Link Stephanie L, Rampon Garrett, Osmon Stephen, Scalzo Anthony J, Rumack Barry H
Saint Louis University Pulmonary and Critical Care Medicine, St. Louis, MO, USA.
University of Kansas Pulmonary and Critical Care Medicine, Kansas City, MO, USA.
Clin Toxicol (Phila). 2022 Apr;60(4):472-477. doi: 10.1080/15563650.2021.1996591. Epub 2021 Oct 28.
Acetaminophen (N-acetyl-para-aminophenol or APAP) is the leading cause of acute liver failure worldwide. Standard therapy for APAP overdose is with IV N-acetylcysteine (NAC). However, overdose patients treated with NAC can still incur hepatotoxicity in some circumstances. Fomepizole has proven safety in methanol and ethylene glycol poisoning and is a potent CYP2E1 and c-Jun-N-terminal Kinase (JNK) inhibitor that is effective even in the metabolic phase.
We present a prospective case series of 14 consecutive, high-risk patients who had elevated APAP levels after overdose who were treated with fomepizole as an adjunct to standard IV-NAC. The attending toxicologist utilized clinical judgement to determine the use of fomepizole, especially if APAP levels persisted due to altered half-life or risk factors for toxicity.
There were no unfavorable outcomes in any patient, which were better than expected.
This case series has demonstrated the safety of fomepizole in high-risk APAP overdose. The efficacy of fomepizole needs to be further elucidated through controlled clinical trials on a larger scale. In massive APAP overdoses, fomepizole should be considered as an adjunct due to the known failure rate of NAC and the safety profile of fomepizole.
对乙酰氨基酚（N - 乙酰 - 对氨基酚或APAP）是全球急性肝衰竭的主要病因。APAP过量的标准治疗方法是静脉注射N - 乙酰半胱氨酸（NAC）。然而，在某些情况下，接受NAC治疗的过量患者仍可能发生肝毒性。甲吡唑已被证明在甲醇和乙二醇中毒治疗中具有安全性，并且是一种有效的CYP2E1和c - Jun氨基末端激酶（JNK）抑制剂，即使在代谢阶段也有效。
我们报告了一个前瞻性病例系列，连续14例高危患者在过量服用APAP后APAP水平升高，接受甲吡唑作为标准静脉注射NAC的辅助治疗。主治毒理学家利用临床判断来确定甲吡唑的使用，特别是当APAP水平因半衰期改变或毒性风险因素而持续升高时。
所有患者均未出现不良后果，情况好于预期。
该病例系列证明了甲吡唑在高危APAP过量治疗中的安全性。甲吡唑的疗效需要通过更大规模的对照临床试验进一步阐明。在大量APAP过量的情况下，鉴于已知的NAC失败率和甲吡唑的安全性，应考虑将甲吡唑作为辅助治疗药物。
