Extracorporeal cardiopulmonary resuscitation (ECPR) is expected to benefit the rescue of selected patients, particularly those who are refractory to conventional cardiopulmonary resuscitation (CPR).¹ Considering its invasive procedure and considerable resources, establishing a helpful criterion for initiating ECPR remains crucial. Low-flow duration (LFD) is one of the most common criteria to identify candidates for ECPR.¹ However, the association between LFD and favorable neurological outcome has not been sufficiently investigated in out-of-hospital cardiac arrests (OHCAs). This study aimed to assess (1) whether LFD was associated with 1-month survival or favorable neurological outcome after ECPR and (2) the interplay between the documented cardiac rhythms and LFD on neurological outcomes of ECPR.

The CRITICAL study (Comprehensive Registry of Intensive Cares for OHCA Survival) was a multicenter, prospective cohort study of patientswithOHCA in Osaka Prefecture, Japan, involving 14 institutions.² This secondary analysis of the CRITICAL study included adult patients ≥18 years of age with OHCA who received ECPR before the return of spontaneous circulation from July 1, 2012, to December 31, 2016. LFD was defined as the time interval from initiation of any CPR (bystander CPR or CPR by emergency medical services personnel) to the initiation of ECPR. The information on the initiation of bystander CPR was obtained by emergency medical services interview with the bystanders before leaving the scene. LFD was classified into the following tertiles: short (23–45 minutes), middle (46–57 minutes), and long (58–117 minutes). The primary outcome was 1-month survival with favorable neurological outcome defined by Cerebral Performance Category 1 or 2. The secondary outcome was 1-month survival. First, we visually described the nonlinear relationship between LFD and the estimated probability of favorable neurological outcome using restricted cubic spline in the univariable logistic regression model based on prehospital and in-hospital first documented cardiac rhythm (shockable-shockable [ie, sustained shockable rhythm] or other). Second, to investigate the effect of LFD on each outcome, we applied univariable and multivariable logistic regression analyses, adjusting for age (continuous), sex, cause of arrest (cardiac or noncardiac), and prehospital and in-hospital first documented rhythm (sustained shockable rhythm or other). This study was approved by the ethics committees of the participating hospitals.

During the study period, 9822 patients with OHCA were registered, and 256 patients were eligible for our analysis. The proportion of favorable neurological outcome was 22.0% (22 of 100), 17.1% (14 of 82), and 6.8% (5 of 74) in the short, middle, and long groups, respectively. Although the probability of favorable neurological outcome decreased as LFD increased, those with sustained shockable rhythm had a higher chance of achieving favorable neurological outcome than those with other rhythms when they received ECPR at the same LFDs (Figure [A]). In the multivariable logistic regression analysis, the probability of favorable neurological outcome decreased as LFD increased (P for trend=0.016). In terms of the secondary outcome, there was no significant association between the difference in LFD and 1-month survival (Figure [B]).

Figure. Low-flow duration and outcomes of extracorporeal cardiopulmonary resuscitation (ECPR) after out-of-hospital cardiac arrest (OHCA).A, Probability of Cerebral Performance Category (CPC) 1 or 2 by low-flow duration of extracorporeal cardiopulmonary resuscitation (ECPR) according to the documented cardiac rhythm during cardiopulmonary resuscitation. Sustained shockable rhythm meant that the combination of prehospital first documented cardiac rhythm and in-hospital first documented cardiac rhythm was shockable-shockable; other rhythms included shockable-nonshockable, nonshockable-shockable, or nonshockable-nonshockable. B, Outcomes from out-of-hospital cardiac arrest by the timing of the initiation of ECPR. *Adjusted for age, sex, cause of arrest, and prehospital and in-hospital rhythm.

Only 1 study, which included 105 patients with OHCA and 377 with in-hospital cardiac arrest, was adjusted for potential confounders; that study observed that increased LFD was associated with a poorer probability of favorable neurological outcome,³ and this was consistent with our findings. Another important strength of our study was the inclusion of only patients with OHCA in our investigation of the impact of LFD. Because characteristics, resuscitation process, and resuscitation strategies are different between patients with OHCA and in-hospital cardiac arrest, our findings may offer important evidence for the criteria of initiating ECPR in patients with OHCA.

We also observed the association between documented rhythm and favorable neurological outcome. For low-quality CPR, the insufficient tissue oxygen delivery to the myocardium may have a higher likelihood of causing rhythm conversion from initial shockable rhythm to pulseless electric activity/asystole, resulting in greater ischemia/reperfusion injury than a high-quality CPR.^4,5 In contrast, long LFDs may improve the likelihood of favorable neurological outcome in case of patients with sustained shockable rhythm whose cerebral blood flow would be relatively maintained.^4,5 Other interventions known to have a positive impact on favorable neurological outcome such automated external defibrillator use, CPR pauses, and quality of CPR might also have influenced our outcome. Therefore, the decision to initiate ECPR depends on the documented rhythms during the resuscitation process in addition to the length of LFDs.

Our study has several inherent limitations. First, measuring the time during OHCA was extremely difficult, and any time measurement from bystander CPR until arrival of the emergency medical services would be a very rough estimate. Therefore, the main results of this study were based on rough estimates, and we could not demonstrate some cutoff estimates. Second, the protocol to introduce ECPR in each participating institution was unknown, and there could be other biases among hospitals and treating physicians. Third, we did not obtain information on comorbidities, medications, or activities of daily living of each patient.

In conclusion, an increase in LFD was associated with a decrease in neurological outcome. Furthermore, the effect of LFD differed according to the cardiac rhythms during resuscitation.

The authors are deeply indebted to all members of the CRITICAL study group for their contributions. In addition, they are deeply grateful to all the emergency medical services personnel for collecting Utstein data and to Ikuko Nakamura and Yumiko Murai for supporting the CRITICAL study. They also thank their colleagues from the Osaka University Center of Medical Data Science and Advanced Clinical Epidemiology Investigator’s Research Project for their providing insight and expertise for our research.

This study was supported by a scientific research grant from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (15H05006, 17K11572, and 19K09393). The funding organization did not contribute to the study design; collection, management, analysis, and interpretation of data; writing of the article; or the decision to submit the article for publication.

None.

The data, analytical methods, and study materials will not be made available to other researchers for purposes of reproducing the results or replicating the procedure.

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

体外心肺复苏（ECPR）有望使选定的患者受益，特别是对常规心肺复苏（CPR）难以治疗的患者。¹考虑到其侵入性程序和大量资源，建立启动ECPR的有用标准仍然至关重要。低流量持续时间（LFD）是确定ECPR候选人的最常见标准之一。^1个但是，尚未在院外心脏骤停（OHCA）中充分研究LFD与良好的神经系统结果之间的关联。这项研究旨在评估（1）LFD是否与ECPR后的1个月生存或良好的神经系统结局有关，以及（2）记录的心律与LFD对ECPR的神经系统结局之间的相互作用。

CRITICAL研究（OHCA生存期重症监护综合注册）是一项针对日本大阪府OHCA患者的多中心，前瞻性队列研究，涉及14个机构。²此CRITICAL研究的二级分析包括从2012年7月1日至2016年12月31日在自发性循环恢复之前接受ECPR的OHCA≥18岁的成年患者。LFD定义为开始任何CPR的时间间隔（旁观者心肺复苏或紧急医疗服务人员的心肺复苏）开始ECPR。在离开现场之前，通过对旁观者的紧急医疗服务采访获得了关于旁观者进行心肺复苏术的信息。LFD分为以下三分位数：短（23-45分钟），中（46-57分钟）和长（58-117分钟）。主要结局为1个月生存期，其脑功能类别1或2定义为良好的神经系统结局。次要结局为1个月生存期。第一，我们在医院前和医院内首次记录的心律（可电击-可电击[即持续电击性节律]或其他）基于单变量logistic回归模型中，直观地描述了LFD与受限三次样条在有限的三次样条曲线之间的非线性关系。 ）。其次，为了研究LFD对每种结局的影响，我们应用了单变量和多变量logistic回归分析，调整了年龄（连续），性别，停搏原因（心脏或非心脏）以及院前和院内首次记录的节律（维持令人震惊的节奏或其他）。这项研究得到参与医院的伦理委员会的批准。

在研究期间，登记了9822例OHCA患者，其中256例患者符合我们的分析条件。短，中和长组中，神经功能预后良好的比例分别为22.0％（100分之22），17.1％（82分的14）和6.8％（74分的5）。尽管随着LFD的增加，神经功能预后良好的可能性降低，但在相同的LFD下接受ECPR时，持续电击性节律的人获得其他神经节律的机会更大。在多因素logistic回归分析中，随着LFD的增加，神经功能预后良好的可能性降低（P趋势= 0.016）。就次要结局而言，LFD的差异与1个月生存期之间无显着关联（图[B]）。

数字。 院外心脏骤停（OHCA）后低流量持续时间和体外心肺复苏（ECPR）的结果。A，根据心肺复苏过程中记录的心律，通过体外循环心肺复苏（ECPR）的低流量持续时间进行脑功能分类（CPC）1或2的概率。持续的令人震惊的心律，意味着院前首先记录的心律与医院内首先记录的心律的组合是令人震惊的。其他节奏包括震撼性，不可震撼性，不可震撼性或不可震撼性。乙，从ECPR启动时机的院外心脏骤停的结果。*根据年龄，性别，逮捕原因以及院前和院内节奏进行调整。

只有1项研究针对潜在混杂因素进行了调整，其中包括105例OHCA和377例院内心脏骤停。该研究发现，LFD升高与神经功能预后良好的可能性降低相关[ ^3]，这与我们的发现一致。我们研究的另一个重要优势是，在我们对LFD影响的研究中仅纳入OHCA患者。由于OHCA患者和院内心脏骤停的特征，复苏过程和复苏策略不同，我们的发现可能为OHCA患者启动ECPR的标准提供重要证据。

我们还观察到已记录的节律与良好的神经系统预后之间的关联。对于低质量的心肺复苏术，组织氧向心肌的输送不足可能会导致从最初的可电击心律向无脉动电活动/心搏停止的节律转换的可能性更高，与高水平心肺复苏术相比，缺血/再灌注损伤更大。^4,5相反，如果持续持续的休克节律患者的脑血流量相对维持，那么长LFD可能会改善神经功能预后的可能性。^4,5已知对有利的神经系统结局具有积极影响的其他干预措施，例如自动使用体外除颤器，CPR暂停和CPR的质量也可能影响了我们的结局。因此，启动ECPR的决定除取决于LFD的长度外，还取决于复苏过程中记录的节律。

我们的研究有几个固有的局限性。首先，在OHCA期间测量时间非常困难，从旁观者CPR到紧急医疗服务到达之前的任何时间测量都是非常粗略的估计。因此，这项研究的主要结果是基于粗略的估计，我们无法证明某些临界值。其次，在每个参与机构中引入ECPR的协议尚不清楚，并且医院和主治医生之间可能还有其他偏见。第三，我们没有获得有关每个患者的合并症，药物或日常生活活动的信息。

总之，LFD的增加与神经系统预后的降低有关。此外，LFD的作用因复苏过程中的心律而异。

作者对CRITICAL研究小组的所有成员深表感谢。此外，他们深切感谢所有紧急医疗服务人员收集的Utstein数据，并衷心感谢中村郁子（Ikuko Nakamura）和村井由美子（Yumiko Murai）支持的CRITICAL研究。他们还感谢大阪大学医学数据科学中心和高级临床流行病学研究人员的研究项目的同事为我们的研究提供了见识和专业知识。

这项研究得到了日本教育，文化，体育，科学和技术部（15H05006、17K11572和19K09393）的科学研究资助。资助组织没有为研究设计做任何贡献；收集，管理，分析和解释数据；文章写作；或决定将文章提交发表。

没有。

数据，分析方法和研究材料将不会提供给其他研究人员，以用于再现结果或复制程序。

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