Department of Emergency Medicine, Queen's University, Kingston, ON, Canada.
Clin Toxicol (Phila). 2010 Oct;48(8):787-92. doi: 10.3109/15563650.2010.523828.
Rising aminotransferases (ATs) [either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) are one of the first signs of hepatotoxicity following acetaminophen (APAP)] overdose (OD). However, the timing and speed of such rises are not well characterized, hampering early risk prediction.
To describe the kinetics of AT release in acute APAP OD patients who develop hepatotoxicity despite treatment.
A descriptive study of acute APAP OD patients with peak AT > 1,000 IU/L taken from the derivation subset of the Canadian Acetaminophen Overdose Study (CAOS), a large, multicenter retrospective cohort of patients hospitalized for APAP poisoning.
Of 2,488 hospital admissions for acute APAP OD, 94 met inclusion criteria. Treatment with acetylcysteine, mostly intravenously, was begun in all cases within 24 h of ingestion. The initial AT concentration was already elevated in most patients at presentation [median 211 (IQR 77-511) IU/L obtained at 15.3 (12.1-19.2) h postingestion], and exceeded 100 IU/L in almost all patients within 24 h of ingestion. Serum AT concentrations rose rapidly [doubling time 9.5 h (95% CI: 8.7-10.4 h)], especially in patients who developed AT > 1,000 IU/L within 48 h of ingestion. Coagulopathy was worse in these patients and in those with an AT > 250 IU/L during the first 12 h of treatment with acetylcysteine.
An abnormal and rapidly doubling AT at presentation is more typical in severely poisoned patients, as judged by the effects on clotting. These data suggest that risk prediction instruments may be improved by incorporating both the serum AT concentration at initiation of antidotal therapy and its rate of change. Further studies using such an approach are warranted.
天冬氨酸转氨酶（AST）或丙氨酸转氨酶（ALT）升高是乙酰氨基酚（APAP）过量（OD）后肝毒性的最早迹象之一。然而，这种升高的时间和速度尚未得到很好的描述，这阻碍了早期风险预测。
描述尽管接受治疗但仍发生肝毒性的急性 APAP OD 患者中 AST 释放的动力学。
对来自加拿大乙酰氨基酚过量研究（CAOS）推导子集中的急性 APAP OD 患者进行描述性研究，这是一项大型多中心回顾性患者队列研究，研究对象为因 APAP 中毒住院的患者。
在 2488 例因急性 APAP OD 住院的患者中，有 94 例符合纳入标准。在摄入后 24 小时内，所有患者均开始接受乙酰半胱氨酸治疗，主要是静脉内给药。大多数患者在就诊时的初始 AST 浓度已经升高[摄入后 15.3（12.1-19.2）小时获得的中位数为 211（IQR 77-511）IU/L]，几乎所有患者在摄入后 24 小时内 AST 浓度均超过 100 IU/L。血清 AST 浓度迅速升高[倍增时间为 9.5 小时（95%CI：8.7-10.4 小时）]，尤其是在摄入后 48 小时内 AST 超过 1000 IU/L 的患者中。这些患者的凝血功能障碍更差，在乙酰半胱氨酸治疗的前 12 小时内 AST 超过 250 IU/L 的患者中也存在这种情况。
根据凝血功能的影响，就诊时出现异常且迅速倍增的 AST 更常见于重度中毒患者。这些数据表明，通过将解毒治疗开始时的血清 AST 浓度及其变化率纳入风险预测工具，可能会改善风险预测工具。需要进一步使用这种方法的研究。
