title: Direct comparison of 20-hour IV, 36-hour oral, and 72-hour oral acetylcysteine for treatment of acute acetaminophen poisoning.
abstract: There is no general consensus among clinicians on the superior route or duration of treatment with N-acetylcysteine (NAC) for acute acetaminophen (APAP) poisoning, and head-to-head studies comparing intravenous (IV) and oral NAC have not been done. Recent 20-hour IV NAC protocol failures in the United States prompted some to question its safety. Our objective was to determine if treatment with the 20-hour IV NAC protocol results in clinical outcomes different from the longer 36-hour oral or 72-hour oral NAC protocols in cases of acute APAP poisoning. We performed a retrospective analysis of all consecutive cases of acute APAP overdose where NAC treatment was initiated within 8 hours of ingestion between January 1, 2002, and December 31, 2007. Outcomes were survival, transplant, and death; secondary outcomes were based on King's College Criteria; interrater reliability was calculated with a kappa score. Out of 4642 cases of APAP overdose, 795 met study inclusion criteria: 213 were treated with 20-hour IV protocol, 213 with the 36-hour oral protocol, and 369 with the 72-hour oral protocol. The mean age in these groups was 25 years [95% confidence interval (CI): 22-26], 26 years (95%CI: 23-29), and 27 years (95%CI: 25-28), respectively. The mean 4-hour APAP concentration was 199 μg/mL (95%CI: 188-211), 174 μg/mL (95%CI: 164-184), and 205 μg/mL (95%CI: 195-216), respectively. No cases of transplant or death occurred, and secondary outcomes were rare. When administered within 8 hours of acute APAP poisoning, the 20-hour IV treatment protocol was as effective as the longer 36-hour oral and 72-hour oral treatment protocols. Further study is needed to determine outcome differences between IV and oral NAC when treatment is initiated >8 hours after overdose or in cases of coingestion with other drugs.
authors.affiliation: Department of Emergency Medicine, Advocate Christ Medical Center, Oak Lawn, Illinois, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Williamson
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wahl
authors.forename: Mark B
authors.initials: MB
authors.lastname: Mycyk
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D000111:Acetylcysteine / Q000008:administration & dosage* / Q000627:therapeutic use; D000208:Acute Disease; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D000931:Antidotes / Q000008:administration & dosage* / Q000627:therapeutic use; D002648:Child; D004334:Drug Administration Schedule; D062787:Drug Overdose / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000931:Antidotes; D000082:Acetaminophen; D000111:Acetylcysteine