Impact of Transient Return of Spontaneous Circulation and Downtime on Neurological Outcomes following Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest: A Single-Center Retrospective Study

Impact of Transient Return of Spontaneous Circulation and Downtime on Neurological Outcomes following Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest: A Single-Center Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of Transient Return of Spontaneous Circulation and Downtime on Neurological Outcomes following Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest: A Single-Center Retrospective Study Takehiro Homma, Tatsuhiro Shibata, Kenta Murotani, Yoshihisa Matsushima, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8585435/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract Background Despite recent advancements in cardiopulmonary resuscitation (CPR), the prognosis of out-of-hospital cardiac arrest (OHCA) remains poor. Extracorporeal CPR (ECPR) offers potential benefits for patients with refractory OHCA. Identifying the factors associated with neurological outcomes at 180 days and their interactions remains critical for optimizing patient selection. Methods This single-center retrospective study included 65 patients with OHCA treated with ECPR at Kurume University Hospital between 2016 and 2023. Factors associated with the neurological outcomes at 180 days were evaluated using logistic regression and decision tree analyses. Results Favorable neurological outcomes at 180 days were recorded in 18 (27.7%) patients. Transient return of spontaneous circulation (ROSC) (odds ratio (OR): 6.25, 95% confidence interval (CI): 1.82–24.82) and shorter downtime (OR: 0.94, 95% CI: 0.89–0.98) were independently associated with favorable neurological outcomes. Decision tree analysis revealed that the presence of transient ROSC and bystander CPR are upstream factors associated with favorable neurological outcomes, and that the absence of transient ROSC with prolonged downtime was associated with poor outcomes. Conclusion Transient ROSC and shorter downtime were independently associated with favorable neurological outcomes at 180 days in patients treated with ECPR. Using a decision-tree model, we visualized how these key factors interact to influence long-term neurological recovery, highlighting their potential importance in refining the patient selection process for ECPR. Trial registration Not applicable. Refractory cardiac arrest Out-of-hospital cardiac arrest extracorporeal cardiopulmonary resuscitation Extracorporeal membrane oxygenation Neurological outcome Transient return of spontaneous circulation Downtime Figures Figure 1 Background Out-of-hospital cardiac arrest (OHCA) remains a leading cause of mortality, despite significant advancements in cardiopulmonary resuscitation (CPR) over the past decade[ 1 – 3 ]. Survival with functional recovery to hospital discharge remains low, ranging from 5% to 10%[ 4 ]. Notably, a longer CPR duration is inversely associated with favorable neurological outcomes at 1 month[ 5 ]. Previous investigations have revealed that the survival rate of patients transported to the hospital who do not achieve return of spontaneous circulation (ROSC) is < 4%[ 6 , 7 ]. In refractory cardiac arrest, extracorporeal CPR (ECPR) provides mechanical circulatory support (MCS) via veno-arterial extracorporeal membrane oxygenation (VA-ECMO), allowing the identification and treatment of reversible causes[ 8 – 12 ]. Several randomized trials have investigated ECPR versus conventional CPR with mixed results; some trials demonstrated improved survival with ECPR, while others showed no significant differences [ 8 , 9 , 13 ]. These studies indicated that ECPR may be effective under certain conditions. One critical factor is patient eligibility for ECPR; however, there is no consensus on the inclusion and exclusion criteria. The inclusion criteria in previous studies have varied, including age, initial rhythm, witnessed arrest, bystander CPR, and time from cardiac arrest to hospital arrival[ 8 , 12 , 14 , 15 ]. Multiple factors are associated with the survival and neurological recovery of patients treated with ECPR[ 16 – 18 ]. Previous studies reported that shorter low-flow duration, shockable rhythm, higher arterial pH, lower serum lactate levels, and younger age are associated with better outcomes[ 16 , 17 ]. Transient ROSC has also been linked to improved prognosis[ 18 ]. Among these prognostic factors, transient ROSC and the duration of low-flow were considered “final common pathway” indicators, reflecting the restoration of cerebral perfusion and total ischemic burden, respectively. Although several studies have examined neurological outcomes after ECPR, most have focused on short-term endpoints such as 30-day survival or outcomes at hospital discharge. Data on long-term neurological recovery remain limited, particularly in real-world clinical settings[ 9 , 12 ]. Therefore, this study aimed to identify factors associated with favorable neurological outcomes at 180 days among patients with OHCA who underwent ECPR through logistic regression analysis and to further explore potential interactions among these candidate factors using a decision-tree model. By extending the follow-up period and integrating an exploratory analysis of factor interactions, this study aimed to provide additional insights into patient selection and long-term neurological prognosis after ECPR. Methods Aim, design, and setting of the study This is a single-center retrospective study aimed to identify factors associated with favorable neurological outcomes at 180 days among patients with OHCA who underwent ECPR, explore potential interactions among these candidate factors, and provide insights into patient selection and long-term neurological prognosis after ECPR. Patients Consecutive patients with OHCA who underwent ECPR at the Advanced Emergency and Critical Care Center of Kurume University Hospital between January 2016 and December 2023 were enrolled. Individuals aged < 18 years were excluded. The ECPR inclusion criteria were as follows: shockable rhythm on the patient’s initial ECG monitor, age < 75 years, independence in activities of daily living (ADL), and arrival at the hospital within 45 min of onset. For patients with non-shockable rhythm, the inclusion criteria were age < 75 years, independence in ADL, cardiac arrest witnessed by emergency medical service (EMS) teams, and suspicion of cardiogenic cardiac arrest based on symptoms, medical history, and physical examination. Individuals with a “do not attempt resuscitation” order, those with a family expressing a refusal willingness, and those with an existing terminal illness were excluded. Moreover, patients were excluded if the cause of cardiac arrest was actively suspected to be non-cardiogenic or if the physician assessed the patient as unlikely to survive owing to the absence of witnesses and signs of life, such as agonal respiration, pupillary light reflex, or any physical movement. These criteria were developed with reference to the inclusion criteria used in the SAVE-J study and other prior ECPR studies in Japan, and were adapted to fit our institutional workflow and real-world practice[ 12 , 19 ]. Extracorporeal membrane oxygenation ( ECMO) system and ECPR management All patients included in the study were transferred directly to a fluoroscopy room within the Advanced Emergency and Critical Care Center. Our institution employed the Terumo VA-ECMO system (CAPIOX™, Terumo, Tokyo, Japan) and the MERA Unified VA-ECMO system (UNIMO™, Senko Medical Trading Co., Tokyo, Japan) as the MCS devices. Additional MCS, including intraaortic balloon pumping (IABP) (Datascope CS100™/CS300™ or Cardiosave IABP Hybrid™, Getinge Japan, Tokyo, Japan) or a transcatheter heart pump (Impella®, Abiomed Inc., Danvers, MA, USA), was performed based on the primary physician’s decision at the initiation of VA-ECMO and coronary artery angiography. Since its introduction in April 2019, Impella has become the primary choice for adjunctive MCS, except in patients with bleeding complications or vascular access problems. Femoral artery and vein cannulation were performed using 17–19 Fr and 21–25 Fr catheters, respectively, based on body size, using the percutaneous Seldinger technique while continuing conventional CPR (CCPR). In cases where multiple punctures were necessary, echo-guided punctures were performed, and wire manipulation was performed under fluoroscopic guidance for both procedures. Mechanical chest compression, using devices such as LUCAS®3 (Physio-Control/Jolife AB, Lund, Sweden) or CLOVER3000™ (KOHKEN Medical CO. Ltd., Tokyo, Japan), was performed in some instances. Post-ECPR management The patients were transferred to the Cardiac Care Unit (CCU) within the Advanced Emergency and Critical Care Center, and their hemodynamic status was continuously monitored using a Swan-Ganz catheter, an oxygen saturation monitor attached to the right hand, and a regional oxygen saturation monitor attached to the forehead and front shins. VA-ECMO flow was maintained at 60 ml/kg/min to achieve a mean arterial pressure of ≥ 65 mmHg and a mixed venous oxygen saturation of > 60%. This flow rate was sustained until the serum lactate level decreased to < 2 mmol/L. Vasopressors, such as noradrenaline, were administered to maintain the mean arterial pressure, and red blood cell transfusions were performed to maintain hemoglobin levels above 10 g/dl while managing VA-ECMO. The core body temperature was regulated between 34 ℃ and 36 ℃ during the initial 24 h and then gradually increased by 0.25 ℃ every hour until a core body temperature of 37 ℃ was achieved. Once serum lactate levels dropped below 2 mmol/L, the weaning process from VA-ECMO was initiated. Following successful weaning from VA-ECMO, removal of the IABP or Impella was performed upon recovery of the patient’s cardiac function. Unfractionated heparin was used as the anticoagulant, with activated thromboplastin time monitored every 6 h (target range: 50–60 s) or activated clotting time assessed multiple times daily (target range: 160–180 s). Endpoints and definitions The primary outcome was the identification of factors associated with favorable neurological outcomes at 180 days in patients who underwent ECPR for refractory OHCA. The secondary outcome was the interactions between the factors associated with favorable neurological outcomes. Neurological outcomes were assessed using the Glasgow- Pittsburgh Cerebral Performance Category (CPC). CPCs 1 and 2 were considered favorable neurological outcomes, while CPCs 3, 4, and 5 were considered poor outcomes. Initial shockable rhythm was defined as ventricular fibrillation or pulseless ventricular tachycardia. Transient ROSC was defined as any palpable pulse or measurable blood pressure ≥ 1 min before ECMO initiation, either before or after hospital arrival[ 20 ]. Downtime was defined as the duration from the witnessed cardiopulmonary arrest or the last health check to the initiation of VA-ECMO, including low-flow time (the time between the onset of CPR and ROSC) and no-flow time (the time from collapse to the initiation of CPR)[ 21 ]. Arterial blood gas analysis and biochemical tests were performed immediately after ECPR. Statistical analysis All statistical analyses were performed using the JMP Student Edition version 18.2.1 software (SAS Institute Japan, Tokyo, Japan). Statistical significance was defined as a two-sided p < 0.05. Continuous variables are expressed as medians (interquartile range [IQR]). Continuous and categorical variables were compared using the Wilcoxon rank-sum and the chi-squared tests, respectively. To determine the factors associated with a favorable neurological outcome at 180 days, univariate logistic regression analysis was conducted. Age, sex, witnessed bystander CPR, shockable rhythm, transient ROSC, downtime, arterial pH, and serum lactate concentration were evaluated using univariate analysis. As transient ROSC and downtime represent clinically established core prognostic factors reflecting the restoration of cerebral perfusion and ischemic burden, respectively, these two variables were included a priori in the multivariable logistic regression model, irrespective of their univariate significance. Missing data were present only for arterial pH and serum lactate levels (n = 2 per group). Because the proportion of missing data was small and unlikely to influence the results, these variables were handled using a complete-case analysis without imputation. A decision tree model was then constructed using the Partition platform in JMP, with the neurological outcome (CPCs 1–2 vs. CPCs 3–5) as the response variable and the same candidate predictors used in the univariate analysis as explanatory variables to explore interactions and stratification patterns among predictors. The split points were derived algorithmically using the partition platform in a data-driven manner without a subjective cutoff specification, ensuring the reproducibility of the splitting rule. Results Study population and baseline characteristics Between January 2016 and December 2023, 66 consecutive patients with OHCA underwent ECPR. Among them, one patient aged < 18 years was excluded, leaving 65 eligible patients. Of these patients, 18 (27.7%) had favorable neurological outcomes at 180 days. The median patient age was 61 (IQR, 53–69) years, and 89.2% of patients were men (Table 1 ). In 86.2% of the patients, the initial rhythm was shockable, and bystander CPR was performed in 72.3% of the patients. The median time from call to arrival at the hospital was 33 (IQR: 28–42) min, the time from first medical contact to departure from the field was 10 (IQR: 8–13) min, the time from departure from the field to hospital arrival was 13 (IQR: 7–21) min, the time from hospital arrival to ECMO initiation was 17 (IQR: 14–23) min, and the downtime was 49 (IQR: 38–60) min. Arterial blood gas analysis immediately after ECPR revealed that the median pH value was 6.98 (IQR: 6.85–7.11), and the median serum lactate level was 13.6 (IQR: 11.2–16.0) mmol/L. The most common cause of cardiac arrest was ischemic heart disease (80.0%), including acute coronary syndrome, which was observed in 53.8% of patients. Transient ROSC was recorded in 38.5% of the patients. For post-resuscitation therapy, target temperature management was completed in 90.8%, and the percutaneous coronary intervention procedure was performed in 49.2% of patients (Table 2 ). As additional MCS to VA-ECMO, IABP and Impella were used in 35.4% and 46.2% of the patients, respectively. Table 1 Baseline characteristics stratified by neurological outcomes at 180 days All (n = 65) CPC 1–2 (n = 18) CPC 3–5 (n = 47) P values** Age, years 61 [ 53–69 ] 63 [49–71] 61 [54–68] 0.907 Males, n (%) 58 (89.2) 15 (83.3) 43 (91.5) 0.343 Body mass index, kg/m 2 24.5 [22.6–26.6] 24.7 [21.5–26.6 ] 24.5 [23.1–27.0 ] 0.698 Past History, n (%) Hypertension 33 (55.0) 10 (55.6) 23 (54.8) 0.955 Hyperlipidemia 24 (39.3) 5 (27.8) 19 (44.2) 0.232 Diabetes Mellitus 23 (37.7) 4 (22.2) 19 (44.2) 0.107 Smoking 36 (63.2) 9 (52.9) 27 (67.5) 0.297 Chronic Heart Failure 10 (17.0) 5 (27.8) 5 (12.2) 0.142 Prior Myocardial Infarction 9 (15.0) 4 (22.2) 5 (11.9) 0.305 Prior Stroke 9 (14.8) 2 (11.1) 7 (16.3) 0.604 Initial cardiac rhythm Shockable 56 (86.2) 16 (88.9) 40 (85.1) 0.693 Pulseless electrical activity 9 (13.8) 2 (11.1) 7 (14.9) 0.693 Witnessed arrest 52 (80.0) 16 (88.9) 36 (76.6) 0.268 Bystander’s CPR 47 (72.3) 16 (88.9) 31 (66.0) 0.065 Call to hospital, min 33 [28–42] 33 [25–38] 33 [28–43] 0.393 First medical contact to departure from the field interval, min 10 [ 8 – 13 ] 10 [ 8 – 12 ] 10 [ 7 – 15 ] 0.637 Departure from the field to hospital arrival, min 13 [ 7 – 21 ] 11 [ 7 – 15 ] 13 [ 8 – 21 ] 0.590 Hospital arrival to ECMO time, min 17 [ 14 – 23 ] 17 [ 13 – 22 ] 17 [ 14 – 25 ] 0.730 Downtime, min 49 [38–60] 41 [32–50] 51 [42–65] 0.009 Arrived during off-hours 26 (40.0) 7 (38.9) 19 (40.4) 0.910 Use of epinephrine in the field 35 (57.4) 10 (62.5) 25 (55.6) 0.630 Serum lactate concentration, mmol/L 13.6 [11.2–16.0] 13.7 [9.7–15.3] 13.6 [11.4–16.8] 0.215 Arterial pH 6.98 [6.85–7.11] 7.01 [6.94–7.20] 6.97 [6.83–7.08] 0.096 Etiology of arrest Ischemic heart disease 52 (80.0) 11 (61.1) 41 (87.2) 0.019 Acute coronary syndrome 35 (53.8) 7 (38.9) 28 (59.6) 0.134 Non-ischemic heart disease 3 (4.6) 1 (5.6) 2 (4.3) 0.823 Idiopathic arrhythmia 6 (9.2) 4 (22.2) 2 (4.3) 0.025 Pulmonary embolism 1 (1.5) 1 (5.6) 0 (0.0) 0.103 Others 3 (4.6) 1 (5.6) 2 (4.3) 0.823 Transient ROSC 25 (38.5) 12 (66.7) 13 (27.7) 0.004 * Numbers show median value [interquartile range] or n/N (%) in brackets ** P values were calculated using Pearson’s chi-square test or the Wilcoxon rank-sum test for comparisons between CPC 1–2 and CPC 3–5 groups. N – number of patients, CPC: cerebral performance category, CPR: cardiopulmonary resuscitation, ECMO: extracorporeal membrane oxygenation, ROSC: return of spontaneous circulation Table 2 In-hospital treatments and clinical outcomes stratified by neurological outcomes at 180 days All (n = 65) CPC 1–2 (n = 18) CPC 3–5 (n = 47) P values** Target temperature management 59 (90.8) 16 (88.9) 43 (91.5) 0.746 PCI procedure 32 (49.2) 7 (38.9) 25 (53.2) 0.302 Additional MCS on ECMO IABP 23 (35.4) 3 (16.7) 20 (42.6) 0.051 Impella 30 (46.2) 11 (61.1) 19 (40.4) 0.134 Duration of ECMO, hours 90.2 [51.9–125.2] 91.8 [68.3–111.1] 90.2 [51.3–133.2] 0.889 Successful ECMO weaning 41 (63.1) 18 (100) 23 (48.9) < 0.001 Survival at 30 days 30 (46.2) 18 (100) 12 (25.5) < 0.001 Survival at 180 days 23 (35.4) 18 (100) 5 (10.6) < 0.001 * Numbers show median value [interquartile range] or n/N (%) in brackets ** P values were calculated using Pearson’s chi-square test or the Wilcoxon rank-sum test for comparisons between CPC 1–2 and CPC 3–5 groups. N – number of patients, CPC: cerebral performance category, ECMO: extracorporeal membrane oxygenation, IABP: intra-aortic balloon pumping, PCI: percutaneous coronary intervention, PVAD: Percutaneous Ventricular Assist Device, TTM: targeted temperature management, Comparison between favorable and unfavorable outcomes Between the favorable and unfavorable neurological outcome groups, the downtime was shorter in the favorable outcome group (median 41 vs. 51 min, p = 0.009). Additionally, in the favorable neurological group, the incidences of ischemic heart disease and idiopathic arrhythmia as causes of cardiac arrest were lower (61.1% vs. 87.2%) and higher (22.2% vs. 4.3%), respectively, and transient ROSC was more frequently observed (66.7% vs. 27.7%) (Table 1 ). However, there was no significant difference in serum lactate concentration between the two groups (median 13.7 vs. 13.6 mmol/L, p = 0.215). Factors associated with favorable neurological outcomes at 180 days Univariate analysis revealed bystander CPR (odds ratio [OR], 4.13; 95% confidence interval [CI], 1.00–28.18), transient ROSC (OR, 5.23; 95% CI, 1.68–17.91), and downtime (OR, 0.95; 95% CI, 0.90–0.98) were identified as significant prediction of favorable neurological outcomes. Multivariate analysis revealed that transient ROSC (OR, 6.25; 95% CI, 1.82–24.82) and downtime (OR, 0.94; 95% CI, 0.89–0.98) remained significantly and independently associated with favorable neurological outcomes (Table 3 ). Table 3 Univariate and multivariate logistic regression analyses for predictors of favorable neurological outcomes at 180 days CI: confidence interval, CPR: cardiopulmonary resuscitation, OR: odds ratio, ROSC: return of spontaneous circulation Univariate Multivariate Variables OR 95%CI P value OR 95%CI P value Age, year 0.98 0.94–1.03 0.467 Male 0.47 0.09–2.58 0.361 Witnessed 2.44 0.57–16.98 0.246 Bystander CPR 4.13 1.00–28.18 0.049 Shockable rhythm 1.40 0.30–10.07 0.687 Transient ROSC 5.23 1.68–17.91 0.004 6.25 1.82–24.82 0.003 Downtime, min 0.95 0.90–0.98 0.004 0.94 0.89–0.98 0.003 Arterial pH 12.79 0.59–380.14 0.105 Serum lactate concentration, mmol/L 0.91 0.78–1.04 0.156 Data analysis using the decision-tree model Decision-tree model analysis revealed that the first split was based on whether transient ROSC was observed ( Figure ). In the group with transient ROSC, the next split was based on whether bystander CPR was performed. In the group without transient ROSC, the subsequent split was determined based on whether the downtime was < 49 minutes. The splits in the decision tree were aligned with significant variables in the multivariate logistic regression, and the model appeared to be medically interpretable and valid. Figure demonstrates that cases without transient ROSC had fewer patients with favorable neurological outcomes at 180 days (15.0%). In the group with transient ROSC d and bystander CPR, 11 out of 16 patients (68.8%) had favorable neurological outcomes at 180 days. In the group without transient ROSC, but with a downtime < 49 min, six out of 18 patients (33.3%) had favorable neurological outcomes at 180 days. In contrast, in the group without transient ROSC but with a downtime ≥ 49 min, no patients had favorable neurological outcomes at 180 days. Discussion The major finding of this study was the independent association of the occurrence of transient ROSC and shorter downtime with favorable neurological outcomes at 180 days in patients treated with ECPR. The decision-tree model further demonstrated that transient ROSC with bystander CPR was associated with favorable neurological outcomes. In contrast, none of the patients in the group without transient ROSC and with a model-derived downtime threshold of approximately 49 min, as identified by the decision tree, exhibited favorable neurological outcomes. ECPR is a resuscitation method for patients with refractory cardiogenic cardiac arrest who cannot be treated with CCPR[ 8 – 12 ]. However, it is not effective for all patients and should be reserved for those with reversible causes and the potential for neurological recovery. As ECPR requires substantial medical resources and costs[ 22 ], identifying patients who are most likely to benefit from it is essential. Many institutions have therefore developed their own inclusion criteria[ 15 ], and numerous studies have examined individual prognostic factors[ 16 , 18 , 23 – 27 ]. However, neurological outcomes are likely influenced by complex interactions among multiple factors. Our decision-tree analysis complements these previous reports by visualizing such interactions and stratifying patients according to clinically meaningful combinations of variables. In this study, transient ROSC and downtime were associated with neurological outcomes after 180 days. Previous reports have shown that transient ROSC is independently associated with favorable outcomes in patients treated with ECPR, regardless of the timing of ROSC[ 18 ]. Regarding the association between downtime and neurological outcomes, current guidelines recommend establishing ECPR within 60 min of cardiac arrest[ 28 ]. Additionally, results from a multicenter registry in Japan reported favorable outcomes with a low-flow time of < 40 min [ 29 ]. In contrast, our study did not find any association between blood lactate concentration, pH, and neurological outcomes. This discrepancy may be attributed to the timing of blood sampling immediately after ECMO initiation, which might reflect both initial injury severity and reperfusion effects rather than purely the pre-ECMO physiological status[ 30 ]. An analysis of the interaction between factors revealed that favorable neurological outcomes were achieved in the group in which transient ROSC was observed and bystander CPR was performed. This suggests that bystander CPR may act as an upstream facilitator of transient ROSC rather than an independent downstream predictor, consistent with previous studies showing that patients who received bystander CPR were more likely to achieve ROSC than those who did not [ 31 , 32 ]. Conversely, patients who previously achieved ROSC but experienced re-arrest during resuscitation had worse outcomes[ 33 ]. Based on these findings, patients who underwent bystander CPR and achieved transient ROSC, but experienced subsequent cardiac arrest may be suitable candidates for ECPR. By contrast, none of the patients in the group without transient ROSC and with a downtime duration identified by the decision-tree analysis achieved a favorable neurological outcome. This finding suggests that a prolonged ischemic burden may outweigh the potential benefits of ECPR when immediate restoration of cerebral perfusion cannot be achieved. Considering that downtime includes the duration from hospital arrival to ECMO initiation, patients without transient ROSC may only be suitable candidates for ECPR if they are located within a limited geographical area near the hospital. To overcome the practical constraints of time and distance, prehospital ECPR has already been implemented in some regions and has demonstrated logistical feasibility, particularly through mobile ECMO teams or Helicopter Emergency Medical Services. [ 34 – 36 ]. Such strategies may be theoretically relevant for patients without transient ROSC, but with potentially reversible pathology, in whom the window for neurological salvage is highly time dependent. Further studies are warranted to determine whether earlier circulatory support in the prehospital phase can mitigate the detrimental effects of prolonged low-flow time in this subgroup. Limitation Our study has some potential limitations. First, this was a single-center retrospective study with a relatively modest sample size, which may have limited the generalizability of the findings. Second, the study spanned an 8-year period, during which significant changes occurred in our institution’s clinical practices regarding ECPR. Specifically, our institution did not adopt an aggressive ECPR strategy until 2016, and over the subsequent years, our experience may have increased, leading to a more refined patient selection process. In addition, the Impella was not introduced for left ventricular venting at our institution until April 2019. These temporal changes in clinical approaches and technological adoption inevitably introduce variability in outcomes. Moreover, the indications for ECPR were not based on a fully standardized protocol and, in some cases, depended on the discretion of the treatment team, especially for patients near the borderline of the predefined criteria. Therefore, patient selection was not entirely uniform, and patients perceived as more likely to have favorable outcomes may have been preferentially treated with ECPR. This potential selection bias may have influenced the observed associations. Therefore, the findings should be interpreted as associative rather than causal. Despite these limitations, our findings provide valuable preliminary insights into the factors associated with favorable neurological outcomes after ECPR. Future prospective studies with larger sample sizes are warranted to establish the appropriate patient selection criteria. Finally, our findings were affected by factors specific to our institution and the regional healthcare system, such as the time from emergency calls to hospital arrival and the timing of Impella introduction. Consequently, generalizing these results to other healthcare settings, including international contexts, should be done with caution when extrapolating to different healthcare systems. Conclusions Transient ROSC and shorter downtime were independently associated with favorable neurological outcomes at 180 days in patients treated with ECPR. Decision tree analysis further demonstrated that these factors interacted synergistically to determine long-term prognosis as assessed at 180 days. Bystander CPR appeared to function as an upstream factor facilitating transient ROSC rather than as an independent downstream predictor, which may explain its prognostic impact in the interaction analysis. By contrast, the absence of transient ROSC combined with prolonged downtime, as identified by the decision tree, was associated with poor neurological outcomes at 180 days. These findings suggest that data-driven risk stratification may assist in refining the patient selection process for ECPR, although confirmation in larger multicenter studies is required. Abbreviations ADL activities of daily living CCU cardiac care unit CI confidence interval CPR cardiopulmonary resuscitation CPC cerebral performance category CCPR conventional cardiopulmonary resuscitation EMS emergency medical service ECMO extracorporeal membrane oxygenation ECPR extracorporeal cardiopulmonary resuscitation IQR interquartile range IABP intraaortic balloon pumping MCS mechanical circulatory support OR odds ratio OHCA Out-of-hospital cardiac arrest ROSC return of spontaneous circulation VA-ECMO venoarterial extracorporeal membrane oxygenation Declarations Ethics approval and consent to participate The study protocol was approved by the Kurume University Hospital Ethics Committee (Approval: No. 24291) and was conducted in accordance with the Declaration of Helsinki. Owing to the retrospective design of the study, patient consent was obtained using the opt-out method, as approved by the ethics committee. Consent for publication Not applicable. Availability of data and materials The datasets are not publicly available due to ethical and privacy restrictions, but are available from the corresponding author on reasonable request with approval from the Ethics Committee of Kurume University. Competing interests The authors declare that they have no competing interests. Funding Not applicable. Authors’ contributions TH contributed to the conceptualization, methodology, investigation, formal analysis, visualization, writing, review, and editing of the original draft. TS contributed to project administration, investigation, data curation, writing, review, and editing of the original draft. KM contributed to the formal analysis, validation, writing, review, and editing of the original draft. Y M, KS, KH, MO, OT, and Y F contributed to the writing, review, and editing of the original draft. All authors read and approved the final manuscript. 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Richardson ASC, Tonna JE, Nanjayya V, Nixon P, Abrams DC, Raman L, Bernard S, Finney SJ, Grunau B, Youngquist ST, et al. Extracorporeal Cardiopulmonary Resuscitation in Adults. Interim Guideline Consensus Statement From the Extracorporeal Life Support Organization. ASAIO J. 2021;67:221–8. Shoji K, Ohbe H, Kudo D, Tanikawa A, Kobayashi M, Aoki M, Hamaguchi T, Nagashima F, Inoue A, Hifumi T, et al. Low-flow time and outcomes in out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation. Am J Emerg Med. 2024;75:37–41. Dusik M, Rob D, Smalcova J, Havranek S, Karasek J, Smid O, Brodska HL, Kavalkova P, Huptych M, Bakker J, Belohlavek J. Serum lactate in refractory out-of-hospital cardiac arrest: Post-hoc analysis of the Prague OHCA study. Resuscitation 2023:109935. Milewski R, Lewko J, Milewska G, Baranowska A, Lankau A, Orzechowska M, Krajewska-Kulak E. Actions Taken by Bystanders During Sudden Cardiac Arrest: Analysis of Emergency Medical Service Documentation in Poland. J Clin Med 2024, 13. Zhou G, Wang Y, Sun Z, Yuan M, Ma Y, Wu Q, Wu C, Xu J, Li Y, Liu Y, et al. Survival outcome among patients with out-of-hospital cardiac arrest who received cardiopulmonary resuscitation in China: a systematic review and meta-analysis. Eur J Med Res. 2023;28:8. Salcido DD, Sundermann ML, Koller AC, Menegazzi JJ. Incidence and outcomes of rearrest following out-of-hospital cardiac arrest. Resuscitation. 2015;86:19–24. Ali S, Moors X, van Schuppen H, Mommers L, Weelink E, Meuwese CL, Kant M, van den Brule J, Kraemer CE, Vlaar APJ, et al. A national multi centre pre-hospital ECPR stepped wedge study; design and rationale of the ON-SCENE study. Scand J Trauma Resusc Emerg Med. 2024;32:31. Singer B, Hla TTW, Abu-Habsa M, Davies G, Wrigley F, Faulkner M, Finney SJ. Sub30: Feasibility study of a pre-hospital extracorporeal membrane oxygenation (ECMO) in patients with refractory out-of-hospital cardiac arrest in London, United Kingdom. Resuscitation 2024:110455. Lamhaut L, Hutin A, Puymirat E, Jouan J, Raphalen JH, Jouffroy R, Jaffry M, Dagron C, An K, Dumas F, et al. A Pre-Hospital Extracorporeal Cardio Pulmonary Resuscitation (ECPR) strategy for treatment of refractory out hospital cardiac arrest: An observational study and propensity analysis. Resuscitation. 2017;117:109–17. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 16 Feb, 2026 Reviews received at journal 14 Feb, 2026 Reviewers agreed at journal 14 Feb, 2026 Reviews received at journal 09 Feb, 2026 Reviewers agreed at journal 21 Jan, 2026 Reviewers agreed at journal 20 Jan, 2026 Reviewers invited by journal 14 Jan, 2026 Editor invited by journal 14 Jan, 2026 Editor assigned by journal 14 Jan, 2026 Submission checks completed at journal 14 Jan, 2026 First submitted to journal 12 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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16:43:27","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":131663,"visible":true,"origin":"","legend":"","description":"","filename":"0c7c7222dcb64b8c865eebc5721b01001structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8585435/v1/b1ca6cecd892b91f4795befc.xml"},{"id":100611692,"identity":"1181980b-61ed-40dc-83af-830138f3fcc6","added_by":"auto","created_at":"2026-01-19 16:42:49","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":142867,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8585435/v1/5dfb653e61f63494140d63f7.html"},{"id":100611531,"identity":"c017fefe-088d-4371-87b1-1853d22c806a","added_by":"auto","created_at":"2026-01-19 16:41:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":139080,"visible":true,"origin":"","legend":"\u003cp\u003eDecision-tree model\u003cstrong\u003e a\u003c/strong\u003enalysis of data of patients treated with ECPR using a tree model.\u003c/p\u003e\n\u003cp\u003eECPR, extracorporeal cardiopulmonary resuscitation; CPR, cardiopulmonary resuscitation; ROSC, return of spontaneous circulation\u003c/p\u003e","description":"","filename":"Figure20260109.png","url":"https://assets-eu.researchsquare.com/files/rs-8585435/v1/866ffb2db50b855dc628b5d4.png"},{"id":100614317,"identity":"9b39c8b0-cf2a-4ca2-8049-5d5e956f3ec5","added_by":"auto","created_at":"2026-01-19 17:18:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1132725,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8585435/v1/e6866a92-204a-4ee0-a4a0-696401964862.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of Transient Return of Spontaneous Circulation and Downtime on Neurological Outcomes following Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest: A Single-Center Retrospective Study","fulltext":[{"header":"Background","content":"\u003cp\u003eOut-of-hospital cardiac arrest (OHCA) remains a leading cause of mortality, despite significant advancements in cardiopulmonary resuscitation (CPR) over the past decade[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Survival with functional recovery to hospital discharge remains low, ranging from 5% to 10%[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Notably, a longer CPR duration is inversely associated with favorable neurological outcomes at 1 month[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Previous investigations have revealed that the survival rate of patients transported to the hospital who do not achieve return of spontaneous circulation (ROSC) is \u0026lt;\u0026thinsp;4%[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn refractory cardiac arrest, extracorporeal CPR (ECPR) provides mechanical circulatory support (MCS) via veno-arterial extracorporeal membrane oxygenation (VA-ECMO), allowing the identification and treatment of reversible causes[\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Several randomized trials have investigated ECPR versus conventional CPR with mixed results; some trials demonstrated improved survival with ECPR, while others showed no significant differences [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. These studies indicated that ECPR may be effective under certain conditions. One critical factor is patient eligibility for ECPR; however, there is no consensus on the inclusion and exclusion criteria. The inclusion criteria in previous studies have varied, including age, initial rhythm, witnessed arrest, bystander CPR, and time from cardiac arrest to hospital arrival[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMultiple factors are associated with the survival and neurological recovery of patients treated with ECPR[\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Previous studies reported that shorter low-flow duration, shockable rhythm, higher arterial pH, lower serum lactate levels, and younger age are associated with better outcomes[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Transient ROSC has also been linked to improved prognosis[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Among these prognostic factors, transient ROSC and the duration of low-flow were considered \u0026ldquo;final common pathway\u0026rdquo; indicators, reflecting the restoration of cerebral perfusion and total ischemic burden, respectively.\u003c/p\u003e \u003cp\u003eAlthough several studies have examined neurological outcomes after ECPR, most have focused on short-term endpoints such as 30-day survival or outcomes at hospital discharge. Data on long-term neurological recovery remain limited, particularly in real-world clinical settings[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Therefore, this study aimed to identify factors associated with favorable neurological outcomes at 180 days among patients with OHCA who underwent ECPR through logistic regression analysis and to further explore potential interactions among these candidate factors using a decision-tree model. By extending the follow-up period and integrating an exploratory analysis of factor interactions, this study aimed to provide additional insights into patient selection and long-term neurological prognosis after ECPR.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eAim, design, and setting of the study\u003c/h2\u003e \u003cp\u003eThis is a single-center retrospective study aimed to identify factors associated with favorable neurological outcomes at 180 days among patients with OHCA who underwent ECPR, explore potential interactions among these candidate factors, and provide insights into patient selection and long-term neurological prognosis after ECPR.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatients\u003c/h3\u003e\n\u003cp\u003e Consecutive patients with OHCA who underwent ECPR at the Advanced Emergency and Critical Care Center of Kurume University Hospital between January 2016 and December 2023 were enrolled. Individuals aged\u0026thinsp;\u0026lt;\u0026thinsp;18 years were excluded. The ECPR inclusion criteria were as follows: shockable rhythm on the patient\u0026rsquo;s initial ECG monitor, age\u0026thinsp;\u0026lt;\u0026thinsp;75 years, independence in activities of daily living (ADL), and arrival at the hospital within 45 min of onset. For patients with non-shockable rhythm, the inclusion criteria were age\u0026thinsp;\u0026lt;\u0026thinsp;75 years, independence in ADL, cardiac arrest witnessed by emergency medical service (EMS) teams, and suspicion of cardiogenic cardiac arrest based on symptoms, medical history, and physical examination. Individuals with a \u0026ldquo;do not attempt resuscitation\u0026rdquo; order, those with a family expressing a refusal willingness, and those with an existing terminal illness were excluded. Moreover, patients were excluded if the cause of cardiac arrest was actively suspected to be non-cardiogenic or if the physician assessed the patient as unlikely to survive owing to the absence of witnesses and signs of life, such as agonal respiration, pupillary light reflex, or any physical movement. These criteria were developed with reference to the inclusion criteria used in the SAVE-J study and other prior ECPR studies in Japan, and were adapted to fit our institutional workflow and real-world practice[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eExtracorporeal membrane oxygenation (\u003c/b\u003e \u003cb\u003eECMO) system and ECPR management\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAll patients included in the study were transferred directly to a fluoroscopy room within the Advanced Emergency and Critical Care Center. Our institution employed the Terumo VA-ECMO system (CAPIOX\u0026trade;, Terumo, Tokyo, Japan) and the MERA Unified VA-ECMO system (UNIMO\u0026trade;, Senko Medical Trading Co., Tokyo, Japan) as the MCS devices. Additional MCS, including intraaortic balloon pumping (IABP) (Datascope CS100\u0026trade;/CS300\u0026trade; or Cardiosave IABP Hybrid\u0026trade;, Getinge Japan, Tokyo, Japan) or a transcatheter heart pump (Impella\u0026reg;, Abiomed Inc., Danvers, MA, USA), was performed based on the primary physician\u0026rsquo;s decision at the initiation of VA-ECMO and coronary artery angiography. Since its introduction in April 2019, Impella has become the primary choice for adjunctive MCS, except in patients with bleeding complications or vascular access problems.\u003c/p\u003e \u003cp\u003eFemoral artery and vein cannulation were performed using 17\u0026ndash;19 Fr and 21\u0026ndash;25 Fr catheters, respectively, based on body size, using the percutaneous Seldinger technique while continuing conventional CPR (CCPR). In cases where multiple punctures were necessary, echo-guided punctures were performed, and wire manipulation was performed under fluoroscopic guidance for both procedures. Mechanical chest compression, using devices such as LUCAS\u0026reg;3 (Physio-Control/Jolife AB, Lund, Sweden) or CLOVER3000\u0026trade; (KOHKEN Medical CO. Ltd., Tokyo, Japan), was performed in some instances.\u003c/p\u003e\n\u003ch3\u003ePost-ECPR management\u003c/h3\u003e\n\u003cp\u003eThe patients were transferred to the Cardiac Care Unit (CCU) within the Advanced Emergency and Critical Care Center, and their hemodynamic status was continuously monitored using a Swan-Ganz catheter, an oxygen saturation monitor attached to the right hand, and a regional oxygen saturation monitor attached to the forehead and front shins. VA-ECMO flow was maintained at 60 ml/kg/min to achieve a mean arterial pressure of \u0026ge;\u0026thinsp;65 mmHg and a mixed venous oxygen saturation of \u0026gt;\u0026thinsp;60%. This flow rate was sustained until the serum lactate level decreased to \u0026lt;\u0026thinsp;2 mmol/L. Vasopressors, such as noradrenaline, were administered to maintain the mean arterial pressure, and red blood cell transfusions were performed to maintain hemoglobin levels above 10 g/dl while managing VA-ECMO.\u003c/p\u003e \u003cp\u003eThe core body temperature was regulated between 34 ℃ and 36 ℃ during the initial 24 h and then gradually increased by 0.25 ℃ every hour until a core body temperature of 37 ℃ was achieved. Once serum lactate levels dropped below 2 mmol/L, the weaning process from VA-ECMO was initiated. Following successful weaning from VA-ECMO, removal of the IABP or Impella was performed upon recovery of the patient\u0026rsquo;s cardiac function. Unfractionated heparin was used as the anticoagulant, with activated thromboplastin time monitored every 6 h (target range: 50\u0026ndash;60 s) or activated clotting time assessed multiple times daily (target range: 160\u0026ndash;180 s).\u003c/p\u003e\n\u003ch3\u003eEndpoints and definitions\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was the identification of factors associated with favorable neurological outcomes at 180 days in patients who underwent ECPR for refractory OHCA. The secondary outcome was the interactions between the factors associated with favorable neurological outcomes.\u003c/p\u003e \u003cp\u003eNeurological outcomes were assessed using the Glasgow- Pittsburgh Cerebral Performance Category (CPC). CPCs 1 and 2 were considered favorable neurological outcomes, while CPCs 3, 4, and 5 were considered poor outcomes. Initial shockable rhythm was defined as ventricular fibrillation or pulseless ventricular tachycardia. Transient ROSC was defined as any palpable pulse or measurable blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;1 min before ECMO initiation, either before or after hospital arrival[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Downtime was defined as the duration from the witnessed cardiopulmonary arrest or the last health check to the initiation of VA-ECMO, including low-flow time (the time between the onset of CPR and ROSC) and no-flow time (the time from collapse to the initiation of CPR)[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Arterial blood gas analysis and biochemical tests were performed immediately after ECPR.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using the JMP Student Edition version 18.2.1 software (SAS Institute Japan, Tokyo, Japan). Statistical significance was defined as a two-sided p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Continuous variables are expressed as medians (interquartile range [IQR]). Continuous and categorical variables were compared using the Wilcoxon rank-sum and the chi-squared tests, respectively. To determine the factors associated with a favorable neurological outcome at 180 days, univariate logistic regression analysis was conducted. Age, sex, witnessed bystander CPR, shockable rhythm, transient ROSC, downtime, arterial pH, and serum lactate concentration were evaluated using univariate analysis. As transient ROSC and downtime represent clinically established core prognostic factors reflecting the restoration of cerebral perfusion and ischemic burden, respectively, these two variables were included a priori in the multivariable logistic regression model, irrespective of their univariate significance. Missing data were present only for arterial pH and serum lactate levels (n\u0026thinsp;=\u0026thinsp;2 per group). Because the proportion of missing data was small and unlikely to influence the results, these variables were handled using a complete-case analysis without imputation. A decision tree model was then constructed using the Partition platform in JMP, with the neurological outcome (CPCs 1\u0026ndash;2 vs. CPCs 3\u0026ndash;5) as the response variable and the same candidate predictors used in the univariate analysis as explanatory variables to explore interactions and stratification patterns among predictors. The split points were derived algorithmically using the partition platform in a data-driven manner without a subjective cutoff specification, ensuring the reproducibility of the splitting rule.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStudy population and baseline characteristics\u003c/h2\u003e \u003cp\u003eBetween January 2016 and December 2023, 66 consecutive patients with OHCA underwent ECPR. Among them, one patient aged\u0026thinsp;\u0026lt;\u0026thinsp;18 years was excluded, leaving 65 eligible patients. Of these patients, 18 (27.7%) had favorable neurological outcomes at 180 days. The median patient age was 61 (IQR, 53\u0026ndash;69) years, and 89.2% of patients were men (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In 86.2% of the patients, the initial rhythm was shockable, and bystander CPR was performed in 72.3% of the patients. The median time from call to arrival at the hospital was 33 (IQR: 28\u0026ndash;42) min, the time from first medical contact to departure from the field was 10 (IQR: 8\u0026ndash;13) min, the time from departure from the field to hospital arrival was 13 (IQR: 7\u0026ndash;21) min, the time from hospital arrival to ECMO initiation was 17 (IQR: 14\u0026ndash;23) min, and the downtime was 49 (IQR: 38\u0026ndash;60) min. Arterial blood gas analysis immediately after ECPR revealed that the median pH value was 6.98 (IQR: 6.85\u0026ndash;7.11), and the median serum lactate level was 13.6 (IQR: 11.2\u0026ndash;16.0) mmol/L. The most common cause of cardiac arrest was ischemic heart disease (80.0%), including acute coronary syndrome, which was observed in 53.8% of patients. Transient ROSC was recorded in 38.5% of the patients. For post-resuscitation therapy, target temperature management was completed in 90.8%, and the percutaneous coronary intervention procedure was performed in 49.2% of patients (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). As additional MCS to VA-ECMO, IABP and Impella were used in 35.4% and 46.2% of the patients, respectively.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics stratified by neurological outcomes at 180 days\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll (n\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCPC 1\u0026ndash;2 (n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCPC 3\u0026ndash;5 (n\u0026thinsp;=\u0026thinsp;47)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP values**\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 [ 53\u0026ndash;69 ]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 [49\u0026ndash;71]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61 [54\u0026ndash;68]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.907\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMales, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (89.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (83.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43 (91.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.343\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.5 [22.6\u0026ndash;26.6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.7 [21.5\u0026ndash;26.6 ]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.5 [23.1\u0026ndash;27.0 ]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.698\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePast History, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (55.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (55.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (54.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.955\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperlipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (39.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (27.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (44.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes Mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (37.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (44.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.107\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (63.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (52.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (67.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.297\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic Heart Failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (17.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (27.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (12.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.142\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior Myocardial Infarction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (11.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.305\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior Stroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (14.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (16.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.604\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInitial cardiac rhythm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShockable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (86.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (88.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (85.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.693\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulseless electrical activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (14.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.693\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWitnessed arrest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (88.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (76.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.268\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBystander\u0026rsquo;s CPR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47 (72.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (88.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (66.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.065\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCall to hospital, min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 [28\u0026ndash;42]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 [25\u0026ndash;38]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 [28\u0026ndash;43]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.393\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst medical contact to departure from the field interval, min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 [\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 [\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 [\u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11 CR12 CR13 CR14\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.637\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeparture from the field to hospital arrival, min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 [\u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 [\u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11 CR12 CR13 CR14\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 [\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.590\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital arrival to ECMO time, min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 [\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 [\u003cspan additionalcitationids=\"CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 [\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.730\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDowntime, min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 [38\u0026ndash;60]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 [32\u0026ndash;50]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51 [42\u0026ndash;65]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArrived during off-hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (40.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.910\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of epinephrine in the field\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (57.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (55.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.630\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum lactate concentration, mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.6 [11.2\u0026ndash;16.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.7 [9.7\u0026ndash;15.3]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.6 [11.4\u0026ndash;16.8]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.215\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArterial pH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.98 [6.85\u0026ndash;7.11]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.01 [6.94\u0026ndash;7.20]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.97 [6.83\u0026ndash;7.08]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.096\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEtiology of arrest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIschemic heart disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (61.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (87.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute coronary syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (53.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (59.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.134\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-ischemic heart disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (4.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.823\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIdiopathic arrhythmia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary embolism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.103\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (4.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.823\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTransient ROSC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (38.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (27.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e* Numbers show median value [interquartile range] or n/N (%) in brackets\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e** P values were calculated using Pearson\u0026rsquo;s chi-square test or the Wilcoxon rank-sum test for comparisons between CPC 1\u0026ndash;2 and CPC 3\u0026ndash;5 groups.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eN \u0026ndash; number of patients, CPC: cerebral performance category, CPR: cardiopulmonary resuscitation, ECMO: extracorporeal membrane oxygenation, ROSC: return of spontaneous circulation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIn-hospital treatments and clinical outcomes stratified by neurological outcomes at 180 days\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll (n\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCPC 1\u0026ndash;2 (n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCPC 3\u0026ndash;5 (n\u0026thinsp;=\u0026thinsp;47)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP values**\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTarget temperature management\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e59 (90.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (88.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e43 (91.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.746\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCI procedure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32 (49.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25 (53.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.302\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdditional MCS on ECMO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIABP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23 (35.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20 (42.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImpella\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30 (46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (61.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e19 (40.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.134\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of ECMO, hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e90.2 [51.9\u0026ndash;125.2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91.8 [68.3\u0026ndash;111.1]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e90.2 [51.3\u0026ndash;133.2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.889\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuccessful ECMO weaning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e41 (63.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23 (48.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurvival at 30 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30 (46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12 (25.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurvival at 180 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23 (35.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (10.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e* Numbers show median value [interquartile range] or n/N (%) in brackets\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e** P values were calculated using Pearson\u0026rsquo;s chi-square test or the Wilcoxon rank-sum test for comparisons between CPC 1\u0026ndash;2 and CPC 3\u0026ndash;5 groups.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eN \u0026ndash; number of patients, CPC: cerebral performance category, ECMO: extracorporeal membrane oxygenation, IABP: intra-aortic balloon pumping, PCI: percutaneous coronary intervention, PVAD: Percutaneous Ventricular Assist Device, TTM: targeted temperature management,\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eComparison between favorable and unfavorable outcomes\u003c/h3\u003e\n\u003cp\u003eBetween the favorable and unfavorable neurological outcome groups, the downtime was shorter in the favorable outcome group (median 41 vs. 51 min, p\u0026thinsp;=\u0026thinsp;0.009). Additionally, in the favorable neurological group, the incidences of ischemic heart disease and idiopathic arrhythmia as causes of cardiac arrest were lower (61.1% vs. 87.2%) and higher (22.2% vs. 4.3%), respectively, and transient ROSC was more frequently observed (66.7% vs. 27.7%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). However, there was no significant difference in serum lactate concentration between the two groups (median 13.7 vs. 13.6 mmol/L, p\u0026thinsp;=\u0026thinsp;0.215).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eFactors associated with favorable neurological outcomes at 180 days\u003c/h2\u003e \u003cp\u003eUnivariate analysis revealed bystander CPR (odds ratio [OR], 4.13; 95% confidence interval [CI], 1.00\u0026ndash;28.18), transient ROSC (OR, 5.23; 95% CI, 1.68\u0026ndash;17.91), and downtime (OR, 0.95; 95% CI, 0.90\u0026ndash;0.98) were identified as significant prediction of favorable neurological outcomes. Multivariate analysis revealed that transient ROSC (OR, 6.25; 95% CI, 1.82\u0026ndash;24.82) and downtime (OR, 0.94; 95% CI, 0.89\u0026ndash;0.98) remained significantly and independently associated with favorable neurological outcomes (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eUnivariate and multivariate logistic regression analyses for predictors of favorable neurological outcomes at 180 days\u003c/b\u003e CI: confidence interval, CPR: cardiopulmonary resuscitation, OR: odds ratio, ROSC: return of spontaneous circulation\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eMultivariate\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.94\u0026ndash;1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.467\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.09\u0026ndash;2.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.361\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWitnessed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.57\u0026ndash;16.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.246\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBystander CPR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u0026ndash;28.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.049\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShockable rhythm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.30\u0026ndash;10.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.687\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTransient ROSC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.68\u0026ndash;17.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.82\u0026ndash;24.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDowntime, min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.90\u0026ndash;0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.89\u0026ndash;0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArterial pH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.59\u0026ndash;380.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum lactate concentration, mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.78\u0026ndash;1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eData analysis using the decision-tree model\u003c/h2\u003e \u003cp\u003eDecision-tree model analysis revealed that the first split was based on whether transient ROSC was observed (\u003cb\u003eFigure\u003c/b\u003e). In the group with transient ROSC, the next split was based on whether bystander CPR was performed. In the group without transient ROSC, the subsequent split was determined based on whether the downtime was \u0026lt;\u0026thinsp;49 minutes. The splits in the decision tree were aligned with significant variables in the multivariate logistic regression, and the model appeared to be medically interpretable and valid. \u003cb\u003eFigure\u003c/b\u003e demonstrates that cases without transient ROSC had fewer patients with favorable neurological outcomes at 180 days (15.0%). In the group with transient ROSC d and bystander CPR, 11 out of 16 patients (68.8%) had favorable neurological outcomes at 180 days. In the group without transient ROSC, but with a downtime\u0026thinsp;\u0026lt;\u0026thinsp;49 min, six out of 18 patients (33.3%) had favorable neurological outcomes at 180 days. In contrast, in the group without transient ROSC but with a downtime\u0026thinsp;\u0026ge;\u0026thinsp;49 min, no patients had favorable neurological outcomes at 180 days.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe major finding of this study was the independent association of the occurrence of transient ROSC and shorter downtime with favorable neurological outcomes at 180 days in patients treated with ECPR. The decision-tree model further demonstrated that transient ROSC with bystander CPR was associated with favorable neurological outcomes. In contrast, none of the patients in the group without transient ROSC and with a model-derived downtime threshold of approximately 49 min, as identified by the decision tree, exhibited favorable neurological outcomes.\u003c/p\u003e \u003cp\u003eECPR is a resuscitation method for patients with refractory cardiogenic cardiac arrest who cannot be treated with CCPR[\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, it is not effective for all patients and should be reserved for those with reversible causes and the potential for neurological recovery. As ECPR requires substantial medical resources and costs[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], identifying patients who are most likely to benefit from it is essential. Many institutions have therefore developed their own inclusion criteria[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], and numerous studies have examined individual prognostic factors[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan additionalcitationids=\"CR24 CR25 CR26\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. However, neurological outcomes are likely influenced by complex interactions among multiple factors. Our decision-tree analysis complements these previous reports by visualizing such interactions and stratifying patients according to clinically meaningful combinations of variables.\u003c/p\u003e \u003cp\u003eIn this study, transient ROSC and downtime were associated with neurological outcomes after 180 days. Previous reports have shown that transient ROSC is independently associated with favorable outcomes in patients treated with ECPR, regardless of the timing of ROSC[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Regarding the association between downtime and neurological outcomes, current guidelines recommend establishing ECPR within 60 min of cardiac arrest[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Additionally, results from a multicenter registry in Japan reported favorable outcomes with a low-flow time of \u0026lt;\u0026thinsp;40 min [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In contrast, our study did not find any association between blood lactate concentration, pH, and neurological outcomes. This discrepancy may be attributed to the timing of blood sampling immediately after ECMO initiation, which might reflect both initial injury severity and reperfusion effects rather than purely the pre-ECMO physiological status[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAn analysis of the interaction between factors revealed that favorable neurological outcomes were achieved in the group in which transient ROSC was observed and bystander CPR was performed. This suggests that bystander CPR may act as an upstream facilitator of transient ROSC rather than an independent downstream predictor, consistent with previous studies showing that patients who received bystander CPR were more likely to achieve ROSC than those who did not [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Conversely, patients who previously achieved ROSC but experienced re-arrest during resuscitation had worse outcomes[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Based on these findings, patients who underwent bystander CPR and achieved transient ROSC, but experienced subsequent cardiac arrest may be suitable candidates for ECPR. By contrast, none of the patients in the group without transient ROSC and with a downtime duration identified by the decision-tree analysis achieved a favorable neurological outcome. This finding suggests that a prolonged ischemic burden may outweigh the potential benefits of ECPR when immediate restoration of cerebral perfusion cannot be achieved. Considering that downtime includes the duration from hospital arrival to ECMO initiation, patients without transient ROSC may only be suitable candidates for ECPR if they are located within a limited geographical area near the hospital. To overcome the practical constraints of time and distance, prehospital ECPR has already been implemented in some regions and has demonstrated logistical feasibility, particularly through mobile ECMO teams or Helicopter Emergency Medical Services. [\u003cspan additionalcitationids=\"CR35\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Such strategies may be theoretically relevant for patients without transient ROSC, but with potentially reversible pathology, in whom the window for neurological salvage is highly time dependent. Further studies are warranted to determine whether earlier circulatory support in the prehospital phase can mitigate the detrimental effects of prolonged low-flow time in this subgroup.\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLimitation\u003c/h2\u003e \u003cp\u003eOur study has some potential limitations. First, this was a single-center retrospective study with a relatively modest sample size, which may have limited the generalizability of the findings. Second, the study spanned an 8-year period, during which significant changes occurred in our institution\u0026rsquo;s clinical practices regarding ECPR. Specifically, our institution did not adopt an aggressive ECPR strategy until 2016, and over the subsequent years, our experience may have increased, leading to a more refined patient selection process. In addition, the Impella was not introduced for left ventricular venting at our institution until April 2019. These temporal changes in clinical approaches and technological adoption inevitably introduce variability in outcomes. Moreover, the indications for ECPR were not based on a fully standardized protocol and, in some cases, depended on the discretion of the treatment team, especially for patients near the borderline of the predefined criteria. Therefore, patient selection was not entirely uniform, and patients perceived as more likely to have favorable outcomes may have been preferentially treated with ECPR. This potential selection bias may have influenced the observed associations. Therefore, the findings should be interpreted as associative rather than causal. Despite these limitations, our findings provide valuable preliminary insights into the factors associated with favorable neurological outcomes after ECPR. Future prospective studies with larger sample sizes are warranted to establish the appropriate patient selection criteria. Finally, our findings were affected by factors specific to our institution and the regional healthcare system, such as the time from emergency calls to hospital arrival and the timing of Impella introduction. Consequently, generalizing these results to other healthcare settings, including international contexts, should be done with caution when extrapolating to different healthcare systems.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eTransient ROSC and shorter downtime were independently associated with favorable neurological outcomes at 180 days in patients treated with ECPR. Decision tree analysis further demonstrated that these factors interacted synergistically to determine long-term prognosis as assessed at 180 days. Bystander CPR appeared to function as an upstream factor facilitating transient ROSC rather than as an independent downstream predictor, which may explain its prognostic impact in the interaction analysis. By contrast, the absence of transient ROSC combined with prolonged downtime, as identified by the decision tree, was associated with poor neurological outcomes at 180 days. These findings suggest that data-driven risk stratification may assist in refining the patient selection process for ECPR, although confirmation in larger multicenter studies is required.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eADL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eactivities of daily living\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCCU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecardiac care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCPR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecardiopulmonary resuscitation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCPC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecerebral performance category\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCCPR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econventional cardiopulmonary resuscitation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEMS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eemergency medical service\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eECMO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eextracorporeal membrane oxygenation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eECPR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eextracorporeal cardiopulmonary resuscitation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einterquartile range\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIABP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintraaortic balloon pumping\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMCS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emechanical circulatory support\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eodds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOHCA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOut-of-hospital cardiac arrest\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eROSC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ereturn of spontaneous circulation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVA-ECMO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003evenoarterial extracorporeal membrane oxygenation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Kurume University Hospital Ethics Committee (Approval: No. 24291) and was conducted in accordance with the Declaration of Helsinki. Owing to the retrospective design of the study, patient consent was obtained using the opt-out method, as approved by the ethics committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets are not publicly available due to ethical and privacy restrictions, but are available from the corresponding author on reasonable request with approval from the Ethics Committee of Kurume University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors\u0026rsquo; contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTH contributed to the conceptualization, methodology, investigation, formal analysis, visualization, writing, review, and editing of the original draft. TS contributed to project administration, investigation, data curation, writing, review, and editing of the original draft. KM contributed to the formal analysis, validation, writing, review, and editing of the original draft. Y M, KS, KH, MO, OT, and Y F contributed to the writing, review, and editing of the original draft. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe sincerely thank the EMS personnel of the Kurume Kouiki Fire Department and the Tosu-Miyaki Area Fire Department for their dedicated efforts and the staff of Kurume University Hospital for their contributions to the treatment and care of the patients included in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eYan S, Gan Y, Jiang N, Wang R, Chen Y, Luo Z, Zong Q, Chen S, Lv C. The global survival rate among adult out-of-hospital cardiac arrest patients who received cardiopulmonary resuscitation: a systematic review and meta-analysis. Crit Care. 2020;24:61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrasner JT, Wnent J, Herlitz J, Perkins GD, Lefering R, Tjelmeland I, Koster RW, Masterson S, Rossell-Ortiz F, Maurer H, et al. Survival after out-of-hospital cardiac arrest in Europe - Results of the EuReCa TWO study. Resuscitation. 2020;148:218\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBerdowski J, Berg RA, Tijssen JG, Koster RW. Global incidences of out-of-hospital cardiac arrest and survival rates: Systematic review of 67 prospective studies. Resuscitation. 2010;81:1479\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBuick JE, Drennan IR, Scales DC, Brooks SC, Byers A, Cheskes S, Dainty KN, Feldman M, Verbeek PR, Zhan C, et al. Improving Temporal Trends in Survival and Neurological Outcomes After Out-of-Hospital Cardiac Arrest. Circ Cardiovasc Qual Outcomes. 2018;11:e003561.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoto Y, Funada A, Goto Y. Relationship Between the Duration of Cardiopulmonary Resuscitation and Favorable Neurological Outcomes After Out-of-Hospital Cardiac Arrest: A Prospective, Nationwide, Population-Based Cohort Study. J Am Heart Assoc. 2016;5:e002819.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDrennan IR, Lin S, Sidalak DE, Morrison LJ. Survival rates in out-of-hospital cardiac arrest patients transported without prehospital return of spontaneous circulation: an observational cohort study. Resuscitation. 2014;85:1488\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Graaf C, Beesems SG, Koster RW. Time of on-scene resuscitation in out of-hospital cardiac arrest patients transported without return of spontaneous circulation. Resuscitation. 2019;138:235\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYannopoulos D, Bartos J, Raveendran G, Walser E, Connett J, Murray TA, Collins G, Zhang L, Kalra R, Kosmopoulos M, et al. Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single centre, open-label, randomised controlled trial. Lancet. 2020;396:1807\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBelohlavek J, Smalcova J, Rob D, Franek O, Smid O, Pokorna M, Horak J, Mrazek V, Kovarnik T, Zemanek D, et al. Effect of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment on Functional Neurologic Outcome in Refractory Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2022;327:737\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRob D, Smalcova J, Smid O, Kral A, Kovarnik T, Zemanek D, Kavalkova P, Huptych M, Komarek A, Franek O, et al. Extracorporeal versus conventional cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest: a secondary analysis of the Prague OHCA trial. Crit Care. 2022;26:330.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePerman SM, Elmer J, Maciel CB, Uzendu A, May T, Mumma BE, Bartos JA, Rodriguez AJ, Kurz MC, Panchal AR et al. 2023 American Heart Association Focused Update on Adult Advanced Cardiovascular Life Support: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. \u003cem\u003eCirculation\u003c/em\u003e 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSakamoto T, Morimura N, Nagao K, Asai Y, Yokota H, Nara S, Hase M, Tahara Y, Atsumi T, Group S-JS. Extracorporeal cardiopulmonary resuscitation versus conventional cardiopulmonary resuscitation in adults with out-of-hospital cardiac arrest: a prospective observational study. Resuscitation. 2014;85:762\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuverein MM, Delnoij TSR, Lorusso R, Brandon Bravo Bruinsma GJ, Otterspoor L, Elzo Kraemer CV, Vlaar APJ, van der Heijden JJ, Scholten E, den Uil C, et al. Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest. N Engl J Med. 2023;388:299\u0026ndash;309.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHsu CH, Meurer WJ, Domeier R, Fowler J, Whitmore SP, Bassin BS, Gunnerson KJ, Haft JW, Lynch WR, Nallamothu BK, et al. Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest (EROCA): Results of a Randomized Feasibility Trial of Expedited Out-of-Hospital Transport. Ann Emerg Med. 2021;78:92\u0026ndash;101.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlenazi A, Aljanoubi M, Yeung J, Madan J, Johnson S, Couper K. Variability in patient selection criteria across extracorporeal cardiopulmonary resuscitation (ECPR) systems: A systematic review. Resuscitation. 2024;204:110403.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDebaty G, Babaz V, Durand M, Gaide-Chevronnay L, Fournel E, Blancher M, Bouvaist H, Chavanon O, Maignan M, Bouzat P, et al. Prognostic factors for extracorporeal cardiopulmonary resuscitation recipients following out-of-hospital refractory cardiac arrest. A systematic review and meta-analysis. Resuscitation. 2017;112:1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChahine J, Kosmopoulos M, Raveendran G, Yannopoulos D, Bartos JA. Impact of age on survival for patients receiving ECPR for refractory out-of-hospital VT/VF cardiac arrest. Resuscitation. 2023;193:109998.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOtani T, Hifumi T, Inoue A, Abe T, Sakamoto T, Kuroda Y, group S-JIs. Transient return of spontaneous circulation related to favourable outcomes in out-of-hospital cardiac arrest patients resuscitated with extracorporeal cardiopulmonary resuscitation: A secondary analysis of the SAVE-J II study. Resusc Plus. 2022;12:100300.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTanimoto A, Sugiyama K, Tanabe M, Kitagawa K, Kawakami A, Hamabe Y. Out-of-hospital cardiac arrest patients with an initial non-shockable rhythm could be candidates for extracorporeal cardiopulmonary resuscitation: a retrospective study. Scand J Trauma Resusc Emerg Med. 2020;28:101.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInoue A, Hifumi T, Sakamoto T, Okamoto H, Kunikata J, Yokoi H, Sawano H, Egawa Y, Kato S, Sugiyama K, et al. Extracorporeal cardiopulmonary resuscitation in adult patients with out-of-hospital cardiac arrest: a retrospective large cohort multicenter study in Japan. Crit Care. 2022;26:129.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheskes S, Drennan IR. No flow time, bystander low flow time and EMS system response time: Are we looking at two sides of the same coin? \u003cem\u003eResuscitation\u003c/em\u003e 2021, 167:412\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOhbe H, Ogura T, Matsui H, Yasunaga H. Extracorporeal cardiopulmonary resuscitation for acute aortic dissection during cardiac arrest: A nationwide retrospective observational study. Resuscitation. 2020;156:237\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAxtell AL, Funamoto M, Legassey AG, Moonsamy P, Shelton K, D'Alessandro DA, Villavicencio MA, Sundt TM, Cudemus GA. Predictors of Neurologic Recovery in Patients Who Undergo Extracorporeal Membrane Oxygenation for Refractory Cardiac Arrest. J Cardiothorac Vasc Anesth. 2020;34:356\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDebaty G, Lamhaut L, Aubert R, Nicol M, Sanchez C, Chavanon O, Bouzat P, Durand M, Vanzetto G, Hutin A, et al. Prognostic value of signs of life throughout cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest. Resuscitation. 2021;162:163\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMenozzi M, Oddo M, Peluso L, Dessartaine G, Sandroni C, Citerio G, Payen JF, Taccone FS. Early Neurological Pupil Index Assessment to Predict Outcome in Cardiac Arrest Patients Undergoing Extracorporeal Membrane Oxygenation. ASAIO J 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOtani T, Sawano H, Natsukawa T, Nakashima T, Oku H, Gon C, Takahagi M, Hayashi Y. Low-flow time is associated with a favorable neurological outcome in out-of-hospital cardiac arrest patients resuscitated with extracorporeal cardiopulmonary resuscitation. J Crit Care. 2018;48:15\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu HY, Wang CH, Chi NH, Huang SC, Chou HW, Chou NK, Chen YS. Effect of interplay between age and low-flow duration on neurologic outcomes of extracorporeal cardiopulmonary resuscitation. Intensive Care Med. 2019;45:44\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRichardson ASC, Tonna JE, Nanjayya V, Nixon P, Abrams DC, Raman L, Bernard S, Finney SJ, Grunau B, Youngquist ST, et al. Extracorporeal Cardiopulmonary Resuscitation in Adults. Interim Guideline Consensus Statement From the Extracorporeal Life Support Organization. ASAIO J. 2021;67:221\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShoji K, Ohbe H, Kudo D, Tanikawa A, Kobayashi M, Aoki M, Hamaguchi T, Nagashima F, Inoue A, Hifumi T, et al. Low-flow time and outcomes in out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation. Am J Emerg Med. 2024;75:37\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDusik M, Rob D, Smalcova J, Havranek S, Karasek J, Smid O, Brodska HL, Kavalkova P, Huptych M, Bakker J, Belohlavek J. Serum lactate in refractory out-of-hospital cardiac arrest: Post-hoc analysis of the Prague OHCA study. Resuscitation 2023:109935.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMilewski R, Lewko J, Milewska G, Baranowska A, Lankau A, Orzechowska M, Krajewska-Kulak E. Actions Taken by Bystanders During Sudden Cardiac Arrest: Analysis of Emergency Medical Service Documentation in Poland. J Clin Med 2024, 13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou G, Wang Y, Sun Z, Yuan M, Ma Y, Wu Q, Wu C, Xu J, Li Y, Liu Y, et al. Survival outcome among patients with out-of-hospital cardiac arrest who received cardiopulmonary resuscitation in China: a systematic review and meta-analysis. Eur J Med Res. 2023;28:8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalcido DD, Sundermann ML, Koller AC, Menegazzi JJ. Incidence and outcomes of rearrest following out-of-hospital cardiac arrest. Resuscitation. 2015;86:19\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAli S, Moors X, van Schuppen H, Mommers L, Weelink E, Meuwese CL, Kant M, van den Brule J, Kraemer CE, Vlaar APJ, et al. A national multi centre pre-hospital ECPR stepped wedge study; design and rationale of the ON-SCENE study. Scand J Trauma Resusc Emerg Med. 2024;32:31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSinger B, Hla TTW, Abu-Habsa M, Davies G, Wrigley F, Faulkner M, Finney SJ. Sub30: Feasibility study of a pre-hospital extracorporeal membrane oxygenation (ECMO) in patients with refractory out-of-hospital cardiac arrest in London, United Kingdom. Resuscitation 2024:110455.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLamhaut L, Hutin A, Puymirat E, Jouan J, Raphalen JH, Jouffroy R, Jaffry M, Dagron C, An K, Dumas F, et al. A Pre-Hospital Extracorporeal Cardio Pulmonary Resuscitation (ECPR) strategy for treatment of refractory out hospital cardiac arrest: An observational study and propensity analysis. Resuscitation. 2017;117:109\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Refractory cardiac arrest, Out-of-hospital cardiac arrest, extracorporeal cardiopulmonary resuscitation, Extracorporeal membrane oxygenation, Neurological outcome, Transient return of spontaneous circulation, Downtime","lastPublishedDoi":"10.21203/rs.3.rs-8585435/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8585435/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eDespite recent advancements in cardiopulmonary resuscitation (CPR), the prognosis of out-of-hospital cardiac arrest (OHCA) remains poor. Extracorporeal CPR (ECPR) offers potential benefits for patients with refractory OHCA. Identifying the factors associated with neurological outcomes at 180 days and their interactions remains critical for optimizing patient selection.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis single-center retrospective study included 65 patients with OHCA treated with ECPR at Kurume University Hospital between 2016 and 2023. Factors associated with the neurological outcomes at 180 days were evaluated using logistic regression and decision tree analyses.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFavorable neurological outcomes at 180 days were recorded in 18 (27.7%) patients. Transient return of spontaneous circulation (ROSC) (odds ratio (OR): 6.25, 95% confidence interval (CI): 1.82\u0026ndash;24.82) and shorter downtime (OR: 0.94, 95% CI: 0.89\u0026ndash;0.98) were independently associated with favorable neurological outcomes. Decision tree analysis revealed that the presence of transient ROSC and bystander CPR are upstream factors associated with favorable neurological outcomes, and that the absence of transient ROSC with prolonged downtime was associated with poor outcomes.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eTransient ROSC and shorter downtime were independently associated with favorable neurological outcomes at 180 days in patients treated with ECPR. Using a decision-tree model, we visualized how these key factors interact to influence long-term neurological recovery, highlighting their potential importance in refining the patient selection process for ECPR.\u003c/p\u003e\u003ch2\u003eTrial registration\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e","manuscriptTitle":"Impact of Transient Return of Spontaneous Circulation and Downtime on Neurological Outcomes following Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest: A Single-Center Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-19 15:38:56","doi":"10.21203/rs.3.rs-8585435/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-16T07:44:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-14T14:17:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"230584116307058670701245488765605202720","date":"2026-02-14T12:52:09+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-09T14:59:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"125887362362560474645355493402441226772","date":"2026-01-21T08:24:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"15715613106689000560450257914054362068","date":"2026-01-20T14:34:27+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-15T02:26:51+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-14T10:05:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-14T07:35:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-14T07:34:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2026-01-12T21:39:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"418dae15-ad3a-42d8-830f-5669dd115129","owner":[],"postedDate":"January 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T08:57:55+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-19 15:38:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8585435","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8585435","identity":"rs-8585435","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}