Methionine and Cysteamine in Paracetamol (Acetaminophen) Overdose, Prospective Controlled Trial of Early Therapy

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Abstract
We have studied forty patients who were at risk of hepatic, renal, pancreatic or myocardial injury as a consequence of severe paracetamol overdosage and who were admitted to hospital within 10 h of ingestion. These were sequentially randomized into three treatment groups, comprising intravenous cysteamine therapy (3.6 g over 20 h, n = 14), oral methionine (10 g over 16 h, n = 13) or supportive therapy only (intravenous 10% dextrose with vitamins, n=13). All groups were matched for age, ingestion-treatment interval and severity of poisoning as estimated by stated amount ingested and a logarithmic paracetamol blood level index. One death occurred in the supportive therapy (S) group. Significant differences in peak serum aspartate aminotransferase levels were seen with geometric means in S of 1046 U/l, in cysteamine treatment of 96 U/l and in methionine treatment of 139 Ull (Wilcoxon sum of ranks p < 0.01 in favour of methionine, p < 0.002 in favour of cysteamine). Hepatic necrosis, as shown by ‘blind’ histological assessment, was significantly less frequent in actively treated patients (methionine p < 0.05, cysteamine p < 0.01). These differences in favour of cysteamine and methionine were also reflected in peak serum bilirubin and prothrombin ratio. No significant effects of active treatment were shown for serial plasma creatinine, serum amylase, myocardial enzymes or ECG changes. We conclude that in the context of a prospective controlled trial of active agents: A convincing hepatoprotective effect of early i.v. cysteamine and oral methionine has been demonstrated. No clear difference in efficacy of the two antidotes has been shown. Early methionine administration is associated with few, if any, undesirable side-effects.