Extracorporeal carbon dioxide removal for patients with acute respiratory failure: a systematic review and meta-analysis

Background Acute respiratory failure (ARF) is a common clinical critical syndrome with substantial mortality. Extracorporeal carbon dioxide removal (ECCO2R) has been proposed for the treatment of ARF. However, whether ECCO2R could provide a survival advantage for patients with ARF is still controversial. Methods Electronic databases (PubMed, Embase, Web of Science, and the Cochrane database) were searched from inception to 30 April 2022. Randomized controlled trials (RCTs) and observational studies that examined the following outcomes were included: mortality, length of hospital and ICU stay, intubation and tracheotomy rate, mechanical ventilation days, ventilator-free days (VFDs), respiratory parameters, and reported adverse events. Results Four RCTs and five observational studies including 1173 participants with ARF due to COPD or ARDS were included in this meta-analysis. Pooled analyses of related studies showed no significant difference in overall mortality between ECCO2R and control group, neither in RCTs targeted ARDS or acute hypoxic respiratory failure patients (RR 1.05, 95% CI 0.83 to 1.32, p = 0.70, I-2 =0.0%), nor in studies targeted patients with ARF secondary to COPD (RR 0.80, 95% CI 0.58 to 1.11, p = 0.19, I-2 =0.0%). A shorter duration of ICU stay in the ECCO2R group was only obtained in observational studies (WMD -4.25, p < 0.01), and ECCO2R was associated with a longer length of hospital stay (p = 0.02). ECCO2R was associated with lower intubation rate (p < 0.01) and tracheotomy rate (p = 0.01), and shorter mechanical ventilation days (p < 0.01) in comparison to control group in ARF patients with COPD. In addition, an improvement in pH (p = 0.01), PaO2 (p = 0.01), respiratory rate (p < 0.01), and PaCO2 (p = 0.04) was also observed in patients with COPD exacerbations by ECCO2R therapy. However, the ECCO2R-related complication rate was high in six of the included studies. Conclusions Our findings from both RCTs and observational studies did not confirm a significant beneficial effect of ECCO2R therapy on mortality. A shorter length of ICU stay in the ECCO2R group was only obtained in observational studies, and ECCO2R was associated with a longer length of hospital stay. ECCO2R was associated with lower intubation rate and tracheotomy rate, and shorter mechanical ventilation days in ARF patients with COPD. And an improvement in pH, PaO2, respiratory rate and PaCO2 was observed in the ECCO2R group. However, outcomes largely relied on data from observational studies targeted patients with ARF secondary to COPD, thus further larger high-quality RCTs are desirable to strengthen the evidence on the efficacy and benefits of ECCO2R for patients with ARF. Key messages ECCO2R therapy did not confirm a significant beneficial effect on mortality. ECCO2R was associated with lower intubation and tracheotomy rate, and shorter mechanical ventilation days in patients with ARF secondary to COPD. An improvement in pH, PaO2, respiratory rate, and PaCO2 was observed in ECCO2R group in patients with COPD exacerbations. Evidence for the future application of ECCO2R therapy for patients with ARF. The protocol of this meta-analysis was registered on PROSPERO (CRD42022295174).