A Randomized Trial of Brief Versus Extended Seizure Prophylaxis After Aneurysmal Subarachnoid Hemorrhage.
A Randomized Trial of Brief Versus Extended Seizure Prophylaxis After Aneurysmal Subarachnoid Hemorrhage.
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DOI：
10.1007/s12028-017-0440-5
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发表时间：
2018-04
影响因子：
3.5
通讯作者：
Dhar R
中科院分区：
文献类型：
--
作者：
Human T;Diringer MN;Allen M;Zipfel GJ;Chicoine M;Dacey R;Dhar R
10-20% 的蛛网膜下腔出血 (SAH) 患者会出现癫痫发作，主要发生在急性期。然而，抗惊厥预防仍存在争议，研究表明短期疗程可能就足够了，而较长时间的暴露可能会导致更差的结果。尽管如此，在缺乏对照试验来指导实践的情况下，患者继续接受不同的化学预防。本研究的目的是比较动脉瘤性蛛网膜下腔出血后短暂与长期癫痫发作预防。我们进行了一项前瞻性、单中心、随机、开放标签试验，比较左乙拉西坦 (LEV) 的短期（三天）疗程与延长治疗（直至出院）。主要结局是院内癫痫发作。次要结局包括停药和功能结局。当试验因入组缓慢而终止时，84 名 SAH 患者被随机分组。短暂 LEV 组中 35 名患者中有 3 名 (9%) 发生院内癫痫发作，而延长组中 49 名患者中有 1 名 (2%) 发生院内癫痫发作 (p=0.2)。扩展组中有 10 名 (20%) 人过早停止 LEV，主要是由于镇静作用。 CT 扫描显示的早期脑损伤 (EBI) 患者中，五次癫痫发作中的四次（包括一次随机分组前）发生（调整后 OR 12.5，95% CI 1.2-122，p=0.03）。短期 LEV 组更有可能获得良好的功能结果 (mRS 0-2)（83% vs. 61%，p=0.04）。尽管看到了获益的趋势，但这项研究不足以证明延长 LEV 预防癫痫发作的优越性。癫痫发作主要发生在影像学 EBI 患者中，表明有针对性的预防可能更好。需要更大规模的试验来评估 SAH 的最佳化学预防，特别是考虑到接受长期治疗的患者预后较差。
Seizures occur in 10–20% of patients with subarachnoid hemorrhage (SAH), predominantly in the acute phase. However, anticonvulsant prophylaxis remains controversial, with studies suggesting a brief course may be adequate and longer exposure may be associated with worse outcomes. Nonetheless, in the absence of controlled trials to inform practice, patients continue to receive variable chemoprophylaxis. The objective of this study was to compare brief vs. extended seizure prophylaxis after aneurysmal SAH. We performed a prospective, single-center, randomized, open-label trial of a brief (three-day) course of levetiracetam (LEV) vs. extended treatment (until hospital discharge). The primary outcome was in-hospital seizure. Secondary outcomes included drug discontinuation and functional outcome. 84 SAH patients had been randomized when the trial was terminated due to slow enrollment. In-hospital seizures occurred in 3 (9%) of 35 in the brief LEV group vs. 1 (2%) of 49 in the extended group (p=0.2). 10 (20%) of the extended group discontinued LEV prematurely, primarily due to sedation. Four of five seizures (including one pre-randomization) occurred in patients with early brain injury (EBI) on CT scans (adjusted OR 12.5, 95% CI 1.2–122, p=0.03). Good functional outcome (mRS 0–2) was more likely in the brief LEV group (83% vs. 61%, p=0.04). This study was underpowered to demonstrate superiority of extended LEV for seizure prophylaxis, although a trend to benefit was seen. Seizures primarily occurred in those with radiographic EBI, suggesting targeted prophylaxis may be preferable. Larger trials are required to evaluate optimal chemoprophylaxis in SAH, especially in light of worse outcomes in those receiving extended treatment.
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