The role of ECMO in COVID‐19: Can it provide rescue therapy in those who are critically ill?

Abstract Arising from the city of Wuhan, Hubei province in China, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 has been rapidly spreading since its first presentation in late 2019. The World Health Organization declared a pandemic on the 11th March 2020, and as of 29th of April 2020 more than 3 million cases have been reported worldwide with over 225 000 confirmed deaths. Where mechanical ventilation may not be enough, extracorporeal membrane oxygenation (ECMO) could play a role as a form of rescue therapy and may provide beneficial results in the hands of skilled clinicians in centers with experience of using ECMO appropriately in selected patients. Our understanding of COVID‐19 is ever‐changing and the need for intensive care beds is rising, which means that ECMO will surely play a key role in the near future.


| INTRODUCTION
Arising from the city of Wuhan, Hubei province in China, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading since its first presentation in late 2019. The World Health Organization (WHO) declared a pandemic on the 11th March 2020, and as of late April 2020 more than 2.7 million cases have been reported worldwide. We are in unprecedented times fighting a pathogen that is not fully understood.
Those who suffer from this illness may experience a clinical course ranging from being asymptomatic to having a minor illness, and in a significant minority a severe form of viral pneumonia, which can result in respiratory failure and death.

SARS-CoV-2 is an RNA virus and part of the family of
Coronaviruses and the third of its kind to affect humans in recent decades. It is thought to gain entry into type 2 pneumocytes via the ACE2 receptor, and the cytokine storm that is created in response to this virus can result in acute respiratory distress syndrome (ARDS), which can severely impair gas exchange. 1 Where mechanical ventilation may not be enough to provide sufficient oxygenation, extracorporeal membrane oxygenation (ECMO) may play a role as a form of rescue therapy and may provide beneficial results in the hands of skilled clinicians in centers with experience of ECMO use in appropriately selected patients. 2

| LITERATURE SEARCH METHOD
A comprehensive literature search is done through the available electronic database to identify articles that reported the use of ECMO and mechanical circulatory support in COVID-19 patients. The keywords used were "mechanical circulatory," "extra-corporeal membrane oxygenation," "SARS-CoV-2," "SARS-CoV," "ECMO," "VA-ECMO OR VV-ECMO" "COVID-19" "mechanical support." The search terms were used as keywords and in combination as MeSH terms to maximize the output from literature findings. References of each included article is crosschecked for any possible relevant study.

| WHEN SHOULD WE USE ECMO IN COVID-19 PATIENTS?
ECMO is a form of cardiopulmonary bypass and can be divided into venovenous (VV-ECMO) and venoarterial (VA-ECMO), which can be used in the setting of respiratory failure and cardiogenic shock, respectively. VV-ECMO can provide respiratory support and can replace the gas exchange function of the lungs and minimize ventilator-induced lung injury, barotrauma, and oxygen toxicity. VA-ECMO can provide both respiratory and hemodynamic support and may be of use to COVID-19 patients who sustain myocardial injury leading to refractory cardiogenic shock. 3 The WHO has provided guidelines on managing ARDS, which focus on ventilation strategies that have proven to be useful in the setting of ARDS in the past. They advise on using lower tidal volumes (4-8 mL/kg predicted body weight), lower inspiratory pressure (plateau pressure <30 cmH20), prone ventilation greater than 12 hours, and conservative fluid management, and ECMO usage has been advised in expert centers. 4 Patient selection is crucial when considering ECMO and those who are inappropriately selected stand a much lower chance of survival. Extracorporeal Life Support Organization (ELSO) has provided selection criteria needed for ECMO referral. If in spite of optimal ventilation strategies, neuromuscular blockade, appropriate PEEP, prone positioning, and the use of pulmonary vasodilators, patients develop the following criteria: PaO2/FiO2 less than 60mm Hg for greater than 6 hours, PaO2 /FiO2 less than 50mm Hg less than 3 hours or pH less than 7.20 + PaCO2 greater than 80mm Hg for less than 6 hours, and do not have any contraindications, they may be suitable for ECMO referral. 5 They have set a list of relative and absolute contraindications such as advanced age, multiorgan failure, advanced lung disease, and severe acute neurological injury to name a few ( Table 1). The Murray score ( had been known to develop ARDS. VV-ECMO was offered to those who failed optimal ventilation strategies and were found to have lower inhospital mortality, better PaO2/FiO2 ratios, and fewer instances of organ failure. 7 The use of ECMO has also emerged during the H1N1 pandemic and several studies have reported on their outcomes during that period. 8 Noah et al 9 found that mortality rates during the H1N1 pandemic of 2009 were almost twice as much in non-ECMO patients when compared with ECMO patients; 52.5% and 27.5%, respectively.
When considering ECMO a question of when to intervene arises: in the setting of COVID-19, would early use of ECMO be beneficial or should patients be placed on mechanical ventilation first and then transitioned to ECMO should they continue to deteriorate? There may be two separate components to hypoxemic respiratory failure: those with normal or high compliance, and those with low compliance and severe hypoxia. ECMO may not be indicated until lung compliance worsens or hypoxemia that is deemed to be severe sets in. 10 Combes et al placed a group of patients with non-COVID-related ARDS immediately on VV-ECMO and found than after a period of 60 days there was no significant difference between the early application of ECMO and the control group, which followed conventional treatment.
Twenty-eight percent of their patients, however, needed to cross over to the ECMO group for refractory hypoxemia. 11 T A B L E 1 Indications for ECMO use in COVID-19

Indications
(1) Hypoxic respiratory failure despite optimal ventilation strategies (as per ELSO guidelines for ARDS)