Extracorporeal cardiopulmonary resuscitation for in- and out-of-hospital cardiac arrest: systematic review and meta-analysis of propensity score-matched cohort studies

Abstract

Introduction: In this systematic review and meta-analysis of propensity score-matched cohort studies, we quantitatively summarize whether venoarterial extracorporeal membrane oxygenation (VA-ECMO) used as extracorporeal cardiopulmonary resuscitation (ECPR), compared with conventional cardiopulmonary resuscitation (CCPR), is associated with improved rates of 30-day and long-term favorable neurological outcomes and survival in patients resuscitated from in- and out-of-hospital cardiac arrest.

Methods: We searched MEDLINE via PubMed, Embase, Scopus, and Google Scholar for eligible studies on January 14, 2019. All searches were limited to studies published between January 2000 and January 2019. Two investigators independently evaluated the quality (or certainty) of evidence according to GRADE guidelines. Pooled results are presented as relative risks (RRs) with 95% confidence intervals (CIs).

Results: Six cohort studies using propensity score-matched analysis were included, totaling 1108 matched patients. Pooled analyses showed that ECPR was likely associated with improved 30-day and long-term favorable neurological outcome in adults compared to CCPR for in- and out-of-hospital cardiac arrest (RR = 2.02, 95% CI = 1.29-3.16; I² = 20%, P = 0.002; very low-quality evidence) and (RR = 2.86, 95% CI = 1.64-5.01; I² = 0%, P = 0.0002; moderate-quality evidence), respectively. When we analyzed in- and out-of-hospital cardiac arrest separately, ECPR was likely associated with improved 30-day favorable neurological outcome compared to CCPR for in-hospital cardiac arrest (RR = 2.18, 95% CI = 1.24-3.81; I² = 9%, P = 0.006; very low-quality evidence), but not for out-of-hospital cardiac arrest (RR = 2.61, 95% CI = 0.56-12.20; I² = 59%, P = 0.22; very low-quality evidence). ECPR was also likely associated with improved long-term favorable neurological outcome compared to CCPR for in-hospital cardiac arrest (RR = 2.50, 95% CI = 1.33-4.71; I² = 0%, P = 0.005; moderate-quality evidence) and out-of-hospital cardiac arrest (RR = 4.64, 95% CI = 1.41-15.25; I² = 0%, P = 0.01; moderate-quality evidence).

Conclusions: Our analysis suggests that VA-ECMO used as ECPR may improve long-term favorable neurological outcomes and survival when compared to the best standard of care in a selected patient population. Therefore, it is imperative for well-designed randomized clinical trials to obtain a higher level of scientific evidence to ensure optimal outcomes for cardiac arrest patients.

Keywords: cardiopulmonary resuscitation; extracorporeal life support; extracorporeal membrane oxygenation; in‐hospital cardiac arrest; out‐of‐hospital cardiac arrest.

FIGURE 1

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) study flow diagram. Notes: Adapted from Moher et al.³⁴

FIGURE 2

Forest plot of comparison of 30‐day favorable neurological outcome in adults with cardiac arrest. Squares or diamonds to the right of the solid vertical line favor the intervention group (ECPR) over the control group (conventional cardiopulmonary resuscitation), but this is conventionally significant (P < 0.05) only if the horizontal line or diamond does not overlap the solid line. The result and its 95% confidence interval (CI) are presented by a diamond, with the risk ratio (95% CI) and its statistical significance given alongside. Squares indicate study‐specific risk ratios (RRs). Horizontal lines indicate 95% CIs. A diamond indicates the pooled RR with 95% CI. I² indicates the percentage of total variations across the studies that are due to heterogeneity rather than change. The weight indicates how much an individual study contributes to the pooled estimate. M‐H stands for the Mantel‐Haenszel method in meta‐analysis. Random indicates that a random‐effects method was adopted for generating the meta‐analysis results. The certainty of evidence for this outcome was graded as very low‐quality based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.

FIGURE 3

Forest plot of comparison of long‐term favorable neurological outcome in adults with cardiac arrest. Squares or diamonds to the right of the solid vertical line favor the intervention group (ECPR) over the control group (conventional cardiopulmonary resuscitation), but this is conventionally significant (P < 0.05) only if the horizontal line or diamond does not overlap the solid line. The result and its 95% confidence interval (CI) are presented by a diamond, with the risk ratio (95% CI) and its statistical significance given alongside. Squares indicate study‐specific risk ratios (RRs). Horizontal lines indicate 95% CIs. A diamond indicates the pooled RR with 95% CI. I² indicates the percentage of total variations across the studies that are due to heterogeneity rather than change. The weight indicates how much an individual study contributes to the pooled estimate. M‐H stands for the Mantel‐Haenszel method in meta‐analysis. Random indicates that a random‐effects method was adopted for generating the meta‐analysis results. The certainty of evidence for this outcome was graded as moderate‐quality based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.

FIGURE 4

Forest plot of comparison of 30‐day survival in adults with cardiac arrest. Squares or diamonds to the right of the solid vertical line favor the intervention group (ECPR) over the control group (conventional cardiopulmonary resuscitation), but this is conventionally significant (P < 0.05) only if the horizontal line or diamond does not overlap the solid line. The result and its 95% confidence interval (CI) are presented by a diamond, with the risk ratio (95% CI) and its statistical significance given alongside. Squares indicate study‐specific risk ratios (RRs). Horizontal lines indicate 95% CIs. A diamond indicates the pooled RR with 95% CI. I² indicates the percentage of total variations across the studies that are due to heterogeneity rather than change. The weight indicates how much an individual study contributes to the pooled estimate. M‐H stands for the Mantel‐Haenszel method in meta‐analysis. Random indicates that a random‐effects method was adopted for generating the meta‐analysis results. Notes: The certainty of evidence for this outcome was graded as very low‐quality based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.

FIGURE 5

Forest plot of comparison of long‐term survival in adults with cardiac arrest. Squares or diamonds to the right of the solid vertical line favor the intervention group (ECPR) over the control group (conventional cardiopulmonary resuscitation), but this is conventionally significant (P < 0.05) only if the horizontal line or diamond does not overlap the solid line. The result and its 95% confidence interval (CI) are presented by a diamond, with the risk ratio (95% CI) and its statistical significance given alongside. Squares indicate study‐specific risk ratios (RRs). Horizontal lines indicate 95% CIs. A diamond indicates the pooled RR with 95% CI. I² indicates the percentage of total variations across the studies that are due to heterogeneity rather than change. The weight indicates how much an individual study contributes to the pooled estimate. M‐H stands for the Mantel‐Haenszel method in meta‐analysis. Random indicates that a random‐effects method was adopted for generating the meta‐analysis results. Notes: The certainty of evidence for this outcome was graded as low‐quality based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.