A randomised controlled trial of non-invasive ventilation compared with extracorporeal carbon dioxide removal for acute hypercapnic exacerbations of chronic obstructive pulmonary disease

Abstract

Background Patients presenting with acute hypercapnic respiratory failure due to exacerbations of chronic obstructive pulmonary disease (AECOPD) are typically managed with non-invasive ventilation (NIV). The impact of low-flow extracorporeal carbon dioxide removal (ECCO2R) on outcome in these patients has not been explored in randomised trials. Methods Open-label randomised trial comparing NIV (NIV arm) with ECCO2R (ECCO2R arm) in patients with AECOPD at high risk of NIV failure (pH < 7.30 after ≥ 1 h of NIV). The primary endpoint was time to cessation of NIV. Secondary outcomes included device tolerance and complications, changes in arterial blood gases, hospital survival. Results Eighteen patients (median age 67.5, IQR (61.5–71) years; median GOLD stage 3 were enrolled (nine in each arm). Time to NIV discontinuation was shorter with ECCO2R (7:00 (6:18–8:30) vs 24:30 (18:15–49:45) h, p = 0.004). Arterial pH was higher with ECCO2R at 4 h post-randomisation (7.35 (7.31–7.37) vs 7.25 (7.21–7.26), p < 0.001). Partial pressure of arterial CO2 (PaCO2) was significantly lower with ECCO2R at 4 h (6.8 (6.2–7.15) vs 8.3 (7.74–9.3) kPa; p = 0.024). Dyspnoea and comfort both rapidly improved with commencement of ECCO2R. There were no severe or life-threatening complications in the study population. There were no episodes of major bleeding or red blood cell transfusion in either group. ICU and hospital length of stay were longer with ECCO2R, and there was no difference in 90-day mortality or functional outcomes at follow-up. Interpretation There is evidence of benefit associated with ECCO2R with time to improvement in respiratory acidosis, in respiratory physiology and an immediate improvement in patient comfort and dyspnoea with commencement of ECCO2R. In addition, there was minimal clinically significant adverse events associated with ECCO2R use in patients with AECOPD at risk of failing or not tolerating NIV. However, the ICU and hospital lengths of stay were longer in the ECCO2R for similar outcomes. Trial registration The trial is prospectively registered on ClinicalTrials.gov: NCT02086084. Registered on 13th March 2014, https://clinicaltrials.gov/ct2/show/NCT02086084?cond=ecco2r&draw=2&rank=8

Extracorporeal Carbon Dioxide Removal With the Hemolung in Patients With Acute Respiratory Failure: A Multicenter Retrospective Cohort Study*

“…However, there are substantial differences in the CO 2 removal capacities of the ECCO 2 R devices used in recent studies, and the optimal blood flow required for clinical practice is yet to be defined (14–17). Although randomized controlled trials (RCTs) are now being published (8, 18, 19), the efficacy of ECCO 2 R devices in acute or acute on chronic hypercapnic respiratory failure is poorly understood. In part, this is because of the heterogeneity of the patient pathologies including those with acute and chronic hypercapnic acidosis (11, 14, 16, 20).…”

Effects of extracorporeal CO2 removal on gas exchange and ventilator settings: a systematic review and meta-analysis

“…Additional file 1 : Table S3 shows the parameters available for each included study. Risk of bias assessment (Robins-I tool) revealed 4 studies with a low risk [ 31 , 34 – 36 ], 14 with moderate risk [ 6 , 8 , 19 , 30 , 33 , 37 – 44 ], and 30 with serious risk [ 4 , 18 , 21 – 29 , 32 , 45 – 60 ]. Three studies were categorized as critical risk [ 61 – 63 ] (Additional file 1 : Figure S1).…”

“…We identified three RCTs: two with mild to moderate ARDS patients [ 20 , 31 ]. And one with AECOPD patients on NIV [ 36 ]. The aim of the ARDS trials was to reduce the invasiveness of ventilation to an “ultraprotective level” in the ECCO 2 R arms, while standard “protective” ventilation was used in the control arms.…”

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

“…The eligible studies were conducted from 1994 to 2022 with a total number of 1173 patients. Among the included studies, two were conducted in multiple countries [ 18 , 23 ], two were from the United Kingdom [ 19 , 21 ], and other studies were conducted in France [ 22 ], America [ 20 ], Turkey [ 26 ], Germany [ 25 ], Italy [ 24 ]. The sample sizes ranged from 18 to 412, with a median of 50 patients.…”

“…Within the three RCTs, no statistically significant difference was observed in overall mortality between the ECCO 2 R group and control group (RR 1.05, 95% CI 0.83 to 1.32, p = 0.70, I 2 =0.0%, Figure 2 ). The other RCT [ 21 ] and observational studies [ 22–26 ] targeted patients with ARF secondary to COPD. Pooled result of the five studies also showed similar overall mortality (RR 0.80, 95% CI 0.58 to 1.11, p = 0.19, I 2 =0.0%, Figure 3 ), and the result was largely dependent on observational studies (RR 0.77, 95% CI 0.55 to 1.08, p = 0.13, I 2 =0.0%, Figure 3 ).…”