The value of plasma acetaminophen half-life in antidote-treated acetaminophen overdosage

A plasma acetaminophen (INN, paracetamol) half-life of more than 4 hours has been correlated with hepatotoxicity in acetaminophen overdosing not treated with an antidote. Acetaminophen half-life has not been studied in patients receiving the antidote N -acetylcysteine.

Prospectively, 112 patients with acetaminophen overdosage all treated with intravenous N -acetylcysteine were studied. A minimum of 2 plasma acetaminophen values >20 micromol/L were available for calculation of acetaminophen half-life, assuming first-order kinetics.

Overall, the median acetaminophen half-life was 5.4 hours (range, 0.8-119.7 hours). Forty-eight patients with no or little hepatotoxicity (ALT <1000 U/L), 43 patients with hepatotoxicity without encephalopathy, and 21 patients with hepatotoxicity and encephalopathy had acetaminophen half-lives of 3.0 hours (range, 0.8-10.0 hours), 6.4 hours (range, 1.3-19.0 hours), and 18.4 hours (range, 4.6-119.7 hours), respectively (P <.001). An acetaminophen half-life >4 hours was observed in 71 patients, and 56 of those (79%) had hepatotoxicity (ALT >1000 U/L or coma). Thirty-three of 41 patients (81%) with an acetaminophen half-life <4 hours had no hepatotoxicity. A receiver operating characteristic curve analysis showed that an acetaminophen half-life of 5.5 hours provided better discrimination; hepatotoxicity was therefore present in 49 of 54 patients with an acetaminophen half-life >5.5 hours (positive predictive value, 91%) and in 15 of 58 patients with a half-life below this limit (negative predictive value, 74%) despite treatment with N -acetylcysteine.

Acetaminophen half-life correlates well with the degree of liver damage in patients treated with the antidote N-acetylcysteine. Longer half-lives reflect a greater toxic effect on the liver.