Current knowledge gaps in extracorporeal respiratory support

Abstract

Extracorporeal life support (ECLS) for acute respiratory failure encompasses veno-venous extracorporeal membrane oxygenation (V-V ECMO) and extracorporeal carbon dioxide removal (ECCO2R). V-V ECMO is primarily used to treat severe acute respiratory distress syndrome (ARDS), characterized by life-threatening hypoxemia or ventilatory insufficiency with conventional protective settings. It employs an artificial lung with high blood flows, and allows improvement in gas exchange, correction of hypoxemia, and reduction of the workload on the native lung. On the other hand, ECCO2R focuses on carbon dioxide removal and ventilatory load reduction (“ultra-protective ventilation”) in moderate ARDS, or in avoiding pump failure in acute exacerbated chronic obstructive pulmonary disease. Clinical indications for V-V ECLS are tailored to individual patients, as there are no absolute contraindications. However, determining the ideal timing for initiating extracorporeal respiratory support remains uncertain. Current ECLS equipment faces issues like size and durability. Innovations include intravascular lung assist devices (ILADs) and pumpless devices, though they come with their own challenges. Efficient gas exchange relies on modern oxygenators using hollow fiber designs, but research is exploring microfluidic technology to improve oxygenator size, thrombogenicity, and blood flow capacity. Coagulation management during V-V ECLS is crucial due to common bleeding and thrombosis complications; indeed, anticoagulation strategies and monitoring systems require improvement, while surface coatings and new materials show promise. Moreover, pharmacokinetics during ECLS significantly impact antibiotic therapy, necessitating therapeutic drug monitoring for precise dosing. Managing native lung ventilation during V-V ECMO remains complex, requiring a careful balance between benefits and potential risks for spontaneously breathing patients. Moreover, weaning from V-V ECMO is recognized as an area of relevant uncertainty, requiring further research. In the last decade, the concept of Extracorporeal Organ Support (ECOS) for patients with multiple organ dysfunction has emerged, combining ECLS with other organ support therapies to provide a more holistic approach for critically ill patients. In this review, we aim at providing an in-depth overview of V-V ECMO and ECCO2R, addressing various aspects of their use, challenges, and potential future directions in research and development.

Extracorporeal organ support for critically ill patients: Overcoming the past, achieving the maximum at present, and redefining the future

“…In the oxygenator, O 2 is transferred through the hollow fibers of a membrane, most commonly consisting of polymethylpentene, which has replaced the silicone membranes previously used. This allows gas exchange while simultaneously restricting the fluid exchange[ 29 , 30 ]. To achieve optimal oxygenation, high blood flow (up to and sometimes more than 4000 mL/min) is required through the oxygenator.…”

“…Furthermore, sufficient fluid volume and hemoglobulin levels should be maintained to achieve adequate oxygen delivery. Despite advances in technology, the process of ECMO cannulation, the requirement of high blood flow, and the necessity for anticoagulation can induce major complications such as bleeding and thrombosis, hemolysis, pulmonary edema and/or hemodynamic instability during the initiation of therapy, hypoxemia, and VILI[ 27 , 29 , 31 ]. Nevertheless, in the modern era, VV-ECMO is more feasible, and its application has been proven to be related to favorable outcomes among patients with severe ARDS.…”

“…Moreover, modern low-flow polymethylpentene membranes can be applied using the RRT platform, with the advantage of enhanced feasibility[ 18 , 33 ]. Although ECCO 2 R has shown promising results and fewer complications than VV-ECMO in ARDS patients, hypercapnic respiratory failure due to the acute exacerbation of chronic obstructive pulmonary disease remains the main indication for ECCO 2 R therapy[ 29 , 34 ].…”