Wat Ricky, Mammi Marco, Paredes Jose, Haines Jordan, Alasmari Mohammed, Liew Aaron, Lu Victor M, Arnaout Omar, Smith Timothy R, Gormley William B, Aglio Linda S, Mekary Rania A, Zaidi Hasan
Department of Pharmaceutical Business and Administrative Sciences, School of Pharmacy, MCPHS University, Boston, Massachusetts, USA.
Department of Neurosurgery, Computational Neuroscience Outcomes Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
World Neurosurg. 2019 Feb;122:433-440. doi: 10.1016/j.wneu.2018.11.076. Epub 2018 Nov 20.
The use of antiepileptic drugs (AEDs) to prevent early posttraumatic seizure (PTS) for patients with severe traumatic brain injury (TBI) is currently recommended, although published studies present contradictory results concerning the protective effect of AEDs.
The purpose of this study was to quantify the association between the use of prophylactic AEDs, particularly of the 4 main drugs of interest (phenytoin, levetiracetam, valproate, or carbamazepine) versus placebo or no treatment, and risk of early seizures after TBI.
A comprehensive search was performed on PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. The selection criteria were English written randomized controlled trials (RCTs) and observational studies, comparing AEDs with placebo or no treatment, for prevention of early PTS. Random-effects models were used to calculate pooled relative risk (RR). Subgroup analysis and meta-regression were used to assess heterogeneity sources.
This research included 3 RCTs (750 patients) and 6 observational studies (3362 patients), analyzing the efficacy of phenytoin, levetiracetam, and valproate. The pooled RR estimate across RCTs trended toward a protective effect (RR, 0.58; 95% confidence interval, 0.20-1.72; I = 59.5%); a significant protective association was shown when pooling the results across all 6 observational studies (RR, 0.42; 95% confidence interval, 0.29-0.62; I = 0%). When stratifying the observational studies by drug, no significant difference was observed (P interaction = 0.73). Begg and Egger tests indicated no publication bias among observational studies.
Only modest evidence suggested effectiveness of AEDs as prophylaxis of early PTS. Phenytoin was the most studied drug; more prospective studies are needed to assess the efficacy of other AEDs.
目前推荐使用抗癫痫药物（AEDs）预防重度创伤性脑损伤（TBI）患者早期创伤后癫痫（PTS），尽管已发表的研究关于AEDs的保护作用呈现出相互矛盾的结果。
本研究的目的是量化预防性使用AEDs，尤其是4种主要相关药物（苯妥英钠、左乙拉西坦、丙戊酸盐或卡马西平）与安慰剂或不治疗相比，与TBI后早期癫痫发作风险之间的关联。
在PubMed、Embase、Cochrane图书馆和ClinicalTrials.gov上进行了全面检索。选择标准为英文撰写的随机对照试验（RCTs）和观察性研究，比较AEDs与安慰剂或不治疗，用于预防早期PTS。采用随机效应模型计算合并相对风险（RR）。亚组分析和meta回归用于评估异质性来源。
本研究纳入3项RCTs（750例患者）和6项观察性研究（3362例患者），分析苯妥英钠、左乙拉西坦和丙戊酸盐的疗效。RCTs的合并RR估计值有显示出保护作用的趋势（RR，0.58；95%置信区间，0.20 - 1.72；I² = 59.5%）；汇总所有6项观察性研究的结果时显示出显著的保护关联（RR，0.42；95%置信区间，0.29 - 0.62；I² = 0%）。按药物对观察性研究进行分层时，未观察到显著差异（P交互作用 = 0.73）。Begg和Egger检验表明观察性研究中无发表偏倚。
仅有适度证据表明AEDs作为早期PTS预防有效。苯妥英钠是研究最多的药物；需要更多前瞻性研究来评估其他AEDs的疗效。
