Fomepizole for the treatment of ethylene glycol poisoning
Fomepizole for the treatment of ethylene glycol poisoning
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DOI：
10.1056/nejm199903183401102
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发表时间：
1999-03-18
影响因子：
158.5
通讯作者：
Kulig, K
中科院分区：
文献类型：
--
作者：
Brent, J;McMartin, K;Kulig, K
背景乙二醇中毒可引起代谢性酸中毒和肾衰竭，并可能导致死亡。标准的治疗方法是用酒精抑制酒精脱氢酶，给予中毒剂量，并进行预防性血液透析。我们研究了一种新的乙醇脱氢酶抑制剂，在治疗乙二醇中毒的疗效。方法我们给19例乙二醇中毒（血浆乙二醇浓度，大于或等于20毫克每分升[3.2毫摩尔每升]）的患者静脉注射氟吡唑。符合特定标准的患者还接受了血液透析。持续给药，直至血浆乙二醇浓度低于20 mg/dl。酸碱状态，肾功能，fomepizole的动力学，和乙二醇代谢进行了评估，在预定的intervention.Results 15例患者最初有酸中毒（平均血清碳酸氢盐浓度，72.9 mmol/L）。酸-碱状态在开始使用福美唑治疗后数小时内趋于正常化。1例重度酸中毒患者死亡。在9例患者中，治疗期间肾功能下降;入组时，所有9例患者的血清肌酐浓度均较高，血浆乙醇酸盐浓度显著升高（≥ 97.7 mg/dl [12.9 mmol/L]）。入组时血清肌酐浓度正常的10例患者在治疗期间均未发生肾损伤;所有10例患者的血浆乙醇酸盐浓度均≥ 76.8 mg/dl（10.1 mmol/L）。肾损伤是独立的初始血浆乙二醇浓度。乙醇酸盐的血浆浓度和草酸盐（乙二醇的主要代谢物）的尿排泄在开始福美唑治疗后一致下降。氟吡唑引起的不良反应很少。结论对于乙二醇中毒患者，在中毒过程早期给予氟吡唑可以通过抑制有毒代谢物的形成来预防肾损伤。（N Engl J Med 1999; 340：832-8.）(C)1999年，马萨诸塞州医学会。
Background Ethylene glycol poisoning causes metabolic acidosis and renal failure and may cause death. The standard treatment is inhibition of alcohol dehydrogenase with ethanol, given in intoxicating doses, and adjunctive hemodialysis. We studied the efficacy of fomepizole, a new inhibitor of alcohol dehydrogenase, in the treatment of ethylene glycol poisoning.Methods We administered intravenous fomepizole to 19 patients with ethylene glycol poisoning (plasma ethylene glycol concentration, greater than or equal to 20 mg per deciliter [3.2 mmol per liter]). Patients who met specific criteria also underwent hemodialysis. Treatment was continued until plasma ethylene glycol concentrations were less than 20 mg per deciliter. Acid-base status, renal function, the kinetics of fomepizole, and ethylene glycol metabolism were assessed at predetermined intervals.Results Fifteen of the patients initially had acidosis (mean serum bicarbonate concentration, 72.9 mmol per liter). Acid-base status tended to normalize within hours after the initiation of treatment with fomepizole. One patient with extreme acidosis died. In nine patients, renal function decreased during therapy; at enrollment, all nine had high serum creatinine concentrations and markedly elevated plasma glycolate concentrations (greater than or equal to 97.7 mg per deciliter [12.9 mmol per liter]). None of the 10 patients with normal serum creatinine concentrations at enrollment had renal injury during treatment; all 10 had plasma glycolate concentrations at or below 76.8 mg per deciliter (10.1 mmol per liter). Renal injury was independent of the initial plasma ethylene glycol concentration. The plasma concentration of glycolate and the urinary excretion of oxalate, the major metabolites of ethylene glycol, uniformly fell after the initiation of fomepizole therapy. Few adverse effects were attributable to fomepizole.Conclusions In patients with ethylene glycol poisoning, fomepizole administered early in the course of intoxication prevents renal injury by inhibiting the formation of toxic metabolites. (N Engl J Med 1999; 340:832-8.) (C) 1999, Massachusetts Medical Society.