COMPARATIVE STUDY
JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL

Lactulose vs polyethylene glycol 3350—electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial

Robert S Rahimi, Amit G Singal, Jennifer A Cuthbert, Don C Rockey
JAMA Internal Medicine 2014, 174 (11): 1727-33
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IMPORTANCE: Hepatic encephalopathy (HE) is a common cause of hospitalization in patients with cirrhosis. Pharmacologic treatment for acute (overt) HE has remained the same for decades.

OBJECTIVE: To compare polyethylene glycol 3350-electrolyte solution (PEG) and lactulose treatments in patients with cirrhosis admitted to the hospital for HE. We hypothesized that rapid catharsis of the gut using PEG may resolve HE more effectively than lactulose.

DESIGN, SETTING, AND PARTICIPANTS: The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE.

INTERVENTIONS: Participants were block randomized to receive treatment with PEG, 4-L dose (n = 25), or standard-of-care lactulose (n = 25) during hospitalization.

MAIN OUTCOMES AND MEASURES: The primary end point was an improvement of 1 or more in HE grade at 24 hours, determined using the hepatic encephalopathy scoring algorithm (HESA), ranging from 0 (normal clinical and neuropsychological assessments) to 4 (coma). Secondary outcomes included time to HE resolution and overall length of stay.

RESULTS: A total of 25 patients were randomized to each treatment arm. Baseline clinical features at admission were similar in the groups. Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01); 1 patient was discharged before final analysis and 1 refused participation. The mean (SD) HESA score at 24 hours for patients receiving standard therapy changed from 2.3 (0.9) to 1.6 (0.9) compared with a change from 2.3 (0.9) to 0.9 (1.0) for the PEG-treated groups (P = .002). The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P = .01). Adverse events were uncommon, and none was definitely study related.

CONCLUSIONS AND RELEVANCE: PEG led to more rapid HE resolution than standard therapy, suggesting that PEG may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute HE.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01283152.

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Daniel Schwartz

Interesting study that tackles a real problem in managing patients with hepatic encephalopathy.

I note that the lactulose group didn't have their dose titrated to effect ( ie frequency of BMs per day).

Will others be changing practice as a result of this study?

11

Michael Montazeri

One benefit of lactulose is that it can be given rectally to some effect if the patient is intolerant of oral intake; it would be interesting to know if PEG can as well. The 4L volume poses some problems especially considering that these patients are altered; nasogastric tube administration of such a large volume might take longer (and would not necessarily reduce aspiration risk).

5

Ricardo Raymondi

Such results are, in my opinion, not so surprising. It's known that after bowel preparation for colonoscopy the bowel load of bacteria returns to normal level only after 4 weeks, so such interventions have a high capacity on promoting a true bowel "cleaning".
Actually, in clinical practice, mainly among patients with variceal bleeding, the use of enemas (with or without lactulose) is an useful and commonly used tool, since removal of blood from bowel lumen clearly hasten the resolution of encephalopaty in such patients. And, indeed, there is no risk of aspiration for obvious reasons.

2

Thomas Schussler

The cost of the 2 is probably equivalent. Having an encephalopathic patient drink a gallon is not practical and I suspect will lead to causes of aspiration in some.

2

Manish Singh

Interesting study. Have seen many pt responding to lactulose. But never tried PEG for HE. I would like to know the dosing and frequency for PEG in HE patients.

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