Background—Out-of-hospital cardiac arrest (OHCA) commonly presents with non-shockable rhythms (asystole and pulseless electrical activity (PEA)). Whether antiarrhythmic drugs are safe and effective when these evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia (VF/VT)) during resuscitation is not known.Methods—Adults with non-traumatic 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 pre-specified analysis in a separate cohort who initially presented with non-shockable OHCA and were randomized upon 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.Results—Of 37,889 patients with OHCA, 3,026 with initial VF/VT and 1,063 with initial non-shockable-turned-shockable rhythms were treatment-eligible, randomized and received their assigned drug. Baseline characteristics among non-shockable-turned-shockable patients were balanced across treatment arms except that placebo recipients included fewer men and were less likely to receive bystander-CPR. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug and ancillary antiarrhythmic drugs than placebo-recipients (p<0.05). In all, 16 (4.1%) amiodarone, 11 (3.1%) lidocaine and 6 (1.9%) placebo-treated patients survived to hospital discharge (p=0.24). There was no significant interaction of treatment assignment and discharge survival with the initiating OHCA rhythm (asystole, PEA, or VF/VT); survival in each of these categories was consistently higher with active-drugs, though the trends were not statistically significant. Adjusted absolute differences (95% confidence interval) in survival from non-shockable-turned-shockable arrhythmias with amiodarone vs placebo were 2.3% (-0.3, 4.8), p=0.08 and for lidocaine vs placebo 1.2% (-1.1, 3.6), p=0.30. Over one-half of these survivors were functionally independent or required minimal assistance. Drug-related adverse effects were infrequent.Conclusions—Outcome from non-shockable-turned-shockable OHCA is poor, but not invariably fatal. Though 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.Clinical Trial Registration—URL: ClinicalTrials.gov Unique Identifier: NCT01401647

背景-院外心脏骤停（OHCA）通常表现为不可电击的节律（心搏停止和无脉搏电活动（PEA））。尚不清楚在复苏过程中抗心律不齐药物发展为令人震惊的心律（室颤/无脉性室性心动过速（VF / VT））是否安全有效。方法—对≥1次电击后随时有非创伤性OHCA，血管通路和VF / VT的成年人进行前瞻性随机双盲研究，以接受医护人员的胺碘酮，利多卡因或安慰剂治疗。先前曾报道有初次电击难治性VF / VT的患者。当前的研究是在一个单独的队列中进行的预先指定的分析，该队列最初呈现不可电击的OHCA，随后在发展为休克难治性VF / VT时被随机分组​​。主要结局是出院生存。次要结果包括出院功能状态和药物相关不良影响。结果—在37,889例OHCA患者中，有3,026例初始VF / VT和1,063例初始不可电击转为可电击的节律符合治疗要求，被随机分配并接受了分配的药物。非休克转休克患者的基线特征在各治疗组之间是平衡的，除了安慰剂接受者的男性人数较少且接受旁观者心肺复苏术的可能性较小。与安慰剂接受者相比，该队列中的活性药物接受者需要较少的电击，补充剂量的指定药物和辅助性抗心律失常药物（p <0.05）。总共有16名（4.1％）胺碘酮，11名（3.1％）利多卡因和6名（1.9％）安慰剂治疗的患者存活至出院（p = 0.24）。起始OHCA节律（心搏停止，PEA或VF / VT）与治疗分配和出院生存率之间无显着相互作用；尽管活性趋势在统计学上不显着，但活性药物在所有这些类别中的存活率始终较高。胺碘酮与安慰剂相比，不可电击转为电击性心律失常生存的校正绝对差（95％置信区间）为2.3％（-0.3，4.8），p = 0.08；利多卡因与安慰剂的校正为1.2％（-1.1，3.6） ，p ＝ 0.30。这些幸存者中有一半以上在功能上独立或需要的援助很少。药物相关的不良反应很少见。这些幸存者中有一半以上在功能上独立或需要的援助很少。药物相关的不良反应很少见。这些幸存者中有一半以上在功能上独立或需要的援助很少。药物相关的不良反应很少见。结论—非电击转为电击的OHCA的结果较差，但并非总是致命的。尽管在统计学上不显着，但胺碘酮或利多卡因后的生存点估计值高于安慰剂，且没有增加不良反应或致残风险，并且与先前观察到的用这些药物治疗初始难治性VF / VT的有利趋势一致。在一起的发现可能标志着临床益处，需要进一步的研究。临床试验注册— URL：ClinicalTrials.gov唯一标识符：NCT01401647