Article, see p 877

Treatment of out-of-hospital cardiac arrest (OHCA) implies a multidisciplinary approach, including the immediate provision of high-quality cardiopulmonary resuscitation, targeted temperature management, consideration of immediate coronary angiography, and early neurological evaluation for prognostication. It is a common condition, with an incidence of 360 000 cases in the United States each year. Despite early resuscitation, the prognosis at hospital discharge remains poor, with mortality rates reaching 50% to 60%,¹ and many survivors showing long-term neurological disability.² Among hospital admission parameters, an initial shockable rhythm (ie, ventricular fibrillation/ventricular tachycardia) and a shorter time from basic life support to return of spontaneous circulation are favorable prognostic markers.³ Refractory cardiac arrest, defined by the failure to restore spontaneous circulation despite conventional cardiopulmonary resuscitation with repeated defibrillation attempts and administration of amiodarone, is associated with a poorer prognosis, with favorable neurological outcome observed in less than 20% of cases.⁴

Extracorporeal cardiopulmonary resuscitation (ECPR) using extracorporeal membrane oxygenation (ECMO) for hemodynamic support is being used more frequently for refractory cardiac arrest.⁵ A meta-analysis of observational studies conducted in patients treated with EPCR for OHCA reported variable survival rates with acceptable neurological function, ranging from 8% to 50%.⁶ Data from this meta-analysis suggest that a shorter low-flow duration, initial shockable cardiac rhythm, higher initial pH value, and lower serum lactate concentration on admission are associated with better survival rates with acceptable neurological outcomes.⁶ Moreover, prolonged cardiopulmonary resuscitation (CPR) is associated with severe metabolic disturbances with uncertain consequences on organ injury and outcomes. Of note, the probability of a favorable neurological outcome in ECPR patients is highly dependent on the duration of standard CPR before ECMO initiation. In a recent large multicenter study investigating 523 patients treated with ECPR for OHCA, a CPR duration >90 minutes was associated with very low hospital survival rates, below 5%.⁷ Multivariate analysis identified transient restoration of spontaneous circulation before ECMO implantation and prehospital ECMO implantation as independent predictors of hospital survival.

In this issue of Circulation, Bartos et al report improved hospital survival for refractory OHCA patients treated with ECPR, compared with patients treated with conventional CPR. The authors retrospectively evaluated 160 consecutive adults with refractory OHCA with shockable rhythm treated with the University of Minnesota ECPR (UMN-ECPR) protocol, which has been published previously.⁸ This strict protocol applied to adult patients with refractory OHCA of presumed cardiac origin included 3 essential steps. First, patients were carefully screened in the prehospital setting by paramedics, and rapid transport with ongoing mechanical CPR to the cardiac catheterization laboratory was performed. Second, prespecified criteria for resuscitation continuation were applied at hospital arrival to identify patients deemed eligible for ultrasound-guided percutaneous peripheral venoarterial ECMO cannulation. Coronary angiography with coronary intervention as indicated was then applied, and all patients received targeted temperature management to 34°C via an intravascular cooling catheter. Third, if an organized cardiac rhythm could not be established after 90 minutes of stabilized hemodynamics and treatment of a reversible cause of cardiac arrest, the patient was declared dead. Patients received systematic transthoracic echocardiography evaluation within 24 hours after hospital admission for evaluation of left ventricular lateral wall thickness as a surrogate marker of ischemic myocardial injury. The primary outcome was neurologically favorable survival, defined by a score of 1 to 2 on the Cerebral Performance Category at hospital discharge. Cerebral outcomes of the UMN-ECPR cohort were compared with a cohort of patients enrolled in the amiodarone arm of the ALPS (Amiodarone, Lidocaine, or Placebo Study) trial.⁴ The UMN-ECPR cohort and ALPS cohort were remarkably comparable for common prehospital predictors of outcome, including witnessed arrest, bystander CPR, and location of cardiac arrest. UMN-ECPR patients received a longer mean duration of professional CPR (60 minutes), as compared with conventional CPR patients from the ALPS cohort (35 minutes). A higher neurologically favorable survival was observed in the UMN-ECPR patients (33%), as compared with standard CPR patients (23%) in unadjusted analyses (odds ratio, 1.59 [95% CI, 1.09–2.32]). Adjusted analyses for the patient and arrest characteristics (ie, age, sex, race, witnessed arrest, bystander CPR, public location, and CPR duration) confirmed a significant survival benefit of ECPR over conventional CPR (adjusted odds ratio, 20.80 [95% CI, 8.65–50.03]). When analyzing the effect of CPR duration on the outcome, a significant survival benefit was observed for UMN-ECPR patients compared with ALPS patients at each CPR duration interval. Overall, the relative risk reduction for death or poor neurological outcome was 29% (95% CI, 18%–41%) for patients receiving between 20 and 59 minutes of CPR and 19% (95% CI, 10%–27%) for patients receiving more than 60 minutes of CPR. The study had limitations inherent to its single-center and observational design. Data on the primary outcome was collected retrospectively, using two different functional scales for evaluation of neurological disability in the two cohorts. Moreover, data on long-term functional outcomes and health-related quality of life were not collected.

No randomized, controlled trials on the use of ECPR for refractory OHCA have been conducted to date. Among observational studies, only 4 cohorts with more than 100 ECPR patients reported outcome comparison between ECPR and standard CPR, including the study by Bartos et al^7,9–11 (Table). These studies were heterogeneous in terms of inclusion criteria (ie, strict restriction to shockable rhythms), prehospital management (ie, “load and go” vs “treat on the scene”), ECPR (ie, “prehospital” vs “in-hospital”) protocols, and statistical methods used for matching patients. This heterogeneity led to inconsistency in reported outcomes. Of note, a recent large population-based registry reported similar low survival rates between 525 patients with managed ECPR and 12 666 patients with conventional CPR, with no significant effect of ECPR on outcomes after adjustment on confounders. Therefore, the results published by Bartos et al are highly encouraging and call for a better selection of patients and a protocolized use of ECPR for adults with refractory OHCA, rather than a use left at the discretion of physicians, likely resulting in poor outcomes with inappropriate use of medical resources and increased cost.

Table. Studies With More Than 100 ECPR Patients Reporting Outcome Comparison Between ECPR-Treated and CCPR-Treated Patients

Data are median (interquartile range) or mean, unless otherwise stated. aOR indicates adjusted odds ratio; CCPR, conventional cardiopulmonary resuscitation; CPC, Cerebral Performance Category score; ECPR, extracorporeal cardiopulmonary resuscitation; mRS, modified Rankin scale; pVT, pulseless ventricular tachycardia; VF, ventricular fibrillation; and VT, ventricular tachycardia.

*Twenty percent in sustained VF/pVT group vs 3% in conversion to pulseless electrical activity (PEA)/asystole group.

†Four percent in sustained VF/pVT group vs 1% in conversion to PEA/asystole group.

In conclusion, Bartos et al should be congratulated for this important study reporting neurological outcomes of refractory OHCA adult patients treated by ECPR with an a priori defined protocol including stringent patient selection criteria. This study increases available evidence supporting the use of extracorporeal life support for wisely selected cardiac arrest patients. While waiting for high-quality evidence from randomized, controlled trials, ECPR may be considered for selected patients as rescue therapy when conventional CPR efforts are failing.¹² We advocate for the use of ECPR in patients <75 years with refractory OHCA of presumed cardiac origin with an initial shockable rhythm, and anticipated duration of CPR inferior or equal to 90 minutes before ECMO start. Lactate level and oxygenation status at hospital arrival may represent important criteria for resuscitation continuation decisions that should be further investigated.

Future research should focus on implementing ECPR programs with strict patient selection criteria in ECMO centers and on developing algorithms for early prognostication of patients on ECMO. A systematic multidisciplinary approach is needed to avoid continuing futile and expensive therapies when poor neurological outcomes are likely but also to avoid inappropriate withdrawal of life-sustaining therapies in patients who may otherwise have a chance of achieving meaningful neurological recovery.^13,14 In line with these objectives, core outcome measurements in future prognostic studies should not be restricted to hospital survival but should include at least functional outcome assessment at 3 and 6 months, information on timing and causes of death, and health-related quality of life at 1 year.¹⁵

Dr Sonneville has received grants from the French Ministry of Health, the French Society of Intensive Care Medicine, and the European Society of Intensive Care Medicine, and lecture fees from Baxter.Dr Schmidt has received lecture fees from Getinge, Draeger, and Xenios.

The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.

https://www.ahajournals.org/journal/circ

文章，请参见第877页

院外心脏骤停（OHCA）的治疗意味着多学科的方法，包括立即提供高质量的心肺复苏，目标温度管理，考虑立即进行冠状动脉造影以及早期神经学评估以进行预后。这是一种普遍情况，在美国每年发生36万例。尽管进行了早期复苏，但出院时的预后仍然很差，死亡率达到50％至60％¹，许多幸存者表现出长期的神经功能障碍。²在医院的入院参数中，初始的令人震惊的心律（即室颤/室性心动过速）和从基本生活支持到恢复自然循环的时间较短是良好的预后指标。³难治性心脏骤停的定义是尽管进行常规的心肺复苏并反复进行除纤颤和胺碘酮治疗，但仍无法恢复自发循环，预后较差，在不到20％的病例中观察到良好的神经系统预后。⁴

使用体外膜氧合（ECMO）进行血液动力学支持的体外心肺复苏（ECPR）被更频繁地用于难治性心脏骤停。⁵对接受EPCR治疗OHCA的患者进行的观察性研究的荟萃分析报告，存活率可变，神经功能可接受，范围为8％至50％。⁶来自这项荟萃分析的数据表明，入院时较短的低血流持续时间，初始可电击的心律，较高的初始pH值和较低的血清乳酸浓度与较好的生存率和可接受的神经学预后相关。⁶此外，长时间的心肺复苏（CPR）与严重的代谢紊乱有关，对器官损伤和预后的影响尚不确定。值得注意的是，ECPR患者神经功能预后良好的可能性高度依赖于ECMO启动前标准CPR的持续时间。在最近的一项大型多中心研究中，研究了523例接受ECPR OHCA治疗的患者，CPR持续时间> 90分钟与非常低的医院存活率（低于5％）相关。⁷多元分析表明，ECMO植入前和院前ECMO植入前自然循环的短暂恢复是医院生存的独立预测指标。

在本期《循环》杂志中，Bartos等人报道了与常规CPR治疗相比，使用ECPR治疗的难治性OHCA患者的住院存活率有所提高。作者回顾性评估了160例连续的成年人，这些成年人接受过明尼苏达大学ECPR（UMN-ECPR）协议治疗的难治性节律性难治性OHCA，该协议已于之前发表。⁸这项严格的方案适用于假定的心脏起源难治性OHCA的成年患者，包括3个基本步骤。首先，在院前环境中由医护人员仔细筛查患者，然后将进行中的机械CPR快速转运到心脏导管实验室。第二，在医院到达时采用预先确定的复苏持续标准，以识别被认为有资格接受超声引导的经皮外周静脉动脉ECMO插管的患者。然后应用指示的冠状动脉介入术进行冠状动脉造影，并且所有患者均通过血管内冷却导管接受了针对性的温度管理，达到34°C。第三，如果在90分钟稳定的血流动力学和可逆性心脏骤停原因的治疗后仍无法建立有组织的心律，则该患者被宣布死亡。患者入院后24小时内接受系统的经胸超声心动图评估，以评估左心室侧壁厚度作为缺血性心肌损伤的替代指标。主要结局是神经学上有利的生存期，即出院时脑功能分类的1到2分。将UMN-ECPR队列的脑结局与ALPS（胺碘酮，利多卡因或安慰剂研究）试验的胺碘酮组的患者队列进行了比较。患者入院后24小时内接受了系统的经胸超声心动图评估，以评估左心室侧壁厚度作为缺血性心肌损伤的替代指标。主要结局是神经学上有利的生存期，即出院时脑功能分类中的1到2分。将UMN-ECPR队列的脑结局与ALPS（胺碘酮，利多卡因或安慰剂研究）试验的胺碘酮组的患者队列进行了比较。患者入院后24小时内接受系统的经胸超声心动图评估，以评估左心室侧壁厚度作为缺血性心肌损伤的替代指标。主要结局是神经学上有利的生存期，即出院时脑功能分类中的1到2分。将UMN-ECPR队列的脑结局与ALPS（胺碘酮，利多卡因或安慰剂研究）试验的胺碘酮组的患者队列进行了比较。⁴UMN-ECPR队列和ALPS队列在院前常见的预后指标（包括目击者，旁观者CPR和心脏骤停的位置）方面具有显着可比性。与来自ALPS队列的常规CPR患者（35分钟）相比，UMN-ECPR患者接受专业CPR的平均持续时间更长（60分钟）。在未经调整的分析中，与标准CPR患者（23％）相比，UMN-ECPR患者（33％）观察到更高的神经学上的有利生存（优势比为1.59 [95％CI，1.09–2.32]）。对患者和逮捕特征（即年龄，性别，种族，目击逮捕，旁观者CPR，公共场所和CPR持续时间）进行调整后的分析证实，与传统CPR相比，ECPR具有明显的生存获益（调整后的优势比为20.80 [95％CI ，8.65–50.03]）。在分析CPR持续时间对结局的影响时，在每个CPR持续时间间隔，与ALPS患者相比，UMN-ECPR患者观察到了显着的生存获益。总体而言，接受CPR 20至59分钟的患者，死亡或神经系统预后不良的相对风险降低为29％（95％CI，18％–41％）和19％（95％CI，10％–27％）适用于接受CPR 60分钟以上的患者。该研究在其单中心和观察设计方面存在固有的局限性。回顾性收集主要结果的数据，使用两种不同的功能量表评估两个队列中的神经功能障碍。此外，未收集有关长期功能结局和与健康相关的生活质量的数据。在每个CPR持续时间间隔内，与ALPS患者相比，UMN-ECPR患者具有显着的生存获益。总体而言，接受CPR 20至59分钟的患者，死亡或神经系统预后不良的相对风险降低为29％（95％CI，18％–41％）和19％（95％CI，10％–27％）适用于接受CPR 60分钟以上的患者。该研究在其单中心和观察设计方面存在固有的局限性。回顾性收集主要结果的数据，使用两种不同的功能量表评估两个队列中的神经功能障碍。此外，未收集有关长期功能结局和与健康相关的生活质量的数据。在每个CPR持续时间间隔内，与ALPS患者相比，UMN-ECPR患者具有显着的生存获益。总体而言，接受CPR 20至59分钟的患者，死亡或神经系统预后不良的相对风险降低为29％（95％CI，18％–41％）和19％（95％CI，10％–27％）适用于接受CPR 60分钟以上的患者。该研究在其单中心和观察设计方面存在固有的局限性。回顾性收集主要结果的数据，使用两种不同的功能量表评估两个队列中的神经功能障碍。此外，未收集有关长期功能结局和与健康相关的生活质量的数据。接受CPR 20至59分钟的患者为18％–41％，接受CPR 60分钟以上的患者为19％（95％CI，10％–27％）。该研究在其单中心和观察设计方面存在固有的局限性。回顾性收集主要结果的数据，使用两种不同的功能量表评估两个队列中的神经功能障碍。此外，未收集有关长期功能结局和与健康相关的生活质量的数据。接受CPR 20至59分钟的患者为18％–41％，接受CPR 60分钟以上的患者为19％（95％CI，10％–27％）。该研究在其单中心和观察设计方面存在固有的局限性。回顾性收集主要结果的数据，使用两种不同的功能量表评估两个队列中的神经功能障碍。此外，未收集有关长期功能结局和与健康相关的生活质量的数据。

迄今为止，尚未进行关于使用ECPR治疗难治性OHCA的随机对照试验。在观察性研究中，只有4个队列中有100多名ECPR患者报告了ECPR与标准CPR的结局比较，包括Bartos等[ ^7,9-11]的研究（表）。这些研究在纳入标准（即严格限制可电击的节律），院前管理（即“随身携带”与“现场治疗”），ECPR（即“院前”与“医院内”）方面存在异质性”）协议，以及用于匹配患者的统计方法。这种异质性导致报告结果不一致。值得注意的是，最近的一项基于人群的大型注册研究报告了525例接受ECPR的患者和12 666例常规CPR的患者的生存率相似，并且对混杂因素进行调整后，ECPR对预后没有明显影响。因此，Bartos等人发表的结果令人鼓舞，并呼吁对患有难治性OHCA的成年人进行更好的患者选择和ECPR规程使用，而不是由医生自行决定使用，

表。超过100名ECPR患者的研究报告了ECPR治疗和CCPR治疗患者的结果比较

除非另有说明，否则数据为中位数（四分位间距）或平均值。aOR表示调整后的优势比；CCPR，常规心肺复苏；每次点击费用，脑功能类别得分；ECPR，体外心肺复苏；mRS，改良的Rankin量表；pVT，无脉性室性心动过速；室颤，心室纤颤；和室速，室速。

*持续性VF / pVT组为20％，而转换为无脉电活动（PEA）/心搏停止组为3％。

†持续VF / pVT组为4％，而转化为PEA /心搏停止组为1％。

总之，对于这项重要的研究报告了由ECPR治疗的难治性OHCA成年患者的神经学结局，采用先验定义的方案（包括严格的患者选择标准），应对此Bartos等人表示祝贺。这项研究增加了可用的证据，支持明智选择心脏骤停患者使用体外生命支持。在等待来自随机对照试验的高质量证据时，当常规的CPR努力失败时，可以考虑将ECPR作为选定患者的急救疗法。¹²我们主张在心律不佳的OHCA ＜75岁，假定的心脏起源难治性OHCA且初始电击节律不佳且预期CPR持续时间小于或等于ECMO开始前90分钟的患者中使用ECPR。医院到达时的乳酸水平和氧合状态可能代表了复苏持续决策的重要标准，应进一步研究。

未来的研究应侧重于在ECMO中心以严格的患者选择标准实施ECPR计划，并开发针对ECMO患者的早期预后的算法。需要一种系统的多学科方法，以避免在可能出现不良神经学预后的情况下继续进行无效且昂贵的治疗，而且还需要避免可能有可能实现有意义的神经学恢复的患者不适当地撤消维持生命的治疗方法。^13,14为达到这些目标，未来预后研究中的核心结局指标不应仅限于医院生存，而应至少包括3个月和6个月的功能结局评估，有关时间和死亡原因以及与健康相关的质量的信息寿命为1年。¹⁵

Sonneville博士获得了法国卫生部，法国重症监护医学会和欧洲重症监护医学协会的赠款，并获得了百特的演讲费。Schmidt博士获得了Getinge，Draeger和Xenios的演讲费。

本文表达的观点不一定是编辑者或美国心脏协会的观点。

https://www.ahajournals.org/journal/circ