Department of Emergency Medicine, Queen's University, Kingston, ON, Canada.
Clin Toxicol (Phila). 2010 Oct;48(8):793-9. doi: 10.3109/15563650.2010.523829. Epub 2010 Oct 8.
The first available predictors of hepatic injury following acetaminophen (APAP) overdose are the serum APAP and aminotransferases [AT, i.e., aspartate (AST) aminotransferase or alanine (ALT) aminotransferase].
We describe the initial value, rate of change, and interrelationship between these biomarkers in patients who develop hepatotoxicity despite treatment following acute overdose. A new parameter, the APAP × AT multiplication product, is proposed for early risk stratification.
We conducted a descriptive study of individuals selected from a multicenter retrospective cohort of patients hospitalized for APAP poisoning. We selected those acute APAP overdose patients who subsequently developed AT > 1,000 IU/L. Rising serum AT values were compared to simultaneously measured (or estimated) falling serum APAP. The APAP × AT was expressed relative to initiation of acetylcysteine therapy and grouped by time to meeting hepatotoxicity criteria.
In the 94 cases studied, serum APAP concentrations were still appreciable [median 570 (interquartile range (IQR) 314-983) μmol/L] at the time of the first measured AT [211 (77-511) IU/L at 15.3 (12.1-19.2) h post-ingestion], yielding an initial APAP × AT of 99,000 (52,000-240,000) μmol × IU/L(2). Because serum AT rose rapidly (doubling time 9.5 h ) and APAP fell slowly (half-life 4.8 h), the multiplication product remained elevated during the first 12-24 h of antidotal therapy, especially among patients who developed earlier hepatotoxicity (AT > 1,000 IU/L).
The APAP × AT multiplication product, calculated at the time of presentation and after several h of antidotal therapy, holds promise as a new risk predictor following APAP overdose. It requires neither graphical interpretation nor accurate time of ingestion, two limitations to current risk stratification.
在服用对乙酰氨基酚（APAP）过量后，最早可预测肝损伤的指标是血清 APAP 和氨基转移酶[即天冬氨酸（AST）氨基转移酶或丙氨酸（ALT）氨基转移酶]。
我们描述了尽管在急性过量后进行了治疗，但仍发生肝毒性的患者中这些生物标志物的初始值、变化率和相互关系。提出了一种新的参数，即 APAP×AT 乘积，用于早期风险分层。
我们对多中心回顾性队列中住院治疗的 APAP 中毒患者进行了描述性研究。我们选择了那些随后发生 ALT>1000IU/L 的急性 APAP 过量患者。与同时测量（或估计）的血清 APAP 下降相比，比较了上升的血清 ALT 值。APAP×AT 表示相对于乙酰半胱氨酸治疗开始的时间，并按达到肝毒性标准的时间分组。
在 94 例研究病例中，在首次测量 ALT 时[摄入后 15.3（12.1-19.2）小时时为 211（77-511）IU/L]，血清 APAP 浓度仍然相当高[中位数 570（四分位距（IQR）314-983）μmol/L]，得出初始 APAP×AT 为 99000（52000-240000）μmol×IU/L（2）。由于血清 ALT 迅速升高（倍增时间 9.5 小时），APAP 缓慢下降（半衰期 4.8 小时），因此在解毒治疗的前 12-24 小时，特别是在较早发生肝毒性的患者（ALT>1000IU/L）中，乘法产物仍然升高。
APAP×AT 乘积，在出现时和解毒治疗数小时后计算，有望成为 APAP 过量后新的风险预测因子。它既不需要图形解释，也不需要摄入时间的准确性，这是目前风险分层的两个限制。
