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 > or = 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 (2.7-4.2 mmol/l) in those without risk factors, compared with 3.0 mmol/l (2.4-3.9 mmol/l) in those with chronic excess ethanol intake (P < 0.001 by Mann Whitney test) and 2.5 mmol/l (1.9-2.8 mmol/l) in patients with other risk factors (P < 0.001). Multivariate analysis found that serum urea concentrations were not independently associated with hepatotoxicity. CONCLUSION: Low serum urea concentration is not an independent risk factor for hepatotoxicity after paracetamol overdose.

Does the patient history predict hepatotoxicity after acute paracetamol overdose?

BACKGROUND: Initial management of patients who were presented to hospital after acute paracetamol overdose depends on the suspected amount ingested and more than 12 g is potentially fatal. However, the validity of this approach has received comparatively little attention. METHODS: The present study is sought to establish whether the stated paracetamol dose might predict systemic exposure and risk of hepatotoxicity. A prospective observational study of consecutive patients presenting to the Emergency Department due to acute paracetamol overdose was performed. Serum paracetamol concentrations between 4 and 15 h post-ingestion were compared with the Rumack-Matthew '200-line' nomogram, and hepatotoxicity was defined by prothrombin time ratio >1.3 or alanine transaminase > or =1000 U/l. RESULTS: There were 987 patients, and the stated quantity of paracetamol ingested was 0-12 g in 475 (48.1%), >12 g in 349 (35.4%) and unknown in 163 (16.5%). Ingestion of >12 g was associated with paracetamol concentration above the '200-line' in 31.8% (95% CI 27.1-36.9%) vs. 3.2% (1.9-5.2%), P < 0.0001 by chi2 proportional test, and associated with hepatotoxicity in 6.9% (4.6-10.1%) vs. 1.3% (0.5-2.8%), P = 0.0001. CONCLUSION: Therefore, ingestion of >12 g predicted higher paracetamol exposure and increased risk of hepatotoxicity and supports the validity of patient history in this context.