Concise Critical Appraisal: Timing of Prone Positioning During Venovenous ECMO for ARDS

The 2013 Prone Positioning in Severe Acute Respiratory Distress Syndrome (PROSEVA) trial established that, when properly utilized, prone positioning (PP) improves 28- and 90-day mortality rates of patients with acute respiratory distress syndrome (ARDS).¹ Equivocal results of recent studies have failed to define the population most likely to benefit from PP, and intensivists have limited guidance on how and when to start PP trials.

Taccone et al established that the more critically severe the ARDS, the greater benefit the patient would derive from PP.² No patient population epitomizes severe ARDS more than patients meeting criteria for venovenous (VV) extracorporeal membrane oxygenation (ECMO). Giani et al set out to show that, not only is PP beneficial in this population, but the earlier the patient can be initiated on PP trials (≤ 5 days), the higher the probability of being discharged alive from the intensive care unit (ICU) at 90 days (primary end point).³

The authors extracted data from the European Prone Positioning During Extracorporeal Membrane Oxygenation (EuroPronECMO) study. Of the original 889 patients, 223 patients were included in the early PP group (≤ 5 days), and 77 patients in the late PP group (> 5 days). In addition to the primary outcome, the authors also tracked in-hospital mortality rates, success of ECMO weaning, the probability of being discharged alive from the ICU, and improvements in respiratory system compliance.

A longer time to the first PP after ECMO initiation was associated with a lower probability of being discharged alive from the ICU (adjusted hazard ratio 0.90 for each day increase; 95% CI, 0.87-0.93). The early PP group had a cumulative 90-day probability of being discharged from the ICU, 61% versus 36% in the late PP group (P < 0.001). Additionally, the early PP group was associated with shorter ECMO duration (P < 0.001), lower ICU mortality (P = 0.003), and lower hospital mortality (P = 0.003). There was also greater improvement to respiratory compliance (P = 0.038), thought to be associated with the development of fibrosis later in ARDS, which would preclude lung collapse reversibility.

One limitation of this study is that the groups were not homogenous. The patients in the early PP group were older and had a higher Sequential Organ Failure Assessment score than those in the late PP group. Patients in the early PP group also had higher rates of malignancy, vascular disease, COVID-19 etiology, use of nitric oxide, and PP use pre-ECMO. To combat heterogeneity, a propensity match was also performed on 45 patients in both the early and late PP groups. ICU mortality in the early PP group was 31% versus 58% in the late PP group (P = –0.011). Additionally, the 45 patients in the early PP group were more likely to be discharged alive from the ICU at 90 days (P = 0.003).

This study validates the improvement in ICU mortality associated with PP in the propensity-matched VV ECMO populations of the original EuroPronECMO study⁴ and replicates the mortality improvement associated with PP in a VV ECMO subgroup meta-analysis of 1836 patients.⁵ What is lacking is a randomized controlled trial that shows similar results; studies are in progress.

The knowledge gap met by this study is validation of the expert opinion that earlier is better for PP in the VV ECMO population. The study had several limitations. First, the time cutoff of five days was arbitrarily chosen; more research is needed to find the optimal time to start PP after VV ECMO cannulation. Second, this was a retrospective study of a European population, so its adaptability may be limited. Third, the study design limited any discussion on 90-day mortality or long-term functional outcomes. Finally, most limiting is that, as a pooled data analysis, there is a lack of hemodynamic and right ventricular function data for the patient populations, both of which play a significant role in all the outcomes evaluated.

References

1. Guérin C, Reignier J, Richard JC, et al; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013 Jun 6;368(23):2159-2168.
2. Taccone P, Pesenti A, Latini R, et al; Prone-Supine II Study Group. Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2009 Nov 11;302(18):1977-1984.
3. Giani M, Rezoagli E, Guervilly C, et al; European Prone positioning During Extracorporeal Membrane Oxygenation (EuroPronECMO) Investigators. Timing of prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome. Crit Care Med. 2023 Jan 1;51(1):25-35.
4. Giani M, Rezoagli E, Guervilly C, et al; EuroPronECMO Investigators. Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a pooled individual patient data analysis. Crit Care. 2022 Jan6;26(1):8.
5. Papazian L, Schmidt M, Hajage D, et al. Effect of prone positioning on survival in adult patients receiving venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis. Intensive Care Med. 2022 Mar;48(3):270-280.