Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-analysis

Abstract

Importance: Treatment with noninvasive oxygenation strategies such as noninvasive ventilation and high-flow nasal oxygen may be more effective than standard oxygen therapy alone in patients with acute hypoxemic respiratory failure.

Objective: To compare the association of noninvasive oxygenation strategies with mortality and endotracheal intubation in adults with acute hypoxemic respiratory failure.

Data sources: The following bibliographic databases were searched from inception until April 2020: MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and LILACS. No limits were applied to language, publication year, sex, or race.

Study selection: Randomized clinical trials enrolling adult participants with acute hypoxemic respiratory failure comparing high-flow nasal oxygen, face mask noninvasive ventilation, helmet noninvasive ventilation, or standard oxygen therapy.

Data extraction and synthesis: Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a bayesian framework to derive risk ratios (RRs) and risk differences along with 95% credible intervals (CrIs) were conducted. GRADE methodology was used to rate the certainty in findings.

Main outcomes and measures: The primary outcome was all-cause mortality up to 90 days. A secondary outcome was endotracheal intubation up to 30 days.

Results: Twenty-five randomized clinical trials (3804 participants) were included. Compared with standard oxygen, treatment with helmet noninvasive ventilation (RR, 0.40 [95% CrI, 0.24-0.63]; absolute risk difference, -0.19 [95% CrI, -0.37 to -0.09]; low certainty) and face mask noninvasive ventilation (RR, 0.83 [95% CrI, 0.68-0.99]; absolute risk difference, -0.06 [95% CrI, -0.15 to -0.01]; moderate certainty) were associated with a lower risk of mortality (21 studies [3370 patients]). Helmet noninvasive ventilation (RR, 0.26 [95% CrI, 0.14-0.46]; absolute risk difference, -0.32 [95% CrI, -0.60 to -0.16]; low certainty), face mask noninvasive ventilation (RR, 0.76 [95% CrI, 0.62-0.90]; absolute risk difference, -0.12 [95% CrI, -0.25 to -0.05]; moderate certainty) and high-flow nasal oxygen (RR, 0.76 [95% CrI, 0.55-0.99]; absolute risk difference, -0.11 [95% CrI, -0.27 to -0.01]; moderate certainty) were associated with lower risk of endotracheal intubation (25 studies [3804 patients]). The risk of bias due to lack of blinding for intubation was deemed high.

Conclusions and relevance: In this network meta-analysis of trials of adult patients with acute hypoxemic respiratory failure, treatment with noninvasive oxygenation strategies compared with standard oxygen therapy was associated with lower risk of death. Further research is needed to better understand the relative benefits of each strategy.

Figure 1.. Summary of Study Retrieval and Identification for Network Meta-analysis

Figure 2.. Network Plots for the Association of Noninvasive Oxygenation Strategies With All-Cause Mortality and Intubation

Network geometry shows nodes as interventions and each head-to-head direct comparison as lines connecting these nodes. There is no direct comparison between high-flow nasal oxygen and helmet noninvasive ventilation for any of the study outcomes. The size of the nodes is proportional to the number of participants in each node. The thickness of the connecting line is proportional to the number of randomized clinical trials in each comparison. Both network plots include 1 study (n = 47) that did not report any event of death or intubation and 1 three-group study (face mask noninvasive ventilation, high-flow nasal oxygen, and standard oxygen therapy). Therefore, the total number of comparisons is higher than the number of randomized clinical trials for each outcome. Patients may be included in multiple comparisons, and this is accounted within the bayesian model and does not mean participants are duplicated.

Figure 3.. Forest Plots for the Association of Noninvasive Oxygenation Strategies With Study Outcomes

A, For the primary outcome, all-cause mortality, the longest follow-up was up to 90 days. B, For the secondary outcome, intubation, the longest follow-up was up to 30 days. All outcomes are reported as network risk ratios and absolute risk differences with 95% credible intervals (CrIs). The certainty for each network meta-analysis estimate was estimated based on the 4-step approach suggested by the GRADE Working Group. Initially, each direct and indirect comparison was rated independently using the GRADE approach (risk of bias, inconsistency, indirectness, imprecision), and these were used to rate the network estimate. In case of disagreement between the direct and indirect rating, the network estimate was assigned the higher rating. In the presence of incoherence, the network estimate was assigned the lower rating of the direct/indirect assessment. For estimating risk ratios for the comparison of helmet noninvasive ventilation vs high-flow nasal cannula, only indirect evidence was used because no direct pairwise comparisons were available. The estimated absolute risk of mortality and endotracheal intubation was 30% and 40%, respectively, in the standard oxygen group. Between-study heterogeneity was assessed by using the posterior distribution for τ, τ², and the I² statistic. For all-cause mortality, τ = 0.17 (95% CrI, 0.056-0.23), τ² = 0.0284 (95% Crl, 0.00317-0.0508), and I² = 12%. For endotracheal intubation, τ = 0.21 (95% CrI, 0.07-0.27), τ² = 0.0437 (95% Crl, 0.00554-0.0743), and I² = 15%.