Acetaminophen overdose: a 48-hour intravenous N-acetylcysteine treatment protocol.
OBJECTIVE
To determine the safety and efficacy of a 48-hour IV N-acetylcysteine (IV NAC) treatment protocol for acute acetaminophen overdose.


METHODS
Nonrandomized trial open to all eligible patients.


METHODS
Multicenter; hospitals included moderate- and high-volume private, university, and municipal hospitals in urban and suburban settings.


METHODS
Two hundred twenty-three patients were entered. Of these, 179 met inclusion criteria: acute acetaminophen overdose, plasma acetaminophen concentration above the treatment nomogram line, treatment with IV NAC according to the protocol, and sufficient data to determine outcome.


METHODS
IV NAC treatment consisted of a loading dose of 140 mg/kg followed by 12 doses of 70 mg/kg every four hours.


RESULTS
Patients were grouped for analysis according to risk group based on the initial plasma acetaminophen concentration. Hepatotoxicity (aspartate aminotransferase or alanine aminotransferase of more than 1,000 IU/L) developed in 10% (five of 50) of patients at "probable risk" when IV NAC was started within ten hours of acetaminophen ingestion and in 27.1% (23 of 85) when therapy was begun after ten to 24 hours. Among "high-risk" patients first treated 16 to 24 hours after overdose, hepatotoxicity occurred in 57.9% (11 of 19). There were two deaths (two of 179, 1.1%). Adverse reactions resulting from NAC occurred in 32 of 223 cases (14.3%), consisting in 29 of 32 patients (91% of reactions) of transient, patchy, skin erythema or mild urticaria during the loading dose that did not require discontinuation of therapy.


CONCLUSIONS
This 48-hour IV NAC protocol is safe and effective antidotal therapy for acetaminophen overdose. Based on available data, it is equal to 72-hour oral and 20-hour IV treatment protocols when started early and superior to the 20-hour IV regimen when treatment is delayed. Further study will be required to determine its relative efficacy in the high-risk patient treated very late.
Smilkstein
M J
MJ
Section of Trauma and Emergency Medicine, University of Colorado Health Sciences Center, Denver.
Bronstein
A C
AC
Linden
C
C
Augenstein
W L
WL
Kulig
K W
KW
Rumack
B H
BH
D000082:Acetaminophen / Q000097:blood / Q000506:poisoning*; D000111:Acetylcysteine / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D002648:Child; D062787:Drug Overdose / Q000188:drug therapy; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors
D000082:Acetaminophen; D000111:Acetylcysteine