Department of Clinical Neurosciences, Service of Neurology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
Division of Clinical Pharmacology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
Eur J Neurol. 2022 Sep;29(9):2607-2611. doi: 10.1111/ene.15441. Epub 2022 Jun 21.
Intravenous valproate (VPA) is an established treatment of status epilepticus (SE), but optimal loading dose was not fully assessed. We aimed at analyzing the correlation between VPA loading dose and subsequent plasma levels with clinical response in SE.
This was a retrospective study in one referral center of all consecutive VPA-naïve SE episodes treated with VPA between January 2013 and June 2019, in which total VPA trough plasma levels after intravenous loading dose were available. Response to VPA, defined as last antiseizure medication introduced before SE resolution (without the need for additional treatment), was correlated with VPA loading dose and trough level. Correlations were adjusted for other SE characteristics.
Among 128 SE episodes, 53 (41%) responded to VPA. Median VPA loading dose was 25.2 mg/kg (range, 7-58 mg/kg). Loading doses and total plasma levels were not associated with the probability of response or mortality. Correcting for other possible confounders (number of previously tried treatment, demographics, SE severity) did not alter these findings. Only 3.8% of SE episodes that responded to VPA received >30 mg/kg.
A high loading dose (>30 mg/kg) is not associated with a greater response rate in patients with SE. Therefore, it seems to bring little benefit. If confirmed in further studies, a dosage of 25-30 mg/kg appears adequate in SE.
静脉注射丙戊酸钠（VPA）是治疗癫痫持续状态（SE）的一种既定方法，但最佳负荷剂量尚未完全确定。本研究旨在分析 SE 患者 VPA 负荷剂量与后续血药浓度与临床反应之间的相关性。
这是一项回顾性研究，纳入了 2013 年 1 月至 2019 年 6 月期间在一家转诊中心接受 VPA 治疗的所有 VPA 初治 SE 发作患者，其中所有患者静脉负荷剂量后 VPA 谷浓度均可用。VPA 治疗反应定义为 SE 缓解前最后一次使用的抗癫痫药物（无需额外治疗），与 VPA 负荷剂量和谷浓度相关。相关性调整了 SE 的其他特征。
在 128 例 SE 发作中，53 例（41%）对 VPA 有反应。VPA 负荷剂量中位数为 25.2mg/kg（范围 7-58mg/kg）。负荷剂量和总血浆水平与反应概率或死亡率无关。在调整其他可能的混杂因素（先前尝试的治疗次数、人口统计学、SE 严重程度）后，这些发现没有改变。只有 3.8%对 VPA 有反应的 SE 发作患者接受了 >30mg/kg 的剂量。
在 SE 患者中，高负荷剂量（>30mg/kg）并不与更高的反应率相关。因此，它似乎没有带来很大的益处。如果在进一步的研究中得到证实，25-30mg/kg 的剂量似乎足以治疗 SE。
