Efficacy and safety analysis of sodium valproate for epileptic seizure prevention during the perioperative period in neurosurgical patients
10.3760/cma.j.cn114015-20220310-00200
- VernacularTitle:神经外科围手术期患者应用丙戊酸钠预防癫痫的有效性和安全性分析
- Author:
Chen LIU
1
;
Hao ZHAO
;
Ning WANG
;
Jingjie LI
;
Yanqi CHU
;
Suying YAN
Author Information
1. 首都医科大学宣武医院药学部，国家神经疾病医学中心，国家老年疾病临床医学研究中心，北京 100053
- Publication Type:Journal Article
- Keywords:
Valproic acid;
Neurosurgical procedures;
Perioperative medicine;
Safety;
Epilepsy
- From:
Adverse Drug Reactions Journal
2022;24(8):404-409
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the efficacy and safety of sodium valproate in the prevention of epileptic seizure during the perioperative period in neurosurgical patients.Methods:The medical records in patients, who were treated with sodium valproate during perioperative period in Neurosurgery Department of Xuanwu Hospital, Capital Medical University from March to June 2021, were collected and data including the basic information in patients, use of sodium valproate and the combination drugs, valproic acid blood concentration (reference range: 50-100 mg/L), and adverse reactions was recorded. The effects of the first intravenous dose of valproate and the combination drugs on the blood concentration of valproic acid and the efficacy and safety of sodium valproate in preventing epileptic seizure were analyzed.Results:A total of 107 patients were enrolled, including 48 males and 59 females, aged (54±13) years. The median total dose of sodium valproate administered intravenously was 5 600 mg (range: 800-17 600 mg), the median duration of intravenous therapy was 3 days (range: 1-10 days), and the blood concentration of valproic acid was (53.5±19.6) mg/L. The median hospital stay was 16 days (range: 6-49 days) and no patients had seizures during hospitalization. The first intravenous dose of sodium valproate was insufficient in 38.3% (41/107) of the patients and the valproic acid blood concentration and its compliance rate to the reference range in these patients were significantly lower than those in the patients with appropriate first intravenous dose [(43±21)mg/L vs. (60±16)mg/L, P<0.001; 22.0%(9/41) vs. 78.5% (51/65), P<0.001]. Carbapenems was used for 1 day in combination with sodium valproate in 6 patients, 3 of whom had the blood concentration that was lower than the reference range. However the difference in the blood concentration of valproic acid between patients with and without carbapenems use was not statistically significant[(43±26) mg/L vs. (54±19) mg/L, P=0.187]. In the 107 patients, a total of 60 adverse events occurred in 49 patients (45.8%), including hyperammonemia in 33 patients (30.8%), elevated activated partial thromboplastin time in 12 patients (11.7%), hypofibrinogenemia in 3 patients (2.9%), hyponatremia in 6 patients (5.6%), liver injury in 4 patients (3.7%), and kidney injury and thrombocytopenia in 1 patient (0.9%) each. The severity of adverse reactions was grade 1, 3, and 4 in 39, 9, and 1 patient, respectively. The incidence of serious adverse reactions of grade 3 and above was 9.3% (10/107). Of the 10 patients with serious adverse events, 7 had hyperammonemic encephalopathy, 2 had liver injury, and 1 had hyperammonemic encephalopathy and liver injury. One patient who developed grade 3 adverse reaction died due to primary disease (brain tumor with stroke). Conclusions:The use of sodium valproate during perioperative period in neurosurgery patients to prevent epileptic seizures is safe and effective in general, but adverse reactions such as elevated blood ammonia, liver injury, and coagulation dysfunction may occur. Insufficient first intravenous dose and concomitant use of carbapenems may affect the blood concentration of valproic acid, which should be paid attention to.
