Physiological effects of noninvasive respiratory support strategies in adults with acute hypoxemic respiratory failure: a systematic review and network meta-analysis

Background: In hypoxemic patients, the respective effects of noninvasive respiratory support strategies on lung injury determinants remain unclear, primarily due to the difficulty of obtaining standardized measurements for all interventions within the same study. We conducted a systematic review and network meta-analysis to assess the effects of noninvasive strategies on transpulmonary driving pressure and inspiratory effort in patients with acute hypoxemic respiratory failure. Methods: We conducted a systematic search (Ovid MEDLINE, Embase, Scopus, and PubMed) and performed a network meta-analysis of physiological studies involving hypoxemic adults published up to February 16th, 2025. We included studies that assessed inspiratory effort with esophageal manometry under at least two noninvasive respiratory support strategies [standard oxygen, high-flow nasal oxygen (HFNO), noninvasive ventilation (NIV), and continuous positive airway pressure (CPAP)]. Outcomes included transpulmonary driving pressure, inspiratory effort per breath and per minute, respiratory rate, and gas exchange. Treatment effects are displayed as mean differences [95% confidence intervals]. Results: Among 5876 citations, thirteen studies (n = 312 patients) were included (mean PaO2/FiO2 = 131 (± 48) mmHg, mean respiratory rate = 28 (± 8) breaths*min−1). Compared to standard oxygen, HFNO and CPAP did not affect transpulmonary driving pressure or effort per breath. HFNO and NIV reduced effort per minute (-95 cmH2O*bpm [-140; -49] and -240 cmH2O*bpm [-284; -196], respectively), whereas CPAP did not. NIV lowered effort per breath (-5.9 cmH2O [-7.4; -4.4]) but increased driving pressure (3.4 cmH₂O [1.4; 5.4]). All strategies reduced respiratory rate, with HFNO producing the greatest decrease (HFNO: -5 breaths*min−1 [-6; -4]; CPAP: -2 breaths*min−1 [-4; -1]; NIV: -4 breaths*min−1 [-5; -2]); all interventions improved PaO2/FiO2, with CPAP and NIV showing greater effects than HFNO (CPAP: 67 mmHg [55; 80]; NIV: 82 mmHg [56; 108]; HFNO: 24 mmHg [5; 43]). None of the strategies affected PaCO2. Conclusions: Noninvasive strategies exert distinct physiological effects: HFNO and NIV reduce effort per minute, while only NIV decreases effort per breath but at the cost of increased driving pressure. CPAP has neutral effects on driving pressure and effort. CPAP and NIV provide greater improvements in oxygenation than HFNO. Individualized selection based on effort levels may help balance the benefits and risks of noninvasive support. PROSPERO registration: CRD42024564035.