Abstract Rationale Acute hypoxemic respiratory failure (AHRF) remains a major therapeutic challenge in emergency and intensive care settings, often secondary to pneumonia or acute respiratory distress syndrome (ARDS), among others. Conventional oxygen therapies often fail to achieve adequate oxygenation, prompting the use of advanced non-invasive modalities such as High-Flow Nasal Cannula (HFNC) and Non-Invasive Ventilation (NIV). Although both aim to improve oxygenation and reduce the need for intubation and possibly mortality, their comparative efficacy remains uncertain,with previous studies reporting conflicting results. With the publication of a recent large randomized controlled trial (RENOVATE), an updated systematic review and meta-analysis comparing HFNC and NIV in adults with AHRF is warranted. Methods This review followed PRISMA guidelines and included randomized controlled trials (RCTs) and cohort studies published between 2010 and 2025. Searches were conducted in PubMed, Cochrane Library, Web of Science, and Google Scholar using predefined keywords related to “acute hypoxemic respiratory failure,” “high-flow nasal cannula,” and “non-invasive ventilation.” Studies focusing primarily on hypercapnic or post-extubation respiratory failure were excluded. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool for RCTs and the Joanna Briggs Institute (JBI) checklist for cohort studies. Data synthesis was performed using RevMan version 5.4 software. Pooled odds ratios (ORs) and relative risks (RRs) were calculated with 95% confidence intervals (CIs). Statistical heterogeneity was evaluated using the I² statistic, and publication bias was visually assessed using funnel plots. Results Thirteen RCTs encompassing 5,031 adult patients with AHRF were included in the final analysis. Pooled estimates showed no significant difference in 28-day mortality between HFNC and NIV RR 0.97, 95% CI 0.80-1.16; p = 0.71. The need for endotracheal intubation was not significantly different between the two groups OR 0.76, 95% CI 0.55-1.06; p = 0.11. Secondary outcomes, including improvements in oxygenation indices (PaO2/FiO2 ratio), duration of respiratory support, and complications such as skin breakdown or treatment intolerance, were comparable between HFNC and NIV. Study heterogeneity ranged from 67% to 74%, and funnel plot asymmetry suggested moderate publication bias. Conclusions In adults with acute hypoxemic respiratory failure, HFNC and NIV yield similar mortality outcomes. The need for intubation was slightly lower in HFNC group but remained clinically non-significant. Both modalities demonstrate comparable safety and tolerability. Given the moderate heterogeneity and possible publication bias, these results should be interpreted with caution. Further large-scale, multicenter randomized controlled trials are warranted to identify patient subgroups most likely to benefit from each modality. This abstract is funded by: None
Bajwa et al. (Fri,) studied this question.