Extracorporeal cardiopulmonary resuscitation for cardiac arrest: An updated systematic review
Published on MedED: 18 May 23
Type of article: Clinical Research Summary
MedED Catalogue Reference: MCECS008
Cross-reference: Emergency medicine, Cardiology
Keywords: Out-of-hospital cardiac arrest, OHCA, in-hospital cardiac arrest, IHCA, Extracorporeal cardiopulmonary resuscitation, CPR
Sources: Resucitation
Key Take Aways
1. While the occurrence of both Out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) is high, the research regarding the use of Extracorporeal cardiopulmonary resuscitation (ECPR) remains limited.
2. Challenges related to using ECPR include patient selection, cost, and benefit timings.
3. This review of current research found that while the use of ECPR in adults was favoured in several of the studies, the evidence for its benefits remains low
4. The use of ECPR was not favoured in paediatric patients
5. The overall conclusion of this study was that while there may be benefits to the use of ECPR, it is a relatively expensive procedure, and based on current clinical information, the evidence supporting its general adoption remains low
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Overview | Objectives | Key Endpoints | Findings | Conclusion | Original Research | References
Overview
Out-of-hospital cardiac arrest (OHCA) occurs in more than half a million people in the United States and Europe yearly. Similarly, in-hospital cardiac arrest (IHCA), the incidence is considerable, with the US recording a further 300,000 deaths from IHCA annually. Unsurprisingly the morbidity and mortality rates are high in these cases: 30% of patients with IHCA survive to discharge, and only 10% of OHCA patients survive.
Extracorporeal cardiopulmonary resuscitation (ECPR) is an "advanced rescue therapy, used to support circulation in selected patients with refractory cardiac arrest." 2
While the procedure is recognised by the American Heart Association (AHA) and the European Resuscitation Council (ERC), several questions exist regarding its use, including patient selection and the benefits and timing of the procedure.
In 2018, the International Liaison Committee on Resuscitation (ILCOR) systematically reviews existing literature to address these issues. At the time of its review, no randomised trials were available & what information was available showed weak evidence to support its use. These factors, coupled with the expense of the procedure, resulted in a weak recommendation in the cardiac guidelines.
This study by Mathias et al., set out to update the ILCOR review based on new information studies published between 2018 and 2022.
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Objectives
The study's objective was "…to provide an updated systematic review on the use of extracorporeal cardiopulmonary resuscitation (ECPR) compared with manual or mechanical cardiopulmonary resuscitation during cardiac arrest."
Thirty-five articles were identified, including three trials, 27 observational studies (23 in adults and 4 in children), and six cost-effectiveness studies, of which one was also an observational study.
All articles were published between 2018 and 2022, and the population included adults and children with out-of-hospital or in-hospital cardiac arrest.
The specific study question was framed as follows:
"In adults (≥18 years) and children (<18 years) with cardiac arrest in any setting (out-of-hospital or in-hospital), does ECPR, including extracorporeal membrane oxygenation or cardiopulmonary bypass during cardiac arrest, compared to manual or mechanical CPR, change clinical outcomes."
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Key Endpoints
Mathias J. identified survival and favourable neurological outcomes as key outcomes in their study.
Furthermore:
- Outcomes with comparable time frames were consolidated into unified categories, with mid-term outcomes encompassing intensive care unit discharge, hospital discharge, 30 days, and one month, while long-term outcomes included three months, six months, and one year
- Hazard ratios indicating long-term survival were considered regardless of the follow-up duration
- Information on cannulation success, limb loss and amputations, brain death, and organ donations was collected from descriptive data in the randomized trials
- Meaningful meta-analyses for both randomized trials and observational studies were precluded based on study heterogeneity
- The return of spontaneous circulation (ROSC) outcome was excluded due to the challenge of defining ROSC meaningfully in this population
Findings
Randomised Trials
Three trials comparing ECPR to standard care were identified for inclusion in this review. All three trials were conducted on adult patients with OHCA.
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Research by Yannopoulos et al. included a randomised sample of 30 patients who arrived in the Emergency Room in cardiac arrest and who had a shockable rhythm
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Hsu et al. included 15 patients with cardiac arrest
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Belohlavek et al. included 264 randomised pre-hospital cardiac arrest patients. The rhythm was not considered in their review.
ECPR was initiated in 42% to 80% of patients in the treatment groups.
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The mean time from cardiac arrest to ECPR ranged from 59 to 66 minutes.
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In the trials included in the studies by Yannopoulos et al. and Belohlavek et al., the intervention group obtained immediate access to a catheterization laboratory
Findings
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All trials were terminated before enrolling the intended number of subjects. Effect measures could not be estimated for all outcomes in all trials due to a limited number of events.
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Yannopoulos et al. observed positive survival and favourable neurological status outcomes with the use of ECPR.
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Although the larger trial showed a promising trend, Belohlavek et al. did not observe any statistically significant outcome differences.
Observational Studies in Adults
Twenty-three observational studies in adults were reviewed:
• 14 included patients with OHCA,
• 6 included patients with either OHCA or IHCA, and
• In 3 studies, the setting of cardiac arrest was unclear.
• The median age of exposed patients ranged from 31 to 72 years.
• The number of exposed patients receiving ECPR ranged from 7 to 5612
Findings
• The results of individual studies were inconsistent, although many favoured ECPR
• This risk of bias was assessed as critical for all observational studies, primarily due to the risk of confounding and selection bias
Observations Studies in Children
Four observation studies in children were included:
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The studies included only children with IHCA, and
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ECPR was assessed in-hospital for all four studies
The total number of patients included ranged from 17 to 20,654
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8-15% of patients received ECPR
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The median age was reported in only one study and was recorded as 2.5 years
Findings
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No ECPR was the generally favoured conclusion of all four studies, although the confidence levels were wide
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The risk of bias was assessed as critical
Cost-Effectiveness Studies
Six cost-effectiveness studies were identified, including an observation study that included cost-effectiveness in its analysis.
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The number of patients ranged from 32 to 762
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Perspective, time horizon, assumed costs, the effect of ECPR and utilities varied considerably between the studies.
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Incremental cost-effectiveness ratios ranged from 12,254 – to 155,739 Euros per quality-adjusted life year.
Certainty
The certainty of the evidence from the randomised trials was considered low for adults with OHCA and very low for adults with IHCA.
Based on the previous and present systematic reviews, the evidence was assessed as very low with children with OCHA and ICHA
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Conclusion
ECPR is a resource-intensive and costly procedure that is only available in selected settings. Based on the above findings, the researchers concluded that while the trials suggest there may well be a potential benefit for ECPR, and the overall evidence is low, and the certainty as to who will benefit remains unclear.
References:
1.Mathias J. Holmberg, Asger Granfeldt, Anne-Marie Guerguerian, Claudio Sandroni, Cindy H. Hsu, Ryan M. Gardner, Peter C. Lind, Mark A. Eggertsen, Cecilie M. Johannsen, Lars W. Andersen,. Extracorporeal cardiopulmonary resuscitation for cardiac arrest: An updated systematic review,Resuscitation,Volume 182,2023,109665,ISSN 0300-9572,https://doi.org/10.1016/j.resuscitation.2022.12.003.
2. Shanmugasundaram, M., & Lotun, K. (2018). Refractory Out of Hospital Cardiac Arrest. Current cardiology reviews, 14(2), 109–114. https://doi.org/10.2174/1573403X14666180507155622
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