Acute acetaminophen overdose is associated with dose-dependent hypokalaemia: a prospective study of 331 patients.
Hypokalaemia is a recognized complication of acute acetaminophen overdose. It is unclear whether this might be a pharmacological effect of acetaminophen, or due to association with confounding factors. The present study sought to better characterize the relationship between acetaminophen concentrations and risk of hypokalaemia. A prospective study of patients received N-acetylcysteine treatment within 15 hr of acute acetaminophen ingestion. Serum potassium concentrations were determined before and after N-acetylcysteine. Serum acetaminophen concentrations were used to indicate overall drug exposure by comparison to the Rumack-Matthew nomogram. Hypokalaemia was pre-defined by serum concentrations <3.5 mmol/l, and groups compared by Mann-Whitney tests. There were 331 patients. Median (95% confidence interval) fall in serum potassium concentration after N-acetylcysteine was 0.05 mmol/l (-0.11-0.30 mmol/l) if acetaminophen concentrations were below the 'high-risk' treatment line, 0.30 mmol/l (0.17-0.40 mmol/l) if between the 'high-risk' and 'normal' treatment lines (P = 0.0358), and 0.40 mmol/l (0.20-0.50 mmol/l) if above the 'normal' treatment line (P = 0.0136). A receiver operating characteristic showed that high acetaminophen concentrations were predictive of hypokalaemia (P = 0.0001 versus zero discriminatory line), and 4 hr acetaminophen concentration >156 mmol/l gave 81% sensitivity and 48% specificity. The risk of hypokalaemia after acute acetaminophen overdose depends on the extent of acetaminophen exposure, irrespective of N-acetylcysteine administration and independent of whether vomiting occurred. Acetaminophen appears to cause concentration-dependent hypokalaemia after overdose, and the pharmacological basis requires further consideration.
Scottish Poisons Information Bureau, Royal Infirmary of Edinburgh, Edinburgh, Scotland, UK. s.waring@ed.ac.uk
W Stephen
WS
Waring
Alexandra F L
AF
Stephen
Aleks M
AM
Malkowska
Oliver D G
OD
Robinson
D000082:Acetaminophen / Q000097:blood / Q000506:poisoning*; D000111:Acetylcysteine / Q000627:therapeutic use; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000097:blood / Q000506:poisoning*; D000931:Antidotes / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose; D005260:Female; D006801:Humans; D007008:Hypokalemia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D049451:Nomograms; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D018709:Statistics, Nonparametric
D018712:Analgesics, Non-Narcotic; D000931:Antidotes; D000082:Acetaminophen; D000111:Acetylcysteine