Critical Care, Critical Care Alert, Cardiology

Critical Care Alert: 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

Critical Care Alert

ARTICLE
Belohlavek J, Smalcova J,  Rob 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. JAMA. 2022;327(8):737-747.

BACKGROUND
Refractory cardiac arrest (prolonged and/or cardiac arrest without ROSC in the field) is associated with poor patient outcomes. For these patients, the odds of survival are low when transport to the hospital occurs during ongoing CPR, usually less than 4%.2 One approach for these patients that has garnered significant recent interest is the utilization of extracorporeal cardiopulmonary resuscitation (ECPR).3

ECPR involves cannulating a patient for Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) during active CPR to provide circulatory support for the patient while the underlying etiology of the arrest is reversed (usually in the cath lab). Because ECPR is relatively new, there is significant heterogeneity in ECPR systems around the world. In some systems, physicians cannulate patients in the field prior to transport to the hospital, while in others, patients are cannulated on arrival to the hospital. What does seem to be important for outcomes, however, is that ECPR is part of a larger system that includes EMS and multiple hospital departments that have a standardized process.

Because ECPR for Out of Hospital Cardiac Arrest (OHCA) is a relatively recent development, we lack large, high-quality studies to provide data on outcomes. The only randomized controlled trial to date was conducted in Minneapolis and stopped early after meeting prespecified superiority criteria after enrollment of only 30 patients, demonstrating survival of 43% in the ECPR group vs 7% in the standard ACLS group.Recognizing the need for a more definitive study, the authors of this paper set out to conduct a larger randomized controlled trial over a 7-year time period that compared early transport to the hospital for invasive intervention vs standard ACLS care. 

OBJECTIVE
To determine if early invasive intervention via ​​extracorporeal cardiopulmonary resuscitation (ECPR) in adults in refractory out of hospital cardiac arrest improves 180-day survival with good neurological outcome.

DESIGN
This study is a randomized controlled study in a single center in Prague, Czech Republic. Data collection occurred from March 2013 to October 2020.

INCLUSION CRITERIA

  • Patients aged 18 to 65 receiving resuscitation for a witnessed OHCA of a presumed cardiac etiology
  • ECPR team availability at the hospital

EXCLUSION CRITERIA

  • Unwitnessed arrest or suspected non-cardiac etiology
  • Pregnant patients or patients where pregnancy was suspected
  • ROSC attained within the initial 5-minute period of compressions.
  • Patients with a known do not resuscitate (DNR) order

METHODS
Enrollment occurred when the dispatch center contacted the study coordinator, and a telephone call was established with the coordinator and EMS (randomization phone call). The coordinator then used a web-based system to randomize the patient to the standardized or invasive group. Patients randomized into the standard group received ACLS per European Resuscitation Council guidelines. In the early invasive arm, EMS prioritized early transport of the patient from the field directly to the cath lab for cannulation for ECPR followed by cardiac cath. These patients also received early therapeutic hypothermia. Postresuscitation care was the same in both groups (echo, targeted cooling therapy). 256 patients were enrolled; 124 in the invasive group and 132 in the standard of care group.

OUTCOMES
Primary

  • Favorable neurologic outcome at 180 days (defined as minimal or no neurologic impairment). This was assessed in a blinded fashion by a neurologist.

Secondary

  • 30 day survival with cardiac recovery.
  • Neurologic recovery at any point within 30 days of the cardiac arrest.

KEY RESULTS

  • The study was terminated due to futility per the data and safety monitoring board.
  • Favorable neurologic outcome at 180 days in the invasive strategy group was 31.5% vs 22% in the standard group (​​Odds ratio, 1.63 [95% CI, 0.93 to 2.85]; absolute difference, 9.5% [95% CI, −1.3% to 20.1%]; P = .09)
  • Favorable neurological outcome at 30 days in the invasive strategy group was 30.6% vs 24% in the standard group (odds ratio, 1.99 [95% CI, 1.11 to 3.57]; absolute difference, 12.4% [95% CI, 1.9% to 22.7%]; P = .02).
  • Cardiac recovery at 30 days was 43.5% in the invasive strategy group vs 34.1% in the standard group (odds ratio, 1.49 [95% CI, 0.91 to 2.47]; absolute difference, 9.4% [95% CI, −2.5 to 21%]; P = .12).

LIMITATIONS

  • This was a single-center study.
  • The study was underpowered, which combined with significantly higher than expected survival in the standard group could explain the lack of statistically significant difference for the primary outcome.
  • There was significant crossover between the standard and invasive group, which further decreases the chance of identifying a positive outcome.

EM Take-Aways

  • Despite the statistically negative primary outcome, this study demonstrated a 31.5% survival with favorable 180-day neurological outcome with ECPR. This is consistent with prior data on ECPR survival. The study had a number of barriers to showing a positive outcome including stopping early, being underpowered, and having much better than usual survival in the control arm.
  • Research regarding ECMO in OHCA is limited, and more research is needed. The ARREST trial also looked at ECMO in refractory ventricular fibrillation arrest and had statistically significant outcomes regarding survival and functional status.4
  • Considering ECMO cannulation in refractory cardiac arrest patients with a suspected cardiac etiology is warranted. Successful ECPR requires a seamless system from bystander CPR and EMS integration to cardiac catheterization and ICU care in the hospital. It is important to know your hospital’s ECMO cannulation criteria, if applicable.

References

  1. Dennis  M, Lal  S, Forrest  P,  et al.  In-depth extracorporeal cardiopulmonary resuscitation in adult out-of-hospital cardiac arrest.  J Am Heart Assoc. 2020;9(10):e016521. 
  2. Drennan  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(11):1488-1493. 
  3. Schober  A, Sterz  F, Herkner  H,  et al.  Emergency extracorporeal life support and ongoing resuscitation: a retrospective comparison for refractory out-of-hospital cardiac arrest.  Emerg Med J. 2017;34(5):277-281. 
  4. Yannopoulos  D, Bartos  J, Raveendran  G,  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(10265):1807-1816. 

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