title: Oral or intravenous N-acetylcysteine: which is the treatment of choice for acetaminophen (paracetamol) poisoning?
abstract: BACKGROUND
  The optimal route and duration of administration for N-acetyl-cysteine in the management of acetaminophen (paracetamol) poisoning are controversial. It has been stated on the basis of a selected post-hoc analysis that oral N-acetylcysteine is superior to intravenous N-acetylcysteine in presentations later than 15 hours.
  
  
  OBJECTIVE
  To investigate the efficacy of intravenous or oral N-acetylcysteine.
  
  
  METHODS
  We analyzed a series of acetaminophen poisonings treated with a protocol including activated charcoal and intravenous N-acetylcysteine. The outcomes assessed included use of N-acetylcysteine, adverse effects of intravenous N-acetylcysteine, and the occurrence of hepatotoxicity (transaminase > 1000 U/L). We incorporated 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 acetaminophen that indicated a probable or high risk of hepatotoxicity. The 30 patients who developed hepatotoxicity presented later, took larger amounts, had higher concentrations, and received N-acetylcysteine later than those who did not. No patients received a liver transplant but 2 patients died (one after referral to a transplant unit and one just before). Adverse reactions to intravenous N-acetylcysteine occurred in 6% (12/205) of patients but none prevented completion of the treatment. In the meta-analysis, those with probable or high risk concentrations had similar outcomes with intravenous (pooled n = 341) and oral N-acetylcysteine (pooled n = 1462) administration. Rates of hepatotoxicity for those treated within 10 hours (3 and 6%), late (10-24 hours: 30 and 26%), and overall (0-24 hours: 16 and 19%) were all similar. The proportion of patients classified as presenting later than 10 hours is much greater in the oral N-acetylcysteine studies (64%) than in many of the intravenous N-acetylcysteine studies (38%, 44%, and 63%).
  
  
  CONCLUSIONS
  The differences claimed between oral and intravenous N-acetylcysteine regimes are probably artifactual and relate to inappropriate subgroup analysis. A shorter hospital stay, patient and doctor convenience, and the concerns over the reduction in bioavailability of oral N-acetylcysteine by charcoal and vomiting make intravenous N-acetylcysteine preferable for most patients with acetaminophen poisoning.
authors.affiliation: Department of Clinical Pharmacology, Royal Adelaide Hospital, Australia. nbuckley@mail.rah.sa.gov.au
authors.forename: N A
authors.initials: NA
authors.lastname: Buckley
authors.forename: I M
authors.initials: IM
authors.lastname: Whyte
authors.forename: D L
authors.initials: DL
authors.lastname: O'Connell
authors.forename: A H
authors.initials: AH
authors.lastname: Dawson
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D000111:Acetylcysteine / Q000008:administration & dosage* / Q000009:adverse effects; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002606:Charcoal / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D008107:Liver Diseases / Q000097:blood / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011041:Poisoning / Q000188:drug therapy*; D000637:Transaminases / Q000097:blood
chemical_list: D016166:Free Radical Scavengers; D002606:Charcoal; D000082:Acetaminophen; D000637:Transaminases; D000111:Acetylcysteine