Serum urea concentration and the risk of hepatotoxicity after paracetamol overdose

Background: Glutathione depletion increases the incidence of toxicity after paracetamol overdose. Risk factors for toxicity, including chronic ethanol excess and malnutrition, are associated with low serum urea concentrations. Therefore, we hypothesized that low serum urea concentration might itself be predictive of hepatotoxicity in patients that present to hospital after paracetamol overdose. Methods: The present study prospectively collected data from 1085 patients attending the Emergency Department after paracetamol overdose. Hepatotoxicity was predefined by prothrombin time ratio 1.3 or alanine transaminase 1000 U/l. Serum urea concentrations were considered in a stepwise multiple regression analysis that included paracetamol dose, co-ingestion of ethanol and other drugs, serum concentration,N-acetylcysteine, interval to treatment, vomiting and serum creatinine. Results: Median (IQR) serum urea concentrations were 3.3 mmol/l (2.74.2 mmol/l) in those without risk factors, compared with 3.0 mmol/l (2.43.9 mmol/l) in those with chronic excess ethanol intake (P < 0.001 by Mann Whitney test) and 2.5 mmol/l (1.92.8 mmol/l) in patients with other risk factors (P < 0.001). Multivariate analysis found that serum urea concentrations were not independently associated with hepatotoxicity. Conclusions: Low serum urea concentration is not an independent risk factor for hepatotoxicity after paracetamol overdose.