Unexpected Late Rise in Plasma Acetaminophen Concentrations with Change in Risk Stratification in Acute Acetaminophen Overdoses

BackgroundThe acetaminophen risk analysis nomogram is used to predict hepatotoxicity risk in acute acetaminophen overdose based on a single plasma acetaminophen concentration (PAC) measured between 4 and 24 h after ingestion. There are case reports of patients with acute overdoses of acetaminophen combination products in whom a toxic PAC occurred later after an initial non-toxic PAC at approximately 4 h.ObjectivesThe objective was to describe patients who had an initial non-toxic PAC and a subsequent toxic PAC.MethodsA poison center’s database was searched for records in which patients were administered N-acetylcysteine. Cases were included if they involved an acute overdose of an acetaminophen-containing product with at least 2 plottable PACs, the first of which was obtained at least 4 h after ingestion and was below the treatment line on the nomogram with a subsequent toxic PAC. Data were analyzed for doses, timed PACs, specific acetaminophen preparation, coingestants, activated charcoal administration, and clinical effects.ResultsTwenty patients were included. Thirteen patients ingested combination products. All patients experienced vomiting, neurologic, or cardiovascular effects at presentation or before obtaining the second PAC. Two patients developed hepatotoxicity, one of which died from the complications of acetaminophen-induced hepatotoxicity.ConclusionThe nomogram fails to predict toxicity based on a single PAC in a small subset of patients.