BACKGROUND Antiarrhythmic drugs have not proven to significantly improve overall survival after out-of-hospital cardiac arrest from shock-refractory ventricular fibrillation/pulseless ventricular tachycardia. How this might be influenced by the route of drug administration is not known. METHODS In this prespecified analysis of a randomized, placebo-controlled clinical trial, we compared the differences in survival to hospital discharge in adults with shock-refractory ventricular fibrillation/pulseless ventricular tachycardia out-of-hospital cardiac arrest who were randomly assigned by emergency medical services personnel to an antiarrhythmic drug versus placebo in the ALPS trial (Resuscitation Outcomes Consortium Amiodarone, Lidocaine or Placebo Study), when stratified by the intravenous versus intraosseous route of administration. RESULTS Of 3019 randomly assigned patients with a known vascular access site, 2358 received ALPS drugs intravenously and 661 patients by the intraosseous route. Intraosseous and intravenous groups differed in sex, time-to-emergency medical services arrival, and some cardiopulmonary resuscitation characteristics, but were similar in others, including time-to-intravenous/intrasosseous drug receipt. Overall hospital discharge survival was 23%. In comparison with placebo, discharge survival was significantly higher in recipients of intravenous amiodarone (adjusted risk ratio, 1.26 [95% CI, 1.06-1.50]; adjusted absolute survival difference, 5.5% [95% CI, 1.5-9.5]) and intravenous lidocaine (adjusted risk ratio, 1.21 [95% CI, 1.02-1.45]; adjusted absolute survival difference, 4.7% [95% CI, 0.7-8.8]); but not in recipients of intraosseous amiodarone (adjusted risk ratio, 0.94 [95% CI, 0.66-1.32]) or intraosseous lidocaine (adjusted risk ratio, 1.03 [95% CI, 0.74-1.44]). Survival to hospital admission also increased significantly when drugs were given intravenously but not intraosseously, and favored improved neurological outcome at discharge. There were no outcome differences between intravenous and intraosseous placebo, indicating that the access route itself did not demarcate patients with poor prognosis. The study was underpowered to assess intravenous/intraosseous drug interactions, which were not statistically significant. CONCLUSIONS We found no significant effect modification by drug administration route for amiodarone or lidocaine in comparison with placebo during out-of-hospital cardiac arrest. However, point estimates for the effects of both drugs in comparison with placebo were significantly greater for the intravenous than for the intraosseous route across virtually all outcomes and beneficial only for the intravenous route. Given that the study was underpowered to statistically assess interactions, these findings signal the potential importance of the drug administration route during resuscitation that merits further investigation.

中文翻译：

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静脉内与骨内胺碘酮，利多卡因或安慰剂在院外休克难治性心脏骤停中的存活率。

背景技术抗心律失常药物尚未被证明能显着改善休克难治性室颤/无脉搏性室性心动过速导致的院外心脏骤停后的总体存活率。药物给药途径如何影响这是未知的。方法在一项随机，安慰剂对照的临床试验的预先分析中，我们比较了急诊医疗随机分配的休克难治性心室纤颤/无脉搏性室性心动过速的成年人在院外出院生存率的差异。当通过静脉内或骨内给药方法分层时，在ALPS试验（复苏成果财团胺碘酮，利多卡因或安慰剂研究）中为抗心律不齐药物与安慰剂的治疗服务人员进行比较。结果在3019名随机分配的具有已知血管通路部位的患者中，有2358例接受了静脉内ALPS药物的治疗，另有661例通过了骨内途径进行了治疗。骨内和静脉内治疗组在性别，紧急医疗服务的到达时间以及一些心肺复苏特征方面有所不同，但在其他方面相似，包括静脉内/骨内给药时间。整体出院生存率为23％。与安慰剂相比，静脉内胺碘酮的接受者出院生存率显着更高（调整后的风险比为1.26 [95％CI，1.06-1.50]；调整后的绝对生存期差异为5.5％[95％CI，1.5-9.5]）利多卡因（调整后的风险比，1.21 [95％CI，1.02-1.45]；调整后的绝对生存差异，4.7％[95％CI，0.7-8.8]）；但不接受骨内胺碘酮（风险调整后的比率为0.94 [95％CI，0.66-1.32]）或骨内利多卡因的接受者（风险调整后的比率为1.03 [95％CI，0.74-1.44]）。静脉内但非骨内给药时，入院生存率也显着增加，并且有利于改善出院时的神经学预后。静脉内安慰剂和骨内安慰剂之间没有预后差异，这表明进入途径本身并不能界定预后不良的患者。该研究不足以评估静脉内/骨内药物相互作用，但无统计学意义。结论我们发现在院外心脏骤停期间，与安慰剂相比，胺碘酮或利多卡因的给药途径没有明显的作用改变。然而，在几乎所有结果中，与安慰剂相比，两种药物与安慰剂的作用点估计值明显高于骨内途径，并且仅对静脉途径有益。鉴于这项研究不足以统计评估相互作用，这些发现表明复苏期间药物给药途径的潜在重要性，值得进一步研究。