Dear Editor,
The recently published EOLIA study [1] has failed to demonstrate a 20% increase in survival in patients with very severe acute respiratory distress syndrome (ARDS) using a strategy of early application of veno-venous extracorporeal membrane oxygenation (vvECMO) as compared with low-volume, low-pressure ventilation in combination with rescue therapies including prone positioning (PP), inhaled nitric oxide and neuromuscular blockers. Early, prolonged and repeated sessions of prone positioning (PP) are associated with a substantial outcome benefit in ARDS patients, with a PaO2/FiO2 ratio < 150 mmHg [2]. In the EOLIA trial, there was a difference in the use of PP between the two arms, with 90% of the patients in the control group turned to PP before and/or after randomization, and only 66% of the patients in the ECMO group.
Therefore, we have performed a retrospective observational study to compare outcomes of severe ARDS patients under vvECMO according to the use of PP or lack thereof during their ECMO run in order to assess the potential justification for further randomized clinical trials.
A flow chart, ECMO criteria, management of vvECMO and mechanical ventilation are described in the ESM. We have compared patients with a combination of PP during ECMO (prone ECMO group) to those maintained in supine position (ECMO alone group). See statistical details in the ESM.
During the study period, 168 patients were supported by vvECMO for severe ARDS and were included in the analysis. The main pre-ECMO characteristics and outcomes are presented in Table 1. Among the patients, 91 (54%) were placed at least once in prone position during the ECMO run, whereas 77 (46%) were maintained in supine position during ECMO. Patients in the prone ECMO group were more frequently turned to PP before ECMO. Patients underwent a mean of three PP sessions, with a range from 1 to 17. Patients in the prone ECMO group were more likely to be weaned from ECMO. Accordingly, 30-day, 60-day and 90-day survival rates were significantly higher.
To reduce the risk of bias (indication for PP, severity of illness), we duplicated the comparisons with matching according to age, sex, SOFA, prior duration of mechanical ventilation and prior PP before ECMO. We also found a higher rate of ECMO weaning and better survival rates in a comparative matched study of 50 pairs of patients (see ESM). However, we cannot exclude residual confounding factors that overestimate the effect.
Aside from its positive effects on oxygenation, PP can reduce ventilator-induced lung injury in ARDS patients under ECMO [3, 4]. A further randomized controlled trial should be performed in patients with severe ARDS supported by vvECMO with implementation of systematic PP in one arm. Such a trial would be faced with predictable challenges related to the small number of centres trained in prone-positioning of patients on ECMO and the relatively low percentage of eligible patients after exclusion of contraindications for PP. Determining the best timing and duration of PP in ECMO requires further investigation.
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The authors would like to thank all the ICU nursing staff and the perfusionist’s team.
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According to the French legislation, because of the retrospective design of the study, no inform consent is warranted. The study was registered by the French authority Commission Nationale Informatique et Libertés under the number: CIL/APHM 2018-44.
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Guervilly, C., Prud’homme, E., Pauly, V. et al. Prone positioning and extracorporeal membrane oxygenation for severe acute respiratory distress syndrome: time for a randomized trial?. Intensive Care Med 45, 1040–1042 (2019). https://doi.org/10.1007/s00134-019-05570-9
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DOI: https://doi.org/10.1007/s00134-019-05570-9