Oral or intravenous N-acetylcysteine: Which is the treatment of choice foracetaminophen (paracetamol) poisoning?

Background: The optimal route and duration of administration for N-acetylcy steine in the management of acetaminophen (paracetamol) poisoning are contr oversial. It has been stated on the basis of a selected post-hoc analysis t hat oral N-acetylcysteine is superior to intravenous N-acetylcysteine in pr esentations later than 15 hours. Aim of Study: To investigate the efficacy of intravenous or oral N-acetylcysteine. Patients and Methods: We analyzed a series of acetaminophen poisonings treated with a protocol including acti vated charcoal and intravenous N-acetylcysteine. The outcomes assessed incl uded use of N-acetylcysteine, adverse effects of intravenous N-acetylcystei ne, and the occurrence of hepatotoxicity (transaminase > 1000 U/L). We inco rporated these results in a meta-analysis of previously reported series of acetaminophen poisonings to compare the outcomes from intravenous and oral N-acetylcysteine use. Results: Of 981 patients admitted over 10 years, 4% ( 40) presented later than 24 hours and 10% (100) had concentrations of aceta minophen that indicated a probable or high risk of hepatotoxicity. The 30 p atients who developed hepatotoxicity presented later, took larger amounts, had higher concentrations, and received N-acetylcysteine later than those w ho did not. No patients received a liver transplant but 2 patients died (on e after referral to a transplant unit and one just before). Adverse reactio ns to intravenous N-acetylcysteine occurred in 6% (12/205) of patients but none prevented completion of the treatment. In the meta-analysis, those wit h probable or high risk concentrations had similar outcomes with intravenou s (pooled n = 341) and oral N-acetylcysteine (pooled n = 1462) administrati on. Rates of hepatotoxicity for those treated within 10 hours (3 and 6%), l ate (10-24 hours: 30 and 26%), and overall (0-24 hours: 16 and 19%) were al l similar. The proportion of patients classified as presenting later than 1 0 hours is much greater in the oral N-acetylcysteine studies (64%) than in many of the intravenous N-acetylcysteine studies (38%, 44%, and 63%). Concl usions: The differences claimed between oral and intravenous N-acetylcystei ne regimes are probably artifactual and relate to inappropriate subgroup an alysis. A shorter hospital stay, patient and doctor convenience, and the co ncerns over the reduction in bioavailability of oral N-acetylcysteine by ch arcoal and vomiting make intravenous N-acetylcysteine preferable for most p atients with acetaminophen poisoning.