Long-term anticonvulsant therapy worsens outcome in paracetamol-induced fulminant hepatic failure

Abstract

1. Paracetamol hepatotoxicity has been found to be potentiated by anticonvulsant drugs in animal experiments; isolated case reports in humans suggest that long-term anticonvulsant therapy may also adversely influence outcome following overdose. 2. We compared the clinical course, after paracetamol overdose, of 18 patients on long-term anticonvulsant therapy with corresponding features in two published series of paracetamol-induced fulminant hepatic failure from this unit: 297 patients seen between 1973 and 1985 and a further 99 between October 1986 and April 1988. 3. Mortality in those patients who were taking anticonvulsants, but who did not receive N-acetylcysteine, was higher than in either of these series (93.3% vs 64.6% and vs 57.9%, P less than 0.025). Although not statistically significant, there were also trends towards more severe coma (grade 3 or 4: 93.3% vs 75.4%, 1986-88), acidosis (pH less than 7.30: 40% vs 22.6%, 1973-85) and coagulopathy (prothrombin time greater than 100 s: 53.3% vs 33.7%, 1973-85). In the small number of patients given N-acetylcysteine, mortality was similar to that in the 1986-88 series (1/3 vs 15/42). 4. We conclude that chronic use of anticonvulsants enhances clinical features of paracetamol toxicity and discuss possible mechanisms by which this could be mediated.