Acute acetaminophen overdose is associated with dose-dependent hypokalaemia: a prospective study of 331 patients

Basic Clin Pharmacol Toxicol. 2008 Mar;102(3):325-8. doi: 10.1111/j.1742-7843.2007.00176.x. Epub 2007 Nov 28.


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.

MeSH terms

  • Acetaminophen / blood
  • Acetaminophen / poisoning*
  • Acetylcysteine / therapeutic use
  • Adult
  • Analgesics, Non-Narcotic / blood
  • Analgesics, Non-Narcotic / poisoning*
  • Antidotes / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Overdose
  • Female
  • Humans
  • Hypokalemia / chemically induced*
  • Male
  • Middle Aged
  • Nomograms
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve
  • Risk Factors
  • Statistics, Nonparametric


  • Analgesics, Non-Narcotic
  • Antidotes
  • Acetaminophen
  • Acetylcysteine