Prior to COVID-19, a large international cohort study estimated that acute respiratory distress syndrome (ARDS) accounts for 10% of all admissions to the ICU and almost a quarter of all ventilated patients (JAMA 2016;315:788-800). In addition to considerable mortality, which is as high as 45% in severe disease (JAMA 2016;315:788-800), ARDS is also associated with significant morbidity, including decreased physical quality of life and increased use of health care services, even five years after diagnosis (N Engl J Med 2011;364:1293-304).

Lung injury, including ARDS, is commonly seen in patients with COVID-19, and as such, prevention of ventilator-induced lung injury (VILI) remains the cornerstone of management for the severe form of the disease. This provides a physiologic rationale for use of veno-venous extracorporeal membrane oxygenation (VV-ECMO) as a rescue strategy for severe forms of COVID-19 pneumonia. VV-ECMO facilitates use of “lung rest settings,” i.e., ultra-lung-protective ventilation modalities that can be implemented to minimize VILI and thereby allow lungs to recover from ARDS. Although recent observational studies, meta-analyses, and randomized controlled trials have suggested benefits of VV-ECMO support for patients with ARDS who develop refractory hypoxemia (Intensive Care Med 2020;46:2048-57), the evidence is certainly not unequivocal (Lancet Respir Med 2019;7:163-72).

With over a 100 million confirmed cases reported by the World Health Organization (WHO) at the time of this writing (https://covid19.who.int), the ongoing pandemic has presented challenges to health care systems across the world. The tremendous morbidity and mortality conferred by this novel disease have led to a flurry of scientific investigation into therapies that could potentially mitigate its effects, especially those associated with severe respiratory failure. ECMO, previously used with some success during the 2009 H1N1 pandemic, has been considered (as recommended by the WHO) for severe cases of COVID-19-induced refractory hypoxemia. Similar to current evidence, guidelines also do not offer clear consensus; current NIH COVID-19 treatment guidelines have surmised that insufficient data exist to recommend either for or against routine use of ECMO in patients with refractory hypoxemia secondary to COVID-19 (https://www-covid19treatmentguidelines-nih-gov.proxy.lib.uiowa.edu/critical-care/extracorporeal-membrane-oxygenation/).

Initial experiences surrounding the use of ECMO in patients with COVID-19 described a mortality rate of around 80% (J Crit Care 2020;58:27-8). However, as more data have become available from international cohorts reporting to the Extracorporeal Life Support Organization (ELSO) registry, the estimated in-hospital mortality at 90 days following the initiation of ECMO has dropped to less than 40%, which is consistent with previous mortality rates in non-COVID-19 ECMO-supported patients with ARDS and acute respiratory failure (Lancet 2020;396:1071-8). Although these data are encouraging, they may not be generalizable, as the preponderance of data come from highly experienced ECMO centers, and there is a known relationship between hospital-level volume of ECMO cases and patient outcomes when using ECMO. There are substantially more ELSO-registered ECMO centers today than existed during the 2009 H1N1 pandemic (430 centers vs. 164 centers), and this number will probably increase (Lancet Respir Med 2020;8:1066-8). Schmidt et al. examined the use of ECMO in COVID-19 patients and noted that the median length of ECMO support (20 days) and ICU length of stay (36 days) was very high (compared with a median of 11 days of ECMO support and 23 days in ICU in the EOLIA trial) (Lancet Respir Med 2020;8:1121-31). Thus, while the ability to support patients through their acute respiratory failure using VV-ECMO is an attractive option, the use of VV- ECMO remains highly nuanced and resource-intensive. These factors are especially relevant during the COVID-19 pandemic, where both allocation of limited resources and health care inequity are serious considerations specifically as it pertains to intensive care use.

“The overarching philosophy in the setting of a pandemic is to provide fair and equitable care aimed at maximizing the number of lives saved.”

The broad-based utilization of VV-ECMO as a rescue strategy in the setting of a pandemic therefore deserves greater scrutiny than just physiological utility. ECMO remains an extremely resource-intensive intervention that demands not only specialized equipment but also intense one-on-one monitoring. The COVID-19 pandemic has led to a critical shortage of resources across almost all health care settings, with even resource-rich settings experiencing significant shortages. ICUs have spilled out of their traditional footprints into non-traditional spaces, and many systems contemplated the triage of ventilators as part of implementing crisis standards of care. This challenging execution of critical care has come in addition to severe shortages of PPE, ventilators, commonly used medications, and most notably of trained health care personnel.

Institution of ECMO demands expanded staffing per patient, including higher nursing-to-patient ratios, need for ECMO specialists, and incommensurate medical provider time. In the context of global strains on health care systems, this can theoretically impact the care of non-ECMO patients. It follows then that the use of ECMO should not be considered in a vacuum, as the consequences of choosing to initiate ECMO in a crisis are not just borne by considerations for a single patient alone (Crit Care 2020;24:507). The overarching philosophy in the setting of a pandemic is to provide fair and equitable care aimed at maximizing the number of lives saved. Therefore, the decision to offer an invasive therapy that can only be provided to a select few should be weighed against the broader potential diversion of supportive care to many others at an institutional level. These considerations are even more relevant when examined in the context of COVID-19 due to the sheer volume of patients afflicted.

Inequities in health care manifest in multiple ways, with race, socio-economic status, access, and insurance status being some of the primary drivers. These inequities have clearly translated into worse outcomes among the underprivileged (N Engl J Med 2020;382:2534-43). ECMO support may not be available in many small to midsize community hospitals that do not have access to the resources or expertise required to successfully run an ECMO program. ECMO outcomes are closely linked to timing of initiation (Crit Care 2016;20:392), and the time-sensitive nature of the decision to initiate this therapy also inherently promotes selection on a “first-come-first-served basis.” Such a system may then discriminate against those who may present late to the hospitals due to poor access to health care.

Conditional on the availability of appropriate resources, a streamlined ECMO program in the setting of a pandemic mandates careful planning, judicious resource allocation, and training of personnel to provide complex therapeutic interventions while adhering to strict infection control measures. The complexity of ECMO requires a well-qualified ICU team to deliver care to critically ill patients with ECMO; therefore, the use of ECMO should be limited to expert, high-volume centers. Establishing hub-and-spoke models of care – in which severely ill patients who are eligible for high-end intensive care support, including ECMO, are managed at the hub – might enable improved stratification of critically ill patients (Lancet Respir Med 2020;8:518-26). Equipment and staffing constraints might necessitate rationing of ECMO services and should involve predetermined consensus criteria formulated to empower clinicians during times of crisis while upholding distributive justice. Ethics, social work, palliative, and medicolegal committees should be involved in ethically challenging scenarios. Shared decision-making with family members on aspects of ECMO initiation, continuation, and termination is desirable. Cessation of ECMO support can be both a morally and ethically challenging decision, further magnified during pandemic-related resource constraints. Staff should have access to psychologic support as necessary (ASAIO J 2020;66:707-21).

The use of ECMO as a rescue strategy for severe forms of ARDS is expected to increase as we anticipate it to improve overall outcomes. Decision-making in the current era of the COVID-19 pandemic is further nuanced by broader institutional and societal implications that should be taken into account. As critical care anesthesiologists, we strive to offer optimal care to every patient and, as part of multidisciplinary teams involved in the initiation and management of extracorporeal support, we are also pivotal in the implementation of this limited resource. While we await a definitive answer on the overwhelming superiority of this modality over established ventilation strategies and other adjuncts, the decision to initiate extracorporeal support should be taken with great caution and with multidisciplinary input.

Lovkesh Arora, MBBS, MD, FASA, Clinical Associate Professor, Divisions of Critical Care and Anesthesiology, and ECMO Medical Director, Heart & Vascular Center, University of Iowa Health Care, Iowa City, Iowa.

Lovkesh Arora, MBBS, MD, FASA, Clinical Associate Professor, Divisions of Critical Care and Anesthesiology, and ECMO Medical Director, Heart & Vascular Center, University of Iowa Health Care, Iowa City, Iowa.

Ameeka Pannu, MD, Program Director, Anesthesia Critical Care Medicine Fellowship, Beth Israel Deaconess Medical Center, and Instructor in Anesthesia, Harvard Medical School, Boston.

Ameeka Pannu, MD, Program Director, Anesthesia Critical Care Medicine Fellowship, Beth Israel Deaconess Medical Center, and Instructor in Anesthesia, Harvard Medical School, Boston.

Somnath Bose, MD, FASA, Assistant Professor of Anesthesia, Harvard Medical School, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston.

Somnath Bose, MD, FASA, Assistant Professor of Anesthesia, Harvard Medical School, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston.