**3. Referral, patient selection, and ethics**

ECMO is a complex and resource intensive intervention. Its use is mostly restricted to specialist centres globally. Disease severity, reversibility and patient reserve are important aspects when considering suitability for ECMO. Selection of patients who will ultimately benefit most is crucial to avoid suffering and prolonged futile ICU admission, in addition to appropriate allocation of an expensive, finite, and labourintensive resource.

ECMO played a crucial role in previous respiratory viral outbreaks, such as the Middle East Respiratory Syndrome coronavirus (MERS-CoV2) in 2012, and the influenza A virus subtype hemagglutinin 1 neuraminidase 1 in 2009 (H1N1), with acceptable survival rates ranging from 65% to 77% [34]. However, it was clear from *The Role of VV-ECMO in Severe COVID-19 ARDS DOI: http://dx.doi.org/10.5772/intechopen.107047*

the start of the COVID-19, that this global outbreak would place an even greater strain on healthcare systems worldwide in comparison with its predecessors. Early in the pandemic, definitive data to guide clinical decision making for patient selection in severe COVID-19 was lacking, and established protocols for the initiation of VV ECMO in COVID-19 were therefore largely based on 2 randomised controlled trials of ECMO for non-COVID ARDS [29, 30]. As pandemic phases evolved, ELSO adapted its guideline recommendations in this regard [1]. The 2020 ELSO guidelines, the 2021 ELSO update, and guidelines from other international bodies recommended that VV ECMO should be considered in all patients with COVID-19 and severe refractory hypoxaemia despite optimal conventional therapy [1, 35–38].

Providing complex, finite, and resource intensive therapies such as ECMO during a pandemic has unique challenges [39]. During COVID, referral and selection criteria for VV ECMO had to be redefined during essential resource planning and allocation in order to ethically deploy finite resources. A better understanding of the disease process developed as the pandemic progressed, allowing dynamic modification of these criteria. As a result, regional ECMO services developed individualised approaches to patient selection with a unified aim to ensure that ECMO is offered to those patients who are more likely to reap the most benefit [34, 40, 41]. There is however, some heterogeneity in published selection criteria based on regional variations in demographics, pandemic phase, and resource availability [34, 41].

#### **3.1 Referral criteria**

Referral for ECMO (**Table 1**) should be considered in any COVID-19 patient with potentially reversible acute hypoxaemic respiratory failure, defined as a PaO2/ FiO2 ratio < 80 mm Hg, refractory to maximal conventional therapy as per the ELSO recommended algorithm i.e. treatment of underlying cause, protective lung ventilation, diuresis; followed by prone positioning, increased PEEP, use of neuromuscular blockade, and inhaled pulmonary vasodilators +/− recruitment manoeuvres [1]. Severity of hypoxemia in COVID-19 respiratory failure is characterised by the partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio using thresholds recommended in the EOLIA trial [30]. Early referral is particularly important for patients deteriorating in non-ECMO centres. Referral should be made as early as possible in advance of further deterioration to facilitate timely retrieval and transfer to the designated ECMO centre. ECMO initiation should not be delayed due to resource constraints; delays in initiation are associated with increased mortality in both COVID and non-COVID ARDS [1, 42, 43]. There is no consensus on absolute contraindications for referral in COVID ARDS, except in cases of end-stage respiratory failure unsuitable for lung transplantation, and also when critical care system capacity is at crisis point. The optimal timing of ECMO initiation in relation to intubation remains debatable. In non-COVID ARDS, a duration of mechanical ventilation of 7 days or longer is considered to increase the likelihood of irreversibility [29, 33]. Contrary to this, as discussed in detail below, there is emerging evidence that this has minimal impact on mortality in COVID-19 patients supported with ECMO. However, it is still reasonable to assume based on the available evidence, that earlier initiation is associated with improved survival [34, 40, 41, 44]. Of note, high intensity and prolonged non-invasive ventilation (NIV) in an attempt to avoid intubation during the second wave resulted in delayed initiation of evidenced based lung protective ventilation with an increased incidence of barotrauma. Referral criteria were redefined by some ECMO experts to consider days of high intensity continuous positive airway


**Table 1.**

*Referral criteria for VV ECMO in severe refractory COVID-19.*

pressure (CPAP) or non-invasive ventilation (NIV) as days of mechanical ventilation in an attempt to encourage early referral [41].

### **3.2 Patient selection**

Given the required judicious approach to patient selection during a pandemic with finite resources, how do we determine who will benefit most? Risk factors for poor survival have been identified and are further discussed in the section on mortality and morbidity. Overall, increasing age, ECMO centre experience and pre-existing concomitant disease are substantial factors congruent worldwide. These factors, in addition to premorbid functional capacity, must be considered during the process of referral and when deciding to initiate ECMO, in order to determine a realistic survival and rehabilitation potential, and also expected quality of life after ECMO. For patients with challenging considerations or potential relative contraindications (**Table 2**), it would be reasonable to suggest that at least two ECMO centres should agree that it is appropriate to proceed to ECMO in these cases.

#### **3.3 Ethics and ECMO in a pandemic**

Although there has been intense debate regarding ethical allocation of critical care resources during the COVID-19 pandemic, there has been a paucity of professional guidance specifically relating to ethics and ECMO allocation, with the notable exception of a general ethical guidance document published by ELSO in May 2020 [45]. An international survey of ECMO practitioners (primarily from the ECMOCard group) during the early stages of the pandemic has shed some light on the current ethical climate. Probability of survival if treated, pre-existing disability, functional status, and patient age were the most cited discriminating factors in decision making around maximising patient survival benefit when considering suitability for
