Extracorporeal cardiopulmonary resuscitation versus conventional cardiopulmonary resuscitation in adults with out-of-hospital cardiac arrest: A prospective observational study

doi:10.1016/j.resuscitation.2014.01.031

Resuscitation

Volume 85, Issue 6, June 2014, Pages 762-768

https://doi.org/10.1016/j.resuscitation.2014.01.031 Get rights and content

Abstract

Background

A favorable neurological outcome is likely to be achieved in out-of-hospital cardiac arrest (OHCA) patients with ventricular fibrillation or pulseless ventricular tachycardia (VF/VT) on the initial electrocardiogram (ECG). However, in patients without pre-hospital restoration of spontaneous circulation despite the initial VF/VT, the outcome is extremely low by conventional cardiopulmonary resuscitation (CPR).

Extracorporeal CPR (ECPR) may enhance cerebral blood flow and recovery of neurological function. We prospectively examined how ECPR for OHCA with VF/VT would affect neurological outcomes.

Methods and results

The design of this trial was a prospective, observational study. We compared differences of outcome at 1 and 6 months after OHCA between ECPR group (26 hospitals) and non-ECPR group (20 hospitals). Primary endpoints were the rate of favorable outcomes defined by the Glasgow-Pittsburgh Cerebral Performance and Overall Performance Categories (CPC) 1 or 2 at 1 and 6 months after OHCA. Based on intention-to-treat analysis, CPC 1 or 2 were 12.3% (32/260) in the ECPR group and 1.5% (3/194) in the non-ECPR group at 1 month (P < 0.0001), and 11.2% (29/260) and 2.6% (5/194) at 6 months (P = 0.001), respectively. By per protocol analysis, CPC 1 or 2 were 13.7% (32/234) in the ECPR group and 1.9% (3/159) in the non-ECPR group at 1 month (P < 0.0001), and 12.4% (29/234) and 3.1% (5/159) at 6 months (P = 0.002), respectively.

Conclusions

In OHCA patients with VF/VT on the initial ECG, a treatment bundle including ECPR, therapeutic hypothermia and IABP was associated with improved neurological outcome at 1 and 6 months after OHCA.

Section snippets

Background

A favorable neurological outcome is likely to be achieved in out-of-hospital cardiac arrest (OHCA) patients with ventricular fibrillation or pulseless ventricular tachycardia (VF/VT) on the initial electrocardiogram (ECG). However, in patients without pre-hospital restoration of spontaneous circulation (ROSC) despite the initial VF/VT, the rate of favorable neurological outcome is extremely low by conventional cardiopulmonary resuscitation (CPR).1, 2, 3, 4, 5 In the metabolic phase after

Subjects and methods

The design of this clinical trial was a prospective, observational study registered on a public Web site of the trial registry named “UMIN-CTR” at the URL of https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000001692&type=summary&lang.uage=E. This study followed the description of observational study in the ethical guideline of epidemiological study. In participating hospitals, information concerning objective, method, data management and right to refuse

Statistical analysis

All analyses were performed using statistical software (Statistical Package for Social Sciences (SPSS) version 11.0; SPSS Japan Inc., Tokyo, Japan). Fisher's exact test was used to compare proportions between both groups. Differences with a p value of 0.05 or less were defined as statistically significant.

Results

Between October 2008 and March 31, 2012, a total of 454 patients, including 260 patients in the ECPR group and 194 in the non-ECPR group, were registered. Among these 454 patients, 234 in the ECPR group and 159 in the non-ECPR group were treated according to the protocols (Fig. 1 and Table 1). There were no differences in background factors between the 2 groups (Table 1).

Based on the intention-to-treat analysis, the rate of favorable outcomes was 12.3% in the ECPR group and 1.5% in the non-ECPR

Discussion

In the 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations (CoSTR 2010),²⁰ the International Liaison Committee on Resuscitation (ILCOR) concluded that there was very little evidence as to whether the routine use of ECPR for cardiac arrest should be recommended. In the 2010 American Heart Association Guidelines (AHA-G2010),²¹ the term “extracorporeal life support (ECLS)” was used synonymously with ECPR. The

Limitations

The following effects have or might have influenced our data. First, the limitation of this study includes bias regarding the quality of treatment among the facilities. Because there was no high level of evidence of efficacy of ECPR especially for OHCA before this study, most facilities in our country had a strategy of CPR not on the basis of their clinical capability but on the basis of their policy. However, there were possible differences of quality of care between the ECPR and non-ECPR

Conclusion

In OHCA patients with VF/VT on the initial ECG, the treatment bundle including ECPR, TH, and IABP was associated with improved neurological outcome at 1 and 6 months after OHCA.

Conflict of interest statement

The authors have no conflicts of interest to declare.

Funding source

This study was supported by grants from the Ministry of Health, Labor and Welfare, Japan.

Acknowledgements

We gratefully thank Noriaki Aoki, MD, PhD, MS, MBA (School of Biomedical Informatics, University of Texas – Houston and CHORD-J), Michi Sakai, PhD, MPH (CHORD-J), and Sachiko Ohta, MD, PhD, MS (HIMAP) for their assistance in data collection.

Members of SAVE-J Study Group – Tetsuya Sakamoto MD, PhD, Teikyo University School of Medicine, Tokyo, Japan; Naoto Morimura, MD, PhD, Yokohama City University Graduate School of Medicine, Kanagawa, Japan; Ken Nagao, MD, PhD, Nihon University Surugadai

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Cited by (397)

Extracorporeal cardiopulmonary resuscitation for in- and out-of-hospital cardiac arrest: The race against time
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Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used due to its beneficial outcomes and results compared to conventional CPR. Cardiac arrests can be categorized depending on location: in-hospital cardiac arrest (IHCA) and out-of-hospital cardiac arrest (OHCA). Despite this distinction, studies comparing the two are scarce, especially in comparing outcomes after ECPR. This study compared patient characteristics, cardiac arrest characteristics, and outcomes.
Between 2016 and 2022, patients who underwent ECPR for cardiac arrest at our institution were retrospectively analyzed, depending on the arrest location: IHCA and OHCA. We compared periprocedural characteristics and used multinomial regression analysis to indicate parameters contributing to a favorable outcome.
A total of n = 157 patients (100%) were analyzed (OHCA = 91; IHCA = 66). Upon admission, OHCA patients were younger (53.2 ± 12.4 vs. 59.2 ± 12.6 years) and predominantly male (91.1% vs. 66.7%, p=<0.001). The low-flow time was significantly shorter in IHCA patients (41.1 ± 27.4 mins) compared to OHCA (63.6 ± 25.1 mins). Despite this significant difference, in-hospital mortality was not significantly different in both groups (IHCA = 72.7% vs. OHCA = 76.9%, p = 0.31). Both groups' survival-to-discharge factors were CPR duration, low flow time, and lactate values upon ECMO initiation.
Survival-to-discharge for ECPR in IHCA and OHCA was around 25%, and there was no statistically significant difference between the two cohorts. Factors predicting survival were lower lactate levels before cannulation and lower low-flow time. As such, OHCA patients seem to tolerate longer low-flow times and thus metabolic impairments compared to IHCA patients and may be considered for ECMO cannulation on a broader time span than IHCA.
Cumulative epinephrine dose during cardiac arrest and neurologic outcome after extracorporeal cardiopulmonary resuscitation
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Epinephrine is recommended without an apparent ceiling dosage during cardiac arrest. However, excessive alpha- and beta-adrenergic stimulation may contribute to unnecessarily high aortic afterload, promote post-arrest myocardial dysfunction, and result in cerebral microvascular insufficiency in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR).
This was a retrospective cohort study of adults (≥ 18 years) who received ECPR at large academic ECMO center from 2018 to 2022. Patients were grouped based on the amount of epinephrine given during cardiac arrest into low (≤ 3 mg) and high (> 3 mg) groups. The primary endpoint was neurologic outcome at hospital discharge, defined by cerebral performance category (CPC). Multivariable logistic regression was used to assess the relationship between cumulative epinephrine dosage during arrest and neurologic outcome.
Among 51 included ECPR cases, the median age of patients was 60 years, and 55% were male. The mean cumulative epinephrine dose administered during arrest was 6.2 mg but ranged from 0 to 24 mg. There were 18 patients in the low-dose (≤ 3 mg) and 25 patients in the high-dose (> 3 mg) epinephrine groups. Favorable neurologic outcome at discharge was significantly greater in the low-dose (55%) compared to the high-dose (24%) group (p = 0.025). After adjusting for age, those who received higher doses of epinephrine during the arrest were more likely to have unfavorable neurologic outcomes at hospital discharge (odds ratio 4.6, 95% CI 1.3, 18.0, p = 0.017).
After adjusting for age, cumulative epinephrine doses above 3 mg during cardiac arrest may be associated with unfavorable neurologic outcomes after ECPR and require further investigation.
Etiology-Based Prognosis of Extracorporeal CPR Recipients After Out-of-Hospital Cardiac Arrest: A Retrospective Multicenter Cohort Study
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A better understanding of the relative contributions of various factors to patient outcomes is essential for optimal patient selection for extracorporeal CPR (ECPR) therapy for patients with out-of-hospital cardiac arrest (OHCA). However, evidence on the prognostic comparison based on the etiologies of cardiac arrest is limited.
What is the etiology-based prognosis of patients undergoing ECPR for OHCA?
This retrospective multicenter registry study involved 36 institutions in Japan and included all adult patients with OHCA who underwent ECPR between January 2013 and December 2018. The primary etiology for OHCA was determined retrospectively from all hospital-based data at each institution. We performed a multivariable logistic regression model to determine the association between etiology of cardiac arrest and two outcomes: favorable neurologic outcome and survival at hospital discharge.
We identified 1,781 eligible patients, of whom 1,405 (78.9%) had cardiac arrest because of cardiac causes. Multivariable logistic regression analysis for favorable neurologic outcome showed that accidental hypothermia (adjusted OR, 5.12; 95% CI, 2.98-8.80; P < .001) was associated with a significantly higher rate of favorable neurologic outcome than cardiac causes. Multivariable logistic regression analysis for survival showed that accidental hypothermia (adjusted OR, 5.19; 95% CI, 3.15-8.56; P < .001) had significantly higher rates of survival than cardiac causes. Acute aortic dissection/aneurysm (adjusted OR, 0.07; 95% CI, 0.02-0.28; P < .001) and primary cerebral disorders (adjusted OR, 0.12; 95% CI, 0.03-0.50; P = .004) had significantly lower rates of survival than cardiac causes.
In this retrospective multicenter cohort study, although most patients with OHCA underwent ECPR for cardiac causes, accidental hypothermia was associated with favorable neurologic outcome and survival; in contrast, acute aortic dissection/aneurysm and primary cerebral disorders were associated with nonsurvival compared with cardiac causes.
Factors associated with favourable neurological outcomes following cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A retrospective multi-centre cohort study
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To investigate the factors associated with favourable neurological outcomes in adult patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA).
This retrospective observational study used secondary analysis of the SAVE-J II multicentre registry data from 36 institutions in Japan. Between 2013 and 2018, 2157 patients with OHCA who underwent ECPR were enrolled in SAVE-J II. A total of 1823 patients met the study inclusion criteria. Adult patients (aged ≥ 18 years) with OHCA, who underwent ECPR before admission to the intensive care unit, were included in our secondary analysis. The primary outcome was a favourable neurological outcome at hospital discharge, defined as a Cerebral Performance Category score of 1 or 2. We used a multivariate logistic regression model to examine the association between factors measured at the incident scene or upon hospital arrival and favourable neurological outcomes.
Multivariable analysis revealed that shockable rhythm at the scene [odds ratio (OR); 2.11; 95% confidence interval (CI), 1.16–3.95] and upon hospital arrival (OR 2.59; 95% CI 1.60–4.30), bystander CPR (OR 1.63; 95% CI 1.03–1.88), body movement during resuscitation (OR 7.10; 95% CI 1.79–32.90), gasping (OR 4.33; 95% CI 2.57–7.28), pupillary reflex on arrival (OR 2.93; 95% CI 1.73–4.95), and male sex (OR 0.43; 95% CI 0.24–0.75) significantly correlated with neurological outcomes.
Shockable rhythm, bystander CPR, body movement during resuscitation, gasping, pupillary reflex, and sex were associated with favourable neurological outcomes in patients with OHCA treated with ECPR.
Novel and innovative resuscitation systems in Japan
2024, Resuscitation Plus
Out-of-hospital cardiac arrest (OHCA) is a life-threatening emergency that requires rapid and efficient intervention. Recently, several novel approaches have emerged and have been incorporated into resuscitation systems in some local areas of Japan. This review describes innovative resuscitation systems and highlights their strengths.
First, we discuss the deployment of a physician-staffed ambulance, in which emergency physicians offer advanced resuscitation to patients with OHCA on site. In addition, we describe the experimental practice of extracorporeal membrane oxygenation (ECPR) in a prehospital setting. Second, we describe a physician-staffed helicopter, wherein a medical team provides advanced resuscitation at the scene. We also explain their initiative to provide early ECPR, even in remote areas. Finally, we provide an overview of the “hybrid ER” system which is a “one-fits-all” resuscitation bay equipped with computed tomography and fluoroscopy equipment. This system is expected to help swiftly identify and rule out irreversible causes of cardiac arrest, such as massive subarachnoid hemorrhage, and implement ECPR without delay.
Although these revolutionary approaches may improve the outcomes of patients with OHCA, evidence of their effectiveness remains limited. In addition, it is crucial to ensure cost-effectiveness and sustainability. We will continue to work diligently to assess the effectiveness of these systems and focus on the development of cost-effective and sustainable systems.
Intra-aortic balloon pump in patients with extracorporeal cardiopulmonary resuscitation after cardiac arrest caused by acute coronary syndrome
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This study evaluated the association between intra-aortic balloon pump (IABP) use in patients with out-of-hospital cardiac arrest (OHCA) caused by acute coronary syndrome (ACS) who received extracorporeal cardiopulmonary resuscitation (ECPR) and 30-day outcomes.
This study was a secondary analysis of data from the SAVE-J II study, a retrospective, multicenter registry study involving 36 participating institutions in Japan. Patients with cardiac arrest caused by ACS who received ECPR were divided into two groups depending on whether or not they received IABP. The primary outcome was 30-day survival. Subgroup analysis was performed to detect what type of patients were mostly associated with improved outcomes.
Of 2,157 patients registered in the SAVE-J II study, 877 patients were enrolled in this study, 702 patients in the IABP group and 175 patients in the non-IABP group. Multivariable logistic regression analysis did not reveal a significant difference in 30-day survival (OR 1.37, 95% CI 0.91–2.07, p = 0.13). In the subgroup analysis, 30-day survival among patients without percutaneous coronary intervention (PCI) and stenosis of multiple coronary vessels were associated with IABP use.
IABP use in patients with OHCA with ACS who received ECPR is not associated with 30-day survival. The use of IABP in patients who did not have PCI and have multiple coronary vessel stenoses warrants further study.

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^☆: A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2014.01.031.

¹: The members of SAVE-J Study Group, contributors, participating investigators and coordinators, and participating institutes of this study are listed in Acknowledgements section.

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Clinical PaperExtracorporeal cardiopulmonary resuscitation versus conventional cardiopulmonary resuscitation in adults with out-of-hospital cardiac arrest: A prospective observational study☆

Abstract

Background

Methods and results

Conclusions

Section snippets

Background

Subjects and methods

Statistical analysis

Results

Discussion

Limitations

Conclusion

Conflict of interest statement

Funding source

Acknowledgements

Lancet

Ann Thorac Surg

J Am Coll Cardiol

Resuscitation

J Am Coll Cardiol

Am J Emerg Med

Resuscitation

American Heart Association Guidelines for cardiopulmonary resuscitation and emergency cardiovascular care

Circulation

International consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations

Circulation

Guideline of cardiopulmonary resuscitation for EMS providers

Incidence of ventricular fibrillation in patients with out-of-hospital cardiac arrest in Japan: survey of survivors after out-of-hospital cardiac arrest in Kanto area (SOS-KANTO)

Circ J

Cardiopulmonary resuscitation by bystanders with chest compression only (SOS-KANTO): an observational study

Lancet

Resuscitation after cardiac arrest: a 3-phase time-sensitive model

JAMA

Clinical Paper
Extracorporeal cardiopulmonary resuscitation versus conventional cardiopulmonary resuscitation in adults with out-of-hospital cardiac arrest: A prospective observational study☆