The determining factor of blood decarboxylation is the rate of sweep gas flow ventilating the membrane lung, while PaCO₂ is unaffected when ECMO blood flow and FiO_2ECMO are reduced to <2.5 l/min and 40%, respectively.

CO₂ transfer through the membrane lung also depends on ECMO flow, with maximum transfer being >300 ml/min when ECMO flow is >6 l/min with the Quadrox® oxygenator. However, since CO₂ diffuses 20 times faster than O₂, large amount of CO₂ can be exchanged through the membrane lung even when low flow is applied through the circuit [25]. For instance, recent data showed that PaCO₂ remained unchanged when ECMO blood flow was reduced to <2.5 l/min. Indeed, this property is the basis for developing low-flow extracorporeal CO₂ removal devices, for which CO₂ removal is >70 ml/min at blood flows of only 450 ml/min [31, 32]. Alternatively, sweep gas flow across the oxygenator is the main determinant of CO₂ removal by ECMO [25].

Indications are usually based on: (1) severe hypoxemia (e.g., PaO₂ to FiO₂ ratio <80 mmHg, despite optimization of mechanical ventilation (tidal volume set at 6 ml/kg and trial of PEEP≥10 cm H₂O)) for at least 6 h in patients with potentially reversible respiratory failure and possible recourse to adjunctive therapies (NO, prone position, etc.) and/or or (2) uncompensated hypercapnia with acidemia (pH <7.15) despite the best accepted standard of care for management with a ventilator and/or (3) excessively high end-inspiratory plateau pressure (>32 cm of water). However, considering the CESAR trial, the ongoing EOLIA trial, and the recommendations of the Extra Life Support Organization (ELSO), the thresholds of PaO₂ to FiO₂ ratio, pH, or plateau pressure may vary considerably across studies and guidelines.

Relative contraindications are usually mechanical ventilation for more than 7 days, limited vascular access, and any condition or organ dysfunction that would limit the likelihood of overall benefit from ECMO, such as malignancies with fatal prognosis within 5 years, moribund patients, or those with irreversible neurological pathologies and decisions to limit therapeutic interventions. Contraindication to the use of anticoagulation therapy is mentioned in several reviews or guidelines. However, several publications have stressed that, while using new-coated heparin circuit, anticoagulation on ECMO VV may be safely withheld for days or weeks.

The most recent trial (CESAR trial) which was conducted in the UK from 2001 to 2006 evaluated a strategy of transfer to a single center (Glenfield, Leicester) which had ECMO capability, while the patients randomized to the control group were treated conventionally at designated treatment centers [6]. The primary endpoint combining mortality or severe disability 6 months after randomization was lower for the 90 patients randomized to the ECMO group (37% vs. 53%, p = 0.03). However, results of that trial should be analyzed carefully. First, 22 patients randomized to the ECMO arm did not receive ECMO (died before or during transport, improved with conventional management at the referral center, or had a contraindication to heparin). Second, no standardized protocol for lung-protective mechanical ventilation existed in the control group, and the time spent with “protective” mechanical ventilation was significantly higher in the ECMO arm. Third, more patients received corticosteroids in the ECMO group. In the most recent series, patients benefited from the latest ECMO technology, which include a centrifugal pump, a polymethylpentene membrane oxygenator, and tubing with biocompatible surface treatment. Mortality rates ranged from 36 to 56% in the studies performed in the last 15 years and reporting outcomes of >30 ECMO patients (Table 3.1). Interestingly, ECMO was provided through a mobile ECMO rescue team in some of these studies. For example, in a series of 124 patients treated at a Danish center between 1997 and 2011 [33], survival was 71%, and 85% of these patients received ECMO via a mobile unit before being transferred to the referral hospital. Similarly, in the Regensburg cohort, 59/176 received ECMO at another hospital by a mobile unit [34]. In a multicenter French cohort of 140 patients treated between 2008 and 2012, 68% patients were retrieved via a mobile ECMO team, and their prognosis was comparable to those who received VV-ECMO support in their initial center hospital [35]. ECMO support might also cause severe and potentially life-threatening complications, such as bleeding, infections, intravascular hemolysis, thrombocytopenia, or consumption coagulopathy [35–39].

Mortality rates of ECMO for pandemic influenza A (H₁N₁)-associated ARDS ranged from 14 to 64% in the 16 studies from 11 countries reporting on the experience of ECMO for influenza A (H₁N₁)-associated ARDS [8–10, 35, 40–50]. The Australia and New Zealand collaborative group (ANZICS) was the first to report its experience [8]. Despite extreme disease severity at the time of ECMO initiation (median PaO₂/FiO₂ ratio 56 mmHg, median positive end-expiratory pressure [PEEP] at 18 cm H₂O, and median lung injury score of 3.8), only 25% of the 68 ECMO patients died. A British collaborative cohort series [9] depicted the outcome of 80 patients transferred into ECMO referral centers in United Kingdom of whom 69 received ECMO. Mortality in this cohort was 27.5%. A propensity-matched analysis comparing survival of patients referred for consideration of ECMO to other ARDS patients showed better outcomes for referred patients. Alternatively, mortality of propensity-matched patients treated conventionally was comparable to that of ECMO patients in French ICUs of the REVA network. However, only 50% of ECMO patients were successfully matched with control ARDS patients, while unmatched ECMO patients were younger, suffered more severe respiratory failure, and had considerably lower mortality [10]. Interestingly, a higher plateau pressure under ECMO was independently associated with mortality, indicating for the first time that an ultraprotective ventilation strategy with reduction of plateau pressure to around 25 cm H₂O following ECMO installation might improve outcomes. Lastly, mortality was 29% on a cohort of 49 proven influenza A (H₁N₁) patients from the 14 ECMO centers of the ECMO-NET Italian collaborative group [51]. In this series, patients ventilated for <7 days before ECMO initiation had a significantly higher survival.

Factors associated with poor outcomes after ECMO for acute respiratory failure include older age [34–36, 52–55], a greater number of days of mechanical ventilation before the ECMO establishment [35, 36, 52, 53, 55], a higher number of organ failure [34–36, 52–55], low pre-ECMO respiratory system compliance [55], as well as immunosuppression [35, 55, 56]. Predictive survival models have been recently developed which might help clinicians select appropriate candidates for ECMO [35, 54–57]. For instance, the RESP-score [55] constructed on data extracted from a large multicenter international population (n = 2355) computes 12 simple pre-ECMO parameters to provide a relevant and validated tool predicting survival after ECMO for acute respiratory failure. Cumulative predicted hospital survival were 92, 76, 57, 33, and 18% for five RESP-score risk class I (≥6), II (3 to 5), III (−1 to 2), IV (−5 to −2), and V (≤−6), respectively.

Recent technological advances have improved the safety and the simplicity of ECMO use in ARDS. In addition, mobile ECMO team has made this therapy more accessible for all patients. Actual literature has reported that early implementation of VV-ECMO in refractory and severe ARDS can strongly reduce pressures and volumes applied on the alveoli in order to minimize ventilation-induced lung injury. However, strong evidence of its benefit and optimal timing for cannulation are still lacking. Therefore, results of next multicenter randomized trials (i.e EOLIA trial) are needed before wide spreading this promising technology.