Study objective

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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美国咪达唑仑的真实使用情况以及癫痫持续状态院外治疗的结果

学习目的

指南推荐 10 mg 肌内注射咪达唑仑作为癫痫持续状态的一线治疗选择。然而，在现实世界的实践中，它经常通过鼻内或静脉注射给药，并且剂量较低。因此，我们使用传统和工具变量方法来检查咪达唑仑在全国院外队列中的有效性。

方法

这项针对成人癫痫持续状态的回顾性队列研究使用了 ESO Data Collaborative 研究数据集（2019 年 1 月 1 日至 2019 年 12 月 31 日）。暴露量为咪达唑仑的途径和剂量。我们使用机构治疗模式作为工具进行分层逻辑回归和两阶段最小二乘回归来检查我们的结果、救援治疗和通气支持。

结果

657 个 EMS 机构共发生了 7,634 次院外就诊。20% 的患者通过鼻内注射咪达唑仑，46% 的患者通过静脉注射咪达唑仑，35% 的患者通过肌肉注射咪达唑仑。与肌肉注射相比，鼻内咪达唑仑增加（风险差[RD]，6.5%；95%置信区间[CI]，2.4%至10.5%），静脉注射咪达唑仑减少（RD，-11.1%；95% CI，-14.7%）至-7.5%）救援治疗的风险。通气支持的差异无统计学意义（鼻内 RD，-1.5%；95% CI，-3.2% 至 0.3%；静脉 RD，-0.3%；95% CI，-1.9% 至 1.2%）。较高剂量与较低的救援治疗风险（RD，-2.6％；95％CI，-3.3％至-1.9％）和增加的通气支持相关（RD，0.4％；95％CI，0.1％至0.7％） 。工具变量分析得出了类似的结果，只是剂量与通气支持无关。

结论

咪达唑仑的给药途径和剂量影响临床结果。与肌内给药相比，鼻内给药在终止癫痫持续状态方面可能效果较差，而静脉内给药更有效，尽管这些结果与之前结果之间的差异可能反映了现实世界数据而不是随机数据的性质。