Benzodiazepines and risk for hepatic encephalopathy in patients with cirrhosis and ascites.

Background: There is limited evidence to support the belief that benzodiazepines increase cirrhosis patients' risk of hepatic encephalopathy (HE).

Objective: We aimed to examine the association between benzodiazepine use and HE development in cirrhosis patients.

Methods: We used data on 865 cirrhosis patients with ascites from three trials to study the effect of benzodiazepine use on development of first-time HE. For each patient, we classified periods of benzodiazepine use by the number of days since initiation. We used Cox regression to compare the risk of HE in current benzodiazepine users vs. non-users adjusting for confounders.

Results: Cirrhosis patients were not at increased risk of HE for the first two days of benzodiazepine use, but then faced a five-fold increased risk of HE during days 3 to 10 of benzodiazepine use. The risk of HE was not increased for those who had been using benzodiazepines for more than 28 days.

Conclusion: Cirrhosis patients who had begun using benzodiazepines between 3 and 10 days previously had a markedly increased risk of developing first-time HE. Cirrhosis patients who had been using benzodiazepines for just one or two days or continued use for more than 28 days did not have such an excess risk.