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

Abstract

IMPORTANCEIn patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. OBJECTIVE To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. INTERVENTIONS Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). MAIN OUTCOMES AND MEASURESThe primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. RESULTS Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, −7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, −2.1 [95% CI, −3.8 to −0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device.CONCLUSIONS AND RELEVANCE Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference.

The PANDORA Study: Prevalence and Outcome of Acute Hypoxemic Respiratory Failure in the Pre-COVID-19 Era

“…Second, both ARDS and non-ARDS patients were ventilated with similar strategies (low V t and low Pplat), suggesting that the diagnosis of ARDS does not affect the selection of specific ventilatory settings, despite the fact that there are very few specific RCTs aimed at non-ARDS patients (40). It is possible that clinicians opted for specific strategies for underlying physiologic reasons in non-ARDS patients or simply they opted to follow lung-protective ventilation strategies in the majority of patients with hypoxemia.…”

Right Ventricular Function in Acute Respiratory Distress Syndrome: Impact on Outcome, Respiratory Strategy and Use of Veno-Venous Extracorporeal Membrane Oxygenation

“…Data are too scarce for discussion of any recommendation (Papazian et al, 2019), but an experimental study in a porcine model of ARDS showed that CO 2 removal is able to decrease RV afterload and to improve coupling between the right ventricle and the pulmonary circulation (Morimont et al, 2015). Such a technique could be efficient and valuable in protecting the right ventricle in the case of severe ARDS with significant hypercapnia and RV failure despite application of an RV protective strategy, but probably does not promote ultraprotective ventilation in patients with moderate ARDS (McNamee et al, 2021).…”

The role of acute hypercapnia on mortality and short-term physiology in patients mechanically ventilated for ARDS: a systematic review and meta-analysis

“…V T targeting 6 ml/kg of predicted body weight), and its potential mitigation by extracorporeal CO 2 removal [ 52 ]. In the recent REST randomized clinical trial, the use of extracorporeal CO 2 removal to facilitate UPV, compared with PV, did not significantly reduce 90-day mortality and was associated with more serious adverse events [ 53 ].…”