National Poisons Information Centre, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Clin Ther. 2010 Jan;32(1):60-4. doi: 10.1016/j.clinthera.2010.01.018.
Encephalopathy associated with metronidazole is rare and, in most cases, reversible following discontinuation.
We describe a case of fatal encephalopathy after treatment with high-dose intravenous metronidazole and the potential causes of the irreversibility.
A 38-year-old white woman (weight, 45 kg) received metronidazole among other medications to treat osteomyelitis for 74 days after surgery to correct a spinal neuroarthropathy. An initial dose of 500 mg IV QID was administered. After 6 weeks, the patient was discharged and the dose was changed to 1500 mg IV administered once daily (over 90 minutes) by a visiting nurse. Other treatments included teicoplanin 400 mg once daily and trimethoprimsulfamethoxazole 480 mg BID for the infection, baclofen 25 mg TID for pain associated with a congenital spinal cord lesion with paraplegia, and omeprazole 20 mg once daily for pyrosis. Ten weeks after the start of metronidazole, the patient developed somnolence and dysarthria, changing to encephalopathy with coma on admission 2 weeks later. Despite discontinuation of all medication, including metronidazole, 2 days after admission, the patient's condition appeared to be irreversible. After 8 weeks, her coma was considered permanent, mechanical ventilation was discontinued, and she died. Evaluating all medicines administered, metronidazole, with a Naranjo adverse drug reaction score of 5 (probable), was the most plausible cause of the encephalopathy. The other medicines, including baclofen, had a negative score of -3 to -2 (doubtful). All tests on infections, metabolic disorders, or interactions between medications were negative.
This patient had a fatal encephalopathy, probably associated with long-standing exposure to high plasma concentration peaks of metronidazole, due to a once-daily dose of 1500 mg IV over several weeks.
甲硝唑相关性脑病罕见，大多数情况下停药后可逆转。
我们描述了一例因高剂量静脉用甲硝唑治疗后发生的致命性脑病，并探讨其潜在的不可逆转原因。
一位 38 岁白人女性（体重 45kg），因脊柱神经关节病行手术后行骨髓炎治疗，接受甲硝唑等药物治疗 74 天。初始剂量为 500mg IV QID。6 周后，患者出院，剂量改为 1500mg IV 每日 1 次（90 分钟以上），由上门护士给药。其他治疗包括替考拉宁 400mg 每日 1 次，复方磺胺甲噁唑 480mg 每日 2 次治疗感染，巴氯芬 25mg 每日 3 次治疗与截瘫相关的脊髓病变引起的疼痛，以及奥美拉唑 20mg 每日 1 次治疗胃灼热。甲硝唑治疗 10 周后，患者出现嗜睡和构音障碍，2 周后入院时出现脑病伴昏迷。尽管停用了所有药物，包括甲硝唑，入院后 2 天，患者的病情似乎仍不可逆转。8 周后，她的昏迷被认为是永久性的，停止机械通气，患者死亡。评估所有给予的药物，甲硝唑的 Naranjo 药物不良反应评分为 5（可能），是脑病最可能的原因。其他药物，包括巴氯芬，评分为-3 到-2（可疑）。所有关于感染、代谢紊乱或药物相互作用的检测均为阴性。
本例患者因长期暴露于高浓度的甲硝唑血浆峰值，导致致命性脑病，可能与数周内 1500mg IV 每日 1 次的剂量有关。
