不同类型抗癫痫药物对开颅手术患者术后早期高氨血症发病率的影响

Effect of perioperative use of different types of antiepileptic drugs on the incidence of early postoperative hyperammonia in patients who underwent craniotomy

目的:评价开颅手术患者应用左乙拉西坦、丙戊酸钠和卡马西平等3种不同抗癫痫药(AEDs)诱发高氨血症(AHA)的发生率、发作程度,并分析患者发生AHA的危险因素。方法:纳入2014年4月至2018年9月间在某院神经外科进行开颅手术的108患者,并将其随机分为左乙拉西坦组(n=36)、丙戊酸钠组(n=36)与卡马西平组(n=36)。3组患者术后分别口服左乙拉西坦片、丙戊酸钠片与卡马西平片进行癫痫预防治疗,在术前,手术当天,术后第1,3,7天检测并比较3组患者的血氨浓度、肝功能和凝血指标,评价3组患者术后AHA发生率、血氨浓度、血氨变化趋势及AEDs对患者肝功能和凝血功能的影响。根据术后患者是否发生AHA,将患者分为术后AHA组(n=70)与术后血氨正常组(n=38),比较2组患者的临床特征,评价患者发生AHA的危险因素。结果:左乙拉西坦组、丙戊酸组与卡马西平组分别有24(66.7%)例、29(80.6%)例及17(47.2%)例患者发生AHA,丙戊酸组患者AHA发生率显著高于卡马西平组(χ^2=8.669,P=0.003)。丙戊酸钠组患者术后第3天和第7天血氨浓度及术后血氨的平均浓度均显著高于卡马西平组患者(P=0.023,<0.001,0.028)。术后第7天丙戊酸组患者ALT指标显著低于左乙拉西坦组与卡马西平组(均P<0.001)。影响患者术后发生AHA的危险因素包括:较低的年龄(t=2.061,P=0.042)与较高的术前血氨浓度(t=7.986,P<0.001)。AHA组患者术后总胆红素(t=3.788,P<0.001)、直接胆红素(t=3.329,P=0.001)和血清白蛋白(t=11.624,P<0.001)较术前显著降低,血浆凝血酶原时间显著延长(t=4.109,P<0.001)。而衡量急性肝炎的指标丙氨酸转氨酶没有显著变化(t=0.956,P=0.341)。结论:卡马西平对患者术后血氨浓度影响较小,是开颅手术患者的首选AEDs药物,而丙戊酸钠更适合肝脏氨基转移酶异常的患者。

OBJECTIVE To evaluate the incidence and severity of hyperammonemia(AHA) induced by three different antiepileptic drugs(AEDs) including levetiracetam, sodium valproate and carbamazepine in patients undergoing craniotomy, to analyze the risk factors for AHA in patients. METHODS 108 patients who underwent craniotomy in the Department of Neurosurgery of a hospital between April 2014 and September 2018 were included and randomly divided into levetiracetam group(n=36), sodium valproate group(n=36) and carbamazepine group(n=36).The patients in the three groups were treated with Levetiracetam Tablets, Sodium Valproate Tablets and Carbamazepine Tablets for epilepsy prevention. The serum ammonia concentration, liver function and coagulation indexes were measured and compared before operation on the day of operation, and on the 1 st, 3 rd and 7 th day after operation. The incidence of AHA, blood ammonia concentration, blood ammonia change trend and the effect of AEDs on liver function and coagulation function were evaluated. According to the occurrence of AHA, the patients were divided into AHA group(n=70) and normal blood ammonia group(n=38). The clinical characteristics of the two groups were compared, and the risk factors of AHA were evaluated. RESULTS AHA occurred in 24(66.7%), 29(80.6%) and 17(47.2%) patients in levetiracetam group, valproic acid group and carbamazepine group, respectively. The incidence of AHA in valproic acid group was significantly higher than that in the carbamazepine group(χ^2=8.669, P=0.003). The serum ammonia concentration on the 3 rd and 7 th day and the average serum ammonia concentration after operation in the sodium valproate group were significantly higher than those in the carbamazepine group(P=0.023,<0.001, 0.028). The ALT index of sodium valproate group was significantly lower than that of levetiracetam group and carbamazepine group on the 7 th day after operation(all P<0.001). The risk factors of postoperative AHA were lower age(t=2.061, P=0.042) and higher preoperative blood ammonia concentration(t=7.986, P<0.001). total bilirubin(t=3.788, P<0.001), direct bilirubin(t=3.329, P=0.001) and albumin(t=11.624, P<0.001) were significantly decreased and prothrombin time was significantly prolonged in AHA group(t=4.109, P<0.001). However, alanine aminotransferase, a measure of acute hepatitis, did not change significantly(t=0.956, P=0.341). CONCLUSION Carbamazepine is the first choice of AEDs for patients undergoing craniotomy, and sodium valproate is more suitable for patients with abnormal liver aminotransferase.