“Almost every action within the medical setting either explicitly or implicitly contains two judgements, one ethical and one scientific, and there is constant interplay between what is technically possible and what is morally desirable” (1).

Although traditionally used in neonatology and pediatric medicine for acute respiratory failure, extracorporeal life support (ECLS) is now the standard of care for an expanding number of pediatric and adult medical conditions. ECLS is commonly deployed to allow recovery from potentially reversible conditions, such as acute respiratory distress syndrome (ARDS) and shock; as a bridge to decision, when prognosis is uncertain; as a rescue therapy during cardiopulmonary arrest that is unresponsive to initial resuscitation measures; and as a bridge to transplant or destination therapy with mechanical circulatory support (2–5). Over the last decade, exponential growth of ECLS utilization in adults (6, 7) has surpassed its utilization in children. As of March 2022, 92,389 adults and 79,604 children (age <18 years of age) were supported by ECLS with survival rates ranging from 49% (adults) to 65% (neonates) (8). The COVID-19 pandemic likely contributed to this expansion in the adult population, as 13,341 patients with ARDS secondary to SARS-CoV-2 infection have been managed with ECLS (8–10).

Rapid technological advancements and the exponential expansion of ECLS utilization, as exemplified by the SARS-CoV-2 pandemic, are generating an increasing number of ethical and societal considerations (11–16). Clinical and ethical guidance for the utilization of ECLS are often based on expert consensus, case series, and retrospective cohort analyses due to inherent challenges in prospective outcomes studies and randomized control trials in these populations (17, 18). Over the last decade, clinical guidelines (9, 19–21), position and opinion papers (2, 22–26), surveys of clinician perceptions (27–31), and discourse surrounding ethical considerations (32–36) have proliferated. Notably, explicit discussions regarding ethical considerations are often implied or excluded from these clinical guidelines, position statements, and surveys of clinician perceptions. Furthermore, thoughtful and detailed manuscripts that explicitly highlight general ethical principles often do not provide practical guidance for clinicians. Hence, these limitations in the current medical literature compel further exploration of complex ethical questions through additional empirical and normative research (2). Failure to address ethical implications associated with complex decision making in ECLS increases the risk of unnecessary and undesired burdens for patients, families, staff, and health care systems (37). In addition, institutional, regional and global variation in ECLS application may exacerbate already existing health care disparities (27, 38, 39).

Since its introduction nearly fifty years ago, ECLS has provided life-support to over 170,000 patients globally (8). ECLS is based on John H. Gibbon's work beginning in the 1930s and culminating with the first successful extracorporeal cardiopulmonary bypass case in 1953 enabling surgeons to perform open-heart operations (7, 40). ECLS utilizes an extracorporeal blood pump coupled with a gas exchange unit to provide cardiopulmonary support for patients with severe cardiac and/or respiratory failure. Venovenous (VV) ECLS provides gas exchange and returns blood to a central vein or the right atrium for respiratory support alone. In contrast, venoarterial (VA) ECLS provides gas exchange and cardiovascular support by returning blood to a central artery for combined respiratory and circulatory support. ECLS is often conventionally referred to as ECMO (extracorporeal membrane oxygenation support). However, newer ECLS technologies do not utilize a “membrane oxygenator” leading to the adoption of the newer more inclusive term of ECLS (41).

Historically, the earliest clinical trial with ECLS failed to demonstrate improved survival in adults (42); however, improved outcomes were observed in neonatal and pediatric patients with respiratory or cardiac failure (43–46). Thus, over the subsequent few decades, ECLS was primarily used to support neonates and pediatric patients with acute respiratory and cardiac failure, including children following cardiac surgery. With improvements in technology and experience, indications for the utilization of ECLS have increased rapidly, and include children and adults with acute respiratory failure and shock, as a bridge to decision when prognosis is uncertain, as a bridge to heart and/or lung transplant, and in rescue of patients with cardiac arrest refractory to cardiopulmonary resuscitation (E-CPR) (3–5, 7, 47, 48). Medical conditions that were once absolute contraindications, such as organ failure following stem cell transplant and chimeric antigen T cell therapy (CAR-T), are now reconsidered for support with ECLS (28, 49). Previously the domain of quaternary care centers, technological advancements have led to an increased number and greater variety of types of centers to offer ECLS. When ECLS is not available at certain locations, mobile ECLS programs have allowed patients to be cannulated locally and transferred to specialized ECLS centers (50).

Outcomes following ECLS vary with patient age and indication for support, ranging from >90% survival in neonates with meconium aspiration syndrome, 65% for all pediatric ECLS indications, 46% in adults with ARDS, to 30% in adults following cardiac arrest (2, 6, 9, 51, 52). While overall survival rates for ECLS patients continue to modestly improve for both adults and children (52), utilization in increasingly complex conditions has led to a plateau in mortality rates for certain conditions, such as cardiac failure in children and neonates (53). When evaluating the potential risks and benefits of ECLS, risk of mortality and ECLS-associated morbidities should be assessed. Serious complications, including bleeding, infection, central nervous system injury, severe deconditioning, and acute kidney injury (54–57) are not uncommon. The impact and potential risk to other patients related to ECLS-associated resource utilization (e.g., intensive care nurses, intensive care beds, blood products) also may need to be considered in the global calculus of risk and benefit of ECLS utilization.

As ECLS technology advances at a rapid pace, there are few technical limitations to offering ECLS as a potentially life saving intervention—therefore, “we can.” However, within the context of a wide range of mortality rates, risks for severe morbidities, limited outcome data, and clinician ethical duty to save lives, ECLS clinicians are often faced with the extremely difficult medical and moral decision—“should we?” Unfortunately, there is little ethical guidance to assist bedside clinicians in making these complex decisions.

The following hypothetical cases, based on an amalgam of actual clinical cases, highlight several important ethical dilemmas that arise in the provision of ECLS.

Proactive and explicit exploration through collaboration and research of ethical considerations that arise in clinical cases like these may mitigate potential risks and promote: (1) respect for the well-being and autonomy of patients, families, and staff; (2) optimization of patient outcomes while minimizing undue burdens for patients and families; and (3) responsible, equitable, and fair allocation of resources. Navigating complex and challenging questions that arise in ECLS will hopefully lead to improved quality of patient care through a better understanding of the ethical and societal considerations.

To develop a research agenda to inform ethical guidance for clinicians and institutions in the utilization of ECLS, a multi-disciplinary team of pediatric specialists in ECLS, critical care, cardiothoracic surgery, palliative care, and bioethics convened at a single academic institution. Using an iterative consensus process, a broad range of research questions were collected and refined by the group over a series of monthly meetings for approximately 18 months. The broad list was refined by removing duplicates and then selecting questions according to the following criteria: (1) frequency of occurrence in ECLS; (2) uniqueness to ECLS; (3) urgency; (4) feasibility to study; and (5) potential to advance the practice of ECLS and improve quality of patient care. To create the research agenda, refined questions were categorized into the following themes: (1) scope and frequency of ethical dilemmas involving ECLS; (2) clinical decisions and ethical guidance to initiate, forgo, or discontinue ECLS; (3) approaches to optimize communication with and provide emotional support for families and clinical team members; and (4) research design and implementation in ECLS (Tables 1, 2).

The Seattle Ethics in ECLS Consortium identified and prioritized important ethical questions that warrant further empirical and normative research in the domains of societal decision-making, bedside decision-making, patient/family communication, medical team dynamics, and research ethics. Identifying ethical considerations in the delivery of ECLS is an initial step toward: (1) better understanding the ethical dilemmas encountered, (2) developing approaches to address these ethical dilemmas, and ultimately (3) improving the quality of medical care provided and support for families when utilizing ECLS.

The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author/s.

ML-N founded and led the SEE Consortium and conceptualized the initial manuscript. ML-N and JC co-facilitated the SEE Consortium discussions to develop the ECLS research agenda and drafted, revised, and approved the final manuscript as submitted. JC and JD performed background literature searches. HB, EBo, TB, JD, AD, DM, JR, JT, and BW all participated in the SEE Consortium, vetted the research questions, edited and approved the final manuscript. EBe vetted the research questions, edited and approved the final manuscript. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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