Can a serum acetaminophen concentration obtained less than 4 hours post-ingestion determine which patients do not require treatment with acetylcysteine?

CONTEXT: The interpretation of acetaminophen concentrations obtained prior to 4 hours after an acute, single overdose remains unclear. Patient care decisions in the Emergency Department could be accelerated if such concentrations could reliably exclude the need for treatment.

OBJECTIVE: To determine the agreement between a serum acetaminophen concentration obtained less than 4 hours after an acute ingestion and the subsequent 4 + hour concentration, and the predictive accuracy of early concentrations for identifying patients with potentially toxic exposures.

METHODS: A secondary analysis of patients admitted for acetaminophen poisoning at one of the 34 hospitals in eight Canadian cities from 1980 to 2005. We examined serum acetaminophen concentrations obtained less than 4 hours post-ingestion, and again 4 or more hours post-ingestion. For the diagnostic accuracy analysis, we specified a cutpoint of 100 μg/mL (662 μmol/L) obtained between 2 and 4 hours and a subsequent 4 to 20 hour acetaminophen concentration above the nomogram treatment line of 150 μg/mL (993 μmol/L).

RESULTS: Of 2454 patients identified, 879 (36%) had a subsequent acetaminophen concentration above the nomogram treatment line. The 2-4 hour concentration demonstrated a sensitivity of 0.96 [95% CI; 0.94, 0.97] and a negative likelihood ratio of 0.070 [0.048, 0.10]. Coingested opioids reduced this sensitivity to 0.91 [0.83, 0.95], and antimuscarinics to 0.86 [0.72, 0.94]. Only very low to undetectable acetaminophen concentrations prior to 4 hours reliably excluded a subsequent concentration over the treatment line.

CONCLUSIONS: Applying an acetaminophen concentration cutpoint of 100 μg/mL (662 μmol/L) at 2-4 hours after an acute ingestion as a threshold for repeat testing and/or treatment would occasionally miss potentially toxic exposures. Absorption of acetaminophen is only slightly delayed by coingested opioids or antimuscarinics. Our analysis validates the practice of not retesting when the first post-ingestion acetaminophen concentration is below the lower limit of quantification.