clinical question: Do steroids improve outcomes in patients with severe community-acquired pneumonia and a high inflammatory response?

Bottom line

In patients with severe community-acquired pneumonia (CAP) who have elevated levels of C-reactive protein (CRP), a short course of methylprednisolone decreases treatment failure, mainly by reducing radiographic progression of pulmonary infiltrates within 3 days to 5 days of treatment initiation. The patient population studied here represents a fraction of the patients with severe CAP, so this finding cannot be generalized. Moreover, this study was small and the findings require replication before they can be applied to this population.

Reference: Torres A, Sibila O, Ferrer M, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response. JAMA 2015;313(7):677-686.

Design: Randomized controlled trial (double-blinded); LOE: 1b

Setting: Inpatient (any location)

Synopsis

A previous meta-analysis of randomized controlled trials showed that the addition of steroids for treatment of community-acquired pneumonia decreases hospital length of stay but does not affect other clinical outcomes such as mortality or need for mechanical ventilation (J Hosp Med 2013;8:68-75).

In this study, investigators enrolled patients hospitalized with severe CAP (either risk class V by the Pneumonia Severity Index or as defined by American Thoracic Society) and a CRP level of greater than 15 mg/dL. Immunosuppressed patients or those with diabetes or recent major gastrointestinal bleeding were excluded.

Patients were randomized, using concealed allocation, to receive either methylprednisolone (0.5 mg per kg) every 12 hours (n = 61) or matching placebo (n = 59) for 5 days. The primary outcome was treatment failure. Early treatment failure was defined as clinical deterioration within 72 hours of treatment, whereas late failure was defined as radiographic progression of pulmonary infiltrates by more than 50%, respiratory failure, shock, or death between 3 days and 5 days.

Baseline characteristics were similar in the 2 groups, except for lower procalcitonin levels and less septic shock in the steroid group. Antibiotic treatment on admission was similar in both groups (most commonly ceftriaxone combined with either levofloxacin or azithromycin). The majority of patients were initially admitted to the intensive care unit. In the intention-to-treat analysis, the steroid group had less treatment failure than the placebo group (13% vs 31%; P = .02). This was driven by a higher rate of late treatment failure in the placebo group, primarily due to a greater incidence of radiographic progression of infiltrates. Results were similar after adjusting for potential confounders and imbalances in baseline characteristics (hazard ratio = 0.33, 95% CI 0.12 - 0.90; P = .03). There were no significant differences in length of stay, in-hospital mortality, or adverse events between the 2 groups.

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

Clinical question: Do steroids improve outcomes in patients with severe community-acquired pneumonia and a high inflammatory response?

Bottom line

In patients with severe community-acquired pneumonia (CAP) who have elevated levels of C-reactive protein (CRP), a short course of methylprednisolone decreases treatment failure, mainly by reducing radiographic progression of pulmonary infiltrates within 3 days to 5 days of treatment initiation. The patient population studied here represents a fraction of the patients with severe CAP, so this finding cannot be generalized. Moreover, this study was small and the findings require replication before they can be applied to this population.

Reference: Torres A, Sibila O, Ferrer M, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response. JAMA 2015;313(7):677-686.

Design: Randomized controlled trial (double-blinded); LOE: 1b

Setting: Inpatient (any location)

Synopsis

A previous meta-analysis of randomized controlled trials showed that the addition of steroids for treatment of community-acquired pneumonia decreases hospital length of stay but does not affect other clinical outcomes such as mortality or need for mechanical ventilation (J Hosp Med 2013;8:68-75).

In this study, investigators enrolled patients hospitalized with severe CAP (either risk class V by the Pneumonia Severity Index or as defined by American Thoracic Society) and a CRP level of greater than 15 mg/dL. Immunosuppressed patients or those with diabetes or recent major gastrointestinal bleeding were excluded.

Patients were randomized, using concealed allocation, to receive either methylprednisolone (0.5 mg per kg) every 12 hours (n = 61) or matching placebo (n = 59) for 5 days. The primary outcome was treatment failure. Early treatment failure was defined as clinical deterioration within 72 hours of treatment, whereas late failure was defined as radiographic progression of pulmonary infiltrates by more than 50%, respiratory failure, shock, or death between 3 days and 5 days.

Baseline characteristics were similar in the 2 groups, except for lower procalcitonin levels and less septic shock in the steroid group. Antibiotic treatment on admission was similar in both groups (most commonly ceftriaxone combined with either levofloxacin or azithromycin). The majority of patients were initially admitted to the intensive care unit. In the intention-to-treat analysis, the steroid group had less treatment failure than the placebo group (13% vs 31%; P = .02). This was driven by a higher rate of late treatment failure in the placebo group, primarily due to a greater incidence of radiographic progression of infiltrates. Results were similar after adjusting for potential confounders and imbalances in baseline characteristics (hazard ratio = 0.33, 95% CI 0.12 - 0.90; P = .03). There were no significant differences in length of stay, in-hospital mortality, or adverse events between the 2 groups.

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

Clinical question

Did the 2011 Accreditation Council for Graduate Medical Education resident work hour reforms affect patient outcomes?

Bottom line

Resident work hour reforms were proposed by the Accreditation Council for Graduate Medical Education (ACGME) to reduce resident fatigue (and thus potentially reduce the risk of medical errors), but implementation of the work hour changes also led to concerns over patient safety because of increased handoffs in care. This study shows that work hour reforms had no impact, either positive or negative, on the important patient outcomes of mortality and readmission rates. Other outcomes such as length of stay and number of intensive care unit transfers may need to be examined in future studies to detect more subtle differences. (LOE = 2b)

Reference

Patel MS, Volpp KG, Small DS, et al. Association of the 2011 ACGME resident duty hour reforms with mortality and readmissions among hospitalized Medicare patients. JAMA 2014;312(22):2364-2373.

Study design: Cohort (retrospective)

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis

In 2011, the ACGME instituted work hour reforms for residents that reduced the work hour limit from 30 consecutive hours to 16 hours for first-year residents and 24 hours for all other residents. Investigators in this study evaluated the effect of the 2011 ACGME reforms on 30-day all-location mortality and 30-day all-cause readmissions. Patients included in the study were Medicare patients who were admitted to acute care US hospitals from 2009 to 2012 with acute myocardial infarction, stroke, gastrointestinal bleeding, or congestive heart failure, or those admitted for general, orthopedic, or vascular surgery. Hospitals were classified by their level of teaching intensity using a resident-to-bed ratio defined as the number of residents divided by the number of staffed beds.

In an analysis that adjusted for demographics, co-morbidities, and the presence of surgical complications, the implementation of work hour reforms did not affect 30-day mortality or readmissions in more-intensive teaching hospitals relative to less-intensive teaching hospitals during the postreform year as compared with 2 years before the reform. Multiple factors beyond the implementation of work hour reforms, may have contributed to this lack of effect. First, adherence to the new reforms by residency programs in the first year is unclear. Second, concurrent initiatives to improve patient outcomes during this time may have affected all hospitals, teaching and nonteaching. Finally, the authors suggest that the greater emphasis on resident supervision with the new reforms may have counterbalanced any negative effects of increased resident handoffs.

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

Clinical question

Did the 2011 Accreditation Council for Graduate Medical Education resident work hour reforms affect patient outcomes?

Bottom line

Resident work hour reforms were proposed by the Accreditation Council for Graduate Medical Education (ACGME) to reduce resident fatigue (and thus potentially reduce the risk of medical errors), but implementation of the work hour changes also led to concerns over patient safety because of increased handoffs in care. This study shows that work hour reforms had no impact, either positive or negative, on the important patient outcomes of mortality and readmission rates. Other outcomes such as length of stay and number of intensive care unit transfers may need to be examined in future studies to detect more subtle differences. (LOE = 2b)

Reference

Patel MS, Volpp KG, Small DS, et al. Association of the 2011 ACGME resident duty hour reforms with mortality and readmissions among hospitalized Medicare patients. JAMA 2014;312(22):2364-2373.

Study design: Cohort (retrospective)

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis

In 2011, the ACGME instituted work hour reforms for residents that reduced the work hour limit from 30 consecutive hours to 16 hours for first-year residents and 24 hours for all other residents. Investigators in this study evaluated the effect of the 2011 ACGME reforms on 30-day all-location mortality and 30-day all-cause readmissions. Patients included in the study were Medicare patients who were admitted to acute care US hospitals from 2009 to 2012 with acute myocardial infarction, stroke, gastrointestinal bleeding, or congestive heart failure, or those admitted for general, orthopedic, or vascular surgery. Hospitals were classified by their level of teaching intensity using a resident-to-bed ratio defined as the number of residents divided by the number of staffed beds.

In an analysis that adjusted for demographics, co-morbidities, and the presence of surgical complications, the implementation of work hour reforms did not affect 30-day mortality or readmissions in more-intensive teaching hospitals relative to less-intensive teaching hospitals during the postreform year as compared with 2 years before the reform. Multiple factors beyond the implementation of work hour reforms, may have contributed to this lack of effect. First, adherence to the new reforms by residency programs in the first year is unclear. Second, concurrent initiatives to improve patient outcomes during this time may have affected all hospitals, teaching and nonteaching. Finally, the authors suggest that the greater emphasis on resident supervision with the new reforms may have counterbalanced any negative effects of increased resident handoffs.

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

Clinical question

Did the 2011 Accreditation Council for Graduate Medical Education resident work hour reforms affect patient outcomes?

Bottom line

Resident work hour reforms were proposed by the Accreditation Council for Graduate Medical Education (ACGME) to reduce resident fatigue (and thus potentially reduce the risk of medical errors), but implementation of the work hour changes also led to concerns over patient safety because of increased handoffs in care. This study shows that work hour reforms had no impact, either positive or negative, on the important patient outcomes of mortality and readmission rates. Other outcomes such as length of stay and number of intensive care unit transfers may need to be examined in future studies to detect more subtle differences. (LOE = 2b)

Reference

Patel MS, Volpp KG, Small DS, et al. Association of the 2011 ACGME resident duty hour reforms with mortality and readmissions among hospitalized Medicare patients. JAMA 2014;312(22):2364-2373.

Study design: Cohort (retrospective)

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis

In 2011, the ACGME instituted work hour reforms for residents that reduced the work hour limit from 30 consecutive hours to 16 hours for first-year residents and 24 hours for all other residents. Investigators in this study evaluated the effect of the 2011 ACGME reforms on 30-day all-location mortality and 30-day all-cause readmissions. Patients included in the study were Medicare patients who were admitted to acute care US hospitals from 2009 to 2012 with acute myocardial infarction, stroke, gastrointestinal bleeding, or congestive heart failure, or those admitted for general, orthopedic, or vascular surgery. Hospitals were classified by their level of teaching intensity using a resident-to-bed ratio defined as the number of residents divided by the number of staffed beds.

In an analysis that adjusted for demographics, co-morbidities, and the presence of surgical complications, the implementation of work hour reforms did not affect 30-day mortality or readmissions in more-intensive teaching hospitals relative to less-intensive teaching hospitals during the postreform year as compared with 2 years before the reform. Multiple factors beyond the implementation of work hour reforms, may have contributed to this lack of effect. First, adherence to the new reforms by residency programs in the first year is unclear. Second, concurrent initiatives to improve patient outcomes during this time may have affected all hospitals, teaching and nonteaching. Finally, the authors suggest that the greater emphasis on resident supervision with the new reforms may have counterbalanced any negative effects of increased resident handoffs.

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

Clinical question: For critically ill patients, does daily bathing with chlorhexidine reduce health care–associated infections?

Bottom line

These results show that daily chlorhexidine bathing does not significantly affect the incidence of health care–associated infections. These data conflict with data from prior research, suggesting that more investigation is needed before incorporating chlorhexidine bathing into routine practice, especially given the increased cost with its use and the possibility of the development of chlorhexidine resistance. (LOE = 1b)

Reference: Noto MJ, Domenico HJ, Byrne DW, et al. Chlorhexidine bathing and health care-associated infections. JAMA 2015;313(4):369-378.

Study design: Cross-over trial (randomized)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

Previous studies have shown benefit of daily chlorhexidine bathing in patients at high risk of nosocomial blood stream infections (Daily POEM 7-31-2013; Daily POEM 4-26-2013). In this study, investigators randomized 5 intensive care units at a tertiary care hospital to provide daily bathing of all patients with either 2% chlorhexidine-impregnated cloths or with nonantimicrobial cloths. Each unit followed the assigned protocol for 10 weeks, followed by a 2-week washout period, and then crossed over to the alternate protocol for another 10 weeks. All units crossed over 3 times during the study. Almost 10,000 patients were included in the study. The primary outcome was a composite of health-care associated infections, including central-line associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonia, and Clostridium difficile infections. There was no significant difference detected in the rate of the primary outcome between the chlorhexidine group and the control group with approximately 3 infections per 1000 patient-days in both groups. Adjusting for factors including demographics, co-morbidities, and the unit of admission also did not reveal a difference.

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

Clinical question: For critically ill patients, does daily bathing with chlorhexidine reduce health care–associated infections?

Bottom line

These results show that daily chlorhexidine bathing does not significantly affect the incidence of health care–associated infections. These data conflict with data from prior research, suggesting that more investigation is needed before incorporating chlorhexidine bathing into routine practice, especially given the increased cost with its use and the possibility of the development of chlorhexidine resistance. (LOE = 1b)

Reference: Noto MJ, Domenico HJ, Byrne DW, et al. Chlorhexidine bathing and health care-associated infections. JAMA 2015;313(4):369-378.

Study design: Cross-over trial (randomized)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

Previous studies have shown benefit of daily chlorhexidine bathing in patients at high risk of nosocomial blood stream infections (Daily POEM 7-31-2013; Daily POEM 4-26-2013). In this study, investigators randomized 5 intensive care units at a tertiary care hospital to provide daily bathing of all patients with either 2% chlorhexidine-impregnated cloths or with nonantimicrobial cloths. Each unit followed the assigned protocol for 10 weeks, followed by a 2-week washout period, and then crossed over to the alternate protocol for another 10 weeks. All units crossed over 3 times during the study. Almost 10,000 patients were included in the study. The primary outcome was a composite of health-care associated infections, including central-line associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonia, and Clostridium difficile infections. There was no significant difference detected in the rate of the primary outcome between the chlorhexidine group and the control group with approximately 3 infections per 1000 patient-days in both groups. Adjusting for factors including demographics, co-morbidities, and the unit of admission also did not reveal a difference.

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

Clinical question: For critically ill patients, does daily bathing with chlorhexidine reduce health care–associated infections?

Bottom line

These results show that daily chlorhexidine bathing does not significantly affect the incidence of health care–associated infections. These data conflict with data from prior research, suggesting that more investigation is needed before incorporating chlorhexidine bathing into routine practice, especially given the increased cost with its use and the possibility of the development of chlorhexidine resistance. (LOE = 1b)

Reference: Noto MJ, Domenico HJ, Byrne DW, et al. Chlorhexidine bathing and health care-associated infections. JAMA 2015;313(4):369-378.

Study design: Cross-over trial (randomized)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

Previous studies have shown benefit of daily chlorhexidine bathing in patients at high risk of nosocomial blood stream infections (Daily POEM 7-31-2013; Daily POEM 4-26-2013). In this study, investigators randomized 5 intensive care units at a tertiary care hospital to provide daily bathing of all patients with either 2% chlorhexidine-impregnated cloths or with nonantimicrobial cloths. Each unit followed the assigned protocol for 10 weeks, followed by a 2-week washout period, and then crossed over to the alternate protocol for another 10 weeks. All units crossed over 3 times during the study. Almost 10,000 patients were included in the study. The primary outcome was a composite of health-care associated infections, including central-line associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonia, and Clostridium difficile infections. There was no significant difference detected in the rate of the primary outcome between the chlorhexidine group and the control group with approximately 3 infections per 1000 patient-days in both groups. Adjusting for factors including demographics, co-morbidities, and the unit of admission also did not reveal a difference.

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

Clinical question

Can a procalcitonin-based algorithm reduce antibiotic use in critically ill patients?

Bottom line

A procalcitonin-based algorithm using a 0.1 ng/mL cutoff does not significantly decrease the duration of antibiotic treatment in critically ill patients nor does it reduce length of stay or number of deaths. The rate of decline in the procalcitonin level over the first 72 hours, however, does serve as an independent predictor of short-term and long-term all-cause mortality. (LOE = 1b-)

Reference

Shehabi Y, Sterba M, Garrett PM, et al, for the ProGUARD Study Investigators and the ANZICS Clinical Trials Group. Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. Am J Respir Crit Care Med 2014;190(10):1102-1110.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

Procalcitonin (PCT) is a sepsis biomarker that has been utilized to guide antibiotic use in different patient populations. In this study, the authors tested a PCT-algorithm using a 0.1 ng/mL cut-off to reduce antibiotic exposure in critically ill patients. Patients newly admitted to intensive care units (ICUs) who were receiving antibiotics for suspected infections were randomized, using concealed allocation, to receive PCT-guided care (n = 196) or standard care (n = 198). All patients had PCT levels drawn daily until discharge from the ICU or up to a maximum of 7 days. In the PCT group, antibiotics were stopped if PCT levels were negative (< 0.1 ng/mL), if PCT levels were borderline (0.1 - 0.25 ng/mL) and infection was unlikely, or if PCT levels decreased more than 90% from baseline values. In the standard care group, the treating clinician determined antibiotic use without knowledge of the PCT results. Baseline characteristics of the 2 groups were similar with regard to severity-of-disease scores and baseline PCT values. There was high compliance with the PCT algorithm, with less than 3% of study days when the algorithm was not followed. There was no significant difference detected between the 2 groups for the primary outcome of time to antibiotic cessation. However, duration of antibiotic use was longer than expected in the control group (11 days actual vs 9 days expected), so the study may have been underpowered to detect an expected 25% reduction. Nevertheless, the 2 groups were similar with regard to ICU and hospital lengths of stay, as well as ICU, hospital, and 90-day mortality rates. Of note, the rate of decline in PCT level over the first 72 hours was an independent predictor of hospital mortality and 90-day mortality, with a slower decline corresponding to a higher mortality.

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

Clinical question

Can a procalcitonin-based algorithm reduce antibiotic use in critically ill patients?

Bottom line

A procalcitonin-based algorithm using a 0.1 ng/mL cutoff does not significantly decrease the duration of antibiotic treatment in critically ill patients nor does it reduce length of stay or number of deaths. The rate of decline in the procalcitonin level over the first 72 hours, however, does serve as an independent predictor of short-term and long-term all-cause mortality. (LOE = 1b-)

Reference

Shehabi Y, Sterba M, Garrett PM, et al, for the ProGUARD Study Investigators and the ANZICS Clinical Trials Group. Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. Am J Respir Crit Care Med 2014;190(10):1102-1110.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

Procalcitonin (PCT) is a sepsis biomarker that has been utilized to guide antibiotic use in different patient populations. In this study, the authors tested a PCT-algorithm using a 0.1 ng/mL cut-off to reduce antibiotic exposure in critically ill patients. Patients newly admitted to intensive care units (ICUs) who were receiving antibiotics for suspected infections were randomized, using concealed allocation, to receive PCT-guided care (n = 196) or standard care (n = 198). All patients had PCT levels drawn daily until discharge from the ICU or up to a maximum of 7 days. In the PCT group, antibiotics were stopped if PCT levels were negative (< 0.1 ng/mL), if PCT levels were borderline (0.1 - 0.25 ng/mL) and infection was unlikely, or if PCT levels decreased more than 90% from baseline values. In the standard care group, the treating clinician determined antibiotic use without knowledge of the PCT results. Baseline characteristics of the 2 groups were similar with regard to severity-of-disease scores and baseline PCT values. There was high compliance with the PCT algorithm, with less than 3% of study days when the algorithm was not followed. There was no significant difference detected between the 2 groups for the primary outcome of time to antibiotic cessation. However, duration of antibiotic use was longer than expected in the control group (11 days actual vs 9 days expected), so the study may have been underpowered to detect an expected 25% reduction. Nevertheless, the 2 groups were similar with regard to ICU and hospital lengths of stay, as well as ICU, hospital, and 90-day mortality rates. Of note, the rate of decline in PCT level over the first 72 hours was an independent predictor of hospital mortality and 90-day mortality, with a slower decline corresponding to a higher mortality.

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

Clinical question

Can a procalcitonin-based algorithm reduce antibiotic use in critically ill patients?

Bottom line

A procalcitonin-based algorithm using a 0.1 ng/mL cutoff does not significantly decrease the duration of antibiotic treatment in critically ill patients nor does it reduce length of stay or number of deaths. The rate of decline in the procalcitonin level over the first 72 hours, however, does serve as an independent predictor of short-term and long-term all-cause mortality. (LOE = 1b-)

Reference

Shehabi Y, Sterba M, Garrett PM, et al, for the ProGUARD Study Investigators and the ANZICS Clinical Trials Group. Procalcitonin algorithm in critically ill adults with undifferentiated infection or suspected sepsis. Am J Respir Crit Care Med 2014;190(10):1102-1110.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis

Procalcitonin (PCT) is a sepsis biomarker that has been utilized to guide antibiotic use in different patient populations. In this study, the authors tested a PCT-algorithm using a 0.1 ng/mL cut-off to reduce antibiotic exposure in critically ill patients. Patients newly admitted to intensive care units (ICUs) who were receiving antibiotics for suspected infections were randomized, using concealed allocation, to receive PCT-guided care (n = 196) or standard care (n = 198). All patients had PCT levels drawn daily until discharge from the ICU or up to a maximum of 7 days. In the PCT group, antibiotics were stopped if PCT levels were negative (< 0.1 ng/mL), if PCT levels were borderline (0.1 - 0.25 ng/mL) and infection was unlikely, or if PCT levels decreased more than 90% from baseline values. In the standard care group, the treating clinician determined antibiotic use without knowledge of the PCT results. Baseline characteristics of the 2 groups were similar with regard to severity-of-disease scores and baseline PCT values. There was high compliance with the PCT algorithm, with less than 3% of study days when the algorithm was not followed. There was no significant difference detected between the 2 groups for the primary outcome of time to antibiotic cessation. However, duration of antibiotic use was longer than expected in the control group (11 days actual vs 9 days expected), so the study may have been underpowered to detect an expected 25% reduction. Nevertheless, the 2 groups were similar with regard to ICU and hospital lengths of stay, as well as ICU, hospital, and 90-day mortality rates. Of note, the rate of decline in PCT level over the first 72 hours was an independent predictor of hospital mortality and 90-day mortality, with a slower decline corresponding to a higher mortality.

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

Clinical question

Does early nasoenteric feeding decrease the rate of infections or death in patients hospitalized with severe acute pancreatitis?

Bottom line

In patients with severe acute pancreatitis, early nasoenteric feeding initiated within 24 hours of presentation, as compared with oral feeding after 72 hours, does not improve mortality or reduce the rate of major infections. (LOE = 1b-)

Reference

Bakker OJ, van Brunschot S, van Santvoort HC, et al, for the Dutch Pancreatitis Study Group. Early versus on-demand nasoenteric tube feeding in acute pancreatitis. N Engl J Med 2014;371(21):1983-1993.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ward only)

Synopsis

Previous observational studies suggest that early nasoenteric feeding in patients with acute pancreatitis may reduce the rate of major infections by stimulating intestinal motility, reducing bacterial overgrowth, and increasing splanchnic blood flow. Using concealed allocation, these authors randomized patients presenting to the emergency department with severe acute pancreatitis to receive either early nasoenteric tube feeding initiated within 24 hours (n = 102) or oral feeding started at 72 hours (n = 106). If the oral diet was not tolerated, tube feeding was initiated after 96 hours. The 2 groups were similar at baseline: the mean age was 65 years and 60% of the patients had evidence of systemic inflammatory response syndrome (SIRS). Analysis was by intention to treat. One third of patients in the oral group eventually required tube feeding. For the primary composite end point of death or major infection (infected pancreatic necrosis, bacteremia, or pneumonia), there was no significant difference detected between the 2 groups. When the outcomes of major infection and death were examined separately, the 2 groups again had comparable results. Finally, patients in both groups had similar rates of admission to the intensive care unit and similar need for mechanical ventilation. Given fewer-than-expected events in the control group, it is possible that the study was too small to detect a difference in the primary outcome, if such a difference exists.

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

Clinical question

Does early nasoenteric feeding decrease the rate of infections or death in patients hospitalized with severe acute pancreatitis?

Bottom line

In patients with severe acute pancreatitis, early nasoenteric feeding initiated within 24 hours of presentation, as compared with oral feeding after 72 hours, does not improve mortality or reduce the rate of major infections. (LOE = 1b-)

Reference

Bakker OJ, van Brunschot S, van Santvoort HC, et al, for the Dutch Pancreatitis Study Group. Early versus on-demand nasoenteric tube feeding in acute pancreatitis. N Engl J Med 2014;371(21):1983-1993.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ward only)

Synopsis

Previous observational studies suggest that early nasoenteric feeding in patients with acute pancreatitis may reduce the rate of major infections by stimulating intestinal motility, reducing bacterial overgrowth, and increasing splanchnic blood flow. Using concealed allocation, these authors randomized patients presenting to the emergency department with severe acute pancreatitis to receive either early nasoenteric tube feeding initiated within 24 hours (n = 102) or oral feeding started at 72 hours (n = 106). If the oral diet was not tolerated, tube feeding was initiated after 96 hours. The 2 groups were similar at baseline: the mean age was 65 years and 60% of the patients had evidence of systemic inflammatory response syndrome (SIRS). Analysis was by intention to treat. One third of patients in the oral group eventually required tube feeding. For the primary composite end point of death or major infection (infected pancreatic necrosis, bacteremia, or pneumonia), there was no significant difference detected between the 2 groups. When the outcomes of major infection and death were examined separately, the 2 groups again had comparable results. Finally, patients in both groups had similar rates of admission to the intensive care unit and similar need for mechanical ventilation. Given fewer-than-expected events in the control group, it is possible that the study was too small to detect a difference in the primary outcome, if such a difference exists.

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

Clinical question

Does early nasoenteric feeding decrease the rate of infections or death in patients hospitalized with severe acute pancreatitis?

Bottom line

In patients with severe acute pancreatitis, early nasoenteric feeding initiated within 24 hours of presentation, as compared with oral feeding after 72 hours, does not improve mortality or reduce the rate of major infections. (LOE = 1b-)

Reference

Bakker OJ, van Brunschot S, van Santvoort HC, et al, for the Dutch Pancreatitis Study Group. Early versus on-demand nasoenteric tube feeding in acute pancreatitis. N Engl J Med 2014;371(21):1983-1993.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ward only)

Synopsis

Previous observational studies suggest that early nasoenteric feeding in patients with acute pancreatitis may reduce the rate of major infections by stimulating intestinal motility, reducing bacterial overgrowth, and increasing splanchnic blood flow. Using concealed allocation, these authors randomized patients presenting to the emergency department with severe acute pancreatitis to receive either early nasoenteric tube feeding initiated within 24 hours (n = 102) or oral feeding started at 72 hours (n = 106). If the oral diet was not tolerated, tube feeding was initiated after 96 hours. The 2 groups were similar at baseline: the mean age was 65 years and 60% of the patients had evidence of systemic inflammatory response syndrome (SIRS). Analysis was by intention to treat. One third of patients in the oral group eventually required tube feeding. For the primary composite end point of death or major infection (infected pancreatic necrosis, bacteremia, or pneumonia), there was no significant difference detected between the 2 groups. When the outcomes of major infection and death were examined separately, the 2 groups again had comparable results. Finally, patients in both groups had similar rates of admission to the intensive care unit and similar need for mechanical ventilation. Given fewer-than-expected events in the control group, it is possible that the study was too small to detect a difference in the primary outcome, if such a difference exists.

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

Clinical question

Is intermittent proton pump inhibitor (PPI) therapy comparable with continuous-infusion PPI for the treatment of patients with high-risk bleeding ulcers who have undergone endoscopic therapy?

Bottom line

For patients with high-risk bleeding ulcers who have been treated endoscopically, treatment with intermittent proton pump inhibitor (PPI) therapy is as effective as continuous infusion of PPIs for the prevention of rebleeding. This systematic review, however, was not able to determine the most optimal intermittent PPI regimen for this purpose because the included studies included used various dosing schedules and administration routes. (LOE = 1a)

Reference

Sachar H, Vaidya K, Laine L. Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: A systematic review and meta-analysis. JAMA Intern Med 2014;174(11):1755-1762.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis

Current guidelines recommend that patients with bleeding ulcers and endoscopic evidence of active bleeding, nonbleeding visible vessels, and adherent clots should receive an intravenous bolus dose of PPI followed by a continuous PPI infusion for 72 hours to prevent rebleeding. In this study, investigators searched multiple databases including MEDLINE, EMBASE, and the Cochrane Register to find randomized clinical trials that evaluated this continuous PPI regimen versus the use of intermittent PPIs for the treatment of these high-risk bleeding ulcers. The intermittent PPI regimens differed in both dosage and administration, from pantoprazole 40 mg given orally every 12 hours to pantoprazole 80 mg given intravenously once, followed by 40 mg intravenously every 6 hours.

Two authors independently performed the search, selected studies for inclusion, extracted data, and assessed the risk of bias for included studies. Ten of the 13 selected studies reported on the primary outcome of recurrent bleeding within 7 days and found that intermittent PPI use was noninferior to continuous-infusion PPI therapy, with the noninferiority margin predefined as an absolute risk difference of 3%. Noninferiority criteria were also met for the secondary outcomes, including rebleeding at 3 days or 30 days, mortality, need for surgical intervention, need for transfusion, and hospital length of stay. No publication or reporting biases were detected.

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

Clinical question

Is intermittent proton pump inhibitor (PPI) therapy comparable with continuous-infusion PPI for the treatment of patients with high-risk bleeding ulcers who have undergone endoscopic therapy?

Bottom line

For patients with high-risk bleeding ulcers who have been treated endoscopically, treatment with intermittent proton pump inhibitor (PPI) therapy is as effective as continuous infusion of PPIs for the prevention of rebleeding. This systematic review, however, was not able to determine the most optimal intermittent PPI regimen for this purpose because the included studies included used various dosing schedules and administration routes. (LOE = 1a)

Reference

Sachar H, Vaidya K, Laine L. Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: A systematic review and meta-analysis. JAMA Intern Med 2014;174(11):1755-1762.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis

Current guidelines recommend that patients with bleeding ulcers and endoscopic evidence of active bleeding, nonbleeding visible vessels, and adherent clots should receive an intravenous bolus dose of PPI followed by a continuous PPI infusion for 72 hours to prevent rebleeding. In this study, investigators searched multiple databases including MEDLINE, EMBASE, and the Cochrane Register to find randomized clinical trials that evaluated this continuous PPI regimen versus the use of intermittent PPIs for the treatment of these high-risk bleeding ulcers. The intermittent PPI regimens differed in both dosage and administration, from pantoprazole 40 mg given orally every 12 hours to pantoprazole 80 mg given intravenously once, followed by 40 mg intravenously every 6 hours.

Two authors independently performed the search, selected studies for inclusion, extracted data, and assessed the risk of bias for included studies. Ten of the 13 selected studies reported on the primary outcome of recurrent bleeding within 7 days and found that intermittent PPI use was noninferior to continuous-infusion PPI therapy, with the noninferiority margin predefined as an absolute risk difference of 3%. Noninferiority criteria were also met for the secondary outcomes, including rebleeding at 3 days or 30 days, mortality, need for surgical intervention, need for transfusion, and hospital length of stay. No publication or reporting biases were detected.

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

Clinical question

Is intermittent proton pump inhibitor (PPI) therapy comparable with continuous-infusion PPI for the treatment of patients with high-risk bleeding ulcers who have undergone endoscopic therapy?

Bottom line

For patients with high-risk bleeding ulcers who have been treated endoscopically, treatment with intermittent proton pump inhibitor (PPI) therapy is as effective as continuous infusion of PPIs for the prevention of rebleeding. This systematic review, however, was not able to determine the most optimal intermittent PPI regimen for this purpose because the included studies included used various dosing schedules and administration routes. (LOE = 1a)

Reference

Sachar H, Vaidya K, Laine L. Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: A systematic review and meta-analysis. JAMA Intern Med 2014;174(11):1755-1762.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (ward only)

Synopsis

Current guidelines recommend that patients with bleeding ulcers and endoscopic evidence of active bleeding, nonbleeding visible vessels, and adherent clots should receive an intravenous bolus dose of PPI followed by a continuous PPI infusion for 72 hours to prevent rebleeding. In this study, investigators searched multiple databases including MEDLINE, EMBASE, and the Cochrane Register to find randomized clinical trials that evaluated this continuous PPI regimen versus the use of intermittent PPIs for the treatment of these high-risk bleeding ulcers. The intermittent PPI regimens differed in both dosage and administration, from pantoprazole 40 mg given orally every 12 hours to pantoprazole 80 mg given intravenously once, followed by 40 mg intravenously every 6 hours.

Two authors independently performed the search, selected studies for inclusion, extracted data, and assessed the risk of bias for included studies. Ten of the 13 selected studies reported on the primary outcome of recurrent bleeding within 7 days and found that intermittent PPI use was noninferior to continuous-infusion PPI therapy, with the noninferiority margin predefined as an absolute risk difference of 3%. Noninferiority criteria were also met for the secondary outcomes, including rebleeding at 3 days or 30 days, mortality, need for surgical intervention, need for transfusion, and hospital length of stay. No publication or reporting biases were detected.

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

Clinical question

Is polyethylene glycol 3350-electrolyte solution an effective treatment for hospitalized patients with acute hepatic encephalopathy?

Bottom line

Polyethylene glycol 3350-electrolyte solution (PEG) is a safe and effective therapy for the initial treatment of acute hepatic encephalopathy (HE) in hospitalized patients. As compared with lactulose alone, the use of PEG alone during the first 24 hours of presentation worked better at improving symptoms of HE. The benefit beyond this time is less clear as both groups in this study received lactulose after 24 hours. (LOE = 1b)

Reference

Rahimi RS, Singal AG, Cuthbert JA, Rockey DC. Lactulose vs. polyethylene glycol 3350-electrolyte solution for treatment of overt hepatic encephalopathy: The HELP randomized clinical trial. JAMA Intern Med 2014;174(11):1727-1733.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (ward only)

Synopsis

Lactulose has long been used as the standard therapy for the treatment of acute HE. This study evaluated the efficacy of PEG as compared with lactulose for the initial treatment of HE. Using concealed allocation, investigators randomized 50 adult patients with cirrhosis and evidence of acute HE to receive either PEG or lactulose.

Patients in the PEG group received 4 L of PEG orally or via nasogastric tube as a single dose over 4 hours. Patients in the lactulose group received 20 g to 30 g lactulose orally or via nasogastric tube for 3 or more doses over 24 hours, or a single dose of 200 g lactulose via rectal tube. Grade of HE was determined prior to treatment and again at 24 hours using the hepatic encephalopathy scoring algorithm (HESA).

After 24 hours, all patients received lactulose per the standard of care. Baseline characteristics of the 2 groups were similar, with an average age of 56 years and similar Model of End-stage Liver Disease (MELD) scores. Analysis was by intention to treat. Patients in both groups had a mean baseline HE grade of 2.3. For the primary outcome of improvement in HE grade by 1 or more at 24 hours, PEG was more effective than lactulose (91% vs 52% patients with improved scores, P < .01). Furthermore, the median time to HE resolution was shorter in the PEG group (1 day vs 2 days, P =.01) with a trend toward decreased hospital length of stay (4 days vs 8 days, P =.07). There were no adverse events that were definitively attributed to the study medications in either group.

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

Clinical question

Is polyethylene glycol 3350-electrolyte solution an effective treatment for hospitalized patients with acute hepatic encephalopathy?

Bottom line

Polyethylene glycol 3350-electrolyte solution (PEG) is a safe and effective therapy for the initial treatment of acute hepatic encephalopathy (HE) in hospitalized patients. As compared with lactulose alone, the use of PEG alone during the first 24 hours of presentation worked better at improving symptoms of HE. The benefit beyond this time is less clear as both groups in this study received lactulose after 24 hours. (LOE = 1b)

Reference

Rahimi RS, Singal AG, Cuthbert JA, Rockey DC. Lactulose vs. polyethylene glycol 3350-electrolyte solution for treatment of overt hepatic encephalopathy: The HELP randomized clinical trial. JAMA Intern Med 2014;174(11):1727-1733.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (ward only)

Synopsis

Lactulose has long been used as the standard therapy for the treatment of acute HE. This study evaluated the efficacy of PEG as compared with lactulose for the initial treatment of HE. Using concealed allocation, investigators randomized 50 adult patients with cirrhosis and evidence of acute HE to receive either PEG or lactulose.

Patients in the PEG group received 4 L of PEG orally or via nasogastric tube as a single dose over 4 hours. Patients in the lactulose group received 20 g to 30 g lactulose orally or via nasogastric tube for 3 or more doses over 24 hours, or a single dose of 200 g lactulose via rectal tube. Grade of HE was determined prior to treatment and again at 24 hours using the hepatic encephalopathy scoring algorithm (HESA).

After 24 hours, all patients received lactulose per the standard of care. Baseline characteristics of the 2 groups were similar, with an average age of 56 years and similar Model of End-stage Liver Disease (MELD) scores. Analysis was by intention to treat. Patients in both groups had a mean baseline HE grade of 2.3. For the primary outcome of improvement in HE grade by 1 or more at 24 hours, PEG was more effective than lactulose (91% vs 52% patients with improved scores, P < .01). Furthermore, the median time to HE resolution was shorter in the PEG group (1 day vs 2 days, P =.01) with a trend toward decreased hospital length of stay (4 days vs 8 days, P =.07). There were no adverse events that were definitively attributed to the study medications in either group.

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

Clinical question

Is polyethylene glycol 3350-electrolyte solution an effective treatment for hospitalized patients with acute hepatic encephalopathy?

Bottom line

Polyethylene glycol 3350-electrolyte solution (PEG) is a safe and effective therapy for the initial treatment of acute hepatic encephalopathy (HE) in hospitalized patients. As compared with lactulose alone, the use of PEG alone during the first 24 hours of presentation worked better at improving symptoms of HE. The benefit beyond this time is less clear as both groups in this study received lactulose after 24 hours. (LOE = 1b)

Reference

Rahimi RS, Singal AG, Cuthbert JA, Rockey DC. Lactulose vs. polyethylene glycol 3350-electrolyte solution for treatment of overt hepatic encephalopathy: The HELP randomized clinical trial. JAMA Intern Med 2014;174(11):1727-1733.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (ward only)

Synopsis

Lactulose has long been used as the standard therapy for the treatment of acute HE. This study evaluated the efficacy of PEG as compared with lactulose for the initial treatment of HE. Using concealed allocation, investigators randomized 50 adult patients with cirrhosis and evidence of acute HE to receive either PEG or lactulose.

Patients in the PEG group received 4 L of PEG orally or via nasogastric tube as a single dose over 4 hours. Patients in the lactulose group received 20 g to 30 g lactulose orally or via nasogastric tube for 3 or more doses over 24 hours, or a single dose of 200 g lactulose via rectal tube. Grade of HE was determined prior to treatment and again at 24 hours using the hepatic encephalopathy scoring algorithm (HESA).

After 24 hours, all patients received lactulose per the standard of care. Baseline characteristics of the 2 groups were similar, with an average age of 56 years and similar Model of End-stage Liver Disease (MELD) scores. Analysis was by intention to treat. Patients in both groups had a mean baseline HE grade of 2.3. For the primary outcome of improvement in HE grade by 1 or more at 24 hours, PEG was more effective than lactulose (91% vs 52% patients with improved scores, P < .01). Furthermore, the median time to HE resolution was shorter in the PEG group (1 day vs 2 days, P =.01) with a trend toward decreased hospital length of stay (4 days vs 8 days, P =.07). There were no adverse events that were definitively attributed to the study medications in either group.

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

For patients presenting with early septic shock, does early goal-directed therapy reduce mortality?

Bottom line

As compared with usual resuscitation care, early goal-directed therapy (EGDT) using central venous monitoring does not improve mortality in patients presenting to the emergency department with septic shock.

Reference

ARISE Investigators; ANZICS Clinical Trials Group, Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371(16):1496-1506.

Study design

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

Setting

Inpatient (ICU only)

Synopsis

A recent trial showed that protocolized care using EGDT for the treatment of septic shock does not decrease mortality (N Engl J Med 2014;370:1683-1693). The current study supports these findings. Using concealed allocation, investigators randomized patients presenting to the emergency department with evidence of septic shock to either EGDT or usual care. For the EGDT group (n = 793), clinicians followed a 6-hour resuscitation protocol with central venous hemodynamic monitoring to guide the use of fluids, vasopressors, inotropes, and transfusions. For the usual care group (n = 798), care was at the discretion of the treating physicians, but central venous monitoring was not permitted during the 6-hour intervention. Analysis was by intention to treat and the 2 groups were similar at baseline. Additionally, adherence to the EGDT protocol was high and loss to follow-up was low. During the 6-hour resuscitation, patients in the EGDT group received a greater volume of intravenous fluids and were more likely to have received vasopressors (67% vs 58%), transfusions (14% vs 7%), or dobutamine (15% vs 3%). For the primary outcome of 90-day mortality, however, there was no significant difference detected between the 2 groups. Furthermore, there were no significant differences in the use of renal replacement therapy, in-hospital mortality, or length of hospital stay.

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

For patients presenting with early septic shock, does early goal-directed therapy reduce mortality?

Bottom line

As compared with usual resuscitation care, early goal-directed therapy (EGDT) using central venous monitoring does not improve mortality in patients presenting to the emergency department with septic shock.

Reference

ARISE Investigators; ANZICS Clinical Trials Group, Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371(16):1496-1506.

Study design

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

Setting

Inpatient (ICU only)

Synopsis

A recent trial showed that protocolized care using EGDT for the treatment of septic shock does not decrease mortality (N Engl J Med 2014;370:1683-1693). The current study supports these findings. Using concealed allocation, investigators randomized patients presenting to the emergency department with evidence of septic shock to either EGDT or usual care. For the EGDT group (n = 793), clinicians followed a 6-hour resuscitation protocol with central venous hemodynamic monitoring to guide the use of fluids, vasopressors, inotropes, and transfusions. For the usual care group (n = 798), care was at the discretion of the treating physicians, but central venous monitoring was not permitted during the 6-hour intervention. Analysis was by intention to treat and the 2 groups were similar at baseline. Additionally, adherence to the EGDT protocol was high and loss to follow-up was low. During the 6-hour resuscitation, patients in the EGDT group received a greater volume of intravenous fluids and were more likely to have received vasopressors (67% vs 58%), transfusions (14% vs 7%), or dobutamine (15% vs 3%). For the primary outcome of 90-day mortality, however, there was no significant difference detected between the 2 groups. Furthermore, there were no significant differences in the use of renal replacement therapy, in-hospital mortality, or length of hospital stay.

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

For patients presenting with early septic shock, does early goal-directed therapy reduce mortality?

Bottom line

As compared with usual resuscitation care, early goal-directed therapy (EGDT) using central venous monitoring does not improve mortality in patients presenting to the emergency department with septic shock.

Reference

ARISE Investigators; ANZICS Clinical Trials Group, Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371(16):1496-1506.

Study design

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

Setting

Inpatient (ICU only)

Synopsis

A recent trial showed that protocolized care using EGDT for the treatment of septic shock does not decrease mortality (N Engl J Med 2014;370:1683-1693). The current study supports these findings. Using concealed allocation, investigators randomized patients presenting to the emergency department with evidence of septic shock to either EGDT or usual care. For the EGDT group (n = 793), clinicians followed a 6-hour resuscitation protocol with central venous hemodynamic monitoring to guide the use of fluids, vasopressors, inotropes, and transfusions. For the usual care group (n = 798), care was at the discretion of the treating physicians, but central venous monitoring was not permitted during the 6-hour intervention. Analysis was by intention to treat and the 2 groups were similar at baseline. Additionally, adherence to the EGDT protocol was high and loss to follow-up was low. During the 6-hour resuscitation, patients in the EGDT group received a greater volume of intravenous fluids and were more likely to have received vasopressors (67% vs 58%), transfusions (14% vs 7%), or dobutamine (15% vs 3%). For the primary outcome of 90-day mortality, however, there was no significant difference detected between the 2 groups. Furthermore, there were no significant differences in the use of renal replacement therapy, in-hospital mortality, or length of hospital stay.

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

Clinical question

Does a lower transfusion threshold for critically ill patients with septic shock affect outcomes?

Bottom line

Using a lower threshold for transfusion for patients with septic shock in the intensive care unit (ICU) decreases the number of transfusions received without affecting mortality.

Reference

Holst LB, Haase N, Wetterslev J, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 2014;371(15):1381-1391.

Study design

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

Setting

Inpatient (ICU only)

Synopsis

Using partial blinding and concealed allocation, these investigators randomized ICU patients with septic shock and a hemoglobin level of less than 9 g/dL to receive red blood cell transfusions at either a higher threshold (< 9 g/dL) or a lower threshold (< 7 g/dL). The intervention continued for the entire ICU stay, to a maximum of 90 days. The 2 groups were similar at baseline with an average age of 67 years and a median Sepsis-Related Organ Failure Assessment (SOFA) score of 10 out of 24. Analysis was by intention to treat. Not suprisingly, patients in the higher threshold group received twice as many transfusions as those in the lower threshold group (3088 transfusions vs 1545; P < .001). Notably, one third of the patients in the lower-threshold group required no transfusions at all compared with only 1% in the higher-threshold group (P < .001). For the primary outcome of death at 90 days, there was no significant difference detected between the 2 groups. The per-protocol analysis, which excluded patients with major protocol violations, also showed the same result. Secondary outcomes, including the use of life support and the number of ischemic events in the ICU (eg, acute myocardial or cerebral ischemia), were also similar in the 2 groups.

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

Clinical question

Does a lower transfusion threshold for critically ill patients with septic shock affect outcomes?

Bottom line

Using a lower threshold for transfusion for patients with septic shock in the intensive care unit (ICU) decreases the number of transfusions received without affecting mortality.

Reference

Holst LB, Haase N, Wetterslev J, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 2014;371(15):1381-1391.

Study design

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

Setting

Inpatient (ICU only)

Synopsis

Using partial blinding and concealed allocation, these investigators randomized ICU patients with septic shock and a hemoglobin level of less than 9 g/dL to receive red blood cell transfusions at either a higher threshold (< 9 g/dL) or a lower threshold (< 7 g/dL). The intervention continued for the entire ICU stay, to a maximum of 90 days. The 2 groups were similar at baseline with an average age of 67 years and a median Sepsis-Related Organ Failure Assessment (SOFA) score of 10 out of 24. Analysis was by intention to treat. Not suprisingly, patients in the higher threshold group received twice as many transfusions as those in the lower threshold group (3088 transfusions vs 1545; P < .001). Notably, one third of the patients in the lower-threshold group required no transfusions at all compared with only 1% in the higher-threshold group (P < .001). For the primary outcome of death at 90 days, there was no significant difference detected between the 2 groups. The per-protocol analysis, which excluded patients with major protocol violations, also showed the same result. Secondary outcomes, including the use of life support and the number of ischemic events in the ICU (eg, acute myocardial or cerebral ischemia), were also similar in the 2 groups.

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

Clinical question

Does a lower transfusion threshold for critically ill patients with septic shock affect outcomes?

Bottom line

Using a lower threshold for transfusion for patients with septic shock in the intensive care unit (ICU) decreases the number of transfusions received without affecting mortality.

Reference

Holst LB, Haase N, Wetterslev J, et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 2014;371(15):1381-1391.

Study design

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

Setting

Inpatient (ICU only)

Synopsis

Using partial blinding and concealed allocation, these investigators randomized ICU patients with septic shock and a hemoglobin level of less than 9 g/dL to receive red blood cell transfusions at either a higher threshold (< 9 g/dL) or a lower threshold (< 7 g/dL). The intervention continued for the entire ICU stay, to a maximum of 90 days. The 2 groups were similar at baseline with an average age of 67 years and a median Sepsis-Related Organ Failure Assessment (SOFA) score of 10 out of 24. Analysis was by intention to treat. Not suprisingly, patients in the higher threshold group received twice as many transfusions as those in the lower threshold group (3088 transfusions vs 1545; P < .001). Notably, one third of the patients in the lower-threshold group required no transfusions at all compared with only 1% in the higher-threshold group (P < .001). For the primary outcome of death at 90 days, there was no significant difference detected between the 2 groups. The per-protocol analysis, which excluded patients with major protocol violations, also showed the same result. Secondary outcomes, including the use of life support and the number of ischemic events in the ICU (eg, acute myocardial or cerebral ischemia), were also similar in the 2 groups.

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