Kudenchuk Peter J, Leroux Brian G, Daya Mohamud, Rea Thomas, Vaillancourt Christian, Morrison Laurie J, Callaway Clifton W, Christenson James, Ornato Joseph P, Dunford James V, Wittwer Lynn, Weisfeldt Myron L, Aufderheide Tom P, Vilke Gary M, Idris Ahamed H, Stiell Ian G, Colella M Riccardo, Kayea Tami, Egan Debra, Desvigne-Nickens Patrice, Gray Pamela, Gray Randal, Straight Ron, Dorian Paul
Department of Medicine, Division of Cardiology, University of Washington and King County Emergency Medical Services, Public Health-Seattle & King County, WA (P.J.K., T.R.).
Department of Biostatistics, University of Washington Clinical Trial Center, Seattle, WA (B.G.L.).
Circulation. 2017 Nov 28;136(22):2119-2131. doi: 10.1161/CIRCULATIONAHA.117.028624. Epub 2017 Sep 13.
Out-of-hospital cardiac arrest (OHCA) commonly presents with nonshockable rhythms (asystole and pulseless electric activity). It is unknown whether antiarrhythmic drugs are safe and effective when nonshockable rhythms evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia [VF/VT]) during resuscitation.
Adults with nontraumatic OHCA, vascular access, and VF/VT anytime after ≥1 shock(s) were prospectively randomized, double-blind, to receive amiodarone, lidocaine, or placebo by paramedics. Patients presenting with initial shock-refractory VF/VT were previously reported. The current study was a prespecified analysis in a separate cohort that initially presented with nonshockable OHCA and was randomized on subsequently developing shock-refractory VF/VT. The primary outcome was survival to hospital discharge. Secondary outcomes included discharge functional status and adverse drug-related effects.
Of 37 889 patients with OHCA, 3026 with initial VF/VT and 1063 with initial nonshockable-turned-shockable rhythms were treatment-eligible, were randomized, and received their assigned drug. Baseline characteristics among patients with nonshockable-turned-shockable rhythms were balanced across treatment arms, except that recipients of a placebo included fewer men and were less likely to receive bystander cardiopulmonary resuscitation. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo (<0.05). In all, 16 (4.1%) amiodarone, 11 (3.1%) lidocaine, and 6 (1.9%) placebo-treated patients survived to hospital discharge (=0.24). No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). Survival in each of these categories was consistently higher with active drugs, although the trends were not statistically significant. Adjusted absolute differences (95% confidence interval) in survival from nonshockable-turned-shockable arrhythmias with amiodarone versus placebo were 2.3% (-0.3, 4.8), =0.08, and for lidocaine versus placebo 1.2% (-1.1, 3.6), =0.30. More than 50% of these survivors were functionally independent or required minimal assistance. Drug-related adverse effects were infrequent.
Outcome from nonshockable-turned-shockable OHCA is poor but not invariably fatal. Although not statistically significant, point estimates for survival were greater after amiodarone or lidocaine than placebo, without increased risk of adverse effects or disability and consistent with previously observed favorable trends from treatment of initial shock-refractory VF/VT with these drugs. Together the findings may signal a clinical benefit that invites further investigation.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT01401647.
院外心脏骤停（OHCA）通常表现为不可电击心律（心脏停搏和无脉电活动）。在复苏过程中，当不可电击心律演变为可电击心律（心室颤动/无脉性室性心动过速[VF/VT]）时，抗心律失常药物是否安全有效尚不清楚。
对≥1次电击后任何时间出现非创伤性OHCA、建立血管通路且发生VF/VT的成年人，由护理人员进行前瞻性随机、双盲分组，分别给予胺碘酮、利多卡因或安慰剂。初始电击难治性VF/VT患者此前已有报道。本研究是在一个单独队列中的预先设定分析，该队列最初表现为不可电击的OHCA，在随后出现电击难治性VF/VT时进行随机分组。主要结局是存活至出院。次要结局包括出院时的功能状态和药物相关不良反应。
在37889例OHCA患者中，3026例初始为VF/VT，1063例初始为不可电击转为可电击心律，符合治疗条件，被随机分组并接受指定药物治疗。不可电击转为可电击心律患者的基线特征在各治疗组间均衡，但安慰剂组男性较少，接受旁观者心肺复苏的可能性较小。与安慰剂组相比，该队列中使用活性药物的患者所需电击次数、指定药物补充剂量及辅助抗心律失常药物更少（P<0.05）。共有16例（4.1%）接受胺碘酮治疗、11例（3.1%）接受利多卡因治疗和6例（1.9%）接受安慰剂治疗的患者存活至出院（P=0.24）。初始OHCA心律（心脏停搏、无脉电活动或VF/VT）与治疗分组和出院存活率之间未发生显著交互作用。尽管趋势无统计学意义，但活性药物在这些类别中的存活率始终较高。胺碘酮与安慰剂相比，不可电击转为可电击心律失常患者存活的校正绝对差异（95%置信区间）为2.3%（-0.3，4.8），P=0.08；利多卡因与安慰剂相比为1.2%（-1.1，3.6），P=0.30。这些幸存者中超过50%功能独立或仅需极少帮助。药物相关不良反应不常见。
不可电击转为可电击的OHCA预后较差，但并非必然致命。尽管无统计学意义，但胺碘酮或利多卡因治疗后的存活点估计值高于安慰剂，且不良反应或残疾风险未增加，与先前观察到的这些药物治疗初始电击难治性VF/VT的有利趋势一致。这些发现共同表明可能存在临床获益，值得进一步研究。
