Effectiveness and safety of lactulose retention enema in cirrhotic patients with grade 3 or grade 4 hepatic encephalopathy
Keywords:Complete reversal, Grade 3 and Grade 4 Hepatic encephalopathy, Hepatic encephalopathy, Hospitalization, Lactulose retention enema, West haven criteria
Background: Hepatic encephalopathy (HE) is a complex, reversible neuropsychiatric syndrome. The present study evaluated the clinical effectiveness and safety of lactulose retention enema for the treatment of Grade 3 or 4 HE (West Haven Criteria, WHC) in Indian patients.
Methods: This retrospective, open-label, uncontrolled cohort study was conducted at three study centers in India. Patients of either gender (18-65 years) admitted to the hospital with liver cirrhosis having Grade 3 or 4 HE were included. The primary endpoint was to evaluate complete reversal of Grade 3 and 4 HE after 24 h and 48h. The secondary endpoints were grade shift at 24 and 48 h before and after administration of lactulose enema, time to complete reversal of Grade 3 or 4 HE, and mortality. Safety was also evaluated.
Results: Overall, retrospective records of 50 patients were evaluated. Complete reversal of Grade 3 or 4 HE was observed in a statistically significant (p<0.0001) proportion (95% confidence interval) of patients at 24 h (n=40, 80% [66. 3%-90.0%]) and 48 h (n=45, 90% [78. 2%-96.7%]) after treatment. After 24 h of treatment, majority of the patients were noted with Grade 2 (78%) HE. Further improvement was noted after 48 h of treatment with majority of the patients having Grade 2 (40%) and Grade 1 (48%) HE. Mean (SD) time for complete reversal of Grade 3 or 4 HE was 25.39±8.85 h after treatment. All death cases observed (n=6, 12.0%) were assessed as unrelated to the treatment by the investigator, but rather related to the underlying disease and/or precipitating factors. Four non-serious adverse drug reactions in two patients and one rectal device-associated complication in one patient were noted during the patient record reviews.
Conclusions: Lactulose retention enema was clinically effective and resulted in complete reversal of Grade 3 or 4 HE in the majority of patients. It was overall well-tolerated.
Shawcross DL, Dunk AA, Jalan R, Kircheis G, de Knegt RJ, Laleman W, et al. How to diagnose and manage hepatic encephalopathy: a consensus statement on roles and responsibilities beyond the liver specialist. Eur J Gastroenterol Hepatol. 2016;28:146-52.
Poordad FF. Review article: the burden of hepatic encephalopathy. Aliment Pharmacol Ther. 2007;25:3-9.
Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. J Hepatol. 2014;61:642-59.
Jawaro T, Yang A, Dixit D, Bridgeman MB. Management of Hepatic Encephalopathy: A Primer. Ann Pharmacother. 2016;50:569-77.
Wong RJ, Gish RG, Ahmed A. Hepatic encephalopathy is associated with significantly increased mortality among patients awaiting liver transplantation. Liver Transpl. 2014;20:1454-61.
Prakash R, Mullen KD. Mechanisms, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol. 2010;7:515-25.
Leise MD, Poterucha JJ, Kamath PS, Kim WR. Management of hepatic encephalopathy in the hospital. Mayo Clin Proc. 2014;89:241-53.
Al Sibae MR, McGuire BM. Current trends in the treatment of hepatic encephalopathy. Ther Clin Risk Manag. 2009;5:617-26.
Sharma P, Sharma BC. Management of overt hepatic encephalopathy. J Clin Exp Hepatol. 2015;5:S82-7.
Uribe M, Campollo O, Vargas F, Ravelli GP, Mundo F, Zapata L, et.al. Acidifying enemas (lactitol and lactose) vs. nonacidifying enemas (tap water) to treat acute portal-systemic encephalopathy: a double-blind, randomized clinical trial. Hepatology. 1987;7:639-43.
Kersh ES, Rifkin H. Lactulose Enemas. Ann Intern Med. 1973;78:81-84.
Van Waes L, van Egmond J, Demeulenaere L. Emergency treatment of portal-systemic encephalopathy with lactulose enemas. A controlled study. Acta Clin Belg. 1979;34:122-9.
Ratnaike RN, Hicks EP, Hislop IG. The rectal administration of lactulose. Aust N Z J Med. 1975;5:137-40.
Raza MA, Bhatti RS, Akram J. Effect of rectal lactulose administration with oral therapy on time to recovery from hepatic encephalopathy: a randomized study. Ann Saudi Med. 2004;24:374-7.
Sharma P, Sharma BC. Management Patterns of Hepatic Encephalopathy: A Nationwide Survey in India. J Clin Exp Hepatol. 2015;5:199-203.
Lactulose Solution USP (Duphalac® and Duphalac® Enema) [drug label]. India: Abbott India Limited; 2014.
Sharma P, Sharma BC, Agrawal A, Sarin SK. Primary prophylaxis of overt hepatic encephalopathy in patients with cirrhosis: an open labeled randomized controlled trial of lactulose versus no lactulose. J Gastroenterol Hepatol. 2012;27:1329-35.
Sharma BC, Sharma P, Agrawal A, Sarin SK. Secondary prophylaxis of hepatic encephalopathy: an open-label randomized controlled trial of lactulose versus placebo. Gastroenterology. 2009;137:885-91.
Phongsamran PV, Kim JW, Cupo Abbott J, Rosenblatt A. Pharmacotherapy for hepatic encephalopathy. Drugs. 2010;70:1131-48.
Blei AT, Córdoba J. Practice Parameters Committee of the American College of Gastroenterology. Hepatic Encephalopathy. Am J Gastroenterol. 2001;96:1968-76.