Medical Policy

This document addresses the use of extracorporeal carbon dioxide removal (ECCO₂R), a minimally invasive, low-flow veno-venous or venous-arterial procedure used to treat acute hypercapnic respiratory failure or as an alternative to standard extracorporeal membrane oxygenation (ECMO).

Investigational and Not Medically Necessary:

Extracorporeal carbon dioxide removal is considered investigational and not medically necessary for all conditions, including but not limited to acute hypercapnic respiratory failure.

The Hemolung^® Respiratory Assist System (LivaNova, London, UK) received De Novo classification on 11/13/2021. Per that classification, the Hemolung Respiratory Assist System is indicated for respiratory support that provides extracorporeal carbon dioxide (CO2) removal from the patient's blood for up to 5 days in adults with acute, reversible respiratory failure for whom ventilation of CO2 cannot be adequately or safely achieved using other available treatment options and continued clinical deterioration is expected. This is the only ECCO₂R device available in the U.S.

Clinical Trials

Bein and colleagues (2013) evaluated the use of arteriovenous extracorporeal CO₂ elimination (avECCO₂-R) with low tidal volume ventilation in individuals with ARDS. A total of 79 individuals with established ARDS with moderate hypercapnia were enrolled. Forty individuals were randomized to receive avECCO₂-R with mechanical ventilation at a low tidal volume rate of 3 ml/kg/PBW. The ECCRO₂R devices used in this trial was the iLA AV Novalung (Fresenius Medical Care, Bad Homberg, Denmark). Thirty-nine control-group individuals received only mechanical ventilation at a rate of 6 ml/kg/PBW. The primary outcome was the proportion of ventilator-free days (VFD) at 28 and 60 days. There were no statistical differences between the groups in VFD-28 (10.0 ± 8 days, 9.3 ± 9 days in the control group; p=0.779) or VFD-60 (33.2 ± 20 days, 29.2 ± 21 days in the control group; p=0.469). Mortality rates were low (17.5% in the treatment group, 15.4% in the control group) and did not differ between the groups. In the treatment group, ECCO₂-R-related complications graded as temporary and moderate occurred in 3 individuals. The authors concluded that the use of low tidal volume ventilation combined with ECCO₂-R was safe and feasible but was not associated with a significant reduction in the duration of mechanical ventilation needed.

Fanelli (2016) reported on the safety and feasibility of low-flow veno-venous ECCO₂R treatment using Hemolung in a prospective study involving 15 individuals with moderate acute respiratory distress syndrome (ARDS) who were mechanically ventilated. The authors aimed to study lower tidal volumes in combination with ECCO₂R in an attempt to reduce the likelihood of ventilator-induced lung injury. Individual tidal volumes (VT) were reduced from 6 mg/kg/predicted body weight (PBW) to 4 mg/kg/PBW; positive end-expiratory pressure (PEEP) was increased from 23 to 25 cm H₂O. ECCO₂R began when individuals developed respiratory acidosis at pH < 7.25 and partial pressure of arterial CO₂ (PaCO₂₎ > 60 mmHg. The potential for weaning from ultra-protective ventilation and ECCO₂R was assessed daily. Participants who remained stable for at least 12 hours with plateau pressure (Pplat) < 25 cm H₂O and PaCO₂ < 50 mmHg (allowing for respiratory rate [RR] up to 30-35/min) were discontinued from ECCO₂R and the venous catheter removed. At baseline, all participants had a PaO₂/FiO₂ ≤ 200 and they were ventilated with a conventional protective ventilation strategy. After initiation of ECCO₂R, a VT of 4.29 ± 0.5 mL/kg was achieved and respiratory acidosis was significantly corrected, with pH and PaCO₂ returning to within 10% of baseline values obtained at VT=6 mL/kg. The median number of days on ECCO₂R was 3 (range, 2-4). The reduction in VT was associated with a significant reduction in Pplat from 27.7 ± 1.6 to 23.9 ± 1 cm H₂O (p<0.05) at day 1 and this difference remained significant throughout the study period. Two study-related adverse events were reported including intravascular hemolysis and kinking of the ECCO₂R catheter. The overall mortality at day 28 was 47%. Among the 8 survivors, 6 were successfully weaned from both ECCO₂R and mechanical ventilation while 2 were still dependent on ventilator support at 28 days.

McNamee (2021) and colleagues published the results of the REST trial, a multicenter, randomized, allocation-concealed, open-label clinical trial investigating whether lower tidal volume ventilation facilitated by ECCO₂R with a Hemolung device compared with standard care improves outcomes in individuals with acute hypoxemic respiratory failure requiring intensive care. A total of 412 participants were randomized to receive lower tidal volume ventilation facilitated by ECCO₂R for at least 48 hours (n=202) with a maximum of 7 days, or standard care with conventional low tidal volume ventilation (n=210). The primary outcome was all-cause mortality 90 days after randomization. The 90 day mortality rate was 41.5% in the ECCO₂R group compared to 39.5% in the standard care group, a difference of 2.0% (95% confidence interval [CI], -7.6% to 11.5%; p=0.68). There were significantly fewer mean ventilator-free days at day 28 in the ECCO₂R group (7.1 days) compared to the standard care group (9.2 days; mean difference, -2.1 [95% CI, -3.8 to -0.3]; p=0.02). There were no significant between-group differences in other secondary outcomes which included: duration of ventilation, need for ECMO at day 7, mortality at 28 days, and duration of ICU or hospital stay. Serious adverse events were reported for 62 participants (31%) in the ECCO₂R group and 18 participants (9%) in the standard care group. Serious adverse events included intracranial hemorrhage in 9 participants (4.5%) compared to 0 (0%) and bleeding at other sites in 6 participants (3.0%) compared to 1 (0.5%) in the ECCO₂R and standard care groups, respectively. Overall, 21 participants experienced 22 serious adverse events related to the study device. The trial was stopped early due to futility and feasibility following recommendations from the study’s data monitoring and ethics committee. Lower tidal volume ventilation facilitated by ECCO₂R did not result in a reduction in mortality at 90 days compared to standard care in individuals requiring mechanical ventilation for acute hypoxemic respiratory failure. The authors note that it is possible the trial was underpowered to detect a clinically important difference, particularly because the trial was stopped before recruitment of the planned sample size (n=1120) was achieved.

Azzi (2021) reported the results of a retrospective controlled trial involving 51 participants with acute exacerbation of chronic obstructive pulmonary disease (COPD) and failure of noninvasive mechanical ventilation (NIV). Participants were treated with ECCO₂R or invasive mechanical ventilation (n=26 vs. 25, respectively). The ECCO₂R device used in this study was the iLA AV. At baseline, the two groups were similar, with the exception that the ECCO₂R group had significantly higher BMI (30 kg/m² vs 25 kg/m², p=0.035). The primary endpoint was to record ECCO₂R failure, defined as transition to invasive mechanical ventilation or death by day 90. Failure of ECCO₂R  treatment was reported in 5 (19%) participants, with 4 (15%) intubated and 1 dying before intubation due to multiple organ failure. Among the intubated participants, 3 were no longer alive at day 90. A total of 7 (28%) participants in the control group died before 90 days (between group difference p=0.26). No significant differences between groups were reported with regard to improvements in pH and PaCO₂ values. Similarly, no significant differences between groups were reported in either ICU or overall hospital length of stay. Major bleeding events occurred in 6 (23%) participants in the ECCO₂R group, with ECCO₂R treatment discontinued due to bleeding for 3 (11%) participants. Other adverse events reported included hemolysis due to ECCO₂R (n=3), thrombocytopenia <100 G/L (n=6), circuit thrombosis leading to premature discontinuation of ECCO₂R (n=3). In the control group, 8 (32%) participants experienced ventilator-associated pneumonia, 25 hemodynamic instability events with catecholamine administration requirement occurred in 19 participants (76%), and self-extubation was observed in 6 participants. A total of 3 (12%) participants died due to invasive mechanical ventilation-related complications. The authors concluded that ECCO₂R provided significant improvement of pH and PaCO₂ in this population and led to avoidance of invasive ventilation in 85% of cases with low complication rates.

Nagler (2022) reported the results of a retrospective comparative study involving 47 consecutive participants experiencing respiratory failure requiring intervention and treated with either venovenous ECMO (n=24) or ECCO₂R (n=23). Hemostatic changes between groups were assessed by application of linear mixed effect models. The authors reported no significant differences between groups with regard to change in platelet count (p=0.529) or D-dimer measures (p=0.332). Measures for changes in fibrinogen levels indicated significant differences between groups during treatment (p=0.003). Day 1 fibrinogen level changes from baseline were -0.9% in the ECCO₂R group and -6.1% in the ECMO group. On Day 4, those changes were -0.4% in the ECCO₂R group and -5.6% in the ECMO group. No significant differences between groups were reported with regard to rate of system exchanges, transfusion requirements, number of positive blood cultures, ICU mortality, in-hospital mortality, or 28 day mortality. The authors concluded that their findings suggest that ECCO₂R is not significantly different from VV ECMO in terms of hemocompatibility. The authors concluded that their results indicate a benefit to ECCO₂R with regard to time to improvement in respiratory acidosis, respiratory physiology, patient comfort, and dyspnea. The lack of randomization and blinding limit the generalizability of these results.

Barrett (2022) reported on an randomized controlled trial (RCT) involving 18 participants with acute exacerbation of COPD at high risk of noninvasive ventilation failure (GOLD stage 3) assigned to treatment with either ECCO₂R with the Hemolung (n=9) or continued noninvasive ventilation (n=9). Respiratory rates were reported to be significantly different between groups at baseline and 12 hour post-treatment initiation, with ECCO₂R being significantly higher vs. the noninvasive ventilation group (22 breaths/min vs. 17 breaths/min, p=0.038). Arterial pH was not significantly different between the two groups, but PaCO₂ was significantly lower with ECCO₂R group vs. the noninvasive ventilation group at 4 hours (6.8 kPa vs. 8.3 kPa; p=0.024). Serum bilirubin levels at day 2 were significantly higher with ECCO₂R group vs. the noninvasive ventilation group (14 umol/L vs. 5 umol/L; p=0.013). Likewise, platelets count were lower in the ECCO₂R group at day 2 (96 vs. 225×109/L; p=0.044). Fibrinogen remained significantly higher with ECCO₂R group at baseline, day 1 and day 2 (p< 0.001), days 1 and 2. No severe or life-threatening complications were reported in either group, including major bleeding or transfusion. The number of non-severe complications related to noninvasive ventilation was higher than ECCO₂R, primarily due to discomfort. One participant in the ECCO₂R groups required infusion of platelets and another required invasive ventilation due to hospital acquired pneumonia. Overall, the ICU and hospital length of stays were significantly longer with ECCO₂R group vs. noninvasive ventilation group (161:45 hours vs. 45:49 hours, p=0.001; 240:00 hours vs. 124:00 hours, p=0.014; respectively). Survival to 90 days was not significantly different between groups.

Boyle (2023) published the results of a pre-specified secondary analysis for the REST trial previously, reported by McNamee in 2021, to assess 2-year outcomes. Of the 412 participants originally enrolled into the REST trial, 1-year mortality data was available for 401 (97.3%) with no significant difference between groups. Two-year mortality data was available for 391 participants (94.9%) again with no significant difference between groups. The time-to-death up to 2 years was similar between groups (HR, 1.08; log-rank test p=0.61). The St. George’s Respiratory Questionnaire was completed by 116 (53%) participants alive at 1 year. Partial responses were also received, but no data were provided for the total number of responses. No significant differences between groups were reported with regard to SGRQ total score (p=1.00) or subscale components for  symptoms (p=0.52), activity (p=0.91), or impacts (p=0.83). Montreal Cognitive Assessment (MoCA)-Blind Questionnaire was completed by 115 (56%) patients alive at 1 year, and no significant difference was reported between groups with regard to the proportion who had mild, moderate, or severe cognitive impairment (p=0.41). The authors concluded that lower-tidal volume ventilation vv-ECCO2 R does not affect 1-year mortality when used to treat ARDS with moderate-to-severe AHRF. Additionally, they concluded that among reporting participants, there was “no treatment effect on long-term respiratory function, post-traumatic stress disorder, cognitive dysfunction or health-related quality of life.”

Tiruvoipati (2024) reported the results of a retrospective registry-based study involving participants treated with ECCO₂R using the Hemolung for acute respiratory failure due to a variety of chronic conditions. Data from the Hemolung Registry entered between April 2013 and June 2021 were analyzed for the following measures during the first 36 hours of treatment: improvement in pH and PaCO₂, reduction in ventilation support, respiratory rate, tidal volume, and peak inspiratory pressure (PIP). Survival to ICU discharge, safety and complications were also investigated. A total of 62 participants were included in the study. COPD was the most common indication  for treatment (77.4%), with interstitial lung disease, pulmonary fibrosis, and cystic fibrosis each accounting for 4.8%. “Other” indications accounted for  the remaining 8.1%. A significant improvement was reported in pH (p<0.001), PCO₂ (p<0.001), along with the reduction in respiratory rate (p<0.005), tidal volume (p<0.008), and minute ventilation (p<0.001) over the first 36 hours treatment. No statistically significant difference in PIP were reported within the first 36 hours (p=0.136). No statistically significant differences in demographic variables, anticoagulation management or complication profile were reported between participants who died in the ICU vs. those who were discharged. The most common complication was bleeding, but no differences were reported between survival groups. Multivariable analysis indicated that duration of ECCO₂R treatment was independently associated with ICU discharge (adjusted odds ratio [OR], 1.21; p=0.01). The authors concluded, “These findings support the use of Hemolung therapy in acute-on-chronic respiratory failure patients and provide details on optimizing the application of this therapy in patients with acute-on-chronic respiratory failure.” However, lack of a comparison group and blinding, the retrospective nature of the study, and lack of long-term outcomes limit the generalizability of this data.

Duggal (2024) reported the results of the VENT-AVOID RCT, a prospective, non-blind, randomized, controlled, pivotal trial involving 133 adults with exacerbations of COPD and treated with either ECCO₂R using the Hemolung plus standard care (n=58) or standard care alone (n=55). Participants were further stratified by those failing NIV at high risk of requiring intubation (n=26 in ECCO₂R group and n=22 control group) or those failing to wean from invasive mechanical ventilation after 1 hour (n=32 and n=33, respectively). A total of 5992 total participants were screened, with fewer than 2% enrolled. The primary endpoint of the study was the number of invasive ventilator-free days within the first 5 days after randomization (VFD-5). The secondary endpoints included achieving physiologic targets, avoidance of intubation, ability to communicate orally, eat and drink, average ICU mobility scale score over the first 5 days, medication usage, and incidence of new tracheostomy. A decision to terminate the trial early was made based on slow enrollment throughout the trial, which was exacerbated by the COVID-19 pandemic. The original target enrollment was 180 participants, but 108 participants were included in the per-protocol analysis (n=22 in each group in the noninvasive therapy stratum and n=30 ECCO₂R and n=33 control participants in the invasive ventilation stratum), and 110 participants in the intention-to-treat analysis. The results indicated no significant differences in the median VFD-5 between the ECCO₂R and control groups when controlled by strata (p=0.36). In the NIV stratum, there was no difference between groups with regard to VFD-5 (VFD-5= 5 days in each group, p=1.0). No deaths were reported within the first 5days in the NIV ventilation stratum. In the invasive ventilation stratum, VFD-5 in ECCO₂R arms 2 days and was 0.25 days in the control group (p=0.21). There were two deaths reported in the ECCO₂R group in the invasive stratum in the first 5 days, although the authors reported neither was related to the experimental treatment or mechanical ventilation. In the NIV stratum, PaCO₂ at 2–6 hours and 24 hours was significantly lower in the ECCO₂R group compared with the control group (p=0.02 and 0.03, respectively). No significant differences between groups were reported with regard to the incidence of tracheostomies, ICU mobility, hospital readmission, do-not resuscitate requests, or do-not-intubate requests within either stratum. In the NIV stratum the VFD-30 and time from randomization to ICU and hospital discharge were significantly shorter in the SOC group vs. the ECCO₂R group (p=0.04, 0.001, and 0.002, respectively). Within 24 hours of initiation of ECCO₂R, a significant reduction in dyspnea was reported in the ECCO₂R group compared baseline (p=0.001). In the control group, no change in dyspnea was reported over the same time period (p=0.18). Bleeding was the most common ECCO₂R-related serious adverse event, of which four were definitely, one was probably, and four were possibly related to ECCO₂R. One case of ECCO₂R failure was reported, requiring the participant to be reintubated. In the NIV stratum, all-cause in-hospital mortality was significantly higher in the ECCO₂R group vs. the control group (22% vs. 0%, p=0.02). The ECCO₂R-related deaths resulted from cardiopulmonary arrest secondary to endstage COPD (considered possibly related) and a hemothorax after cannulation (considered definitely related). Similarly, at 60 days, all-cause mortality in the NIV stratum was significantly higher in the ECCO₂R group than in the control group (43% vs. 6%; P=0.01). In the invasive stratum, all-cause in-hospital mortality in the ECCO₂R group was 17%, compared with 15% in the SOC arm (p=0.73). Both in-hospital deaths in the ECCO₂R group were considered possibly related to ECCO₂R and included one hemorrhagic shock and one retroperitoneal hematoma. In the control group, the deaths related to mechanical ventilation resulted from aspiration pneumonia (considered possibly related), septic shock (considered possibly related), and sepsis (considered probably related). All-cause mortality in this stratum at 60 days was 31% in the control group arm compared with 22% in the ECCO₂R group (p=0.72). The results of this trial indicate the resolution of hypercapnia, time to ICU discharge, and in-hospital and 60-day mortality favored the standard of care group. The authors concluded,

Because of the significantly higher mortality in the ECCO₂R arm and the very low intubation rate across the stratum, our study does not support the early application of ECCO₂R in patients with ECOPD who are deemed to be at risk for NIV failure.

Overall, the results of this study indicated that in individuals with exacerbations of COPD, the use of ECCO₂R compared with standard care did not improve VFD-5.

Additionally, there have been a limited number of other articles published reporting on the use of ECCO₂R. These studies are primarily pilot studies, case studies, and retrospective reviews addressing the use of ECCO₂R for the treatment of acute hypercapnic respiratory failure (Abrams, 2013; Allescher, 2021; Bermudez, 2015; Bonin, 2013; Burke, 2013; Cambria, 2024; Fox, 2024; Moss, 2016; Redwan, 2016). These publications have limited generalizability, and their results should be supported by larger, well-designed and implemented trials.

Yu et al. (2021) published a meta-analysis of 25 studies involving 826 participants undergoing ECCO₂R for hypercapnic respiratory failure of any etiology. The study was designed to compare venous ECCO₂R to arterial ECCO₂R. The primary finding was that ICU length of stay was significantly shorted in the venous ECCO₂R group (p=0.05). No differences in in-hospital mortality was reported.

Zhu (2021) published a meta-analysis of 15 studies involving 532 participants with ARDS or COPD. They reported that when compared to control treatments, ECCO₂R did not significantly alter 28-day mortality (p=0.51) or ICU or hospital length of stay (p=0.44 and p=0.928, respectively). The overall adverse event rate was 35% (p<0.001), with bleeding being the most frequent (22%).

Worku (2022) published a meta-analysis involving 10 studies addressing the use of ECCO₂R for moderate to severe ARDS involving 421 participants. They reported no significant changes in oxygenation, respiratory rate or PEEP due to ECCO₂R. Additionally, no significant interactions between driving pressure reduction and baseline driving pressure, partial pressure of arterial carbon dioxide or PaO2:FiO2 ratio were identified in metaregression analysis. Similar to other reports, they identified bleeding and hemolysis as the most common complications. Additionally, they commented,

Heterogeneity amongst studies and devices, a paucity of randomised controlled trials, and variable safety reporting calls for standardisation of outcome reporting. Prospective evaluation of optimal device operation and anticoagulation in high quality studies is required before further recommendations can be made.

Conclusion

To date, the evidence addressing the use of ECCO₂R have produced conflicting results, but in general have not shown improved mortality or improved long term net health outcomes. 

The American Lung Association (ALA) reported that in the U.S., 16.4 million individuals have been diagnosed with COPD (ALA, 2021). Approximately 200,000 ARDS cases are reported each year, with a mortality rate of 30-50% (ACCP, 2020). Both COPD and ARDS can cause hypercapnic respiratory failure.

Hypercapnic respiratory failure occurs when there is a failure to remove carbon dioxide from the body. The partial pressure of carbon dioxide in arterial blood levels (PaCO₂) is elevated and typically is present along with hypoxemia. Standard treatments to oxygenate the blood as well as remove carbon dioxide include extracorporeal membrane oxygenation (EMCO) or mechanical ventilation.

ECCO₂R therapy has been proposed as an alternative treatment, and is designed to provide CO₂ removal at lower blood flow rates (350-550 mL/min) than ECMO. This low flow rate allows for significant CO₂ removal but only minimal blood oxygenation. Lower blood flow rates permit the use of smaller catheters. The goal of ECCO₂R is to reduce ventilation requirements in individuals who are either failing NIV or to minimize ventilator associated morbidity.

ECCO₂R circuits always consist of two cannulas, drainage and return cannulas, and a membrane lung in which the gas exchange takes place. These circuits can be venovenous (VV) or arteriovenous (AV) systems. In the AV system, the individual’s blood pressure provides the pump to move the blood across the membrane. In the VV system, a pump must be included in the circuit (Camporota, 2016).

The Hemolung is noted to be the first fully-integrated system for respiratory dialysis, to provide partial extracorporeal support. The device received FDA De Novo clearance in 2021. However, production and support of the Hemolung device by the manufacturer is set to cease at the end of 2024.

Acute respiratory distress syndrome (ARDS): A rapidly progressive disease in which the alveoli fill with fluid, making breathing and gas exchange very difficult. ARDS occurs when there is direct or indirect trauma to the lungs.

Extracorporeal life support (ECLS): Life supporting procedures which are carried out outside the body and include cardiopulmonary support extracorporeal CO₂ removal, and ECMO.

Extracorporeal membrane oxygenation (ECMO): An invasive technique used to provide total respiratory support by bypassing the heart and lung and providing oxygenation and CO₂ removal. ECMO is generally considered a surgical procedure and performed in the intensive care setting.

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:
For the following procedure codes, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Peer Reviewed Publications:

1. Abrams DC, Brenner K, Burkart KM, et al. Pilot study of extracorporeal carbon dioxide removal to facilitate extubation and ambulation in exacerbations of chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2013; 10(4):307-314.
2. Allescher J, Rasch S, Wiessner JR, et al. Extracorporeal carbon dioxide removal with the Advanced Organ Support system in critically ill COVID-19 patients. Artif Organs. 2021; 45(12):1522-1532.
3. Azzi M, Aboab J, Alviset S, et al. Extracorporeal CO2 removal in acute exacerbation of COPD unresponsive to non-invasive ventilation. BMJ Open Respir Res. 2021; 8(1):e001089.
4. Barrett NA, Hart N, Daly KJR, 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. Ann Intensive Care. 2022; 12(1):36.
5. Bein T, Weber-Carstens S, Goldmann A, 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 Med. 2013; 39(5):847-856.
6. Bermudez CA, Zaldonis D, Fan MH, et al. Prolonged use of the Hemolung Respiratory Assist System as a bridge to redo lung transplantation. Ann Thorac Surg. 2015; 100(6):2330-2333.
7. 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. J Thorac Cardiovasc Surg. 2013; 145(5):e43-e44.
8. Boyle AJ, McDowell C, Agus A, et al. Acute hypoxaemic respiratory failure after treatment with lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal: long-term outcomes from the REST randomised trial. Thorax. 2023; 78(8):767-774.
9. Burki NK, Mani RK, Herth FJF, et al. A novel extracorporeal CO2 removal system: results of a pilot study of hypercapnic respiratory failure in patients with COPD. Chest. 2013; 143(3):678-686.
10. Cambria G, Spelde AE, Olia SE, et al. Extracorporeal carbon dioxide removal to de-escalate venovenous extracorporeal membrane oxygenation in severe COVID-19 acute respiratory distress syndrome. J Cardiothorac Vasc Anesth. 2024; 38(3):717-723.
11. Camporota L, Barrett N. Current applications for the use of extracorporeal carbon dioxide removal in critically ill patients. Biomed Res Int. 2016; 2016:9781695.
12. Combes A, Brodie D, Bartlett R, et al.; International ECMO Network (ECMONet). Position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients. Am J Respir Crit Care Med. 2014; 190(5):488-496.
13. Del Sorbo L, Fan E, Nava S, Ranieri VM. ECCO(2)R in COPD exacerbation only for the right patients and with the right strategy. Intensive Care Med. 2016; 42(11):1830-1831.
14. Del Sorbo L, Pisani L, Filippini C, et al. Extracorporeal Co2 removal in hypercapnic patients at risk of noninvasive ventilation failure: a matched cohort study with historical control. Crit Care Med. 2015; 43(1):120-127.
15. Duggal A, Conrad SA, Barrett NA, et al.; VENT-AVOID Investigators. Extracorporeal carbon dioxide removal to avoid invasive ventilation during exacerbations of chronic obstructive pulmonary disease: VENT-AVOID trial - a randomized clinical trial. Am J Respir Crit Care Med. 2024; 209(5):529-542.
16. Fitzgerald M, Millar J, Blackwood B, et al. Extracorporeal carbon dioxide removal for patients with acute respiratory failure secondary to the acute respiratory distress syndrome: a systematic review. Crit Care. 2014; 18(3):222.
17. Fox S, Mehkri O, Latifi M, et al. Using a low-flow extracorporeal carbon dioxide removal (ECCO 2 R) System in the management of refractory status asthmaticus: a case series. ASAIO J. 2024; 70(5):e70-e74.
18. Kluge S, Braune SA, Engel M, et al. Avoiding invasive mechanical ventilation by extracorporeal carbon dioxide removal in patients failing noninvasive ventilation. Intensive Care Med. 2012; 38(10):1632-1639.
19. Lund LW, Federspiel WJ. Removing extra CO(2) in COPD patients. Curr Respir Care Rep. 2013; 2:131-138.
20. McNamee JJ, Gillies MA, Barrett NA, et al. Effect of lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal vs standard care ventilation on 90-day mortality in patients with acute hypoxemic respiratory failure: the REST randomized clinical trial. JAMA. 2021; 326(11):1013-1023.
21. Morelli A, Del Sorbo L, Pesenti A, et al. Extracorporeal carbon dioxide removal (ECCO(2)R) in patients with acute respiratory failure. Intensive Care Med. 2017; 43(4):519-530.
22. Moss CE, Galtrey EJ, Camporota L, et al. A retrospective observational case series of low-flow venovenous extracorporeal carbon dioxide removal use in patients with respiratory failure. ASAIO J. 2016; 62(4):458-462.
23. Nagler B, Gleiss A, Füreder L, et al. Comparison of hemostatic changes in pump-driven extracorporeal carbon dioxide removal and venovenous extracorporeal membrane oxygenation. ASAIO J. 2022; 68(11):1407-1413.
24. Pisani L, Corcione N, Nava S. Management of acute hypercapnic respiratory failure. Curr Opin Crit Care. 2016; 22(1):45-52.
25. Redwan B, Ziegeler S, Semik M, et al. Single-site cannulation venovenous extracorporeal CO2 removal as bridge to lung volume reduction surgery in end-stage lung emphysema. ASAIO J. 2016; 62(6):743-746.
26. Rodenstein D. The human CO2 market. Respirology. 2016; 21(7):1150-1151.
27. Schmidt M, Jaber S, Zogheib E, et al. Feasibility and safety of low-flow extracorporeal CO(2) removal managed with a renal replacement platform to enhance lung-protective ventilation of patients with mild-to-moderate ARDS. Crit Care. 2018; 22(1):122.
28. Shekar K, Mullany DV, Thomson B, et al. Extracorporeal life support devices and strategies for management of acute cardiorespiratory failure in adult patients: a comprehensive review. Crit Care. 2014; 18(3):219.
29. Sklar MC, Beloncle F, Katsios CM, et al. Extracorporeal carbon dioxide removal in patients with chronic obstructive pulmonary disease: a systematic review. Intensive Care Med. 2015; 41(10):1752-1762.
30. Tiruvoipati R, Akkanti B, Dinh K,et al. Extracorporeal carbon dioxide removal with the Hemolung in patients with acute-on-chronic respiratory failure: a multicenter retrospective cohort study. ASAIO J. 2024; 70(7):594-601.
31. Ventetuolo CE, Muratore CS. Extracorporeal life support in critically ill adults. Am J Respir Crit Care Med. 2014; 190(5):497-508.
32. Worku E, Brodie D, Ling RR, et al. Venovenous extracorporeal CO2 removal to support ultraprotective ventilation in moderate-severe acute respiratory distress syndrome: A systematic review and meta-analysis of the literature. Perfusion. 2023; 38(5):1062-1079.
33. Yu TZ, Tatum RT, Saxena A, et al. Utilization and outcomes of extracorporeal CO2 removal (ECCO2 R): Systematic review and meta-analysis of arterio-venous and veno-venous ECCO2 R approaches. Artif Organs. 2022;46(5):763-774.
34. Zhu Y, Zhen W, Zhang X, et al. Extracorporeal Carbon Dioxide Removal in Patients with Acute Respiratory Distress Syndrome or Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis. Blood Purif. 2022; Aug 29:1-11.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American College of Chest Physicians (ACCP). Executive Summary: Prevention of Acute Exacerbation of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline. Chest. 2015; 147(4): 883 - 893.
2. Extracorporeal Life Support Organization (ELSO). General Guidelines for all ECLS Cases. Version 1.4 August 2017. Available at: https://www.elso.org/Portals/0/ELSO%20Guidelines%20General%20All%20ECLS%20Version%201_4.pdf. Accessed on November 11, 2024.
3. U.S. Food and Drug Administration (FDA). Center for Devices and Radiological Health. Hemolung Respiratory Assist System (ALung Technologies, Inc. Pittsburgh, PA). De Novo clearance. No. DEN210006. November 13, 2021. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf21/DEN210006.pdf. Accessed on November 11, 2024.

1. American Lung Association. Lung Health & Diseases. Available at: http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/. Accessed on November 11, 2024.
   • Acute Respiratory Distress Syndrome (ARDS)
   • Asthma
   • COPD
2. American Thoracic Society. Fact Sheets: Topic Specific. Available at: https://www.thoracic.org/patients/patient-resources/topic-specific/. Accessed on November 11, 2024.
3. National Heart, Lung, and Blood Institute. What is respiratory failure? Last updated March 24, 2022. Available at: https://www.nhlbi.nih.gov/health-topics/respiratory-failure. Accessed on November 11, 2024.

ALung
ECCO2R
Extracorporeal carbon dioxide removal
Hemolung Respiratory Assist System
PrismaLung+
PrisMax 2
Respiratory dialysis system

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.