Review ArticleOpen Access

Extracorporeal CO2 Removal (ECCO2R): Hope or Hype?

DOI: 10.23958/ijirms/vol10-i10/2126· Pages: 369 - 375· Vol. 10, No. 10, (2025)· Published: October 1, 2025
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Abstract

Recent technological advancements have simplified the design of extracorporeal membrane oxygenation devices, paving the way for specialized devices dedicated to the targeted removal of carbon dioxide (CO2) from the body. These CO2 removal devices feature a more streamlined configuration compared to traditional extracorporeal membrane oxygenation devices, operating at lower blood flows to minimize potential complications. Experimental studies have confirmed the viability, efficacy, and safety of extracorporeal CO2 removal, showcasing its potential benefits in human subjects.

Initially conceptualized as an adjunct therapy for individuals with severe acute respiratory distress syndrome, COPD, Status asthmaticus and pulmonary artery hypertension in COPD awaiting lung transplant this approach aimed to optimize protective ventilation strategies. More recently, the application of extracorporeal CO2 removal has given rise to the concept of "ULTRA-Lung protective ventilation," the complete implications of which are still under exploration. Moreover, the technique has demonstrated promising outcomes in addressing exacerbated hypercapnic respiratory failure.

This review delves into the intricate details of the physiological and technical aspects of CO2 removal therapy and its various iterations. Additionally, it presents a comprehensive survey of the existing clinical evidence, illuminating the evolving potential of this innovative approach.

Keywords

Carbon dioxide removalExtracorporeal circulationMechanical VentilationAdult respiratory distress syndromeChronic obstructive pulmonary diseaseBronchial AsthmaLung transplantPulmonary artery HypertensionRespiratory dialysis

References

  1. Davidson AC, Banham S, Elliott M, Kennedy D, Gelder C, Glossop A, et al. BTS/ICS guideline for the ventilatory management of acute hypercapnic respiratory failure in adults. Thorax. 2016;71(Suppl 2):1–35.Google Scholar ↗
  2. Osadnik CR, Tee VS, Carson-Chahhoud KV, Picot J, Wedzicha JA, Smith BJ. Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2017;7:004104.Google Scholar ↗
  3. Ozsancak Ugurlu A, Habesoglu MA. Epidemiology of NIV for Acute Respiratory Failure in COPD Patients: Results from the International Surveys vs. the “Real World.” COPD. 2017;14(4):429–38.Google Scholar ↗
  4. Plant PK, Owen JL, Elliott MW. Non-invasive ventilation in acute exacerbations of chronic obstructive pulmonary disease: long term survival and predictors of in-hospital outcome. Thorax. 2001;56(9):708–12.Google Scholar ↗
  5. Ozyilmaz E, Ugurlu AO, Nava S. Timing of noninvasive ventilation failure: causes, risk factors, and potential remedies. BMC Pulm Med. 2014;14:19.Google Scholar ↗
  6. Barrett NA, Hart N, Daly KJ, Marotti M, Kostakou E, Carlin C, et al. A randomised controlled trial of non-invasive ventilation compared with extracorporeal carbon dioxide removal for acute hypercapnic exacerbations of chronic obstructive pulmonary disease. Annals of Intensive Care. 2022;12(1). doi:10.1186/s13613-022-01006-8.DOI ↗Google Scholar ↗
  7. Zanella A, Castagna L, Salerno D, Scaravilli V, Abd El Aziz El Sayed Deab S, Magni F, et al. Respiratory electrodialysis. A novel, highly efficient extracorporeal CO2 removal technique. American Journal of Respiratory and Critical Care Medicine. 2015;192(6):719–26. doi:10.1164/rccm.201502-0289oc.DOI ↗Google Scholar ↗
  8. Morelli A, Del Sorbo L, Pesenti A, Ranieri VM, Fan E. Extracorporeal carbon dioxide removal (ECCO2R) in patients with acute respiratory failure. Intensive Care Medicine. 2017;43(4):519–30. doi:10.1007/s00134-016-4673-0.DOI ↗Google Scholar ↗
  9. Batchinsky AI, Jordan BS, Regn D, Necsoiu C, Federspiel WJ, Morris MJ, et al. Respiratory dialysis: Reduction in dependence on mechanical ventilation by venovenous extracorporeal CO2 Removal*. Critical Care Medicine. 2011;39(6):1382–7. doi:10.1097/ccm.0b013e31820eda45.DOI ↗Google Scholar ↗
  10. Romay E, Ferrer R. Eliminación extracorpórea de CO2: Fundamentos Fisiológicos y técnicos y principales indicaciones. Medicina Intensiva. 2016;40(1):33–8. doi:10.1016/j.medin.2015.06.001.DOI ↗Google Scholar ↗
  11. Worku E, Brodie D, Ling RR, Ramanathan K, Combes A, Shekar K. Venovenous Extracorporeal Co2 removal to support ultraprotective ventilation in moderate-severe ARDS: A systematic review and meta-analysis of the literature. 2021; doi:10.1101/2021.10.26.21265546.DOI ↗Google Scholar ↗
  12. İNAL V, EFE S. Extracorporeal carbon dioxide removal (ECCO2R) in COPD and ARDS patients with severe hypercapnic respiratory failure. A retrospective case-control study. TURKISH JOURNAL OF MEDICAL SCIENCES. 2021;51(4):2127–35. doi:10.3906/sag-2012-151.DOI ↗Google Scholar ↗
  13. Duiverman ML, Wijkstra PJ. Extracorporeal co2 removal for stable hypercapnic COPD: Is it really worth it? Thorax. 2020;75(10):824–5. doi:10.1136/thoraxjnl-2020-215259.DOI ↗Google Scholar ↗
  14. O’Croinin DF, Nichol AD, Hopkins N, Boylan J, O’Brien S, O’Connor C, et al. Sustained hypercapnic acidosis during pulmonary infection increases bacterial load and worsens lung injury. Critical Care Medicine. 2008; 36: 2128-2135.Google Scholar ↗
  15. O’Toole D, Hassett P, Contreras M, Higgins BD, McKeown ST, McAuley DF, et al. Hypercapnic acidosis attenuates pulmonary epithelial wound repair by an NF-κB dependent mechanism. Thorax. 2009; 64: 976–982.Google Scholar ↗
  16. Vohwinkel CU, Lecuona E, Sun H, Sommer N, Vadász I, Chandel NS, et al. Elevated CO2 levels cause mitochondrial dysfunction and impair cell proliferation. Journal of Biological Chemistry. 2011; 286: 37067–37076.Google Scholar ↗
  17. Lecuona E, Trejo HE, Sznajder JI. Regulation of Na,K-ATPase during acute lung injury. Journal of Bioenergetics and Biomembranes. 2007; 39: 391–395.Google Scholar ↗
  18. Nakahata K, Kinoshita H, Hirano Y, Kimoto Y, Iranami H, Hatano Y. Mild hypercapnia induces vasodilation via adenosine triphosphate- sensitive K+ channels in parenchymal microvessels of the rat cerebral cortex. Anesthesiology. 2003; 99: 1333–1339.Google Scholar ↗
  19. Shiota S, Okada T, Naitoh H, Ochi R, Fukuchi Y. Hypoxia and hypercapnia affect contractile and histological properties of rat diaphragm and hind limb muscles. Pathophysiology. 2004; 11: 23–30.Google Scholar ↗
  20. Tang W, Weil MH, Gazmuri RJ, Bisera J, Rackow EC. Reversible impairment of myocardial contractility due to hypercarbic acidosis in the isolated perfused rat heart. Critical Care Medicine. 1991; 19: 218–224.Google Scholar ↗
  21. Kregenow DA, Swenson ER. The lung and carbon dioxide: implications for permissive and therapeutic hypercapnia. European Respiratory Journal. 2002; 20: 6–11.Google Scholar ↗
  22. Dreyfuss D, Saumon G. Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med. 1998;157(1):294–323.Google Scholar ↗
  23. Frank JA, Parsons PE, Matthay MA. Pathogenetic significance of biological markers of ventilator-associated lung injury in experimental and clinical studies. Chest. 2006;130(6):1906–14.Google Scholar ↗
  24. Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Acute Respiratory Distress Syndrome N, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301–8.Google Scholar ↗
  25. Hager DN, Krishnan JA, Hayden DL, Brower RG, Network ACT. Tidal volume reduction in patients with acute lung injury when plateau pressures are not high. Am J Respir Crit Care Med. 2005;172(10):1241–5.Google Scholar ↗
  26. Amato MB, Meade MO, Slutsky AS, Brochard L, Costa EL, Schoenfeld DA, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372(8):747–55.Google Scholar ↗
  27. Richard JC, Marque S, Gros A, Muller M, Prat G, Beduneau G, et al. Feasibil- ity and safety of ultra-low tidal volume ventilation without extracorporeal circulation in moderately severe and severe ARDS patients. Intensive Care Med. 2019;45(11):1590–8.Google Scholar ↗
  28. Hanks J, Fox S, Mehkri O, Lund LW, Dill T, Duggal A, et al. On the horizon: Extracorporeal carbon dioxide removal. CLEVELAND CLINIC JOURNAL OF MEDICINE. 2022 Dec;89(12):712–8. doi:doi:10.3949/ccjm.89a.21084.DOI ↗Google Scholar ↗
  29. Omecinski K, Cove M, Duggal A, Federspiel W. Extracorporeal Carbon Dioxide Removal (ECCO2R): A Contemporary Review. Applications in Engineering Science. 2022;10:100095. doi:10.1016/j.apples.2022.100095.DOI ↗Google Scholar ↗
  30. Morales-Quinteros L, Del Sorbo L, Artigas A. Extracorporeal carbon dioxide removal for acute hypercapnic respiratory failure. Annals of Intensive Care. 2019;9(1). doi:10.1186/s13613-019-0551-6.DOI ↗Google Scholar ↗
  31. Conrad SA, Broman LM, Taccone FS, Lorusso R, Malfertheiner MV, Pappalardo F, et al. The Extracorporeal Life Support Organization Maastricht Treaty for Nomenclature in Extracorporeal Life Support. A position paper of the Extracorporeal Life Support Organization. American Journal of Respiratory and Critical Care Medicine. 2018;198(4):447–51. doi:10.1164/rccm.201710-2130cp.DOI ↗Google Scholar ↗
  32. Li M, Gu S-C, Xia J-G, Zhan Q-Y. Acute exacerbation of chronic obstructive pulmonary disease treated by extracorporeal carbon dioxide removal. Chinese Medical Journal. 2019;132(20):2505–7. doi:10.1097/cm9.0000000000000461.DOI ↗Google Scholar ↗
  33. Pisani L, Nava S, Desiderio E, Polverino M, Tonetti T, Ranieri VM. Extracorporeal Co2 Removal (ecco2R) in patients with stable COPD with chronic hypercapnia: A proof-of-concept study. Thorax. 2020;75(10):897–900. doi:10.1136/thoraxjnl-2020-214744.DOI ↗Google Scholar ↗
  34. Azzi M, Aboab J, Alviset S, Ushmorova D, Ferreira L, Ioos V, et al. Extracorporeal CO2 Removal in acute exacerbation of COPD not responding to non-invasive ventilation: A single center experience. 2021; doi:10.21203/rs.3.rs-542363/v1.DOI ↗Google Scholar ↗
  35. Giraud R, Banfi C, Assouline B, De Charrière A, Cecconi M, Bendjelid K. The use of extracorporeal CO2 removal in acute respiratory failure. Annals of Intensive Care. 2021;11(1). doi:10.1186/s13613-021-00824-6.DOI ↗Google Scholar ↗
  36. Combes A, Auzinger G, Capellier G, du Cheyron D, Clement I, Consales G, et al. ECCO2R therapy in the ICU: consensus of a European round table meeting. Crit Care. 2020;24(1):490.Google Scholar ↗
  37. EC, Combes A, Brodie D, Ferguson ND, Pesenti AM, Ranieri VM, et al. Determinants of the effect of extracorporeal carbon dioxide removal in the SUPERNOVA trial: implications for trial design. Intensive Care Med. 2019;45(9):1219–30.Google Scholar ↗
  38. Combes A, Fanelli V, Pham T, Ranieri VM. Feasibility and safety of extracorporeal CO2 removal to Goligher enhance protective ventilation in acute respiratory distress syndrome: the SUPERNOVA study. Intensive Care Medicine. 2019; 45: 592-600.Google Scholar ↗
  39. Bein T, Weber-Carstens S, Goldmann A, Müller T, Staudinger T, Brederlau J, et al. Lower tidal volume strategy (≈3 mL/kg) combined with extracorporeal CO2 removal versus ‘conventional’ protective ventilation (6 mL/kg) in severe ARDS: the prospective randomized Xtravent-study. Intensive Care Medicine. 2013; 39: 847–856.Google Scholar ↗
  40. Bonin F, Sommerwerck U, Lund LW, Teschler H. Avoidance of intubation during acute exacerbation of chronic obstructive pulmonary disease for a lung transplant candidate using extracorporeal carbon dioxide removal with the Hemolung. The Journal of Thoracic and Cardiovascular Surgery. 2013;145(5). doi:10.1016/j.jtcvs.2013.01.040.DOI ↗Google Scholar ↗
  41. Kluge S, Braune SA, Engel M, Nierhaus A, Frings D, Ebelt H, et al. Avoiding invasive mechanical ventilation by extracorporeal carbon dioxide removal in patients failing noninvasive ventilation. Intensive Care Medicine. 2012;38(10):1632–9. doi:10.1007/s00134-012-2649-2.DOI ↗Google Scholar ↗
  42. Burki NK, Mani RK, Herth FJF, Schmidt W, Teschler H, Bonin F, et al. A novel extracorporeal co 2 removal system. Chest. 2013;143(3):678–86. doi:10.1378/chest.12-0228.DOI ↗Google Scholar ↗
  43. Karagiannidis C, Strassmann S, Philipp A, Müller T, Windisch W. Veno-venous extracorporeal CO2 removal improves pulmonary hypertension in acute exacerbation of severe COPD. Intensive Care Medicine. 2015;41(8):1509–10. doi:10.1007/s00134-015-3917-8.DOI ↗Google Scholar ↗
  44. Fuehner T, Kuehn C, Hadem J, Wiesner O, Gottlieb J, Tudorache I, et al. Extracorporeal membrane oxygenation in awake patients as bridge to lung transplantation. Am J Respir Crit Care Med. 2012;185(7):763–8.Google Scholar ↗
  45. Bromberger BJ, Agerstrand C, Abrams D, Serra A, Apsel D, Tipograf Y, et al. Extracorporeal carbon dioxide removal in the treatment of status asthmaticus. Critical Care Medicine. 2020;48(12). doi:10.1097/ccm.0000000000004645.DOI ↗Google Scholar ↗
  46. Liu Z, Duarte RV, Bayliss S, Bramley G, Cummins C. Adverse effects of extracorporeal carbon dioxide removal (ECCO2R) for acute respiratory failure: A systematic review protocol. Systematic Reviews. 2016;5(1). doi:10.1186/s13643-016-0270-0.DOI ↗Google Scholar ↗
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