Rocky Mountain Poison and Drug Center-Denver Health,777 Bannock Street, MC 0180, Denver, CO 80204, USA.
Pharmacotherapy. 2010 Feb;30(2):219. doi: 10.1592/phco.30.2.219.
Propylene glycol is a diluent found in many intravenous and oral drugs, including phenytoin, diazepam, and lorazepam. Propylene glycol is eliminated from the body by oxidation through alcohol dehydrogenase to form lactic acid. Under normal conditions, the body converts lactate to pyruvate and metabolizes pyruvate through the Krebs cycle. Lactic acidosis has occurred in patients, often those with renal dysfunction, who were receiving prolonged infusions of drugs that contain propylene glycol as a diluent. We describe a 50-year-old man who experienced severe lactic acidosis after receiving an accidental overdose of lorazepam, which contains propylene glycol. The patient was acutely intoxicated, with a serum ethanol concentration of 406 mg/dl. He had choked on a large piece of meat and subsequently experienced pulseless electrical activity with ventricular fibrillation cardiac arrest. He was brought to the emergency department; within 2 hours, he was admitted to the intensive care unit for initiation of the hypothermia protocol. The patient began to experience generalized tonic-clonic seizures 12 hours later, which resolved after several boluses of lorazepam. A lorazepam infusion was started; however, it was inadvertently administered at a rate of 2 mg/minute instead of the standard rate of 2 mg/hour. Ten hours later, the administration error was recognized and the infusion stopped. The patient's peak propylene glycol level was 659 mg/dl, pH 6.9, serum bicarbonate level 5 mEq/L, and lactate level 18.6 mmol/L. Fomepizole was started the next day and was continued until hospital day 3. Continuous renal replacement therapy was started and then replaced with continuous venovenous hemofiltration (CVVH) for the remainder of the hospital stay. The patient's acidosis resolved by day 3, when his propylene glycol level had decreased to 45 mg/dl. Fomepizole was discontinued, but the patient's prognosis was poor (anoxic brain injury); thus care was withdrawn and the patient died. Although the patient's outcome was death, his lactic acidosis was treated successfully with fomepizole and CVVH. Clinicians should be aware that an iatrogenic overdose of lorazepam may result in severe propylene glycol toxicity, which may be treated with fomepizole and CVVH.
丙二醇是许多静脉内和口服药物中的一种稀释剂，包括苯妥英、地西泮和劳拉西泮。丙二醇通过醇脱氢酶氧化消除，形成乳酸。在正常情况下，身体将乳酸转化为丙酮酸，并通过三羧酸循环代谢丙酮酸。丙二醇作为稀释剂的药物长时间输注后，肾功能不全的患者常发生乳酸酸中毒。我们描述了一位 50 岁的男性，在意外过量使用含有丙二醇的劳拉西泮后出现严重的乳酸酸中毒。患者急性中毒，血清乙醇浓度为 406mg/dl。他被一大块肉噎住，随后出现无脉性电活动伴心室颤动心脏骤停。他被带到急诊室；2 小时内，他被收入重症监护病房开始低温治疗。患者 12 小时后开始出现全身性强直阵挛性癫痫发作，多次给予劳拉西泮后缓解。开始输注劳拉西泮；然而，它被意外地以 2mg/min 而不是标准的 2mg/h 的速度给药。10 小时后，发现给药错误并停止输注。患者的丙二醇峰值水平为 659mg/dl，pH 值 6.9，血清碳酸氢盐水平 5mEq/L，乳酸水平 18.6mmol/L。第二天开始使用甲磺酸氟马唑，持续至入院后第 3 天。开始持续肾脏替代治疗，然后在住院期间剩余时间内更换为连续静脉-静脉血液滤过（CVVH）。患者的酸中毒在第 3 天得到缓解，此时丙二醇水平已降至 45mg/dl。停止使用甲磺酸氟马唑，但患者预后不良（缺氧性脑损伤）；因此停止治疗，患者死亡。尽管患者的结局是死亡，但他的乳酸酸中毒通过甲磺酸氟马唑和 CVVH 成功治疗。临床医生应注意，劳拉西泮的医源性过量可能导致严重的丙二醇毒性，可通过甲磺酸氟马唑和 CVVH 治疗。
