Comparison of the 20-hour intravenous and 72-hour oral acetylcysteine protocols for the treatment of acute acetaminophen poisoning.
OBJECTIVE
To compare outcomes after acute acetaminophen poisoning in 2 large cohorts of patients treated with either the 20-hour intravenous or 72-hour oral acetylcysteine protocol.


METHODS
We conducted a retrospective cohort study with historical control comparing patients treated with one of 2 acetylcysteine regimens. Data for the 20-hour group were obtained from a medical record review of patients on whom the 20-hour intravenous protocol was initiated in Canadian hospitals from 1980 to 2005. The 72-hour group consisted of a historical cohort of patients treated in US hospitals with the 72-hour oral protocol from 1976 to 1985. The primary outcome was hepatotoxicity (aminotransferase levels >1,000 IU/L).


RESULTS
Of the 4,048 patients analyzed, 2,086 were in the 20-hour group and 1,962 were in the 72-hour group. The incidence of hepatotoxicity was 13.9% in the 20-hour group and 15.8% in the 72-hour group (-1.9% absolute difference; 95% confidence interval [CI] -4.2 to 0.3). The relative risk of hepatotoxicity was lower in the 20-hour group when acetylcysteine was initiated within 12 hours of ingestion. The relative risk was lower in the 72-hour group when acetylcysteine was initiated later than 18 hours after ingestion. There was no significant risk difference between groups when acetylcysteine treatment was started 12 to 18 hours after ingestion. One patient in the 20-hour group received a liver transplant and died because of acetaminophen toxicity compared with no liver transplants and 3 deaths in the 72-hour group. Anaphylactoid reactions to intravenous acetylcysteine were reported in 148 of 2,086 patients (7.1%; 95% CI 6.1% to 8.3%). This study is limited by comparison of 2 separate data sets from different countries and study years.


CONCLUSIONS
The risk of hepatotoxicity differed between the 20-hour and 72-hour protocols according to the time to initiation of acetylcysteine. It favored the 20-hour protocol for patients presenting early and favored the 72-hour protocol for patients presenting late after acute acetaminophen overdose.
Yarema
Mark C
MC
Division of Emergency Medicine and Department of Family Medicine, University of Calgary, Calgary, Alberta, Canada. mark.yarema@albertahealthservices.ca
Johnson
David W
DW
Berlin
Randall J
RJ
Sivilotti
Marco L A
ML
Nettel-Aguirre
Alberto
A
Brant
Rollin F
RF
Spyker
Daniel A
DA
Bailey
Benoit
B
Chalut
Dominic
D
Lee
Jacques S
JS
Plint
Amy C
AC
Purssell
Roy A
RA
Rutledge
Tim
T
Seviour
Catherine A
CA
Stiell
Ian G
IG
Thompson
Margaret
M
Tyberg
Jeffrey
J
Dart
Richard C
RC
Rumack
Barry H
BH
D000082:Acetaminophen / Q000506:poisoning*; D000111:Acetylcysteine / Q000008:administration & dosage*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000931:Antidotes; D002170:Canada; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D015331:Cohort Studies; D019091:Critical Pathways; D004334:Drug Administration Schedule; D062787:Drug Overdose / Q000188:drug therapy / Q000401:mortality; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D012189:Retrospective Studies; D012306:Risk; D014481:United States / Q000453:epidemiology; D055815:Young Adult
D000931:Antidotes; D016166:Free Radical Scavengers; D000082:Acetaminophen; D000111:Acetylcysteine