Association of prolonged pre-intubation high-flow nasal cannula duration with survival and successful V-V ECMO liberation in severe ARDS: a retrospective multicenter study

In patients with severe acute respiratory distress syndrome (ARDS), prolonged invasive mechanical ventilation (IMV) prior to veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a known risk factor for poor outcomes. However, the clinical impact of high-flow nasal cannula (HFNC) duration before intubation remains poorly defined. We examined the association between pre-intubation HFNC duration and clinical outcomes, including survival and ECMO liberation. This retrospective multicenter study using the J-CARVE registry analyzed 209 adults with severe ARDS who received HFNC before V-V ECMO (2012–2022). The continuous risk of prolonged HFNC for 60-day in-hospital mortality was evaluated using multivariable logistic regression. Subsequently, patients were stratified into Short (< 3 days) and Long (≥ 3 days) HFNC groups using an exploratory ROC-derived cutoff. Clinical outcomes (60-day in-hospital mortality and successful ECMO liberation) were further analyzed using multivariable Cox and Fine–Gray models. Multivariable logistic regression identified prolonged HFNC duration (analyzed continuously) as an independent risk factor for 60-day in-hospital mortality (adjusted odds ratio 1.22 per 1-day increase; 95% CI 1.07–1.39; P = 0.0035). Sixty-nine patients (33.0%) were in the Long HFNC group. After adjustment, prolonged HFNC (≥ 3 days) was independently associated with a twofold increase in 60-day in-hospital mortality (adjusted Hazard Ratio 2.27; 95% CI 1.24–4.15; P = 0.008). Furthermore, successful ECMO liberation was significantly lower in the Long HFNC group (adjusted Subdistribution Hazard Ratio 0.68; 95% CI 0.50–0.94; P = 0.018). Extended pre-intubation HFNC duration was associated with increased mortality and impaired lung recovery in severe ARDS. Rather than a direct cause of injury, prolonged HFNC likely serves as a complex prognostic marker reflecting disease trajectory and delayed escalation. Clinicians should recognize prolonged HFNC as a continuous trajectory of accumulating risk, rather than relying solely on IMV duration to guide ECMO initiation.