Department of Emergency Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
The Toxikon Consortium, Department of Emergency Medicine, University of Illinois at Chicago, Chicago, IL, USA.
Clin Toxicol (Phila). 2022 Sep;60(9):1006-1011. doi: 10.1080/15563650.2022.2070071. Epub 2022 May 5.
Fomepizole inhibits formation of toxic acetaminophen (APAP) metabolites and may prevent or reverse mitochondrial toxicity. Given these mechanisms, it may be beneficial in patients with severe APAP toxicity. Current patterns of use for this indication are not well-studied.
This is a secondary analysis of patients enrolled in the Toxicology Investigators Consortium (ToxIC) database from January 2015 to July 2020. We queried cases in which APAP was listed as an ingested agent and fomepizole was also administered. We excluded cases in which APAP was not the primary agent, N-acetylcysteine (NAC) was not administered, or fomepizole was explicitly administered for another indication. Additionally, we sent a survey to each ToxIC site that administered fomepizole for APAP toxicity to better understand when, why, and how they were using it for this indication.
Twenty-five cases of fomepizole administration following an APAP ingestion met our inclusion criteria. There were one to four cases per year between 2015 and 2019 and eight cases in 2020. Seventeen of 25 (68%) cases were for a known acute ingestion. Eighteen of 25 (72%) patients developed hepatotoxicity (AST or ALT > 1000 IU/L) and 10 of 25 (40%) developed coagulopathy (PT > 15s). This was an ill patient population, with 18 of 25 (72%) developing metabolic acidosis (pH <7.20), 12 of 25 (48%) were intubated, 9 of 25 (36%) receiving vasopressors, and 6 of 25 (24%) receiving continuous renal replacement therapy. Overall, mortality was 24%.
The use of fomepizole is increasing in frequency in a small subset of critically ill and acutely APAP-poisoned patients.
非那西丁抑制有毒的对乙酰氨基酚（APAP）代谢物的形成，并可能预防或逆转线粒体毒性。鉴于这些机制，它可能对严重 APAP 毒性的患者有益。目前针对该适应症的使用模式尚未得到很好的研究。
这是对 2015 年 1 月至 2020 年 7 月期间入组毒理学家联合会（ToxIC）数据库的患者进行的二次分析。我们查询了 APAP 列为摄入药物且同时给予非那西丁的病例。我们排除了 APAP 不是主要药物、未给予 N-乙酰半胱氨酸（NAC）或明确因其他适应症给予非那西丁的病例。此外，我们向每个给予非那西丁治疗 APAP 毒性的 ToxIC 站点发送了一份调查，以更好地了解他们何时、为何以及如何将其用于该适应症。
25 例 APAP 摄入后给予非那西丁的病例符合我们的纳入标准。2015 年至 2019 年期间每年有 1 至 4 例，2020 年有 8 例。25 例中的 17 例（68%）为已知急性摄入。18 例（72%）患者出现肝毒性（AST 或 ALT>1000 IU/L），10 例（40%）出现凝血功能障碍（PT>15s）。这是一组病情较重的患者，25 例中有 18 例（72%）发生代谢性酸中毒（pH<7.20），12 例（48%）需要插管，9 例（36%）需要血管加压素，6 例（24%）需要持续肾脏替代治疗。总的来说，死亡率为 24%。
在少数危重症和急性 APAP 中毒患者中，非那西丁的使用频率正在增加。
