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Meta-Analysis
. 2025 Oct 28;29(1):456.
doi: 10.1186/s13054-025-05670-7.

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

Luca S Menga #  1   2 , Eleonora Balzani #  3 , Camilla Gelormini  4   5 , Claudia Mastropietro  4   5 , Nicoletta Volpe  4   5 , Riccardo Del Signore  4   5 , Matteo Mondello  4   5 , Alessandro Cardu  4   5 , Luca Delle Cese  4   5 , Tommaso Rosà  4   5 , Sonia D'Arrigo  4   5 , Salvatore M Maggiore  6   7 , Laurent Brochard  1   2 , Massimo Antonelli  4   5 , Giacomo Bellani  3   8 , Domenico L Grieco  9   10
Affiliations
Meta-Analysis

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

Luca S Menga et al. Crit Care. .

Abstract

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.

Keywords: CPAP; High-flow nasal oxygen; Hypoxemic respiratory failure; Network meta-analysis; Noninvasive support; Noninvasive ventilation; Self-inflicted lung injury.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: LSM has received a scholarship from the European Respiratory Society and the Canadian Lung Association. LB’S laboratory has received support for research by Covidien (PAV), Air Liquide (CPR), Philips (equipment for sleep), Fisher & Paykel (high flow therapy) and GE healthcare.MA has received payments for Board participation from Maquet, Air Liquide and Chiesi, and a research grant by GE. DLG has received payments for travel expenses by Getinge, Draeger and Hamilton, personal fees by Draeger, and research grants by Fisher and Paykel and GE.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram of study selection. Flowchart summarizing the identification, screening, eligibility assessment, and inclusion of studies in the systematic review and network meta-analysis
Fig. 2
Fig. 2
Network geometry of included studies. Each node represents a noninvasive respiratory support strategy; node size is proportional to the total number of patients receiving each intervention. Lines between nodes represent direct head-to-head comparisons; line thickness is proportional to the number of studies
Fig. 3
Fig. 3
Effects of noninvasive respiratory strategies on transpulmonary driving pressure. Left panel: standard oxygen therapy as comparator. Right panel: high-flow nasal oxygen (HFNO) as comparator. Dots indicate mean difference estimates; bars represent 95% confidence intervals (CIs)
Fig. 4
Fig. 4
Effects of noninvasive respiratory strategies on inspiratory effort. Upper panels: standard oxygen therapy as comparator. Lower panels: HFNO as comparator. Left side: effort per breath. Right side: effort per minute. Dots represent mean difference estimates; bars represent 95% CIs
Fig. 5
Fig. 5
Effects of noninvasive respiratory strategies on respiratory rate and oxygenation (PaO₂/FiO₂ ratio). Upper panels: standard oxygen therapy as comparator. Lower panels: HFNO as comparator. Left side: respiratory rate. Right side: PaO₂/FiO₂ ratio. Dots represent mean difference estimates; bars represent 95% CIs
Fig. 6
Fig. 6
Sensitivity analysis of noninvasive respiratory strategies. Panels display effects on transpulmonary driving pressure (upper left), inspiratory effort (lower left), respiratory rate (upper right), and oxygenation (PaO₂/FiO₂ ratio; lower right). Standard oxygen is the comparator in all panels. Dots represent mean differences; bars indicate 95% CIs
See this image and copyright information in PMC

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