ECMO-Augmented Resuscitation: Redefining Refractory Cardiac Arrest Management

Despite decades of advancements in conventional cardiopulmonary resuscitation (CPR), survival rates for refractory cardiac arrest remain dismal, with only 0 to 18% of out-of-hospital cardiac arrest (OHCA) patients achieving neurologically intact survival with significant variations observed between different countries and cohorts.[1] A 15-34% survival rate has been reported for in-hospital cardiac arrest (IHCA).[2] Extracorporeal cardiopulmonary resuscitation (ECPR), which combines mechanical CPR with rapid deployment of veno-arterial extracorporeal membrane oxygenation (VA-ECMO), has emerged as a transformative intervention. Technological advancements and implementation strategies in ECPR have contributed to its evolution from a novel intervention to a potential standard care for refractory cardiac arrest. Extracorporeal membrane oxygenation (ECMO) originated in the 1970s as an offshoot of cardiac bypass technology, with its first successful neonatal application documented in 1975 by Bartlett et al. for respiratory failure in newborns.[3] Clinical trials in the 1970s demonstrated that ECMO could sustain life after cardiac and respiratory failure till organ recovery for days to weeks. ECMO use was initially confined to pediatric care but underwent transformative expansion following pivotal trials like the 2009 CESAR (Conventional Ventilation or ECMO for Severe Adults Respiratory Failure) trial. The CESAR trial demonstrated a survival benefit of 63% with ECMO versus 47% with conventional therapy at 6 months for patients with severe adult respiratory distress syndrome.[4] The COVID-19 pandemic propelled ECMO usage worldwide as a salvage therapy for refractory hypoxemia.[5] Subsequent device miniaturization and heparin-free circuits enabled prehospital deployment through mobile ECMO units and changed the standing of ECMO from salvage therapy to Standard Care. ECPR utilizes ECMO and conventional CPR to ensure end-organ perfusion in the body of the cardiac arrest victim. A recent meta-analysis reported the overall survival to discharge of ECPR-treated IHCA victims as 37.9%, with 84.4% of survivors having good neurologic outcomes, which was much higher than the discharge rate of 17.0% among IHCA patients treated with conventional CPR.[6] The ARREST and the Prague randomized controlled trials (RCT) suggested 15 to 60% survival rates with ECPR after OHCA.[7,8] The INCEPTION (Early Extracorporeal CPR for Refractory Out-Of-Hospital Cardiac Arrest) RCT showed a 20% survival rate with ECPR vis-à-vis 16% with conventional CPR but reported more favorable neurologic outcomes.[9] After a prolonged conventional CPR of 15–20min, the probability of survival with good neurological outcome is just 2% as, at best, only 25% to 30% of cardiac output can be achieved, which results in tissue hypoxia, brain damage, and ultimately death. ECPR ensures adequate organ perfusion in patients.[2] Studies suggest that a coronary perfusion pressure (CPP) of at least 15 mmHg is needed for the return of spontaneous circulation (ROSC).[10] ECPR can achieve a coronary perfusion pressure (CPP) of around 25 mmHg compared to about 15 mmHg usually achieved with conventional CPR. ECPR thus potentially improves myocardial perfusion and survival.[11] Lactate is a marker of anaerobic metabolism resulting from tissue hypoperfusion/hypoxia. Its level correlates with the no- and low-perfusion times after cardiac arrest. Early lactate clearance is associated with decreased in-hospital mortality after cardiac arrest. A lactate level of <3.5 mmol/L at 24h predicts survival after ROSC.[12] A <2 mmol/L plasma lactate value up to 12 hours after ROSC predicts a good neurological outcome.[13] Lactate clearance, not lactate concentration, is an important prognostic variable to predict neurological outcomes, and an early high clearance rate is associated with good outcomes. A better lactate reduction rate is achieved with ECPR compared with conventional CPR.[14] ECPR was earlier limited to IHCA due to bulky ECMO equipment and technical complexity. The technological leap in the 2010s heralded a paradigm shift in using ECPR with the availability of portable ECPR systems, which reduced deployment time to <30 minutes. Centrifugal pump technology in ECMO systems offered the advantages of low priming volumes, shorter circuitry, and a lower air emboli risk.[15] In the last five years, the availability of portable, miniaturized ECMO circuits and heparin-coated biocompatible surfaces or other non-thrombogenic substances (enabling longer run times) expanded the use of ECMO to OHCA.[16] The low-weight third-generation ECMO devices (about 8 kg) have auto-priming capability and can be set up in 2 min. There have been advances in femoral cannulation - echo-guided percutaneous femoral access is credited with excellent first-pass success. Distal perfusion catheters have reduced the incidence of limb ischemia.[17] Targeted temperature management to 33°C for 24h improves cerebral performance.[18] Cytosorb adsorbers too can be included in the circuit, which can help significantly reduce circulating cytokines during an ECMO run.[19] ECPR is a time-sensitive, complex intervention that requires a well-trained team of healthcare workers with clearly defined roles. In 2021, the Extracorporeal Life Support Organization (ELSO) consensus group issued guidelines for implementing ECPR and early management following the establishment of ECMO support. ECPR is indicated under the following circumstances after ROSC[20]: Victims 18-75 years of age Cardiac arrest of presumed cardiac etiology Early bystander CPR The initial presenting rhythm is VF/VT Reversible causes of cardiac arrest Persistent shockable rhythm after: - 3 standard defibrillation shocks - 300mg IV/IO bolus of amiodarone Transfer time from field to facility <30 min A facility capable of: - Coronary Angiography - Percutaneous Coronary Intervention - Targeted Temperature Management The exclusion criteria for ECPR include[20]: Inability to provide high-quality CPR ROSC with sustained hemodynamic recovery ≤3 standard defibrillation shocks Known terminal illness Comorbidities with reduced life expectancy Clinical signs of neurological damage or expected poor prognosis Severe heart failure (NYHA III or IV) Severe pulmonary disease A resident of Nursing home/long-term care Pregnancy Revised Trauma Score <11 or Injury Severity Score >15 Threatening hemorrhage Legal documents limiting resuscitation Presence of a reason to contact medical control to withhold resuscitation The expense of ECPR is €12,254–€155,739 per Quality-Adjusted Life Year for hospital-based costs only. This amount does not include the system, infrastructure, or rehabilitation costs. The costs are likely to be higher in smaller centers.[21] Although the benefits of ECPR are well established, there is an ongoing debate on its cost-effectiveness. ECPR is expensive, and the costs for survivors are much higher than those for non-survivors because of more extended hospital stays. Similarly, the cost of ECPR in IHCA is higher than that in OHCA because of better chances of survival and subsequent interventions in IHCA patients. ECPR shows promise in urban settings with short response times, but its effectiveness in rural or resource-limited settings remains uncertain due to longer deployment times and potential logistical challenges. Using it for salvageable young patients in high-volume centers (>30 cases/year) may be economically wise as they have better outcomes.[21] To run an effective ECPR program, Mobile ECMO Units must be set up with a team composed of ECMO consultants, an ECMO perfusionist, a respiratory therapist, and critical care paramedics from the Ambulance Service.[22] Drone ECMO Delivery systems must be developed to deploy ECMO and cannulation kits. ECPR represents the most significant advancement in resuscitation science since the introduction of defibrillation. Future research should focus on optimizing patient selection criteria, reducing deployment times, and exploring the cost-effectiveness of widespread ECPR implementation. ECPR has shown promise as a novel intervention in small-scale studies, necessitating a deeper exploration of its potential through more extensive, randomized controlled trials. Financial support and sponsorship Nil. Conflict of interest There are no conflict of interest.