We report results from a comprehensive cohort study assessing the potential benefits of prone positioning in COVID-19 patients with moderate to severe ARDS. We found a nearly 40% reduction in mortality with prone positioning, an effect that appears sustained on cumulative incidence curves. With respect to physiologic parameters, there were meaningful changes across all ratios and indices to suggest that prone positioning is associated with improvements in within-person physiology and that the benefit may persist beyond three days. Our findings across both analyses were robust to various adjustments, modifications, sensitivity analyses and nested comparative testing.
Fundamentally, this study has three key findings. First, we demonstrated a mortality benefit with prone positioning with a number needed to treat of eight. The durability of the finding is important, and ensuring that it can be replicated in other settings will be essential to justify a recommendation, but we have no evidence to attribute the survival benefit in the intervention arm to bias. Second, it appears that there is a benefit to additional days of prone positioning beyond 3 days. The effect seen with 4–7 days of prone positioning may be heavily influenced by a smaller group that realized a differential benefit, but 34 of 89 positioning sequences
resulted in at least four days of intervention, representing a relatively large proportion of individuals. Third, prone positioning resulted in significant changes in physiologic parameters which may support the underlying hypothesis that prone positioning improves ventilation-perfusion matching.(9, 10) Additionally, we demonstrated the utility of relatively accessible clinical information in the ICU as reasonable surrogates to monitor changes in physiology.
Our results are consistent with recent multi-center data suggesting a mortality benefit of prone positioning in patients with ARDS whether intubated or not.(6–8, 19, 20) There are recommendations for prolonged prone positioning of 12–16 hours daily for mechanically ventilated adult patients with COVID-19 and refractory hypoxemic respiratory failure,(21) but the optimal duration of the intervention, its’ impact on physiologic parameters and details regarding how to organize and structure an intervention team during a crisis have not been completely evaluated. We acknowledge that prone positioning in mechanically ventilated patients is a resource-intensive intervention, particularly in overwhelmed healthcare systems during pandemic conditions. Before adopting prone positioning techniques, staff education and commitment is paramount. If justified by hospitalized patient volume, we recommend identifying personnel and assigning them to a dedicated prone team and tailoring readily available checklists to institutional needs and constraints (Fig. 1).(22)
Some limitations of this study should be noted. First, this is a single center retrospective cohort study in a resource constrained environment under crisis operations. As a result, although patients had critical care needs, they were frequently cared for in ad-hoc intensive care units by non-critical care personnel. The decision to initiate or discontinue the intervention under study was left to the treating primary team without defining endpoints. We attempted to address any residual confounding through IPTW and no differences in the
results were noted. If the prone team was consulted and the patient had moderate to severe ARDS and met criteria for prone positioning, it was felt that they could benefit from the intervention in addition to lung protective ventilation. Although this was pragmatic for this setting, if prone positioning is implemented elsewhere, the prone teams could consider establishing an opt-out approach with tailored entry and exit criteria, normal cadence of evaluation for candidacy for prone positioning and a mechanism for real-time data capture and quality control assessments. Finally, the
results may not be readily generalizable to all populations, in particular those with milder disease and those that don’t reflect the ethnic diversity seen in the Bronx. The institutional mortality proportion was high (> 75%) and therefore the impact of the intervention may be attenuated in the setting of advanced interventions (e.g., extracorporeal membrane oxygenation).
There are also some notable strengths of this work. We were able to collect detailed physiologic data in a structured manner to systematically evaluate the impact of the intervention. Also, our population has been gravely understudied in the COVID-19 pandemic and we’ve been able to contribute significantly to both describing their clinical course as well as critical care interventions for socioeconomically marginalized minority populations. Regarding outcome, we were able to include all patients who would have been eligible for prone positioning as controls creating a sound counterfactual for a contemporaneous comparison of both exposed and unexposed. Finally, compared to existing literature for patients with COVID-19, this study provides results for a large intervention group.