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.