A single-arm clinical trial of a 48-hour intravenous N-acetylcysteine protocol for treatment of acetaminophen poisoning.
BACKGROUND
Acetylcysteine prevents hepatic injury when administered soon after acetaminophen overdose. The most commonly used treatment protocols are a 72-hour oral and a 21-hour intravenous (IV) protocol. Between 1984 and 1994, 409 patients were enrolled in a study to describe the outcomes of patients who were treated using a 48-hour IV protocol. In 1991, an interim analysis reported the first 223 patients. The objective of this manuscript is to report the rates of hepatotoxicity and adverse events occurring during a 48-hour IV acetylcysteine protocol in the entire 409 patient cohort.


METHODS
This was a multicenter, single-arm, open-label clinical trial enrolling patients who presented with a toxic serum acetaminophen concentration within 24 h of acute acetaminophen ingestion. Patients were treated with 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses. Serum aminotransferase activities were measured every 8 h during the protocol, and adverse events were recorded. The primary outcome was the percentage of subjects who developed hepatotoxicity defined as a peak serum aminotransferase greater than 1000 IU/L.


RESULTS
Four hundred and nine patients were enrolled, and 309 met inclusion for the outcome analysis. The overall percentage of patients developing hepatotoxicity was 18.1%, and 3.4% of patients treated within 10 h developed hepatotoxicity. One acetaminophen-related death occurred in a patient treated at 22 h. Adverse events occurred in 28.9% of enrolled subjects; the most common adverse events were nausea, vomiting, and flushing, and no events were rated as serious by the investigator.


CONCLUSIONS
Acetaminophen-overdosed patients treated with IV acetylcysteine administered as 140 mg/kg loading dose followed by 70 mg/kg every 4 h for 12 doses had a low rate of hepatotoxicity and few adverse events. This protocol delivers a higher dose of acetylcysteine which may be useful in selected cases involving very large overdoses.
Rocky Mountain Poison and Drug Center , Denver, CO , USA.
K
K
Heard
B H
BH
Rumack
J L
JL
Green
B
B
Bucher-Bartelson
S
S
Heard
A C
AC
Bronstein
R C
RC
Dart
D000082:Acetaminophen / Q000097:blood / Q000506:poisoning*; D000111:Acetylcysteine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000931:Antidotes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D062787:Drug Overdose; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D013997:Time Factors; D000637:Transaminases / Q000097:blood; D016896:Treatment Outcome; D055815:Young Adult
D000931:Antidotes; D000082:Acetaminophen; D000637:Transaminases; D000111:Acetylcysteine
Acetaminophen; Acetylcysteine; Antidote; Liver injury; Poisoning