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目的探讨静脉给予负荷剂量抗癫痫药物(AED)治疗成人全面惊厥性癫痫持续状态(GCSE)的安全性。方法采用合并数据的方法收集首都医科大学宣武医院2007年1月至2010年1月和2011年6月至2012年5月进行的2项前瞻性随机对照试验(RCT)的结果,分析比较地西泮组、地西泮后续丙戊酸组和地西泮后续苯巴比妥组患者的临床数据。3组患者一线AED治疗均为静脉注射负荷剂量地西泮(0.2 mg/kg,5 mg/min)。二线AED治疗方案:地西泮组为静脉注射负荷剂量地西泮(0.2 mg/kg,5 mg/min)后继续静脉泵注维持量地西泮(4 mg/h,每3分钟增加1μg/kg),地西泮后续丙戊酸组为静脉注射负荷剂量丙戊酸[30 mg/kg,6 mg/(kg·min)]后继续静脉泵注维持量丙戊酸[1～2 mg/(kg·h)],地西泮后续苯巴比妥组为静脉注射负荷剂量苯巴比妥(20 mg/kg,50 mg/min)后继续静脉注射维持量苯巴比妥(100 mg/6 h,50 mg/min),治疗持续至癫痫发作终止后24 h,以后逐渐减量。严密监测患者用药后反应。结果 101例患者纳入研究,男性53例,女性48例;平均年龄(42±16)岁。地西泮组男性20例,女性18例,平均年龄(41±19)岁;地西泮后续丙戊酸组男性22例,女性18例,平均年龄(45±15)岁;地西泮后续苯巴比妥组男性11例,女性12例,平均年龄(41±14)岁。3组患者基线资料差异无统计学意义。地西泮组、地西泮后续丙戊酸组和地西泮后续苯巴比妥组GCSE终止率分别为63.2%(24/38)、57.5%(23/40)和60.9%(14/23),差异无统计学意义(P=0.902)。地西泮组6例(15.8%)出现不良反应,其中呼吸抑制、循环抑制和骨髓抑制分别为2、3和1例;地西泮后续丙戊酸组11例(27.5%)出现不良反应,其中不伴高血氨脑病的轻度血氨升高、轻度肝功能异常和骨髓抑制分别为8、2和1例;地西泮后续苯巴比妥组11例(47.8%)出现不良反应,其中呼吸抑制、循环抑制、轻度肝功能异常和骨髓抑制分别为3、2、5和1例。地西泮组不良反应发生率明显低于地西泮后续苯巴比妥组(P=0.033)。上述不良反应经停药与对症治疗后均可消除。结论静脉给予负荷剂量地西泮或丙戊酸或苯巴比妥治疗成人GCSE均安全有效。用药过程中应密切监测患者的不良反应,特别是对地西泮与苯巴比妥联用的患者。一旦出现不良反应,应及时停药并予以对症治疗。
Objective To investigate the safety of intravenous dose-loading antiepileptic drugs (AEDs) in the treatment of adult generalized convulsive status epilepticus (GCSE). Methods The data from two prospective randomized controlled trials (RCTs) conducted by Xuanwu Hospital of Capital Medical University from January 2007 to January 2010 and June 2011 to May 2012 were collected and analyzed. Pancreatic group, follow-up of valproic acid group of diazepam, and subsequent phenobarbital group of diazepam group. The first-line AED treatments in all three groups were intravenous diazepam (0.2 mg / kg, 5 mg / min). Second-line AED regimen: Diazepam was given intravenously at a loading dose of diazepam (0.2 mg / kg, 5 mg / min) followed by continuous intravenous bolus diazepam (4 mg / h, 1 μg / kg), followed by intravenous injection of valproic acid [30 mg / kg, 6 mg / (kg · min)] for valproic acid in the subsequent valproic acid group, followed by maintenance infusion of valproic acid [1-2 mg / (kg · h)], the phenobarbital group continued phenobarbitone (100 mg / kg, 50 mg / min) after intravenous injection of phenobarbital 6 h, 50 mg / min). The treatment lasted for 24 h after the termination of seizure, and then gradually reduced. Close monitoring of patient response after treatment. Results 101 patients were included in the study, 53 males and 48 females; mean age (42 ± 16) years. In the diazepam group, there were 20 males and 18 females, with an average age of (41 ± 19) years. In the diazepam group, there were 22 males and 18 females (mean age 45 ± 15 years). Diazepam followed Phenobarbital group of 11 males and 12 females, mean age (41 ± 14) years. There was no significant difference in baseline data between the three groups. The discontinuation rates of GCSE in the diazepam group, the subsequent valproic acid group in diazepam, and the subsequent phenobarbital group in diazepam were 63.2% (24/38), 57.5% (23/40) and 60.9% (14/23 ), The difference was not statistically significant (P = 0.902). Six patients (15.8%) in the diazepam group had adverse reactions. Among them, respiratory depression, circulating inhibition and myelosuppression were 2, 3 and 1, respectively. Eleven patients (27.5% Mild hypernatremia, mild liver dysfunction and myelosuppression were 8, 2 and 1, respectively, in those without hyperuricemic ammonia encephalopathy. Adverse reactions were found in 11 (47.8%) of diazepam in the subsequent phenobarbital group , Of which respiratory depression, circulatory depression, mild liver dysfunction and myelosuppression were 3, 2, 5 and 1 cases respectively. The incidence of adverse reactions in the diazepam group was significantly lower than that in the phenobarbital group after diazepam (P = 0.033). The adverse reactions after withdrawal and symptomatic treatment can be eliminated. Conclusion Intravenous loading with either diazepam or valproic acid or phenobarbital is safe and effective in the treatment of GCSE in adults. Patients should be closely monitored for adverse reactions during the course of their medication, especially in patients with diazepam and phenobarbital. In the event of adverse reactions, should be promptly discontinued and symptomatic treatment.