What Is Refractory Hypoxaemia? Who Are the Candidates for Rescue ECMO Support?

Refractory hypoxaemia is reported as a cause of death in only 10-15% of ARDS patients, being multiple organ failure and sepsis the leading causes in the majority of the cases [70].

Esan et al. [71] defined refractory hypoxaemia as PaO₂/FiO₂ ratio <100 mmHg or inability to maintain Pplat <30 cmH₂O despite a tidal volume of 4 mL/kg IBW or the development of barotrauma or an oxygenation index >30. According to the Berlin definition of ARDS [72], the candidates for ECMO as a rescue therapy are in the most severe category group characterized by PaO₂/FiO₂ <100 mmHg with PEEP >5 cmH₂O. In the recently published LUNG SAFE study [73], ECMO was used as a rescue therapy in 48 out of 729 patients with severe ARDS (6.6%) in the 4 weeks enrolment period; assuming that the main reason for ECMO in this group was refractory hypoxaemia, the figure is slightly lower than the 10-15% incidence reported previously and can be explained by the more widespread use in the last 10 years of adjunctive manoeuvres and the adherence to lung-protective mechanical ventilation.

For the ELSO guidelines [74] ECMO “should be considered in hypoxic respiratory failure due to any cause (primary or secondary) when the risk of mortality is 50% or greater (PaO₂/FiO₂ <150 mmHg on FiO₂ >90% and/or Murray score 2-3), and is indicated when the risk of mortality is 80% or greater (PaO₂/FiO₂ <100 mmHg on FiO₂ >90% and/or Murray score 3-4 despite optimal care for 6 h or more)”.

In Table 7.1 we report the main criteria of selection reported in some clinical series and in published and ongoing ECMO trials [28, 41, 55, 56, 60-63, 75-78, 80], whereas in Table 7.2 the real pre-ECMO baseline data are reported from the largest published series in the last 10 years [55, 56, 60-63, 66, 68, 76-79, 81-86].

The idea to insert total ECMO support as a rescue therapy in severe ARDS with persistent hypoxaemia despite “optimal” conventional mechanical ventilation and other less invasive adjunctive treatments (iNO, proning) dates back to the late 1990s from the German and Austrian groups [87, 88]. Interestingly, “optimal” conventional ventilation was already defined to use a protective tidal volume 5-7 mL/kg and a peak pressure limit <35 cmH2O [88], and early referral to specialized centres was already claimed to be important in the overall clinical management of the most severely ill ARDS patients [87].