Oral or Intravenous N-Acetylcysteine for Acetaminophen Poisoning?

Abstract

Acetaminophen (paracetamol, N-acetyl-p-aminophenol) is an effective, mild analgesic, antipyretic agent and is probably the most widely used of all drugs in the world. It does not share the formidable prostaglandin-dependent toxicity of aspirin and other conventional nonsteroidal anti-inflammatory agents, and when used properly, it has an excellent safety record. In many countries, it is fashionable to misuse over-the-counter analgesics for self-poisoning. As a result, acetaminophen has become a victim of its own success, and it is now one of the most commonly encountered substances to be taken deliberately in overdosage. The most important complication of a major overdose of acetaminophen is acute centrilobular hepatic necrosis, but only a small minority of patients is at risk. Before effective antidotal therapy became generally available some 25 years ago, less than 10% of unselected patients referred to the hospital with acetaminophen poisoning suffered severe liver damage (defined as maximum plasma alanine or aspartate aminotransferase exceeding 1,000 IU/L), and 1% to 3% developed fulminant hepatic failure, which in the absence of liver transplantation programs, was often fatal. There were particular problems with acetaminophen overdosage at that time. The severity of poisoning could not be judged initially on clinical grounds because there were no specific symptoms or signs, consciousness was not usually impaired unless other drugs had also been taken, and the maximum abnormalities of liver function tests were delayed for at least 3 days. The severity of poisoning could only be established reliably by measurement of the plasma concentration of acetaminophen in relation to the time since ingestion. In most cases, an overdose of acetaminophen was taken on impulse with no real intention of ending life. It was distressing to care for a young patient who was fully conscious, not appearing to be ill and now wanting to live, who several days later suffered an unpleasant death in hepatic failure. The availability of N-acetylcysteine has transformed the management of severe acetaminophen poisoning. Initial studies with intravenous N-acetylcysteine in the United Kingdom in 100 severely poisoned patients showed that, in comparison with 57 similarly poisoned control patients receiving only supportive therapy, it was virtually 100% effective in preventing severe liver damage, renal failure, and death, provided that it was given