苯巴比妥高血浓度长期治疗5例急性脑炎伴难控制和反复发作癫痫的安全性观察

Observation on safety of prolonged treatment with high blood phenobarbital concentration for acute encephalitis with refractory,repetitive partial seizures in 5 patients

目的：观察苯巴比妥高血浓度长期治疗急性脑炎伴难控制和反复发作癫痫（acuteencephalitis with refractory，repetitive partial seizures，AERRPS）患者的安全性。方法：2003年7月至2008年9月期间入院的脑炎患者，符合Sakuma于2001年提出的AERRPS诊断标准的患者入组，给药方法：200mg苯巴比妥静脉推注或肌内注射后，再以1—1．5mg／（kg·h）静脉滴注或200mg肌内注射或静脉推注，每2—4h1次，每日总量在1．2～2．4g，使苯巴比妥血浓度在24h左右达到100μg/ml。维持时间24～100d。观察苯巴比妥高血浓度治疗时患者的血压、心率及心律、呼吸、皮肤反应、意识、瞳孔、癫痫发作情况，并进行血常规检查、生化分析及长程脑电图监测。预后观察至少6个月。结果：苯巴比妥高血浓度维持期间，5例患者均处于昏迷状态，格拉斯哥昏迷评分（GCS）3～5分，脑电图监测未见爆发-抑制模式。脑干反射大部分保留。自主呼吸全部消失。3例窦性心动过速，2例室性或室上性心动过速。2例血压下降至64～86／40—55mmHg。5例患者的ALT57～385IU／L，AST38—365IU／L，γ-GT54～542IU／L，血氨升高至103．7μmoL／L，皮肤不良反应很轻。肾功能未受影响。当苯巴比妥血浓度降至50μg/ml以下时，患者意识和自主呼吸恢复，不良反应基本消退。结论：苯巴比妥高血浓度长期治疗可能致严重不良反应，因此AERRPS患者使用苯巴比妥高血浓度长期治疗期间必须使用人工辅助呼吸，严密监测，并及时处理出现的不良反应，以利于患者安全。

Objective： To observe the safety of prolonged treatment with high blood phenobarbital concentration for acute encephalitis with refractory, repetitive partial seizures （AERRPS）. Methods： Between July 2003 and September 2008 the in-patients with encephalitis, who met the Sakuma diagnostic criteria for AERRPS in 2001, were enrolled in this study. The dosage and administration were as follows ： an intravenous or intramuscular injection of phenobarbital 200 mg, followed by an IV infusion of 1 - 1.5 mg/（ kg · h） or an intramuscular or intravenous injection of 200 mg every 2 -4 hours. The total daily dosage was 1.2 - 2.4 g. The blood phenobarbital concentration reached 100μg/ml in about 24 hours. The high blood phenobarbital concentration was maintained for 24 - 100 days. During the treatment with high blood phenobarbital concentration, the patients＇ blood pressure, heart rate, heart rhythm, respiration, skin disorders, consciousness, pupils, and seizures were observed. The routine blood test and biochemical analysis were performed. Prolonged EEG monitoring was conducted. The observation on outcome was at least 6 months. Results： During the treatment with high blood phenobarbital concentration, 5 patients were in coma status, the Glasgow coma scales were scored 3 -5. No burst-depression pattern was found under an EEG monitoring. Most of brain stem reflexes remained and spontaneously breathing disappeared. Three cases of sinus tachycardia, 2 cases of ventricular tachycardia or supraventricular tachycardia occurred. Two patients＇blood pressure decreased to 64 -84/40 -55 mmHg. Five patients＇ ALT, AST, and γ-GT levels were 57 -385 IU/L, 38 - 365 IU /L, and 54- 542 IU /L, respectively. The blood ammonia level increased to 103.7 μmol/L. The severity of skin dosorders was mild. Renal function was not affected by the treatment. When blood phenobarbital concentration deerased to 〈 50 μg/ml, the patients＇ consciousness and spontaneous breathing recovered, and adverse reactions were basically disappeared. Conclusion： Prolonged treatment with high blood phenobarbital concentration may cause severe adverse reactions. Therefore, the patients with AERRPS receiving prolonged treatment with high blood phenobarbital concentration should be given artificial ventilation and close monitoring, and the adverse reactions should be managed immediately in order to benefit the patient safety.