Study of High-Velocity Nasal Insufflation vs Noninvasive Positive Pressure Ventilation for Emergency Type 2 Respiratory Failure: Protocol for a Noninferiority Randomized Controlled Trial.

Background: Type 2 respiratory failure (T2RF) is a common and high-risk presentation in the emergency department (ED). Noninvasive positive pressure ventilation (NIPPV) is a standard first-line therapy for T2RF, particularly in acute exacerbations of chronic obstructive pulmonary disease and cardiogenic pulmonary edema. However, NIPPV has limitations, including discomfort, claustrophobia, air leaks, skin injury, and aspiration that may compromise tolerance and lead to treatment failure or escalation to endotracheal intubation. High-velocity nasal insufflation (HVNI), particularly via a single-prong asymmetric cannula configuration, has been proposed to enhance dead-space washout and improve patient comfort. Despite growing interest, robust evidence of evaluation of HVNI in heterogeneous, all-cause T2RF populations in the ED remains limited. Objective: This study aims to determine whether HVNI delivered via a single-prong nasal cannula is noninferior to standard NIPPV in improving ventilation among adult ED patients with T2RF from any cause. Methods: This is a single-center, open-label, noninferiority randomized controlled trial conducted in the ED of a tertiary academic center. Adults aged 21 years and above with T2RF, defined as partial pressure of carbon dioxide (PaCO2) above 45 mm Hg and pH below 7.35 requiring ventilatory support, will be randomized 1:1 to HVNI via a single-prong cannula or standard NIPPV. Allocation will be concealed via an independent web-based platform using variable block sizes. The primary outcome is percentage change in PaCO2 from baseline to 60 minutes after initiation of therapy. A total of 84 patients provide 80% power and one-sided α of 2.5% assuming an SD of 6.65% and noninferiority margin of 4.3%. Analyses will use intention-to-treat and per-protocol approaches, and sensitivity analyses to address missing arterial blood gas results will be conducted. Predefined failure criteria (persistent or worsening acidosis, rising PaCO2, refractory hypoxemia, severe intolerance, and clinical deterioration) will trigger crossover or escalation per protocol. Results: Ethics approval was granted by the local institutional ethics board on February 24, 2025 (reference 2024-4329). Recruitment commenced in January 2026 and is expected to be completed by June 2027. As of July 2026, a total of 19 participants have been enrolled out of a target sample of 84. Data analysis will commence following completion of enrollment, with results expected to be published by 2028. Conclusions: Should HVNI via a single-prong cannula be shown to be noninferior to NIPPV, it may offer a practical alternative to treatment of T2RF in the ED when mask-based interfaces are poorly tolerated or contraindicated, potentially reducing the need for more invasive interventions such as endotracheal intubation and mechanical ventilation.