In up to a third of patients with severe ARDS, traditional targets for lung-protective ventilation may be harmful [1]. These ventilation rates are typically 4 to 8 ml/kg/minute with plateau airway pressures ≤30 cm H2O. Extra-corporeal Life support, ECMO, and ECCO2R can be used to lower the intensity of mechanical ventilation. Extracorporeal carbon dioxide removal (ECCO2R) devices are specialized ECMO machines that concentrate on removing CO2 from the blood, lowering PaCO2, and eventually reducing the work of breathing and mechanical ventilation support. The amount ECCO2R can decrease the strength of mechanical ventilation is proportional to how much CO2 is removed, reducing dependence on the injured native lung. It was postulated that by removing CO2 through ECCO2R, a reduction in mechanical ventilation can be achieved, reducing ventilator-induced lung injury and can improve outcomes.
The Initial Clinical Study
In 1994, Morris et al conducted a randomized controlled study comparing A-V ECCO2R with pressure control inverse ratio ventilation in a group of 40 patients with severe ARDS. The study showed no significant difference in 30-day survival between the two groups, with 33% survival in the ECCO2R arm and 42% in the control arm [2].
More Recent Studies
The two most recent trials evaluated two different ECCO2R designs. They examined how the early identification of patients with hypercapnia, complicating ARDS, may impact outcomes.
The Xtravent-study included 79 patients with ARDS (PaO2/FiO2 <200 mmHg for >24 hours on lung protective ventilation with high PEEP ≥ 12 cm H2O). In the trial the use of AV-ECCO2R with lower tidal volume ventilation (~3 mL/kg/min) was compared to conventional mechanical ventilation (6 mL/kg/min) was evaluated. The primary outcome, the number of ventilator-free days at day 60, was 33.2 ± 20 days in the ECCO2R arm versus 29.2 ± 21 days in the control arm, a difference that was not statistically significant. In patients with more severe hypoxia (PaO2/FIO2 ≤150), a post hoc analysis showed that the ECCO2R group had significantly improved ventilator-free days at 60 days compared to the control group. The ECCO2R group averaged 40.9 ± 12.8 ventilator-free days, while the control group only averaged 28.2 ± 16.4 (p = 0.033) [3].
The REST RCT studied the effects of lower tidal volume ventilation (≤ 3 mL/kg/min) with V-V (single, dual lumen cannula) ECCO2R compared with conventional mechanical ventilation of 6 mL/kg/min. The goal sample size of 1120 patients wasn't reached before the trial was stopped for futility and feasibility reasons. The study reported the results of 412 patients with ARDS (PaO2/FiO2 < 150 mmHg) and found that 90-day survival rates in the control arm were 60.5% versus 58.5% in the ECCO2R arm at day 90. Serious adverse events (mainly bleeding, including intracranial hemorrhage) were reported in 31% of the ECCO2R group and 9% of the control group [4].
The pooled data of the three studies showed no significant difference in mortality between the two groups (37% for ECCO2R patients versus 34% for control patients). In addition, extra-cranial and intra-cranial bleeding incidence was greater in the ECCO2R group.
Conclusion
Even though extracorporeal CO2 removal might appear appealing because it helps reduce the mechanical force of ventilation, evidence showed that this approach failed to improve patient outcomes and should not be used in ARDS patients. It is unknown if there might be a subset of patients who would benefit from this modality at this time.
References
Terragni PP, Rosboch G, Tealdi A, et al. Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med 2007; 175:160-166. DOI: 10.1164/rccm.200607-915OC.
Morris AH, Wallace CJ, Menlove RL, et al. Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome. Am J Respir Crit Care Med 1994; 149:295-305. DOI: 10.1164/ajrccm.149.2.8306022.
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; 39:847-856. DOI: 10.1007/s00134-012-2787-6.
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; 326:1013-1023. DOI: 10.1001/jama.2021.13374