What is E-CPR?
E-CPR is defined as the utilization of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) in patients who experience a sudden and unexpected pulseless condition secondary to the cessation of cardiac mechanical activity.
Rationale for E-CPR
The idea of E-CPR originated due to deficiencies in conventional CPR (C-CPR), which, even under optimal conditions, only delivers 15-25% of normal cardiac output. This leads to rapid hypoperfusion and ischemic damage to vital organs (what is known as the low-flow state). However, E-CPR is able to supply near-normal levels of organ perfusion; therefore, preserve the brain and other vital organs for days or weeks until cardiac recovery takes place.
In addition, E-CPR facilitates coronary interventions, even in patients with sustained ventricular fibrillation, because V-A ECMO provides stable systemic perfusion. Therefore, E-CPR has been considered a way to buy tome for the subsequent diagnosis and treatment of the underlying cause of cardiac arrest. Moreover, it provides better survival rates and neurologic outcomes.
Indications and patient selection for E-CPR
Up to date, there are no universal inclusion criteria for E-CPR. Inclusion criteria commonly used in E-CPR studies are the following:
- Patients aged 18 to 65 or 18 to 70 years
- Witnessed refractory cardiac arrest
- Immediate bystander CPR
- Initial shockable rhythm
- Access to immediate coronary angiography
- An anticipated low-flow period <60 minutes
Other common inclusion criteria for E-CPR include signs of life and end-tidal CO2 level >10 mm Hg on arrival to the emergency department. Their value in E-CPR is yet to be systematically assessed.
When should the transition to E-CPR occur?
No consensus is available regarding the ideal time to switch from C-CPR to E-CPR. Starting E-CPR too early may predispose patients who could potentially recover without it to a complicated and expensive procedure. On the other hand, delaying E-CPR may take away the core benefit of the intervention, which is, reducing low-flow state time and organ ischemia.
Studies showed that after 35 minutes of C-CPR, only less than 1% of patients achieve ROSC with good neurological outcomes. One study revealed that 16 minutes after the initiation of C-CPR by emergency medical services might be the optimal time to proceed to E‐CPR. Another study showed superior neurological outcome with the transition after 21 minutes in selected patients. However, delivering patients to a hospital within ab appropriate time frame presents a challenge to EMS staff. Prehospital E-CPR provides an alternative solution to this challenge.
Outcomes of C-CPR versus E-CPR:
Up to date, no published randomized controlled trial compared C-CPR versus E-CPR. Most of the evidence comes from retrospective and prospective observational studies, and meta-analysis. These studies included patients with out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). For example, the SAVE-J study, a prospective observational study, revealed that patients with OHCA who underwent E-CPR had a better neurological outcome, measured by a cerebral performance category of 1 or 2, compared to those with C-CPR, at 1 month (12.3% vs 1.5%, P<0.0001) and at 6 months (11.2% vs 2.6%, P=0.001). Kim et al. also reported favourable neurological outcomes at 3 months in the E-CPR group. Moreover, some recent systematic reviews have demonstrated trends that link E-CPR with improved survival and neurologic outcomes. Overall, factors that were associated with better outcomes included young age, witnessed arrest, bystander CPR, rhythm of sustained VF/VT, time from OHCA to E-CPR initiation, and acute coronary syndrome.
The latest study regarding E-CPR for OHCA was published in June 2020. It took place in Paris and included 13.191 OHCA cases. Of the 12,396 patients managed with C-CPR, 1061 (8.6%) survived to hospital discharge, compared with 44 (8.4%) of 523 E-CPR patients. E-CPR was attempted but failed in 58 (11%) patients. Factors associated with survival in the E-CPR group included an initial shockable rhythm and transient return of spontaneous circulation (ROSC) prior to E-CPR. This study posed major questions regarding the effectiveness of E-CPR in patients with OHCA. The fact that there was no statistical difference between C-CPR and E-CPR made the science community to realize the need to reevaluate the literature and for more and larger randomized clinical trials.
Pre-hospital ECMO aims to reduce the time to E-CPR initiation and increase potential positive outcomes (Figure 2). A cohort performed in Paris attempted to initiate E-CPR after 20 minutes of failed C-CPR and within 60 minutes of arrest. Outcomes revealed reduced low-flow state by 20 minutes and improved survival with neurologically intact patients up to 29% (21% absolute increase, P<0.001). This concluded that prehospital E‐CPR reduced low‐flow duration significantly and increased the rate of ROSC, but it was not an independent predictor of survival to discharge.
APACAR2 (A Comparative Study Between a Pre‐hospital and an In‐hospital Circulatory Support Strategy (ECMO) in Refractory Cardiac Arrest), an ongoing promising RCT, is randomizing patients with OHCA to either prehospital or hospital E‐CPR groups, depending on their location and predicted transport time to the hospital. It will reveal more about E-CPR use in the prehospital setting.
Limitations and closing remarks:
Current evidence concerning the effectiveness of E-CPR seems low quality, making drawing strong conclusions on OHCA E-CPR impossible. Additionally, positive outcomes may be associated with the whole “E-CPR bundle of care”, which include rapid hospital transfer, C-CPR and coronary angiography. Consequently, the effectiveness of E-CPR on its own is uncertain and more RCTs are needed.
Lastly, the survival rate of approximately 25-30% with E-CPR for IHCA already represents a huge financial and resource burden to the family and healthcare systems. If survival with OHCA E-CPR is potentially less than 10%, is it worth the burden or should we better invest in reducing cardiovascular morbidity and improve conventional bystander CPR?
References and Further Reading
- Berdowski, J., Berg, R. A., Tijssen, J. G., & Koster, R. W. (2010). Global incidences of out-of-hospital cardiac arrest and survival rates: systematic review of 67 prospective studies. Resuscitation, 81(11), 1479-1487.
- Bougouin, W., Dumas, F., Lamhaut, L., Marijon, E., Carli, P., Combes, A., … & Jouven, X. (2020). Extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest: a registry study. European Heart Journal, 41(21), 1961-1971.
- Dennis, M., Lal, S., Forrest, P., Nichol, A., Lamhaut, L., Totaro, R. J., Burns, B., & Sandroni, C. (2020). In-Depth Extracorporeal Cardiopulmonary Resuscitation in Adult Out-of-Hospital Cardiac Arrest. Journal of the American Heart Association, 9(10), e016521.
- Gräsner, J. T., Lefering, R., Koster, R. W., Masterson, S., Böttiger, B. W., Herlitz, J., … & Zeng, T. (2016). EuReCa ONE-27 Nations, ONE Europe, ONE Registry: A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe. Resuscitation, 105, 188–195.
- Grunau, B., Reynolds, J., Scheuermeyer, F., Stenstom, R., Stub, D., Pennington, S., … & Christenson, J. (2016). Relationship between time-to-ROSC and survival in out-of-hospital cardiac arrest ECPR candidates: when is the best time to consider transport to hospital?. Prehospital Emergency Care, 20(5), 615-622.
- Hutin, A., Abu-Habsa, M., Burns, B., Bernard, S., Bellezzo, J., Shinar, Z., … & Lamhaut, L. (2018). Early ECPR for out-of-hospital cardiac arrest: best practice in 2018. Resuscitation, 130, 44-48.
- Hutin, A., Loosli, F., Lamhaut, L., Mantz, B., & Corrocher, R. (2017). How Physicians Perform Prehospital ECMO on the Streets of Paris. Accessed Feb 26, 2021, from https://www.jems.com/patient-care/how-physicians-perform-prehospital-ecmo-on-the-streets-of-paris/
- Inoue, A., Hifumi, T., Sakamoto, T., & Kuroda, Y. (2020). Extracorporeal Cardiopulmonary Resuscitation for Out‐of‐Hospital Cardiac Arrest in Adult Patients. Journal of the American Heart Association, 9(7), e015291.
- Kim, S. J., Jung, J. S., Park, J. H., Park, J. S., Hong, Y. S., & Lee, S. W. (2014). An optimal transition time to extracorporeal cardiopulmonary resuscitation for predicting good neurological outcome in patients with out-of-hospital cardiac arrest: a propensity-matched study. Critical Care, 18(5), 1-15.
- MacLaren, G., Masoumi, A. & Brodie, D. (2020). ECPR for out-of-hospital cardiac arrest: more evidence is needed. Critical Care24, 7
- Nickson, C. (2020). Extracorporeal Membrane Oxygenation. Accessed Feb 26, 2021, from https://litfl.com/ecmo-extra-corporeal-membrane-oxygenation/
- Singer, B., Reynolds, J. C., Lockey, D. J., & O’Brien, B. (2018). Pre-hospital extra-corporeal cardiopulmonary resuscitation. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 26(1), 1-8.
- Tan, B. K. K. (2017). Extracorporeal membrane oxygenation in cardiac arrest. Singapore Medical Journal, 58(7), 446.