Efficacy of HFNC + NIV as initial oxygen therapy in acute respiratory failure: Meta-analysis

Combining non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) may offer complementary benefits in acute respiratory failure (ARF). Prior meta-analyses compared monotherapies or post-extubation combination therapy, but none specifically evaluated NIV + HFNC as the initial strategy to prevent intubation or mortality.

To compare the efficacy of initial NIV + HFNC versus NIV or HFNC monotherapy for preventing intubation and mortality in adults with ARF.

We systematically searched PubMed, Embase, Cochrane Library, and Web of Science (inception to May 31, 2025) for relevant RCTs. Primary outcome was intubation rate; secondary outcome was mortality. Statistical data analysis was performed using RevMan software. Risk of bias was assessed (Cochrane RoB 2).

Six RCTs (N = 764 participants) were included. Compared with monotherapy, combined NIV + HFNC did not significantly affect intubation rates (OR 1.08, 95 % CI 0.79-1.49; P = 0.62; I² = 23 %) or mortality (OR 1.41, 95 % CI 0.60-3.34; P = 0.43; I² = 62 %). Subgroup analyses by control intervention (NIV alone or HFNC alone) and trial design (single-center vs. multi-center) also showed no statistically significant differences. Notably, the largest studies exhibited contrasting trends, potentially attributable to variations in lung-protective ventilation strategies during NIV.

This meta-analysis found no significant benefit of initial NIV + HFNC over monotherapy in reducing intubation or mortality in ARF. Future high-quality RCTs should prioritize standardized protocols, explicit lung-protective NIV settings, and larger sample sizes, with particular emphasis on specific ARF phenotypes that may derive maximal benefit from combined therapy.