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May - 2017


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Fifty Years of Research in ARDS: Is Extracorporeal Circulation the Future of Acute Respiratory Distress Syndrome Management?

A Combes, A Pesenti, V.M Ranieri Am J Resp Crit Care Med, 2017, 195(9);1161-1170


V-V ECMO has taken off over the last decade, due to technology changes, CESAR, and influenza. This article reviews the current knowledge of the physiology, rationale, and results of historical and more recent studies of extracorporeal gas exchange in patients with ARDS. It underlines the need for careful patient selection and management and optimized center organization and discusses what might be future indications of the technique, apart from rescuing patients with lung failure refractory to conventional treatment.

They cover;
- Function of the membrane oxygenator: Membrane oxygenators are artificial organs designed to substitute the gas exchange function of the lungs, as opposed to mechanical ventilators that use the lungs and replace the respiratory muscles. Oxygenation is basically a function of blood flow, while CO2 is a function of sweep speed, although blood flow is a determining factor at lower blood flows with high sweep speed.
- How membrane lung can support gas exchange: they discuss how increasing venous oxygen content can improve arterial oxygenation in the presence of a large intrapulmonary shunt. Also, improved gas exchange may help relieve pulmonary vasoconstriction, reduce physiological dead space, and allow decreased minute ventilation and VILI.
- Historical Studies of Extracorporeal Gas Exchange in Patients with ARDS : the journey from 50s, 70s, 90s, battling bleeding, complications and poor outcomes, to gradual equivalence.
- More Recent Studies of Extracorporeal Gas Exchange in Patients with ARDS:
- CESAR - patients with severe acute resp failure randomised to centralise ECMO or standard care, primary endpoint of 6-month mortality or severe disability was significantly lower for the ECMO group (37 vs. 53%; P = 0.03. The study had two major limitations. Not all patients allocated to the ECMO group received ECMO because some died before or during transportation (5 patients), whereas some others improved with conventional treatment once at the ECMO center (17 patients). Second, because of lack of standardization of ventilation in the control group, only a few patients received a protective ventilatory strategy.
- H1N1 epidemic- Between June and August 2009 in ANZ, 68 patients with severe H1N1 influenza- associated ARDS were treated by ECMO, with a survival rate of 78%. After this appeared in JAMA, many countries instituted an ECMO network, and numerous case series, reporting 70–80% survival rates, were published.
- Rationale for Applying ECCO2R or Venovenous ECMO to Patients with ARDS in 2017 : Since ventilation can cause VILI, ECMO may be beneficial in two clinical settings: to rescue patients from the high risk for death associated with severe hypoxemia, hypercapnia or both, not responding to maximized conventional ventilatory treatment; or to replace mechanical ventilation and minimize/abolish the harmful effects of ventilator-induced lung injury.
- ECLS as Rescue Therapy for Severe Hypoxemia/ Hypercapnia Not Responding to Maximized Conventional Ventilatory Treatment: The optimal time to start ECMO is controversial. ELSO suggests PaO2/FIO2 less than 150 with FIO2 70-100, PEEP 10-20 cm H2O to initiate ECMO. From a clinical perspective, however, this criterion indicates ECMO at a stage of the disease that may not be severely impaired enough. Inclusion criteria of the ongoing EOLIA (Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome) study emphasize PaO2/FIO2 ratios of less than 100 for ECMO. The recent Berlin definition of ARDS suggests PaO2/FIO2 ratios lower than 70 to initiate ECMO.
- ECLS to Minimize/Abolish Ventilator-induced Lung Injury : The use of venovenous ECMO or extracorporeal CO2 removal extracorporeal circulation may allow ultra protective ventilation and possible benefit. preliminary data seem to suggest that use of a superprotective ventilatory strategy supported by the use of ECCO2R attenuated the inflammatory response and shortened the duration of mechanical ventilation (13). More information will be available from the results of an ongoing international multicenter pilot study (SUPERNOVA) to assess the safety and feasibility of MV at 4 ml/kg predicted body weight (facilitated by ECCO2R), and a UK multicenter randomized controlled trial comparing ECCO2R to enable lower VT ventilation versus standard care (REST [Protective Ventilation with Veno-venous Lung Assist in Respiratory Failure]. However, reduction of VT and transpulmonary pressure is not the only aspect of this approach, as a “superprotective” lung strategy may be also theoretically obtained by removing mechanical ventilation to allow spontaneous breathing, although the risk for spontaneous breathing-induced lung injury exists.
- Patients Management under Extracorporeal Gas Exchange: best configuration, ventilation strategy, NMBs, anticoagulation, waking, rehab....
- Center Organization for Successful Extracorporeal Gas Exchange Programs: minimum program volume to be safe, audit and support networks, retrieval systems...
ECMO is in a renaissance period, but much is unknown. So we need to learn more, study more, and be careful.



Mechanical ventilation (MV) remains the cornerstone of acute respiratory distress syndrome (ARDS) management. It guarantees sufficient alveolar ventilation, high FiO2 concentration, and high positive end-expiratory pressure levels. However, experimental and clinical studies have accumulated, demonstrating that MV also contributes to the high mortality observed in patients with ARDS by creating ventilator-induced lung injury. Under these circumstances, extracorporeal lung support (ECLS) may be beneficial in two distinct clinical settings: to rescue patients from the high risk for death associated with severe hypoxemia, hypercapnia, or both not responding to maximized conventional MV, and to replace MV and minimize/abolish the harmful effects of ventilator-induced lung injury. High extracorporeal blood flow venovenous extracorporeal membrane oxygenation (ECMO) may therefore rescue the sickest patients with ARDS from the high risk for death associated with severe hypoxemia, hypercapnia, or both not responding to maximized conventional MV. Successful venovenous ECMO treatment in patients with extremely severe H1N1-associated ARDS and positive results of the CESAR trial have led to an exponential use of the technology in recent years. Alternatively, lower-flow extracorporeal CO2 removal devices may be used to reduce the intensity of MV (by reducing Vt from 6 to 3–4 ml/kg) and to minimize or even abolish the harmful effects of ventilator-induced lung injury if used as an alternative to conventional MV in nonintubated, nonsedated, and spontaneously breathing patients. Although conceptually very attractive, the use of ECLS in patients with ARDS remains controversial, and high-quality research is needed to further advance our knowledge in the field.


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