Investigation of Indicators of N-acetylcysteine Administration in Patients with Acetaminophen Overdose

Abstract

Acetaminophen (APAP) is a major drug that causes acute poisoning, including severe liver damage. In cases of overdose, the serum APAP concentration is used as an indicator for administering the antidote N-acetylcysteine (NAC). However, measuring APAP levels in clinical settings is often challenging; a threshold of 7,500 mg or 150 mg/kg is commonly used for NAC administration. This guideline was developed for Westerners, and its applicability to Japanese individuals is unclear. This study aimed to explore factors other than serum APAP concentration that could quickly lead to NAC administration. We analyzed patients (n = 25) who visited the emergency department of Ogaki Municipal Hospital and had their APAP levels measured between April 2014 and March 2024. Patients were divided into NAC-recommended and non-recommended groups based on the NAC administration line in the Rumack–Matthew nomogram, and APAP intake amounts were compared. The cutoff value was calculated using the receiver operating characteristic (ROC) curve. The median APAP intake (interquartile range) was 9,500 (7,380 – 14,400) mg in the NAC-recommended group and 4,000 (3,925 – 6,250) mg in the non-recommended group (P = 0.045). The calculated cutoff value using the intake curve was 5,200 mg (120 mg/kg). The area under the ROC curve for APAP intake was 0.792, indicating moderate accuracy in event detection (95％ confidence interval: 0.583 – 1), with sensitivity and specificity for detecting NAC administration at 91.7％ and 70.0％, respectively. This study suggests that Japanese patients who ingest more than 5,200 mg or 120 mg/kg of APAP may qualify for NAC administration.