Interventional procedure overview of VA ECMO for extracorporeal cardiopulmonary resuscitation (ECPR) in adults in refractory cardiac arrest

Alexy T, Kalra R, Kosmopoulos M et al. (2023) Initial hospital length of stay and long-term survival of patients successfully resuscitated using extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest. European Heart Journal. Acute Cardiovascular Care 12(3): 175-183

Single centre retrospective study, US

n=160

Follow-up: 4 years (median follow-up: 3 years)

34% people survived the index admission. These survivors required a median 16 days of intensive care and 24 days total hospital stay. Of these, 80% and 72% were alive at 1 and 4 years, respectively. Most deaths within the first year occurred among the patients requiring discharge to a long-term acute care facility.

Larger, more comprehensive systematic literature reviews and meta-analysis included.

Longer-term data included from RCT.

Belohlavek J, Smalcova J, Rob D et al. (2022) 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 327(8): 737-747

Prague OHCA randomised controlled trial

n=256 (124 ECPR)

Follow-up: 180 days (6 months)

In the main analysis, 32% of the ECPR group and 22% of the CCPR group survived to 180 days with good neurologic outcome (OR, 1.63, 95% CI 0.93 to 2.85; p=0.09). At 30 days, neurologic recovery had occurred in 31% in the ECPR group and in 18% in the CCPR group (OR, 1.99, 95% CI 1.11 to 3.57; p=0.02). Bleeding occurred more frequently in the ECPR versus CCPR group (31% vs 15%, respectively).

RCT included in all SLRs

Beyea MM, Tillmann BW, Iansavichene AE et al. (2018) Neurologic outcomes after extracorporeal membrane oxygenation assisted CPR for resuscitation of out-of-hospital cardiac arrest patients: A systematic review. Resuscitation 130: 146-158

Systematic review and meta-analysis

n=NR, 75 studies (case series and cohort studies)

Follow-up: hospital discharge

Among case series, 0 to 71% of patients treated with ECPR survived to discharge with a good neurological outcome. Subgroup analysis of cohort studies demonstrated survival-to-hospital discharge with good neurological recovery in the ECPR group ranged from 8 to 42% compared to 2 to 9% in the CCPR group.

More recent systematic literature reviews with meta-analysis included.

Bougouin W, Dumas F, Lamhaut L et al. (2020) Extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest: a registry study. European Heart Journal 41(21): 1961-1971

Retrospective registry study (France).

n=13,191

Follow-up: hospital discharge

Survival was 8% in ECPR group and 9% in CCPR group (p=0.91). By adjusted multivariate analysis, ECPR was not associated with hospital survival (OR 1.3, 95% CI 0.8 to 2.1; p=0.24). PSM analysis found similar results (OR 0.8, 95% CI 0.5 to 1.3; p=0.41). In the ECPR group, factors associated with hospital survival were initial shockable rhythm (p=0.005), transient ROSC before ECMO (p=0.03), and prehospital ECMO implantation (p=0.002)

Included in SLRs (Pagura 2024)

Chahine J, Kosmopoulos M, Raveendran G et al. (2023) Impact of age on survival for patients receiving ECPR for refractory out-of-hospital VT/VF cardiac arrest. Resuscitation 193: 109998

Single centre retrospective study, US

n=391

Follow-up: hospital discharge

Age was independently associated with neurologically favourable survival to discharge, with a 30% decrease in survival with every 10-year increase in age (OR 0.7, 95% CI 0.57 to 0.87, p=0.001).

Larger, more comprehensive systematic literature reviews and meta-analysis included.

Chen Z, Liu C, Huang J et al. (2019) Clinical efficacy of extracorporeal cardiopulmonary resuscitation for adults with cardiac arrest: meta-analysis with trial sequential analysis. BioMed Research International 2019: 6414673

Systematic review and meta-analysis

n=NR, 13 observational studies

Follow-up: 1 year

ECPR in OHCA and IHCA was associated with a significantly better 30-day survival (RR 1.60, 95% CI 1.25 to 2.06) and 30-day neurologic outcome (RR 2.69, 95% CI 1.63 to 4.46) than CCPR. Relative to CCPR, ECPR improved the survival and neurological outcome of patients who had IHCA. Trial sequential analysis could not confirm better survival and neurologic outcome of ECPR in OHCA patients, suggesting that further studies are needed.

More recent systematic literature reviews included.

Choi DS, Kim TR, Young S et al. (2016) Extracorporeal life support and survival after out-of-hospital cardiac arrest in a nationwide registry: A propensity score-matched analysis. Resuscitation 99: 26-32

Retrospective registry study (Korea).

n=36,547 (320 ECPR)

Follow-up: hospital discharge

There was no significant difference in neurologically favourable survival to discharge between the ECLS group and the non-ECLS group after adjusting for covariates (adjusted OR 0.65, 95% CI 0.41 to 1.04). In the PSM cohort, there was also no significant difference between the two groups (adjusted OR, 0.94, 95% CI 0.41 to 2.14).

Included in SLRs (Zhong 2024, Pagura 2024)

Choi Y, Park JH, Jeong J et al. (2023) Extracorporeal cardiopulmonary resuscitation for adult out-of-hospital cardiac arrest patients: time-dependent propensity score-sequential matching analysis from a nationwide population-based registry. Critical Care 27(1): 87

PSM retrospective registry study (Korea).

n=2,290 (458 ECPR)

Follow-up: hospital discharge

ECPR itself was not associated with good neurological recovery (10% in ECPR and 7% in no ECPR; RR 1.28, 95% CI 0.85 to 1.93), but early ECPR was positively associated with good neurological recovery.

Included in SLRs (Zhong 2024, Pagura 2024)

Downing J, Al F, Reem CS et al. (2022) How effective is extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest? A systematic review and meta-analysis. The American journal of emergency medicine 51: 127-138

Systematic review and meta-analysis

n=3,097, 44 studies

Follow-up: 90 days

ECPR for OHCA showed survival-to-discharge rate of 24%; 18% survived with favourable neurologic function. 30- and 90-days survival rates were both around 18%.

Larger, more recent and comparative systematic literature reviews and meta-analyses included.

Haas NL, Coute RA, Hsu CH et al. (2017) Descriptive analysis of extracorporeal cardiopulmonary resuscitation following out-of-hospital cardiac arrest-An ELSO registry study. Resuscitation 119: 56-62

Retrospective ELSO registry study

n=217

Follow-up: hospital discharge

Reported complications included haemorrhage (31%), limb complications (11%), circuit complications (9%), infection (7%), and seizures (6%). Survival to hospital discharge was 28% (95% CI 22.1 to 34.0%), and male gender was independently associated with mortality (aOR 2.1 (95% CI 1.1 to 4.2, p<0.05). Survival did not differ by region, race, age, or year.

Larger, more recent and comparative systematic literature reviews and meta-analyses included.

Hashem A, Mohamed MS, Alabdullah K, et al. (2023). Predictors of mortality in patients with refractory cardiac arrest supported with VA-ECMO: a systematic review and a meta-analysis. Current Problems in Cardiology, 48(6), 101658.

Systematic review and meta-analysis

n=931,

10 studies

Follow-up: 90 days

The overall mortality was 69%. The predictors for mortality were age over 65 (OR 4.61, 95% CI 1.63 to13.03, p<0.01), history of chronic kidney disease (OR 2.42, 95% CI 1.37 to 4.28, p<0.01), cardiopulmonary resuscitation duration prior to ECMO more than 40 minutes (OR 6.62, 95% CI 1.39 to 9.02, p<0.01), having an initial non-shockable rhythm (OR 2.62, 95% CI 1.85 to 3.70, p<0.01) and sequential organ failure assessment score higher than 14 (OR 12.29, 95% CI 2.71 to 55.74, p<0.01). 

Larger, comparative systematic literature reviews and meta-analyses included.

Havranek S, Fingrova Z, Rob D et al. (2022) Initial rhythm and survival in refractory out-of-hospital cardiac arrest. Post-hoc analysis of the Prague OHCA randomized trial. Resuscitation 181: 289-296

Post-hoc analysis of the Prague OHCA randomised controlled trial

n=256

Follow-up: 180 days (6 months)

Favourable neurological survival at 180 days was achieved in 40% patients with a shockable rhythm and in 5% patients with a non-shockable rhythm (p<0.001). The difference between shockable and non-shockable initial rhythms remained statistically significant (35/72 [49%] versus 4/52 [8%] in the ECPR group and 28/84 [33%] versus 1/48 [2%] in the CCPR group; p<0.001).

Original RCT include in all key evidence systematic reviews.

Heuts S, Ubben JFH, Kawczynski MJ et al. (2024) Extracorporeal cardiopulmonary resuscitation versus standard treatment for refractory out-of-hospital cardiac arrest: a Bayesian meta-analysis. Critical Care 28(1): 217

Bayesian meta-analysis of ARREST, Prague OHCA and INCEPTION RCTs

n=420

Follow-up: 6 months

The Bayesian meta-analysis found a 71% and 76% posterior probability of a clinically relevant ECPR-based treatment effect on 6-month neurologically favourable survival in patients with all rhythms and shockable rhythms.

Original RCTs included in all key evidence systematic reviews.

Heuts S, van de Koolwijk AF, Gabrio A et al. (2024) Extracorporeal life support in cardiac arrest: a post hoc Bayesian re-analysis of the INCEPTION trial. European heart journal. Acute Cardiovascular Care 13(2): 191-200

Bayesian meta-analysis of the INCEPTION RCT

n=134

Follow-up: 30 days

Bayesian re-analysis of the INCEPTION trial estimated a 42% probability of an MCID between ECPR and CCPR in refractory OHCA in terms of 30-day survival with a favourable neurologic outcome.

Original RCT included in all key evidence systematic reviews.

Holmberg MJ, Geri G, Wiberg, S et al. (2018) Extracorporeal cardiopulmonary resuscitation for cardiac arrest: A systematic review. Resuscitation 131: 91-100

Systematic review

n=25 studies

Follow-up: long-term (unclear)

There is inconclusive evidence to either support or refute the use of ECPR for OHCA and IHCA in adults and children.

Larger, more recent comparative systematic literature reviews and meta-analyses included.

Holmberg MJ, Granfeldt A, Guerguerian AM et al. (2023) Extracorporeal cardiopulmonary resuscitation for cardiac arrest: An updated systematic review. Resuscitation 182: 109665

Updated systematic review

n=3 RCTs and 27 observational studies

Follow-up: in-hospital

Results of individual studies were inconsistent, although many studies favoured ECPR. The risk of bias was intermediate for trials and critical for observational studies. The certainty of evidence was very low to low. Study heterogeneity precluded meta-analyses.

Larger, systematic literature reviews and meta-analyses were included.

Kim SJ, Kim HJL, Hee Y et al. (2016) Comparing extracorporeal cardiopulmonary resuscitation with conventional cardiopulmonary resuscitation: A meta-analysis. Resuscitation 103: 106-116

Systematic review and meta-analysis

n=10 studies

Follow-up: 1 year

Survival and good neurological outcome tended to be superior in the ECPR group at 3 to 6 months after arrest. The effect of ECPR on survival to discharge in OHCA was not clearly shown.

Larger, more recent systematic literature reviews and meta-analyses included.

Kruit N, Rattan N, Tian D et al. (2023) Prehospital extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: a systematic review and meta-analysis. Journal of Cardiothoracic and Vascular Anesthesia 37(5): 748-754

Systematic review and meta-analysis

n=222 ECPR,

4 studies

Follow-up: hospital discharge

Overall survival at discharge was 23% (95% CI 15.5 to 33.7; I²=62%). The quality of evidence was assessed to be low, and the overall risk of bias was assessed to be serious, with confounding being the primary source of bias.

Larger, more recent systematic literature reviews and meta-analyses included.

Lunz D, Calabro L, Belliato M et al. (2020) Extracorporeal membrane oxygenation for refractory cardiac arrest: a retrospective multicenter study. Intensive care medicine 46(5): 973-982

Multicentre retrospective study, US

n=423

Follow-up: 3 months

Eighty patients (19%) had favourable neurological outcome. ICU survival was 24%. Favourable neurological outcome rate was lower (9% versus 34%, p<0.01) in OHCA than IHCA and was significantly associated with shorter time from collapse to ECMO.

Larger, more recent systematic literature reviews and meta-analyses included.

Okada Y, Komukai S, Irisawa T et al. (2023) In-hospital extracorporeal cardiopulmonary resuscitation for patients with out-of-hospital cardiac arrest: an analysis by time-dependent propensity score matching using a nationwide database in Japan. Critical Care 27(1): 442

PSM retrospective JAAM-OHCA registry study (Japan)

n=2,566

Follow-up: 30 days

The OR for 30-day survival in the ECPR group was 1.76 (95% CI 1.38 to 2.25) for shockable rhythm and 5.37 (95% CI 2.53 to 11.43) for non-shockable rhythm, compared to controls. For favourable neurological outcomes, the OR in the ECPR group was 1.11 (95% CI 0.82 to 1.49) for shockable rhythm and 4.25 (95% CI 1.43 to 12.63) for non-shockable rhythm, compared to controls.

Included in SLRs (Low 2024)

Patricio D, Peluso L, Brasseur A et al. (2019) Comparison of extracorporeal and conventional cardiopulmonary resuscitation: a retrospective propensity score matched study. Critical Care 23(1): 27

PSM retrospective study (Belgium)

n=160 (80 ECPR)

Follow-up: hospital discharge and 3 months

Survival to ICU discharge was 23% versus 18% in the ECPR and CCPR groups, respectively (p=0.42). At 3 months, 21% ECPR patients and 11% CCPR patients had a favourable outcome (p=0.11).

Included in SLRs (Low 2024, Low 2023, Zhong 2024)

Rob D, Komarek A, Smalcova J et al. (2024) Effect of intra-arrest transport, extracorporeal cardiopulmonary resuscitation, and invasive treatment: a post hoc bayesian reanalysis of a randomized clinical trial. Chest 165(2): 368-370

Bayesian meta-analysis of the Prague OHCA RCT

n=256

Follow-up: 6 months

Bayesian reanalysis of the study primary outcome showed a benefit of the invasive approach compared with standard resuscitation under a broad set of scenarios.

Original RCT included in all key evidence systematic reviews.

Sakamoto T, Morimura N, Nagao K et al. (2014) Extracorporeal cardiopulmonary resuscitation versus conventional cardiopulmonary resuscitation in adults with out-of-hospital cardiac arrest: a prospective observational study. Resuscitation 85(6): 762-8

Single centre prospective study (Japan)

n=160 (80 ECPR)

Follow-up: 6 months

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. CPC 1 or 2 were 12% in the ECPR group and 2% in the non-ECPR group at 1 month (p<0.0001), and 11% and 3% at 6 months (p=0.001), respectively.

Included in SLRs (Zhong 2024, Pagura 2024)

Spangenberg T, Schewel J, Dreher A et al. (2018) Health related quality of life after extracorporeal cardiopulmonary resuscitation in refractory cardiac arrest. Resuscitation 127: 73-78

Single centre retrospective study (Germany)

n=60

Follow-up: 1 year

12-month survival was 31%. HRQoL SF-36 scores of survivors ranged markedly below controls (p<0.0001)

Larger, more recent systematic literature reviews and meta-analyses included.

Suverein MM, Delnoij TSR, Lorusso R et al. (2023) Early extracorporeal CPR for refractory out-of-hospital cardiac arrest. The New England Journal of Medicine 388(4): 299-309

INCEPTION randomised controlled trial

n=160 (70 ECPR)

Follow-up: 6 months

In people with refractory OHCA, ECPR and CCPR had similar effects on survival with a favourable neurological outcome. At 30 days, 14 patients (20%) in the ECPR group were alive with a favourable neurological outcome, compared with 10 patients (16%) in the CCPR group (OR 1.4; 95% CI 0.5 to 3.5; p=0.52). The number of serious adverse events per patient was similar in the two groups.

RCT included all SLRs

Tanimoto A, Sugiyama K, Tanabe M et al. (2020) Out-of-hospital cardiac arrest patients with an initial non-shockable rhythm could be candidates for extracorporeal cardiopulmonary resuscitation: a retrospective study. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 28(1): 101

Single centre retrospective study (Japan)

n=186

Follow-up: hospital discharge

The rate of good outcomes at hospital discharge was not significantly different between the shockable and non-shockable groups (19% versus 16%, p=0.69).

Larger, more recent systematic literature reviews and meta-analyses included.

Ubben JFH, Suverein MM, Delnoij TSR et al. (2024) Early extracorporeal CPR for refractory out-of-hospital cardiac arrest - A pre-planned per-protocol analysis of the INCEPTION-trial. Resuscitation 194: 110033

Per protocol analysis and Bayesian meta-analysis of the INCEPTION RCT

n=81

Follow-up: 30 days

30-day survival with CPC1 or 2 was 15% in the ECPR group versus 9% in the CCPR group (adjusted OR 1.9, 95% CI 0.4 to 9.3; p=0.393). Bayesian analysis showed an 84% posterior probability of any ECPR benefit and a 61% posterior probability of a 5% absolute risk reduction for the primary outcome.

Original RCT included in all key evidence systematic reviews.

Wang J-Y, Chen Y, Dong R et al. (2024) Extracorporeal vs. conventional CPR for out-of-hospital cardiac arrest: A systematic review and meta-analysis. The American journal of emergency medicine 80: 185-193

Systematic review and meta-analysis

n=4,669

2 RCTs and 10 observational studies

Follow-up: hospital discharge, 6 months

The pooled meta-analysis demonstrated that compared to CCRP, ECPR did not improve survival and neurological outcomes at 180 days following OHCA (RR 3.39, 95% CI 0.79 to 14.64; RR 2.35, 95% CI 0.97 to 5.67). While a beneficial effect of ECPR was obtained regarding 30-day survival and neurological outcomes.

Larger, more comprehensive systematic literature reviews and meta-analyses included.

Wongtanasarasin W, Krintratun S, Techasatian W et al. (2023) How effective is extracorporeal life support for patients with out-of-hospital cardiac arrest initiated at the emergency department? A systematic review and meta-analysis. PloS one 18(11): e0289054

Systematic review and meta-analysis

n=51,173,

8 studies

Follow-up: 30 days

ED-initiated ECPR may not be associated with a significant increase in favourable neurological outcomes (OR 1.43, 95% CI 0.30 to 6.70, I²=96%). However, this intervention may be linked to improved survival to hospital discharge (OR 3.34, 95% CI 2.23 to 5.01, I²=17%).

Larger, more comprehensive systematic literature reviews and meta-analyses included.

Yannopoulos D, Bartos J, Raveendran G et al. (2020) 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 396 (10265): 1807-1816

ARREST randomised controlled trial

n=35 (15 ECPR)

Follow-up: 6 months

Survival to hospital discharge was observed in one (7%) of 15 patients in the standard ACLS treatment group versus six (43%) of 14 patients in the early ECMO-facilitated resuscitation group (risk difference 36.2%, 3.7 to 59.2; posterior probability of ECMO superiority 0.9861). The study was terminated at the first preplanned interim analysis after enrolling 30 patients because the posterior probability of ECMO superiority exceeded the prespecified monitoring boundary. Cumulative 6-month survival was significantly better in the early ECMO group than in the standard ACLS group.

RCT included in all SLRs