Acute ethanol coingestion confers a lower risk of hepatotoxicity after deliberate acetaminophen overdose.
OBJECTIVE
Little is known about the clinical significance of acute ethanol coingestion around the time of acetaminophen (paracetamol) overdose. This study prospectively examined the effect of acute ethanol coingestion on risk of hepatotoxicity among patients admitted to hospital for N-acetylcysteine (NAC) therapy after deliberate acetaminophen overdose.


METHODS
This was a prospective observational study and included sequential patients who presented within 24 hours of acute acetaminophen ingestion and required NAC therapy. Significant hepatotoxicity was defined by alanine transaminase > 1,000 U/L or the international normalized ratio > 1.3 after a standardized intravenous administration of 300 mg/kg NAC.


RESULTS
There were 362 patients, including 178 (49.2%) who coingested ethanol acutely. The prevalence of hepatotoxicity was 5.1% (95% CI = 2.6% to 9.5%) in those who ingested ethanol, compared to 15.2% (95% CI = 10.7% to 21.2%) in those who did not (p = 0.0027 by chi-square proportional test). Acute ethanol intake conferred a lower risk of hepatotoxicity in patients who had acetaminophen concentrations above or below the "200-line" and was independent of the interval between ingestion and assessment.


CONCLUSIONS
Acute ethanol intake is associated with a lower risk of hepatotoxicity after acetaminophen overdose. This apparent protective effect cannot be explained solely by lower exposure to acetaminophen in this group, nor differences in the interval between ingestion and initiation of treatment. Further work is required to establish mechanisms by which ethanol might confer protection against hepatotoxicity, so as to identify novel strategies for reducing risk after acute acetaminophen ingestion.
Waring
W Stephen
WS
Scottish Poisons Information Bureau, Royal Infirmary of Edinburgh, Edinburgh, Scotland. s.waring@ed.ac.uk
Stephen
Alexandra F
AF
Malkowska
Aleksandra M
AM
Robinson
Oliver D G
OD
D000082:Acetaminophen / Q000506:poisoning*; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology*; D062787:Drug Overdose; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D012606:Scotland / Q000453:epidemiology; D016728:Self-Injurious Behavior / Q000453:epidemiology
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D000431:Ethanol