Mechanical Power Delivered by Noninvasive Ventilation Contributes to Physio-Anatomical and Clinical Responses to Early Versus Late Proning in COVID-19 Pneumonia.

OBJECTIVES: To study: 1) the effect of prone position (PP) on noninvasive ventilation (NIV)-delivered mechanical power (MP) and 2) the impact of MP on physio-anatomical and clinical responses to early versus late PP in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. DESIGN: Nonrandomized trial with inverse probability of treatment weighted-matched groups. SETTING: HUMANITAS Gradenigo Sub-ICU. PATIENTS: One hundred thirty-eight SARS-CoV-2 pneumonia patients with moderate-to-severe acute hypoxemic respiratory failure (Pao2/Fio2 ratio < 200 mm Hg) receiving NIV from September 1, 2020, to February 28, 2021 (Ethics approval: ISRCTN23016116). INTERVENTIONS: Early PP or late PP or supine position. MEASUREMENTS AND MAIN RESULTS: Respiratory parameters were hourly recorded. Time-weighted average MP values were calculated for each ventilatory session. Gas exchange parameters and ventilatory ratio (VR) were measured 1 hour after each postural change. Lung ultrasonographic scores and circulating biomarkers were assessed daily. MP delivered during the initial 24 hours of NIV (MP [first 24 hr]) was the primary exposure variable. Primary outcomes: 28-day endotracheal intubation and death. Secondary outcomes: oxygen-response, Co2-response, ultrasonographic, and systemic inflammatory biomarker responses after 24 hours of NIV. Fifty-eight patients received early PP + NIV, 26 late PP + NIV, and 54 supine NIV. Early PP group had lower 28-day intubation and death than late PP (hazard ratio [HR], 0.35; 95% CI, 0.19-0.69 and HR, 0.26; 95% CI, 0.07-0.67, respectively) and supine group. In Cox multivariate analysis, (MP [first 24 hr]) predicted 28-day intubation (HR, 1.70; 95% CI, 1.25-2.09; p = 0.009) and death (HR, 1.51; 95% CI, 1.19-1.91; p = 0.007). Compared with supine position, PP was associated with a 35% MP reduction. VR, ultrasonographic scores, and inflammatory biomarkers improved after 24 hours of NIV in the early PP, but not in late PP or supine group. A MP (first 24 hr) greater than or equal to 17.9 J/min was associated with 28-day death (area under the curve, 0.92; 95% CI, 0.88-0.96; p < 0.001); cumulative hours of MP greater than or equal to 17.9 J/min delivered before PP initiation attenuated VR, ultrasonographic, and biomarker responses to PP. CONCLUSIONS: MP delivered by NIV during initial 24 hours predicts clinical outcomes. PP curtails MP, but cumulative hours of NIV with MP greater than or equal to 17.9 J/min delivered before PP initiation attenuate the benefits of PP.

Early prolonged prone position in noninvasively ventilated patients with SARS-CoV-2-related moderate-to-severe hypoxemic respiratory failure: clinical outcomes and mechanisms for treatment response in the PRO-NIV study.

BACKGROUND: Whether prone position (PP) improves clinical outcomes in COVID-19 pneumonia treated with noninvasive ventilation (NIV) is unknown. We evaluated the effect of early PP on 28-day NIV failure, intubation and death in noninvasively ventilated patients with moderate-to-severe acute hypoxemic respiratory failure due to COVID-19 pneumonia and explored physiological mechanisms underlying treatment response. METHODS: In this controlled non-randomized trial, 81 consecutive prospectively enrolled patients with COVID-19 pneumonia and moderate-to-severe (paO2/FiO2 ratio < 200) acute hypoxemic respiratory failure treated with early PP + NIV during Dec 2020-May 2021were compared with 162 consecutive patients with COVID-19 pneumonia matched for age, mortality risk, severity of illness and paO2/FiO2 ratio at admission, treated with conventional (supine) NIV during Apr 2020-Dec 2020 at HUMANITAS Gradenigo Subintensive Care Unit, after propensity score adjustment for multiple baseline and treatment-related variables to limit confounding. Lung ultrasonography (LUS) was performed at baseline and at day 5. Ventilatory parameters, physiological dead space indices (DSIs) and circulating inflammatory and procoagulative biomarkers were monitored during the initial 7 days. RESULTS: In the intention-to-treat analysis. NIV failure occurred in 14 (17%) of PP patients versus 70 (43%) of controls [HR = 0.32, 95% CI 0.21-0.50; p < 0.0001]; intubation in 8 (11%) of PP patients versus 44 (30%) of controls [HR = 0.31, 95% CI 0.18-0.55; p = 0.0012], death in 10 (12%) of PP patients versus 59 (36%) of controls [HR = 0.27, 95% CI 0.17-0.44; p < 0.0001]. The effect remained significant within different categories of severity of hypoxemia (paO2/FiO2 < 100 or paO2/FiO2 100-199 at admission). Adverse events were rare and evenly distributed. Compared with controls, PP therapy was associated with improved oxygenation and DSIs, reduced global LUS severity indices largely through enhanced reaeration of dorso-lateral lung regions, and an earlier decline in inflammatory markers and D-dimer. In multivariate analysis, day 1 CO2 response outperformed O2 response as a predictor of LUS changes, NIV failure, intubation and death. CONCLUSION: Early prolonged PP is safe and is associated with lower NIV failure, intubation and death rates in noninvasively ventilated patients with COVID-19-related moderate-to-severe hypoxemic respiratory failure. Early dead space reduction and reaeration of dorso-lateral lung regions predicted clinical outcomes in our study population. CLINICAL TRIAL REGISTRATION: ISRCTN23016116 . Retrospectively registered on May 1, 2021.