High-flow nasal cannula vs non-invasive ventilation in acute hypoxia: Propensity score matched study.

RATIONALE: The optimal treatment for early hypoxemic respiratory failure is unclear, and both high-flow nasal cannula and non-invasive ventilation are used. Determining clinically relevant outcomes for evaluating non-invasive respiratory support modalities remains a challenge. OBJECTIVES: To compare the effectiveness of initial treatment with high-flow nasal cannula versus non-invasive ventilation for acute hypoxemic respiratory failure. METHODS: We conducted a retrospective cohort study of patients with acute hypoxemic respiratory failure treated with high-flow nasal cannula or non-invasive ventilation within 24 hours of Emergency Department arrival (1/2018-12/2022). We matched patients 1:1 using a propensity score for odds of receiving non-invasive ventilation. The primary outcome was major adverse pulmonary events (28-day mortality, ventilator-free days, non-invasive respiratory support hours) calculated using a Win Ratio. MEASUREMENTS AND MAIN RESULTS: 1,265 patients met inclusion criteria. 795 (62.8%) received high-flow oxygen and 470 (37.2%) received non-invasive ventilation. We propensity score matched 736/1,265 (58.2%) patients. There was no difference between non-invasive ventilation vs high-flow nasal cannula in 28-day mortality (17.7% vs 23.1%, p=0.08) or ventilator-free days (median [Interquartile Range]: 28 [25, 28] vs 28 [13, 28], p=0.50), but patients on non-invasive ventilation required treatment for fewer hours (median 7 vs 13, p< 0.001). Win Ratio for composite major adverse pulmonary events favored non-invasive ventilation (1.26, 95%CI 1.06-1.49, p< 0.001). CONCLUSIONS: In this observational study of patients with acute hypoxemic respiratory failure, initial treatment with non-invasive ventilation was superior to high-flow nasal cannula for major pulmonary adverse events. Evaluation of composite outcomes is important in the assessment of respiratory support modalities.

A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR).

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of COVID-19. METHODS: In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18-79 years (Part 1) or ≥70 years (Part 2) with severe COVID-19, respiratory failure and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90 mg (human anti-GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28. RESULTS: In Part 1 (n=806 randomised 1:1 otilimab:placebo), 71% of otilimab-treated patients were alive and free of respiratory failure at Day 28 versus 67% who received placebo; the model-adjusted difference of 5.3% was not statistically significant (95% CI -0.8-11.4%, p=0.09). A nominally significant model-adjusted difference of 19.1% (95% CI 5.2-33.1%, p=0.009) was observed in the predefined 70-79 years subgroup, but this was not confirmed in Part 2 (n=350 randomised) where the model-adjusted difference was 0.9% (95% CI -9.3-11.2%, p=0.86). Compared with placebo, otilimab resulted in lower serum concentrations of key inflammatory markers, including the putative pharmacodynamic biomarker CC chemokine ligand 17, indicative of GM-CSF pathway blockade. Adverse events were comparable between groups and consistent with severe COVID-19. CONCLUSIONS: There was no significant difference in the proportion of patients alive and free of respiratory failure at Day 28. However, despite the lack of clinical benefit, a reduction in inflammatory markers was observed with otilimab, in addition to an acceptable safety profile.

Safety Assessment of a Noninvasive Respiratory Protocol for Adults With COVID-19.

As evidence emerged supporting noninvasive strategies for coronavirus disease 2019 (COVID-19)-related respiratory distress, we implemented a noninvasive COVID-19 respiratory protocol (NCRP) that encouraged high-flow nasal cannula (HFNC) and self-proning across our healthcare system. To assess safety, we conducted a retrospective chart review evaluating mortality and other patient safety outcomes after implementation of the NCRP protocol (April 3, 2020, to April 15, 2020) for adult patients hospitalized with COVID-19, compared with preimplementation outcomes (March 15, 2020, to April 2, 2020). During the study, there were 469 COVID-19 admissions. Fewer patients underwent intubation after implementation (10.7% [23 of 215]), compared with before implementation (25.2% [64 of 254]) (P < .01). Overall, 26.2% of patients died (24% before implementation vs 28.8% after implementation; P = .14). In patients without a do not resuscitate/do not intubate order prior to admission, mortality was 21.8% before implementation vs 21.9% after implementation. Overall, we found no significant increase in mortality following implementation of a noninvasive respiratory protocol that decreased intubations in patients with COVID-19.

Drotrecogin alfa (activated) in sepsis: initial experience with patient selection, cost, and clinical outcomes.

During a 1-year period, the authors examined clinical experience with drotrecogin alfa, activated for sepsis in a 24-bed medical-surgical intensive care unit. Drotrecogin alfa, activated was administered 46 times to 44 patients (3% of all intensive care unit admissions). Eighty-six percent of patients were on vasopressors; 95% were mechanically ventilated. Mean Acute Physiology and Chronic Health Evaluation II score was 22.0 at admission and 21.9 during the 24 hours before drug administration. The 28-day all-cause mortality was 36.4% and hospital mortality was 43.2%, trending higher (P = .10) than in the PROWESS study, which can be attributed to clinical use in patients who would not have met PROWESS study inclusion criteria. Failure to complete a 96-hour infusion of drotrecogin alfa, activated and transfer from another hospital or nursing home before treatment were associated with poor outcome. Total cost of hospital care, including mean drotrecogin alfa, activated drug cost of 7,312 US dollars, exceeded reimbursement by a mean of 18,227 US dollars.