Mechanical power normalized to aerated lung predicts noninvasive ventilation failure and death and contributes to the benefits of proning in COVID-19 hypoxemic respiratory failure.

Background: Concern exists that noninvasive ventilation (NIV) may promote ventilation-induced lung injury(VILI) and worsen outcome in acute hypoxemic respiratory failure (AHRF). Different individual ventilatory variables have been proposed to predict clinical outcomes, with inconsistent results.Mechanical power (MP), a measure of the energy transfer rate from the ventilator to the respiratory system during mechanical ventilation, might provide solutions for this issue in the framework of predictive, preventive and personalized medicine (PPPM). We explored (1) the impact of ventilator-delivered MP normalized to well-aerated lung (MPWAL) on physio-anatomical and clinical responses to NIV in COVID-19-related AHRF and (2) the effect of prone position(PP) on MPWAL. Methods: We analyzed 216 noninvasively ventilated COVID-19 patients (108 patients receiving PP + NIV and 108 propensity score-matched patients receiving supine NIV) with moderate-to-severe(paO2/FiO2 ratio < 200) AHRF enrolled in the PRO-NIV controlled non-randomized study (ISRCTN23016116).Quantification of differentially aerated lung volumes by lung ultrasonography (LUS) was validated against CT scans. Respiratory parameters were hourly recorded, ABG were performed 1 h after each postural change. Time-weighed average values of ventilatory variables, including MPWAL, and gas exchange parameters (paO2/FiO2 ratio, dead space indices) were calculated for each ventilatory session. LUS and circulating biomarkers were assessed daily. Results: Compared with supine position, PP was associated with a 34% MPWAL reduction, attributable largely to an absolute MP reduction and secondly to an enhanced lung reaeration.Patients receiving a high MPWAL during the 1st 24 h of NIV [MPWAL(day 1)] had higher 28-d NIV failure (HR = 4.33,95%CI:3.09 - 5.98) and death (HR = 5.17,95%CI: 3.01 - 7.35) risks than those receiving a low MPWAL(day 1).In Cox multivariate analyses, MPWAL(day 1) remained independently associated with 28-d NIV failure (HR = 1.68,95%CI:1.15-2.41) and death (HR = 1.69,95%CI:1.22-2.32).MPWAL(day 1) outperformed other power measures and ventilatory variables as predictor of 28-d NIV failure (AUROC = 0.89;95%CI:0.85-0.93) and death (AUROC = 0.89;95%CI:0.85-0.94).MPWAL(day 1) predicted also gas exchange, ultrasonographic and inflammatory biomarker responses, as markers of VILI, on linear multivariate analysis. Conclusions: In the framework of PPPM, early bedside MPWAL calculation may provide added value to predict response to NIV and guide subsequent therapeutic choices i.e. prone position adoption during NIV or upgrading to invasive ventilation, to reduce hazardous MPWAL delivery, prevent VILI progression and improve clinical outcomes in COVID-19-related AHRF. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00325-5.

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 (Pa o2 /F io2 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, C o2 -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.

After the first wave and beyond lockdown: long-lasting changes in emergency department visit number, characteristics, diagnoses, and hospital admissions.

The first wave (FW) of COVID-19 led to a rapid reduction in total emergency department (ED) visits and hospital admissions for other diseases. Whether this represented a transient "lockdown and fear" phenomenon, or a more persisting trend, is unknown. We divided acute from post-wave changes in ED flows, diagnoses, and hospital admissions, in an Italian city experiencing a FW peak followed by nadir. This multicenter, retrospective, cross-sectional study involved five general EDs of a large Italian city (January-August 2020). Percent changes were calculated versus 2019, using four 14-day periods (FW peak, early/mid/late post-wave). ED visits were 147,446 in 2020, versus 214,868 in 2019. During the FW peak, visits were reduced by 66.4% (P < 0.001). The drop was maximum during daytime (69.8%) and for pediatric patients (89.4%). Critical triage codes were unchanged. Reductions were found for all non-COVID-19 diagnoses. Non-COVID-19 hospital admissions were reduced by 39.5% (P < 0.001), involving all conditions except hematologic, metabolic/endocrine, respiratory diseases, and traumas. In the early, mid, and late post-wave periods, visits were reduced by 25.4%, 25.3% and 23.5% (all P < 0.001) respectively. In the late period, reduction was greater for female (27.9%) and pediatric patients (44.6%). Most critical triage codes were unchanged. Oncological, metabolic/endocrine, and hematological diagnoses were unchanged, while other diagnoses had persistent reductions. Non-COVID-19 hospital admissions were reduced by 12.8% (P = 0.001), 6.3% (P = 0.1) and 12.2% (P = 0.001), respectively. Reductions in ED flows, led by non-critical codes, persisted throughout the summer nadir of COVID-19. Hospital admissions for non-COVID-19 diseases had transient changes.