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Abstract
Background. Paracetamol poisoning has been a clinical problem for over 40 years. This article reflects the content of the Louis Roche lecture given on this topic in 2009. Historical context. Initially key work illustrated the relationship between plasma paracetamol concentration and risk of liver injury facilitating the development of antidote strategies. Much of this work was done in the Edinburgh clinical toxicology unit. Discussion. The antidote most widely used, acetylcysteine, was developed in Edinburgh and subsequently shown to be associated with adverse effects. Studies on this aspect and on key problems remaining in patient management are described. These include the identification of patients at greatest risk of toxicity, in order that they may be targeted for appropriate early intervention. More recent work suggests that the inflammatory response to paracetamol-induced liver injury may offer new targets for drug therapy in this major poisoning. Conclusion. Paracetamol poisoning remains a challenging problem, but new approaches to treatment seem possible based on recent experimental studies in animals and humans.