PEG Better and Faster than Lactulose for Initial Treatment of Hepatic Encephalopathy

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.