The Science of ECCO2R

Extracorporeal life support evolved from the use of cardiopulmonary bypass systems to address conditions of refractory lung failure (or cardiopulmonary failure) requiring longer periods of bypass than for which these systems were originally developed.  The complication risks associated extracorporeal life support are primarily associated with the need for large catheters, the exposure of a patient’s blood to foreign materials, which can damage the blood cells and cause the blood to clot, and hence the need to anticoagulate the blood during therapy, which increases risks of bleeding and hemorrhage.

Extracorporeal life support systems are used to support the full function of the lungs in terms of sustaining metabolic oxygen requirements and carbon dioxide elimination.  Of those functions, transfer of oxygen to the blood is the greater physiologic challenge, requiring high extracorporeal blood flows.  Accordingly, such therapy is referred to as extracorporeal membrane oxygenation (ECMO), even though carbon dioxide elimination is an equally important component of life support and is also achieved with ECMO.

Carbon dioxide can be removed from blood at a much higher rate, per unit blood flow, than oxygen can be delivered using membrane-based extracorporeal blood gas exchange devices.  This is, of course, a physiologic result of the mechanisms by which oxygen and carbon dioxide are carried in the blood, as well as the higher solubility and diffusivity of carbon dioxide in blood compared to oxygen.  The concept of extracorporeal carbon dioxide removal (ECCO2R) and the subsequent evolution of ECCO2R therapy derived from the opportunity to capitalize on this difference to develop less invasive (reduced risk) systems for specific indications of acute hypercapnic respiratory failure not requiring significant oxygenation support or removal of the full amount of carbon dioxide production.  Such indications include acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD), and facilitation of lung protective ventilation strategies in patients with moderate to severe Acute Respiratory Distress Syndrome (ARDS).  For such indications, clinically meaningful extracorporeal lung support can be provided with much lower blood flows, allowing the use of smaller catheters.

The approach of low-flow, or partial, ECCO2R (also referred to in the literature as PECOR) was first explored by Gattinoni et al. and published in 1986 (JAMA, 256:7, 881-886). This was an important study which showed that if extracorporeal support was used to provide removal of only 33% of estimated basal CO2 production in patients maintained with noninvasive ventilatory support, significant drops in tidal volume could be achieved with relatively small decreases in PaCO2.

As the technology and understanding of appropriate ECCO2R indications evolved, further reductions in the complication risks and incidence of mechanical failures associated with early devices have been achieved by:

  • Advances in hollow fiber membrane technology
    • Smaller, more durable fibers
    • Mechanisms for prevention of plasma leakage
  • More sophisticated arrangements of hollow fiber membranes
    • Reduces priming volume
    • Reduces blood flow resistance (pressure drop across the device), and
    • Improves the gas exchange efficiency, allowing for reduced fiber surface area and/or flow rate/catheter size
  • The use of centrifugal pumps or non-occlusive pressure-controlled roller pumps
    • Reduces damage to the blood (hemolysis)
    • Reduces the incidence of circuit rupture
  • Biocompatible coatings on the fibers and circuit components
    • Reduces the risk of clot formation
    • Reduces necessary levels of systemic anticoagulation
  • Improvements in catheter designs and insertion techniques
    • Dual-lumen catheters
    • Percutaneous cannulation
  • Simplifications and/or advancements in the system design
    • Reduces risk of mechanical failure
    • Reduces risk of operator error
    • Incorporation of alarms for improved safety

There is mounting clinical evidence supporting the need to conduct larger randomized trials powered to scientifically validate the safety and efficacy of low-flow ECCO2R for indications of avoiding or minimizing time on a ventilator for acute hypercapnic respiratory failure, or to eliminate the adverse effects of hypercapnia that result from lung protective ventilation strategies.

Select publications:

  1. Barrett, N.A., N. Hart, & L. Camporota. (2020) “In vivo carbon dioxide clearance of a low-flow extracorporeal carbon dioxide removal circuit in patients with acute exacerbations of chronic obstructive pulmonary disease.” Perfusion. Published ahead of print
  2. Burki, N. K., R. K. Mani, F. J. F. Herth, et al. (2013). “A Novel Extracorporeal CO2 Removal System: Results of a Pilot Study of Hypercapnic Respiratory Failure in Patients With COPD.” CHEST Journal 143(3): 678-686.
  3. Diehl, J. L., L. Piquilloud, J.-C. M. Richard, et al. (2016). “Effects of extracorporeal carbon dioxide removal on work of breathing in patients with chronic obstructive pulmonary disease.” Intensive Care Med 45(5): 951-2.
  4. Fanelli, V., M. V. Ranieri, J. Mancebo, et al. (2016). “Feasibility and safety of low-flow extracorporeal carbon dioxide removal to facilitate ultra-protective ventilation in patients with moderate acute respiratory distress syndrome.” Critical Care 20(1): 1-7.
  5. Kalbhenn, J., N. Neuffer, B. Zieger, et al. (2017). “Is extracorporeal CO2-Removal really “safe” and “less” invasive? Observation of blood injury and coagulation impairment during ECCO2R.” ASAIO Journal 63(5): 666-671.
  6. Moss, C. E., E. J. Galtrey, L. Camporota, et al. (2016). “A retrospective observational case series of low flow veno-venous extracorporeal carbon dioxide removal use in patients with respiratory failure.” ASAIO J 62(4): 458-62.
  7. Parrilla, F., L. Bergesio, H. Aguirre-Bermeo, et al. (2015). “Ultra-Low Tidal Volumes and Extracorporeal Carbon Dioxide Removal (Hemolung RAS) In ARDS Patients. A Clinical Feasibility Study.” Intensive Care Medicine Experimental 3(Suppl 1): A7.
  8. Rauch, S., H. Roth, T. Deininger, et al. (2015). “Case series of protective ventilation for ARDS using partial extracorporeal CO2 removal.” EuroELSO 2015 4th International Congress: Poster.
  9. Tiruvoipati, R., H. Buscher, J. Winearls, et al. (2016). “Early experience of a new extracorporeal carbon dioxide removal device for acute hypercapnic respiratory failure.” Crit Care Resusc 18(4): 261-269.
  10. Winiszewski, H., F. Aptel, F. Belon, et al. (2018) “Daily use of extracorporeal CO2 removal in a critical care unit: indications and results” Journal of Intensive Care. 6 (36)