The role of ECMO for rescue therapy of respiratory failure in critically ill COVID-19 patients remains controversial [10-13]. In this case report, we present a successful ECMO salvage case in a 51-year-old patient with bilateral SARS-CoV-2 pneumonia and refractory respiratory failure. We illustrate the technical aspects and crucial variables related to the indication and the ultimate positive outcome of this patient. Of note, our ECMO program consists of a multi-disciplinary team of specialists in which all major clinical decisions on ECMO patients are discussed during comprehensive twice daily team rounds attended by intensivists, cardiac surgeons, perfusionists, critical care nurses, pharmacy, and respiratory therapy, as previously described [16]. Monitoring of the ECMO circuit is performed by the perfusion team with 24/7 in-house coverage [16]. The current literature established a consensus that optimal outcomes in patients with profound respiratory failure and ARDS are achieved at specialized centers with full institutional commitment to advanced respiratory therapies [17].
Consistent with current guidelines by the Extracorporeal Life Support Organization (ELSO), our institution has embraced the concept that ECMO should only be considered at programs that have established and dedicated programs [18]. Figure 3 demonstrates the decision-making algorithm for ECMO consideration, endorsed by the ELSO guidelines [17,18]. In addition to the ELSO guidelines we utilize the RESP score developed by ELSO to determine optimal candidates for ECMO intervention. Conversely, while salvage therapies might be considered outside of an existing program, in part due to the poor outcomes associated with this approach, centers are discouraged from embarking on ECMO program development at this time for the singular purpose of providing support for COVID-19 patients [18,19]. Another key component of the successful outcome in the patient presented in this report is the timing of the initiation of therapy. While the literature reports varying thresholds in which veno-venous ECMO should be considered for acute respiratory failure, the general indications are profound respiratory failure refractory to conventional medical and ventilator management [9,20,21]. This includes preceding attempts for “salvage” therapies with inhaled nitric oxide, prone positioning ventilation, and judicious use of paralytic agents [9,20,21]. Patients with profound hypoxemia, hypercapnia, respiratory acidosis, and worsening pulmonary compliance in the absence of mechanical causes are typically considered ECMO candidates [9,20,21]. Contraindications to ECMO include concerns for acute neurologic insults, such as anoxic brain injury, contraindications to anticoagulation, and baseline comorbidities that predict either futility of ECMO or limited 2-year survival [9,20,21]. Current indications for ECMO in COVID-19 patients were recently proposed based on the early experience with the pandemic in China [22,23]. As the pandemic spreads and resources (such as ECMO circuits) become limited, we advocate potentially limiting ECMO to those patients who have the best predicted outcomes. While the Survival After Veno-arterial (SAVE) and RESP scores [14] are helpful in selecting patients, they do not inherently account for some of the existing suggested risk factors for poor ECMO outcomes that should be considered such as acute or worsening end-organ, damage and advancing age. We advocate that those with isolated single organ (pulmonary) dysfunction, few comorbidities, and limited acute – and potentially reversible – end-organ dysfunction. Appropriate candidates should also probably be relatively young and otherwise hemodynamically stable.
As shown in this case report, the most crucial aspect to initiating therapy is the timing between reaching the threshold for indications and the decision to start therapy. While it is reasonable to consider adjuvant therapies – like inhaled nitric oxide and prone positioning ventilation, the care team must define clear thresholds for when the potential success of these adjunctive therapies may be considered exhausted and ECMO therapy should be considered. In essence, especially in the context of COVID-19 patients whose respiratory capacity can deteriorate very quickly, the decision to initiate therapy must be anticipated in advance and before the onset of potentially irreversible end-organ dysfunction. Unequivocal thresholds for considering ECMO are particularly important in this current COVID-19 pandemic as concerns of limited resources are prompting discussions of rationing therapies to those who might benefit the most from their use [24]. It is also important to realize that ECMO might have other potential benefits beyond supporting oxygenation and ventilation needs. When configured in a veno-arterial mode, cardiac output for patients in acute systolic heart failure can be supported [20,21]. As COVID-19 is also associated with hyperpyrexia and cytokine storm, all of which can increased metabolic and oxygenation requirements, ECMO might also play a role in active quiescence of COVID-19 patients [18]. Preliminary United States Food and Drug Administration (FDA) authorization has been given to special “ECMO filters” that might assist in viral clearance [25].
Various other root causes can potentially contribute to the poor outcomes associated with ECMO use in SARS-CoV-2 infected patients [23]. Health care facilities that are not experienced in the management of these extremely ill and complex patients, especially if their respective experience is restricted to a few select patients, may have worse outcomes than established tertiary-referral ECMO centers [16]. This idea of referral to specialized ECMO centers also feeds into the concerns of patient selection and the timing of initiation of therapy – delay in initiation of ECMO might predispose to a potentially worse outcome as the patient might have already reached a “point of no return” with regard to irreversible pathophysiology and evolving multi-organ dysfunction.
Concerns were recently raised that ECMO may contribute to the lymphopenia observed in COVID-19 patients thereby deteriorating the patient’s cellular immune response and ability to clear the SRAS-CoV-2 pathogen effectively [12]. The extra-corporeal circuit has been shown to exaggerate an already dysfunctional immune system [26] and this adverse effect may negatively impact the outcomes of COVID-19 patients [12]. The role of immune-modulating therapies in the setting of advanced COVID-19 infections in mitigating the “cytokine storm” leading to hyperinflammation and adverse outcomes is a topic of intense ongoing investigation [26-29].
It is imperative to understand that ECMO neither treats nor cures a disease, as the fundamental principle of ECMO consists of allowing the lungs to “rest” while the primary therapy, such as antiviral treatment, can take effect with less concern for ventilator- induced lung injury [30,31]. This notion is confirmed in the current case report, where the beneficial adjunctive effects of ECMO likely supported the patient’s viral clearance by the antiviral therapy through the compassionate use indication for remdesivir [15]. An additional benefit of ECMO is to provide improved tissue oxygenation, carbon dioxide clearance, and systemic acid-base balance resolution to avoid end-organ physiologic shock, all of which are significant causes of mortality in the COVID-19 patient [32].
Fundamentally, ECMO should never be considered a primary therapy for any form of acute lung injury, but rather utilized as a lung-protective adjuvant modality that promotes a physiological respite and a “biological milieu” for lung healing and recovery. While the scientific evidence for the benefit of ECMO therapy in patients with severe COVID-19 still awaits further validation [33], the consideration of early referral of patients with respiratory failure from SARS-CoV-2 pneumonia to designated centers of excellence appears justified from a patient safety perspective.