Section of Medical Toxicology, Division of Emergency Medicine, Washington University School of Medicine, Saint Louis, MO, USA.
Department of Emergency Medicine, Naval Medical Center San Diego, San Diego, CA, USA.
Clin Toxicol (Phila). 2020 Jan;58(1):62-64. doi: 10.1080/15563650.2019.1609684. Epub 2019 May 3.
Several reports describe high anion gap metabolic acidosis with 5-oxoproline (5-OP) after acetaminophen exposure, including therapeutic use of acetaminophen. The mechanism may involve disordered glutathione metabolism. It is unknown whether acute acetaminophen overdose consistently causes elevations in 5-oxoproline concentration. We enrolled 23 consecutive adult and adolescent patients with measureable plasma APAP after acute APAP overdose. We used plasma left over in the laboratory after blood tests obtained in clinical care of the patients. We measured plasma [5-OP] by GC/MS. We compared the [5-OP] to laboratory results obtained in the care of these patients to search for correlations. The study had IRB approval. Eighteen patients had non-detectable or normal (<100 μmol/L) 5-oxoproline concentrations. Six more patients had concentrations between 100 μmol/L and 300 μmol/L. There was no significant correlation of 5-OP with APAP, AST, ALT, creatinine, anion gap, INR, or total bilirubin. Limitations of the study include small sample size and treatment with IV N-acetylcysteine for all patients with APAP concentrations above the 150 line of the Rumack Matthew nomogram or with hepatotoxicity. We believe that inherited enzyme deficiencies more likely explain cases of 5-oxoprolinemia. Acetaminophen overdose generally results in normal 5-oxoproline concentrations with some patients having slightly elevated 5-oxoproline concentrations.
几项报告描述了在接触对乙酰氨基酚后出现高阴离子间隙代谢性酸中毒和 5-氧脯氨酸（5-OP），包括对乙酰氨基酚的治疗用途。其机制可能涉及谷胱甘肽代谢紊乱。目前尚不清楚急性对乙酰氨基酚过量是否会持续导致 5-氧脯氨酸浓度升高。我们招募了 23 例连续的急性对乙酰氨基酚过量后可测量血浆对乙酰氨基酚的成年和青少年患者。我们使用了患者临床治疗中血液检测后实验室剩余的血浆。我们通过 GC/MS 测量了血浆 [5-OP]。我们将 [5-OP] 与这些患者护理中获得的实验室结果进行了比较，以寻找相关性。该研究得到了 IRB 的批准。18 例患者的 5-氧脯氨酸浓度低于检测值或正常（<100 μmol/L）。另外 6 例患者的浓度在 100 μmol/L 至 300 μmol/L 之间。5-OP 与对乙酰氨基酚、AST、ALT、肌酐、阴离子间隙、INR 或总胆红素均无显著相关性。该研究的局限性包括样本量小，以及所有对乙酰氨基酚浓度高于 Rumack-Matthew 列线图 150 线或具有肝毒性的患者均接受 IV N-乙酰半胱氨酸治疗。我们认为，遗传酶缺乏更可能解释 5-氧脯氨酸血症的病例。对乙酰氨基酚过量通常会导致正常的 5-氧脯氨酸浓度，有些患者的 5-氧脯氨酸浓度略有升高。
