Dopaminergic agonists for hepatic encephalopathy
Abstract
Background
Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy.
Objectives
To evaluate the beneficial and harmful effects of dopaminergic agonists for patients with hepatic encephalopathy.
Search methods
Trials were identified through The Cochrane Hepato‐Biliary Group Controlled Trials Register (July 2004), The Cochrane Central Register of Controlled Trials (Issue 3, 2004), MEDLINE (1966‐2004/07), EMBASE (1980‐2004/07), manual searches of bibliographies and journals, authors of trials, and pharmaceutical companies.
Selection criteria
All randomised trials comparing dopaminergic agonists versus placebo or no intervention for hepatic encephalopathy.
Data collection and analysis
Trial inclusion and data extraction were made independently by two reviewers. Binary outcomes are reported as odds ratios (OR) with 95% confidence intervals (CI) based on a random effects model. The presence of statistical heterogeneity was explored by the chi‐squared test with significance set at P < 0.1. Potential sources of heterogeneity were explored through subgroup analyses with regard to the type of hepatic encephalopathy and type of dopaminergic agonist.
Main results
Five trials were included. Four trials had low methodological quality. Compared with placebo or no treatment, dopaminergic agonists had no significant effect on the risk of no improvement (OR 0.33, 95% CI 0.01 to 11.25, two trials, 80 patients) or mortality (OR 1.11, 95% CI 0.34 to 3.54, four trials, 139 patients). There was significant heterogeneity (P = 0.09) among trial results on the risk of no improvement, but not on mortality (P = 0.19). The treatment response was not significantly different with regard to the type of hepatic encephalopathy or dopaminergic agonist, but the analyses had very low power to detect potential differences. There was a nonsignificant trend that dopaminergic agonists may be associated with adverse events (OR 8.33, 95% CI 0.37 to 187.74, 2 trials, 13 patients). All adverse events (n = 7) occurred in the experimental group.
Authors' conclusions
This review does not provide evidence that dopaminergic agonists are of benefit to patients with acute or chronic hepatic encephalopathy, or fulminant hepatic failure. The review is limited by the small number of trials performed within this field, the low number of patients randomised in each trial, and the low methodological quality of included trials. Accordingly, there is also insufficient evidence to exclude a potential beneficial effect. Dopaminergic agonists should not be used for hepatic encephalopathy, but may be assessed in future randomised clinical trials.
PICOs
Plain language summary
No evidence to support or refute that dopaminergic agonists have an effect on hepatic encephalopathy
Hepatic encephalopathy occurs in patients with chronic liver disease or fulminant liver failure. Hepatic encephalopathy is associated with changes in mental state, ranging from minor signs of altered brain function to deep coma. Treatment with dopaminergic agonists has been proposed to ameliorate the symptoms. This review does not provide any evidence that dopaminergic agonists have an effect on patients with hepatic encephalopathy. Dopaminergic agonists should not be used for hepatic encephalopathy in clinical practice, but may be assessed in future randomised clinical trials.
