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Early application of prone positioning did not help patients with severe acute respiratory distress syndrome (ARDS) -- mostly from COVID -- get off venovenous extracorporeal membrane oxygenation (VV-ECMO) any faster compared to supine positioning, a randomized trial found.

Among ARDS patients receiving ECMO, an identical 44% of patients were successfully weaned off ECMO after 60 days whether they were placed in sessions of prone positioning or simply kept supine (P=0.64), reported Matthieu Schmidt, MD, of the Hôpital de la Pitié-Salpêtrière in Paris, and colleagues.

Within 90 days, there was no significant difference seen in ECMO duration between prone and supine groups (28 vs 32 days, P=0.13). Also no different were 90-day mortality rates between positions (51% vs 48%, P=0.62), according to the French PRONECMO study published in .

"Despite promising findings in observational studies, prone positioning of patients undergoing ECMO failed to reduce ECMO duration or mortality in this randomized trial," Schmidt and coauthors concluded.

Prone positioning has been , and promotes "better overall ventilation/perfusion matching through a more homogeneous distribution of gas-tissue ratios along the dependent-nondependent axis in addition to decreased levels of lung stress and strain," the investigators explained in their introduction.

But whether the benefit extended to ARDS patients on VV-ECMO was unclear. One had found prone positioning during ECMO for ARDS -- COVID-19 or not -- to be associated with a significant improvement in ventilator-free days and intensive care unit (ICU) survival, Schmidt's group noted.

Prone positioning is strongly recommended in current clinical practice guidelines, noted Ricardo Teijeiro-Paradis, MD, and Niall Ferguson, MD, MSc, both of the University of Toronto, in an .

"Based on these results, routine prone positioning during VV-ECMO does not facilitate earlier liberation from ECMO or improve outcomes. This suggests that on average, prone positioning does not facilitate further lung protection than that already provided with an ultraprotective ventilation strategy facilitated by VV-ECMO," Teijeiro-Paradis and Ferguson wrote.

"Results of the PRONECMO trial may lead us to turn our backs on routine prone-position ventilation during VV-ECMO and face forward toward novel group-specific interventions targeting lung and diaphragm-protective ventilation, early awakening, and patient mobility," the duo commented.

Study authors and editorialists posed several factors that may explain PRONECMO's neutral results for prone positioning.

"First, the majority of enrolled patients were placed in prone position before ECMO, compared with widely variable proportions of patients in previous cohorts. Second, the majority of patients had COVID-19-related ARDS, perhaps with a greater severity of pulmonary injury," Schmidt and colleagues wrote.

They added that a person's response to prone positioning may depend on his or her specific etiology or severity of respiratory illness. "The COVID-19 variant may also contribute to prone positioning response, as less favorable pandemic outcomes were observed in late 2020, and the Delta variant was predominant in France during part of the trial. This contrasts with early reports of prone positioning benefit in COVID-19 patients receiving ECMO during predominance of the wild-type SARS-CoV-2 strain," they wrote.

Additionally, Teijeiro-Paradis and Ferguson suggested that sedation may have played a role in prone positioning's lack of benefit in the trial.

"Not infrequently, our patients develop complete lung collapse/consolidation with resulting tidal volumes far below anatomical dead space," the pair wrote. "Such derecruitment is exacerbated by the lack of respiratory effort due to deep sedation and paralysis often needed to maintain adequate ECMO flow and safe inspiratory pressures. A similar phenomenon may explain the progressive decrease in respiratory system compliance observed in both groups in the PRONECMO study."

The randomized trial was conducted at 14 ICUs in France with clinicians having the experience and capability to perform prone positioning during ECMO. Study participants were patients undergoing ECMO for severe ARDS. From March to December 2021, adult patients were enrolled if they were undergoing invasive mechanical ventilation and were supported by VV-ECMO for less than 48 hours.

The study cohort included 170 patients (median age 51, 35% women). Approximately 93% of the cohort presented with COVID-19-related ARDS, the remainder having bacterial pneumonia or another etiology.

Those assigned to prone positioning underwent at least four prone position sessions of 16 hours during the first 4 days (unless a patient met predefined criteria for early stopping of the prone intervention), whereas the supine ECMO group was not allowed to be put in prone before day 60.

All individuals in the prone group were placed in this position immediately after randomization. Overall, 80% received at least four prone sessions, with discontinuation most commonly due to respiratory system compliance and improvements in oxygenation.

Among the study's limitations were its small sample size and unblinded trial methods. A caveat to the study's generalizability was the observation that approximately 40% of study participants had been enrolled from a single very experienced center, Schmidt and colleagues cautioned.

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