Acute Acetaminophen Overdose Is Associated with Dose‐Dependent Hypokalaemia: A Prospective Study of 331 Patients

Abstract:  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.