Journal Article

Antibiotics With or Without Rifaximin for Acute Hepatic Encephalopathy in Critically Ill Patients With Cirrhosis: A Double-Blind, Randomized Controlled (ARiE) Trial

Avadhanam, Mahathi, Simhadri, Venu, Iyengar, Sowmya, Alla, Manasa, Venishetty, Shantan, Gujjarlapudi, Deepika, Rao, Padaki Nagaraja, Sharma, Mithun, Gupta, Anand, Reddy, Duvvur Nageshwar, Narendran, Ramyashri, Rakam, Kalyan, Premkumar, Madhumita, Shaik, Sameer, Kulkarni, Anand V., Karandikar, Puja, Zuberi, Asim Ahmed

2024

Overview

INTRODUCTION:Critically ill patients with cirrhosis admitted to the intensive care unit (ICU) are usually on broad-spectrum antibiotics because of suspected infection or as a hospital protocol. It is unclear if additional rifaximin has any synergistic effect with broad-spectrum antibiotics in ICU patients with acute overt hepatic encephalopathy (HE).METHODS:In this double-blind trial, patients with overt HE admitted to ICU were randomized to receive antibiotics (ab) alone or antibiotics with rifaximin (ab + r). Resolution (or 2 grade reduction) of HE, time to resolution of HE, in-hospital mortality, nosocomial infection, and changes in endotoxin levels were compared between the 2 groups. A subgroup analysis of patients with decompensated cirrhosis and acute-on-chronic liver failure was performed.RESULTS:Baseline characteristics and severity scores were similar among both groups (92 in each group). Carbapenems and cephalosporin with beta-lactamase inhibitors were the most commonly used ab. On Kaplan-Meier analysis, 44.6% (41/92; 95% confidence interval [CI], 32-70.5) in ab-only arm and 46.7% (43/92; 95% CI, 33.8-63) in ab + r arm achieved the primary objective (P = 0.84).Time to achieve the primary objective (3.65 ± 1.82 days and 4.11 ± 2.01 days; P = 0.27) and in-hospital mortality were similar among both groups (62% vs 50%; P = 0.13). Seven percent and 13% in the ab and ab + r groups developed nosocomial infections (P = 0.21). Endotoxin levels were unaffected by rifaximin. Rifaximin led to lower in-hospital mortality (hazard ratio: 0.39 [95% CI, 0.2-0.76]) in patients with decompensated cirrhosis but not in patients with acute-on-chronic liver failure (hazard ratio: 0.99 [95% CI, 0.6-1.63]) because of reduced nosocomial infections.DISCUSSION:Reversal of overt HE in those on ab was comparable with those on ab + r.

• Publisher: Wolters Kluwer,Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subject: Acute-On-Chronic Liver Failure - drug therapy / Acute-On-Chronic Liver Failure - mortality / Aged / Anti-Bacterial Agents - therapeutic use / Antibiotics / Carbapenems - therapeutic use / Clinical trials / Critical Illness / Cross Infection - drug therapy / Double-Blind Method / Drug Therapy, Combination / Endotoxins - blood / FDA approval / Female / Hepatic Encephalopathy - drug therapy / Hepatic Encephalopathy - etiology / Hospital Mortality / Humans / Intensive Care Units / Liver cirrhosis / Liver Cirrhosis - complications / Liver Cirrhosis - drug therapy / Liver failure / Male / Microbiota / Middle Aged / Mortality / Nosocomial infections / Patients / Polyethylene glycol / Rifamycins - therapeutic use / Rifaximin - therapeutic use / Treatment Outcome