High-flow nasal cannula versus conventional oxygen therapy in adults with acute hypoxemic respiratory failure: an updated systematic review, meta-analysis and trial sequential analysis

HFNC oxygen therapy is widely used for acute hypoxemic respiratory failure (AHRF), yet its superiority over conventional oxygen therapy (COT) remains uncertain. This meta-analysis evaluated HFNC efficacy and safety in adults with AHRF. Five databases were searched from January 2018 through May 2026 for RCTs comparing HFNC with COT in adults with AHRF. Primary outcomes were all-cause mortality and intubation or invasive mechanical ventilation (IMV). Random-effects meta-analyses yielded pooled risk ratios, and mean differences with 95% CIs. Eighteen RCTs (4,882 patients) were included. HFNC did not reduce all-cause mortality (RR 0.98, 95% CI 0.84–1.14; p = 0.79), with consistent effects across short-term and longer-term mortality subgroups. Trial Sequential Analysis indicated that the available evidence for mortality remains inconclusive. HFNC significantly reduced intubation or invasive mechanical ventilation (RR 0.87, 95% CI 0.79–0.97; p = 0.01), and TSA confirmed that this reduction represents a statistically robust finding. This benefit was most evident in mild-to-moderate hypoxemia, non-immunocompromised patients, ICU settings, and isolated hypoxemic respiratory failure. HFNC shortened hospital stay (MD − 0.65 days, 95% CI − 1.23 to − 0.07; p = 0.03). ICU stay, ventilator-free days, ICU mortality, comfort, dyspnea, and adverse events were comparable between groups. HFNC reduces IMV need and hospital stay without a mortality benefit, supporting its use as an effective, safe oxygenation strategy in selected AHRF populations.