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.

Implementation of the ERAS (Enhanced Recovery After Surgery) protocol for hysterectomy in the Piedmont Region with an audit&feedback approach: Study protocol for a stepped wedge cluster randomized controlled trial. A study of the EASY-NET project.

INTRODUCTION: ERAS (Enhanced Recovery After Surgery) is a perioperative program combining multiple evidence-based interventions designed to reduce the surgical stress response. Despite the publication of dedicated guidelines, ERAS application to gynecologic surgery outside clinical studies has been slow and fragmented. To promote the systematic adoption of the ERAS program in the entire regional hospital network in Piedmont an Audit-and-Feedback approach (A&F) has been adopted within a cluster randomized controlled trial, aiming to estimate the true impact of the protocol on a large, unselected population. METHODS: The study protocol provides for a multicenter stepped wedge cluster randomized trial, focused on women undergoing an hysterectomy, for comparison between standard perioperative management and perioperative management according to the ERAS protocol. The primary outcome is the length of hospital stay (LOS). Secondary outcomes are: post-operative complications, quality-of-recovery at 24-hours after surgery, 30-day readmissions, patients' satisfaction, healthcare costs. The compliance to all the ERAS items is monitored with an A&F approach. All the gynecologic units of Piedmont hospitals are involved and all the patients hospitalized for elective hysterectomy in the period of the study are included. Centers, stratified by surgical volume and randomly assigned to four groups, are randomly ordered to activate the ERAS protocol in four periods, every three months. The planned calendar and the total duration of the study have been extended for six months due to the COVID-19 pandemic. The expected sample size of about 2400 patients has a high statistical power (99%) to detect a reduction of LOS of 1 day (effect size 0.5) and to estimate clinically meaningful changes in the other study endpoints. The study protocol has been approved by the Ethical Committee of all participating centers. Study results will be timely circulated within the hospital network and published in peer-reviewed journals. CONCLUSION: Results are expected to demonstrate positive clinical outcomes of the ERAS protocol even when its implementation is directed towards an entire regional network of gynecologic units, and not only towards selected and highly motivated centers. TRIAL REGISTRATION: NCT04063072.