PDF(Pubmed)
Abstract：
BACKGROUND: There are only six past reports of super-refractory status epilepticus induced by spinal anesthesia. None of those patients have died. Only < 15 mg of bupivacaine was administered to all six of them and to our case. Pathophysiology ensuing such cases remains unclear.
METHODS: A 27 year old gravida 2, para 1, mother at 37 weeks of gestation came to the operating theater for an elective cesarean section. She had no significant medical history other than controlled hypothyroidism and one episode of food allergy. Her current pregnancy was uneventful. Her American Society of Anesthesiologists (ASA) grade was 2. She underwent spinal anesthesia and adequate anesthesia was achieved. After 5-7 min she developed a progressive myoclonus. After delivery of a healthy baby, she developed generalized tonic clonic seizures that continued despite the induction of general anesthesia. She had rhabdomyolysis, one brief cardiac arrest and resuscitation, followed by stress cardiomyopathy and central hyperthermia. She died on day four. There were no significant macroscopic or histopathological changes in her brain that explain her super refractory status epilepticus. Heavy bupivacaine samples of the same batch used for this patient were analyzed by two specialized laboratories. National Medicines Quality Assurance Laboratory of Sri Lanka reported that samples failed to confirm United States Pharmacopeia (USP) dextrose specifications and passed other tests. Subsequently, Therapeutic Goods Administration of Australia reported that the drug passed all standard USP quality tests applied to it. Nonetheless, they have detected an unidentified impurity in the medicine.
CONCLUSIONS: After reviewing relevant literature, we believe that direct neurotoxicity by bupivacaine is the most probable cause of super-refractory status epilepticus. Super-refractory status epilepticus would have led to her other complications and death. We discuss probable patient factors that would have made her susceptible to neurotoxicity. The impurity in the drug detected by one laboratory also would have contributed to her status epilepticus. We propose several possible mechanisms that would have led to status epilepticus and her death. We discuss the factors that shall guide investigators on future such cases. We suggest ways to minimize similar future incidents. This is an idiosyncratic reaction as well.
METHODS: A 27 year old gravida 2, para 1, mother at 37 weeks of gestation came to the operating theater for an elective cesarean section. She had no significant medical history other than controlled hypothyroidism and one episode of food allergy. Her current pregnancy was uneventful. Her American Society of Anesthesiologists (ASA) grade was 2. She underwent spinal anesthesia and adequate anesthesia was achieved. After 5-7 min she developed a progressive myoclonus. After delivery of a healthy baby, she developed generalized tonic clonic seizures that continued despite the induction of general anesthesia. She had rhabdomyolysis, one brief cardiac arrest and resuscitation, followed by stress cardiomyopathy and central hyperthermia. She died on day four. There were no significant macroscopic or histopathological changes in her brain that explain her super refractory status epilepticus. Heavy bupivacaine samples of the same batch used for this patient were analyzed by two specialized laboratories. National Medicines Quality Assurance Laboratory of Sri Lanka reported that samples failed to confirm United States Pharmacopeia (USP) dextrose specifications and passed other tests. Subsequently, Therapeutic Goods Administration of Australia reported that the drug passed all standard USP quality tests applied to it. Nonetheless, they have detected an unidentified impurity in the medicine.
CONCLUSIONS: After reviewing relevant literature, we believe that direct neurotoxicity by bupivacaine is the most probable cause of super-refractory status epilepticus. Super-refractory status epilepticus would have led to her other complications and death. We discuss probable patient factors that would have made her susceptible to neurotoxicity. The impurity in the drug detected by one laboratory also would have contributed to her status epilepticus. We propose several possible mechanisms that would have led to status epilepticus and her death. We discuss the factors that shall guide investigators on future such cases. We suggest ways to minimize similar future incidents. This is an idiosyncratic reaction as well.
摘要：
背景：过去只有六篇关于脊髓麻醉诱发超难治性癫痫持续状态的报道。这些病人都没有死亡。仅对所有六个患者和我们的病例施用<15mg布比卡因。此类病例的病理生理学仍不清楚。
方法：一位27岁的孕妇2，第1段，母亲在妊娠37周时来到手术室进行选择性剖宫产。除控制的甲状腺功能减退症和一次食物过敏发作外，她没有明显的病史。她目前的怀孕很顺利。她的美国麻醉医师协会（ASA）成绩为2。她接受了脊髓麻醉，并获得了足够的麻醉。5-7分钟后，她出现了进行性肌阵挛症。一个健康的婴儿出生后，她出现了全身性强直阵挛性癫痫发作，尽管进行了全身麻醉诱导，但仍持续。她有横纹肌溶解症,一次短暂的心脏骤停和复苏，其次是应激性心肌病和中枢高热。她在第四天去世了。她的大脑没有明显的宏观或组织病理学变化，可以解释她的超难治性癫痫持续状态。由两个专门实验室分析了用于该患者的同一批次的重型布比卡因样品。斯里兰卡国家药品质量保证实验室报告说，样品未能确认美国药典（USP）葡萄糖规格，并通过了其他测试。随后，澳大利亚治疗用品管理局报告说，该药物通过了适用于它的所有标准USP质量测试。尽管如此，他们在药物中发现了一种身份不明的杂质。
结论：在查阅相关文献后，我们认为布比卡因的直接神经毒性是导致超难治性癫痫持续状态的最可能原因.超难治性癫痫持续状态会导致她的其他并发症和死亡。我们讨论了可能使她容易受到神经毒性的患者因素。一个实验室检测到的药物中的杂质也会导致她的癫痫持续状态。我们提出了几种可能导致癫痫持续状态及其死亡的机制。我们讨论了将指导调查人员处理未来此类案件的因素。我们提出了减少未来类似事件的方法。这也是一种特殊的反应。
方法：一位27岁的孕妇2，第1段，母亲在妊娠37周时来到手术室进行选择性剖宫产。除控制的甲状腺功能减退症和一次食物过敏发作外，她没有明显的病史。她目前的怀孕很顺利。她的美国麻醉医师协会（ASA）成绩为2。她接受了脊髓麻醉，并获得了足够的麻醉。5-7分钟后，她出现了进行性肌阵挛症。一个健康的婴儿出生后，她出现了全身性强直阵挛性癫痫发作，尽管进行了全身麻醉诱导，但仍持续。她有横纹肌溶解症,一次短暂的心脏骤停和复苏，其次是应激性心肌病和中枢高热。她在第四天去世了。她的大脑没有明显的宏观或组织病理学变化，可以解释她的超难治性癫痫持续状态。由两个专门实验室分析了用于该患者的同一批次的重型布比卡因样品。斯里兰卡国家药品质量保证实验室报告说，样品未能确认美国药典（USP）葡萄糖规格，并通过了其他测试。随后，澳大利亚治疗用品管理局报告说，该药物通过了适用于它的所有标准USP质量测试。尽管如此，他们在药物中发现了一种身份不明的杂质。
结论：在查阅相关文献后，我们认为布比卡因的直接神经毒性是导致超难治性癫痫持续状态的最可能原因.超难治性癫痫持续状态会导致她的其他并发症和死亡。我们讨论了可能使她容易受到神经毒性的患者因素。一个实验室检测到的药物中的杂质也会导致她的癫痫持续状态。我们提出了几种可能导致癫痫持续状态及其死亡的机制。我们讨论了将指导调查人员处理未来此类案件的因素。我们提出了减少未来类似事件的方法。这也是一种特殊的反应。
