Abstract
BACKGROUND: Acute hypercapnic respiratory failure (AHRF) commonly complicates chronic respiratory diseases and is traditionally managed with noninvasive ventilation (NIV), although tolerance and interface-related limitations may reduce adherence. High-flow nasal cannula (HFNC) has been proposed as an alternative, but comparative efficacy in AHRF remains uncertain. METHODS: We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Cochrane Library, Web of Science, and Embase were searched from inception to September 16, 2025, for randomized controlled trials comparing HFNC versus NIV in adults with AHRF. Risk of bias was assessed using Cochrane RoB 2.0. Pooled effects were summarized as risk ratios (RRs) for dichotomous outcomes and standardized mean differences (SMD) for continuous outcomes using fixed- or random-effects models according to heterogeneity. RESULTS: Six randomized controlled trials (sample sizes 30-168) were included. HFNC and NIV showed no significant differences in partial pressure of carbon dioxide (SMD = -0.22, 95% confidence interval [CI]: -0.45 to 0.01; I2 = 20%), arterial pH (SMD = -0.03, 95% CI: -0.28 to 0.22; I2 = 45.2%), intubation (RR = 0.87, 95% CI: 0.41-1.82; I2 = 0%), or mortality (RR = 0.85, 95% CI: 0.47-1.56; I2 = 0%). Egger's test suggested no significant publication bias. CONCLUSION: In adult AHRF, HFNC demonstrated efficacy comparable to NIV for gas-exchange and short-term clinical outcomes. HFNC may be considered an alternative when NIV is not tolerated, with explicit monitoring and timely escalation protocols.