Noninvasive Ventilatory Support of Patients with COVID-19 outside the Intensive Care Units (WARd-COVID).

Rationale: Treatment with noninvasive ventilation (NIV) in coronavirus disease (COVID-19) is frequent. Shortage of intensive care unit (ICU) beds led clinicians to deliver NIV also outside ICUs. Data about the use of NIV in COVID-19 is limited.Objectives: To describe the prevalence and clinical characteristics of patients with COVID-19 treated with NIV outside the ICUs. To investigate the factors associated with NIV failure (need for intubation or death).Methods: In this prospective, single-day observational study, we enrolled adult patients with COVID-19 who were treated with NIV outside the ICU from 31 hospitals in Lombardy, Italy.Results: We collected data on demographic and clinical characteristics, ventilatory management, and patient outcomes. Of 8,753 patients with COVID-19 present in the hospitals on the study day, 909 (10%) were receiving NIV outside the ICU. A majority of patients (778/909; 85%) patients were treated with continuous positive airway pressure (CPAP), which was delivered by helmet in 617 (68%) patients. NIV failed in 300 patients (37.6%), whereas 498 (62.4%) patients were discharged alive without intubation. Overall mortality was 25%. NIV failure occurred in 152/284 (53%) patients with an arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio <150 mm Hg. Higher C-reactive protein and lower PaO2/FiO2 and platelet counts were independently associated with increased risk of NIV failure.Conclusions: The use of NIV outside the ICUs was common in COVID-19, with a predominant use of helmet CPAP, with a rate of success >60% and close to 75% in full-treatment patients. C-reactive protein, PaO2/FiO2, and platelet counts were independently associated with increased risk of NIV failure.Clinical trial registered with ClinicalTrials.gov (NCT04382235).

Relationship between tissue hypoxia and apoptosis: a preliminary observational study.

AIMS: This observational study examined the relationship between tissue hypoxia (PO2 of 30mmHg and 15mmHg) and the development of dysoxia and apoptosis. METHODS: 28 Sprague-Dawley rats were studied in three groups. Group 1 had no interventions (controls; n=6). Graded hypoxia was induced in Group 2 (n =13) and Group 3 (n =9) to achieve a subcutaneous PO2 of < 30mmHg (20 minutes) followed by < 15mmHg (20 minutes). In addition, Group 3 received reoxygenation to baseline after hypoxia. Ileal and cutaneous tissues were assessed for apoptosis (by histology, TUNEL and immunohistochemistry for caspase-3) and dysoxia (tissue lactate concentration and energy charge). RESULTS: An interstitial PO2 < 30mmHg led to statistically significant elevations in skin and gut lactate concentrations from baseline (mean +/-SD: skin, 0.2+/-0.07 to 0.6 +/-0.3mmol/ kg wet weight, P < 0.01; gut, 1 +/-0.7 to 6 +/-4mmol/kg wet weight, P<0.05). With hypoxia, there was an increase in apoptosis scores in the gut villi from baseline in the experimental arms (17% +/-21% to 53% +/-58%, P<0.05 in Group 2; 9% +/-5% to 27%+/-12%, P < 0.05 in Group 3). There was no significant increase in skin apoptosis. No significant correlation was noted between gut lactate concentrations and gut apoptosis (r= -0.28). CONCLUSIONS: In this pilot study, reductions in PO2 to <30mmHg were associated with significant dysoxic changes in the gut and skin. No clear tissue PO2 threshold for the initiation of apoptosis was identified. Further studies with refinements to the experimental model may allow more precise identification of PO2 thresholds that are critical for the development of apoptosis.