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Published in: Intensive Care Medicine 5/2019

01-05-2019 | Acute Respiratory Distress-Syndrome | Seven-Day Profile Publication

Feasibility and safety of extracorporeal CO2 removal to enhance protective ventilation in acute respiratory distress syndrome: the SUPERNOVA study

Published in: Intensive Care Medicine | Issue 5/2019

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Abstract

Purpose

We assessed feasibility and safety of extracorporeal carbon dioxide removal (ECCO2R) to facilitate ultra-protective ventilation (VT 4 mL/kg and PPLAT ≤ 25 cmH2O) in patients with moderate acute respiratory distress syndrome (ARDS).

Methods

Prospective multicenter international phase 2 study. Primary endpoint was the proportion of patients achieving ultra-protective ventilation with PaCO2 not increasing more than 20% from baseline, and arterial pH > 7.30. Severe adverse events (SAE) and ECCO2R-related adverse events (ECCO2R-AE) were reported to an independent data and safety monitoring board. We used lower CO2 extraction and higher CO2 extraction devices (membrane lung cross-sectional area 0.59 vs. 1.30 m2; flow 300–500 mL/min vs. 800–1000 mL/min, respectively).

Results

Ninety-five patients were enrolled. The proportion of patients who achieved ultra-protective settings by 8 h and 24 h was 78% (74 out of 95 patients; 95% confidence interval 68–89%) and 82% (78 out of 95 patients; 95% confidence interval 76–88%), respectively. ECCO2R was maintained for 5 [3–8] days. Six SAEs were reported; two of them were attributed to ECCO2R (brain hemorrhage and pneumothorax). ECCO2R-AEs were reported in 39% of the patients. A total of 69 patients (73%) were alive at day 28. Fifty-nine patients (62%) were alive at hospital discharge.

Conclusions

Use of ECCO2R to facilitate ultra-protective ventilation was feasible. A randomized clinical trial is required to assess the overall benefits and harms.

Clinicaltrials.gov

NCT02282657
Appendix
Available only for authorised users
Footnotes
1
Blood flow with the iLA activve (Novalung) and Cardiohelp® HLS 5.0 (Getinge) can range between 0.5 and 4.5 L/min, but was limited by study protocol to 800–1000 mL/min.
 
2
The study protocol (see online supplement) originally said: “aPTT ratio is maintained at 1.5–2.0 × baseline”. However, the case report form did not ask for aPTT ratio but for absolute aPTT values (see online supplement). This inconsistency was communicated to investigators at the beginning of the study and readers at the moment of publication. For the sake of transparency, we left unchanged study protocol and statement on ClinicalTrials.Gov.
 
3
On ClinicalTrials.Gov (NCT02282657) and in the study protocol (see online supplement) the primary endpoint is formalized as: “achievement of VT reduction to 4 mL/kg while maintaining pH and PaCO2 to ± 20% of baseline values obtained at VT of 6 mL/kg”. This formulation contains an obvious error that is the phrase “maintaining pH to ± 20% of baseline values”. Such variability of pH in fact does not make sense, allowing pH values ranging between 5.92 and 8.88. To avoid confusion and bias we (a) clarified the issue on the protocol with investigators at the beginning of the study; (b) left unchanged the statement on ClinicalTrials.Gov informing the readers about the mistake at the moment of publication.
 
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Metadata
Title
Feasibility and safety of extracorporeal CO2 removal to enhance protective ventilation in acute respiratory distress syndrome: the SUPERNOVA study
Publication date
01-05-2019
Published in
Intensive Care Medicine / Issue 5/2019
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-019-05567-4

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