Department of Neurology, University of California, San Francisco, CA; Weill Institute for Neurosciences, University of California, San Francisco, CA; Philip R. Lee Institute for Health Policy Studies, University of California, San Francisco, CA.
Department of Emergency Medicine, University of California, San Francisco, CA.
Ann Emerg Med. 2022 Oct;80(4):319-328. doi: 10.1016/j.annemergmed.2022.05.024. Epub 2022 Aug 2.
Guidelines recommend 10-mg intramuscular midazolam as the first-line treatment option for status epilepticus. However, in real-world practice, it is frequently administered intranasally or intravenously and is dosed lower. Therefore, we used conventional and instrumental variable approaches to examine the effectiveness of midazolam in a national out-of-hospital cohort.
This retrospective cohort study of adults with status epilepticus used the ESO Data Collaborative research dataset (January 1, 2019, to December 31, 2019). The exposures were the route and dose of midazolam. We performed hierarchical logistic regression and 2-stage least squares regression using agency treatment patterns as an instrument to examine our outcomes, rescue therapy, and ventilatory support.
There were 7,634 out-of-hospital encounters from 657 EMS agencies. Midazolam was administered intranasally in 20%, intravenously in 46%, and intramuscularly in 35% of the encounters. Compared with intramuscular administration, intranasal midazolam increased (risk difference [RD], 6.5%; 95% confidence interval [CI], 2.4% to 10.5%) and intravenous midazolam decreased (RD, -11.1%; 95% CI, -14.7% to -7.5%) the risk of rescue therapy. The differences in ventilatory support were not statistically significant (intranasal RD, -1.5%; 95% CI, -3.2% to 0.3%; intravenous RD, -0.3%; 95% CI, -1.9% to 1.2%). Higher doses were associated with a lower risk of rescue therapy (RD, -2.6%; 95% CI, -3.3% to -1.9%) and increased ventilatory support (RD, 0.4%; 95% CI, 0.1% to 0.7%). The instrumental variable analysis yielded similar results, except that dose was not associated with ventilatory support.
The route and dose of midazolam affect clinical outcomes. Compared with intramuscular administration, intranasal administration may be less effective and intravenous administration more effective in terminating status epilepticus, although the differences between these and previous results may reflect the nature of real-world data as opposed to randomized data.
指南推荐 10mg 肌肉注射咪达唑仑作为癫痫持续状态的一线治疗选择。然而，在实际临床实践中，咪达唑仑常被鼻内或静脉内给药，且剂量较低。因此，我们使用传统和工具变量方法，在全国院外癫痫持续状态患者队列中评估咪达唑仑的疗效。
这是一项回顾性队列研究，纳入了 2019 年 1 月 1 日至 12 月 31 日期间来自 657 个急救医疗服务机构的成人癫痫持续状态患者。暴露因素为咪达唑仑的给药途径和剂量。我们采用分级逻辑回归和两阶段最小二乘法回归，以机构治疗模式作为工具，评估我们的转归、抢救治疗和通气支持。
来自 657 个急救医疗服务机构的 7634 例院外癫痫持续状态患者中，咪达唑仑鼻内给药占 20%，静脉内给药占 46%，肌肉内给药占 35%。与肌肉内给药相比，鼻内咪达唑仑增加（风险差异[RD]，6.5%；95%置信区间[CI]，2.4%至 10.5%），静脉内咪达唑仑降低（RD，-11.1%；95%CI，-14.7%至-7.5%）抢救治疗的风险。通气支持方面的差异无统计学意义（鼻内 RD，-1.5%；95%CI，-3.2%至 0.3%；静脉内 RD，-0.3%；95%CI，-1.9%至 1.2%）。较高的剂量与较低的抢救治疗风险相关（RD，-2.6%；95%CI，-3.3%至-1.9%）和增加的通气支持（RD，0.4%；95%CI，0.1%至 0.7%）。工具变量分析得出了相似的结果，只是剂量与通气支持无关。
咪达唑仑的给药途径和剂量会影响临床转归。与肌肉内给药相比，鼻内给药可能效果较差，静脉内给药效果较好，可终止癫痫持续状态，尽管这些结果与既往结果的差异可能反映了真实世界数据而非随机数据的性质。
