Timing of Endotracheal Intubation After High-Flow Nasal Cannula Initiation in Patients With Mild-to-Moderate Acute Respiratory Distress Syndrome: A Prospective Observational Cohort Study.

BACKGROUND

High-flow nasal cannula (HFNC) is widely used in acute hypoxemic respiratory failure, including mild-to-moderate acute respiratory distress syndrome (ARDS). Some patients deteriorate and require invasive mechanical ventilation, but the appropriate timing of intubation remains uncertain. This study examined the association between intubation within 24 hours of HFNC initiation and clinical outcomes among patients with mild-to-moderate ARDS in whom HFNC failed.

METHODS

This prospective observational cohort included 109 adults with mild-to-moderate ARDS treated at the General Hospital of Athens "G. Gennimatas," Greece, from August 2023 to August 2024. All initially received HFNC and were subsequently intubated. Mild and moderate ARDS were classified by Berlin oxygenation criteria (PaO₂/FiO₂ 201-300 and 101-200 mmHg, respectively). HFNC failure was defined as subsequent endotracheal intubation and invasive mechanical ventilation. A predefined 24-hour cutoff, supported by previous studies, classified patients as early or delayed intubation. Intubation decisions were based on arterial blood gases and overall clinical condition. Outcomes included in-hospital mortality, successful ventilator weaning, hospital and intensive care unit (ICU) length of stay, and duration of the initial controlled mechanical ventilation phase. Multivariable models adjusted for age, sex, body mass index, comorbidity burden, admission blood pressure, and peripheral oxygen saturation.

RESULTS

Twenty-two patients (20.2%) were intubated within 24 hours and 87 (79.8%) after 24 hours. In-hospital death occurred in 0 of 22 patients (0.0%) in the early group and 15 of 87 (17.2%) in the delayed group (p = 0.038). Successful ventilator weaning occurred in 17 of 22 patients (77.3%) and six of 87 (6.9%), respectively (p < 0.001). After adjustment, intubation within 24 hours was associated with lower odds of in-hospital death (OR = 0.03, 95% CI: 0.001-0.89; p = 0.043), although the wide confidence interval indicates substantial uncertainty. The early group had a longer hospital stay (adjusted β = 0.14, 95% CI: 0.03-0.25; p = 0.017), shorter ICU stay (adjusted β = -0.44, 95% CI: -0.72 to -0.17; p = 0.002), and shorter initial controlled mechanical ventilation phase (adjusted β = -0.30, 95% CI: -0.53 to -0.07; p = 0.015).

CONCLUSION

Among patients with mild-to-moderate ARDS requiring invasive mechanical ventilation after HFNC failure, intubation within 24 hours was associated with lower observed in-hospital mortality, more frequent successful ventilator weaning, and shorter ICU and controlled ventilation durations. These findings support close monitoring and timely escalation when deterioration indicates insufficient non-invasive support. The observational design and limited outcome events preclude causal interpretation, and larger multicenter cohorts are needed to confirm these associations.