Non-invasive Oxygenation Strategies for Reducing the Incidence of Pneumonia in Adult Patients with Acute Hypoxemic Respiratory Failure: A Systematic Review and Network Meta-analysis

Non-invasive Oxygenation Strategies for Reducing the Incidence of Pneumonia in Adult Patients with Acute Hypoxemic Respiratory Failure: A Systematic Review and Network Meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Non-invasive Oxygenation Strategies for Reducing the Incidence of Pneumonia in Adult Patients with Acute Hypoxemic Respiratory Failure: A Systematic Review and Network Meta-analysis Satoshi Hokari, Shunsuke Kimata, Masaaki Sakuraya, Hiromu Okano, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5069185/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: In the current guidelines, the usage of non-invasive oxygenation strategies, such as non-invasive positive pressure ventilation (NPPV) and high-flow nasal oxygen (HFNO), for acute hypoxemic respiratory failure (AHRF) are unable to provide conclusive recommendations. We aimed to identify the most optimum respiratory management strategy reducing pneumonia in patients with AHRF. Methods: We searched the four databases for eligible trials. Studies including adults with AHRF and randomized controlled trials comparing two different respiratory management methods (NPPV, HFNO, standard oxygen therapy [SOT], or invasive mechanical ventilation [IMV]) were reviewed. The primary outcome was the incidence of pneumonia. A network meta-analysis was performed a frequentist approach with a multivariate random-effects meta-analysis. Results: We identified 14,263 unique articles, reviewed 126 full-text articles, and finally included 13 studies. Using IMV as the reference, NPPV (risk ratio [RR], 0.23; 95% confidence interval [CI], 0.11–0.51; moderate certainty) and HFNO (RR, 0.24; 95% CI, 0.09–0.64; moderate certainty) were significantly associated with a lower incidence of pneumonia. Compared with SOT, NPPV (RR, 0.55; 95% CI, 0.35–0.84; moderate certainty) but not HFNO (RR, 0.55; 95% CI 0.27–1.13; low certainty) was significantly associated with a lower incidence of pneumonia. The probability of being the best in reducing the incidence of pneumonia among all interventions was higher for NPPV and HFNO, followed by SOT, whereas IMV was the worst. Conclusions: Our findings imply that NPPV and HFNO may be the most effective strategies for primary respiratory management in adults with AHRF to reduce pneumonia. Pulmonology acute hypoxemic respiratory failure invasive mechanical ventilation non-invasive positive pressure ventilation high-flow nasal oxygen pneumonia network meta-analysis ventilator-associated pneumonia Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Acute hypoxemic respiratory failure (AHRF) is frequently found in critically ill patients and associated with high in-hospital mortality [ 1 ]. To reduce the complications associated with invasive mechanical ventilation (IMV), non-invasive oxygenation strategies, such as non-invasive positive pressure ventilation (NPPV) and high-flow nasal oxygen (HFNO), have been widely investigated in patients with AHRF. NPPV is recommended in patients with cardiogenic pulmonary edema [ 2 ] but not in patients with de novo AHRF [ 3 ], which includes acute respiratory distress syndrome (ARDS) and pneumonia as major causes. In a previous large observational study, the usage of NPPV for patients with severe ARDS may be associated with higher intensive care unit mortality [ 4 ]. On the other hand, although HFNO is preferred to manage patients with AHRF [ 5 ], the efficacy of HFNO has not been consistent among patients with de novo AHRF [ 6 , 7 ]. Further research is required to understand the relative benefits and risks of each strategy. A network meta-analysis (NMA) was recently conducted to compare the effectiveness of initial respiratory support in adult patients with de novo AHRF [ 8 ]. This NMA revealed that non-invasive oxygenation strategies were associated with a lower risk of death compared with standard oxygen therapy (SOT). However, no such comparisons were made between IMV and non-invasive oxygenation strategies. Additionally, the risk of adverse events associated with each treatment strategy was unclear in the NMA. In this study, we aimed to identify the most optimum respiratory management strategy reducing pneumonia in patients with AHRF. We conducted an NMA to evaluate the associations of different respiratory management strategies (NPPV, HFNO, SOT, and IMV) with the incidence of pneumonia in adult patients with AHRF. Methods Protocol and registration This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) extension statement for reviews incorporating network meta-analyses [ 9 ]. The protocol has been registered in protocols.io (Protocol integer ID 49629) [ 10 ]. Inclusion criteria We included randomized controlled trials (RCTs) reported in English and Japanese, comparing two of the following four strategies: SOT (nasal cannula, facemask, and venturi mask with limitless flow rate), NPPV (mask type, ventilation mode, and methods of weaning were not limited), HFNO (flow rate and fraction of inspired oxygen were not limited), and IMV (mechanical ventilation via endotracheal intubation, not tracheostomy). This review included adults (age ≥ 18 years) with AHRF, defined by any of the following criteria: new onset (< 7 days) of clinical signs (e.g., tachypnea), radiological signs (e.g. chest X-ray opacities), and hypoxemia. Hypoxemia was defined as the ratio of arterial oxygen partial pressure to fractional inspired oxygen below 300, arterial or percutaneous oxygen saturation < 94% in room air, PaO 2 < 60 mmHg in room air, or < 80 mmHg with oxygen. The primary outcome was the incidence rate of pneumonia (ventilator-associated pneumonia (VAP), aspiration pneumonia, and nosocomial pneumonia were not limited). The secondary outcome was the incidence rate of VAP (VAP was defined in each study). Exclusion criteria Randomized crossover, cluster-randomized, or quasi-experimental trials were excluded. The current meta-analysis excluded studies in which more than half of the patients had congestive heart failure, acute exacerbation of chronic obstructive pulmonary disease (COPD), asthma attack, hypercapnia (PaCO 2 > 50 mmHg), respiratory failure due to post-extubation or trauma, post-surgical status, or do-not-resuscitate orders. We also excluded the studies which had limited intervention in the emergency department or pre-hospital care. Search strategy Databases used for the search of eligible trials were The Cochrane Central Register of Controlled Trials, MEDLINE via PubMed, EMBASE, and Ichushi, a database of Japanese research papers. Because this systematic review was planned for ARDS clinical practice guidelines 2021 in Japan [ 11 ], we also included studies on clinical questions about non-invasive oxygenation strategies in the guideline, using manual search. A literature search was performed on May 30, 2021. The terms used for database search showed in Appendices. Study selection and data extraction At the first screening, two of the five reviewers (HO, TM, SH, SK, and MS) screened the title and abstract. At the second screening, the full text for relevant studies was analysed and data were independently extracted from the included studies into standardized data forms. Disagreements were resolved by discussing with one of the three reviewers not involved in screening the studies. We also asked the original authors for additional details when necessary. After identifying studies in the second screening, we extracted the following study characteristics: methods, participants, interventions, and outcomes. Network geometry Network diagrams were constructed using the Confidence In Network Meta-Analysis (CINeMA) web application [ 12 ], to show the number of studies and patients included in the meta-analysis. We represented network geometry that treatments by nodes and head-to-head comparisons by lines connecting these nodes. The size of the node is proportional to the number of patients, while the thickness of the lines is proportional to the number of studies evaluating each treatment. Quality assessment The risk of bias of outcomes in the eligible studies was independently assessed by two of the five authors using the Cochrane Risk of Bias tool 2.0 [ 13 ] for the following seven domains: (a) random sequence generation, (b) allocation concealment, (c) blinding of participants and personnel, (d) blinding of outcome assessors, (e) incomplete outcome data, (f) selective outcome reporting, and (g) other sources of bias. Each domain of bias was graded as either “low risk,” “unclear risk,” or “high risk.” If there was a discrepancy between the two reviewers, an agreement was reached through discussion. Discrepancy checks were resolved by discussion with a third reviewer, as necessary. Each domain was evaluated in three categories: high risk, low risk, and some concerns. Methods of direct comparison meta-analysis A pairwise meta-analysis was performed using Review Manager version 5.3 [ 14 ]. Forest plots were used for meta-analysis, and the effect size was expressed as a risk ratio (RR) with 95% confidence interval (CI) for categorical data. Outcome measures were pooled using a random-effects model to analyse study-specific effects in the measures. A two-sided p -value < 0.05 was considered statistically significant for all analyses. Methods of network comparison meta-analysis An NMA was performed using a frequentist-based approach with multivariate random-effects meta-analysis, and the effect size was expressed as the RR (95% CI) using the CINeMA web application [ 12 ]. CINeMA is based on the framework that was developed by Salanti et al. [ 15 ] and modified by Nikolakopoulou et al. [ 16 ]. Six domains that influence the level of confidence of NMA results are: (a) within-study bias, (b) reporting bias, (c) indirectness, (d) imprecision, (e) heterogeneity, and (f) incoherence. The covariance between two estimates from the same study indicated the variance of data in the shared arm, as calculated in a multivariable meta-analysis performed for an NMA [ 17 ]. Transitivity was assessed in the incoherence domain using CINeMA. We constructed forest plots of the RR with 95% CI for each treatment strategy in the network. Ranking plots (rankograms) were constructed based on the probability that a given treatment had the highest event rate for each outcome. The surface under the cumulative ranking curve (SUCRA), which is a simple transformation of the mean rank, was used to determine the treatment hierarchy. We calculated values of the SUCRA statistic using the mvmeta command in Stata 15.1 (StataCorp LLC, College Station, TX, USA) [ 18 ]. SUCRA is a percentage that shows how much effectiveness a treatment archives in comparison with a theoretical treatment that is always the best. The larger the SUCRA value, the better the rank of the treatment [ 19 ]. Assessments of the certainty of evidence We evaluated the indirectness, classified as “no”, “some”, or “major” concern, of each study included in the NMA based on its relevance to the research question. The study-level judgments can be combined with a percentage contribution matrix. The approach to imprecision involved comparing the range of treatment effects included in the 95% CI with the range of equivalence. We assessed the heterogeneity of treatment effects for a clinically important risk ratio of 1.25 in prediction interval. Study heterogeneity among trials for each outcome was assessed by visually inspecting forest plots and with an I 2 statistic to quantify inconsistency [ 20 ]. Publication bias was visually assessed using a funnel plot [ 19 ]. The global inconsistency test with a fitting design-by-treatment model was used to identify the disagreement between the direct and indirect estimates as a measure of inconsistency [ 21 ]. The studies were categorized based on the p -value of the global design-by-treatment interaction test: “major concerns” ( 0.10). Studies were also categorized as showing “major concerns” if the design-by-treatment interaction test statistic could not be computed due to the absence of closed loops in the network. The network estimate was rated considering the risk of bias, indirectness, imprecision, heterogeneity, publication bias, and inconsistency [ 22 ]. Search results The search strategy identified 14,263 records. Based on the study selection process, 13 studies (1,254 participants; range, 40–310 participants) [ 7 , 23 – 34 ] were included in this NMA (Fig. 1). The included trials evaluated four different interventions. These included four out of six potential head-to-head comparisons for all types of pneumonia and three out of six potential head-to-head comparisons for VAP. Specifically, nine trials compared NPPV with SOT [ 7 , 24 – 30 , 32 ], one trial compared HFNO with SOT [ 7 ], three trials compared NPPV with IMV [ 23 , 31 , 33 ], and two trials compared NPPV with HFNO [ 7 , 34 ]. No studies compared HFNO with IMV (Fig. 2). Study characteristics and risk of bias assessment The characteristics of each study included in the final meta-analysis dataset are summarized in Table 1 . Three trials (23.1%) included immunocompromised patients [ 27 , 29 , 30 ]. Community-acquired pneumonia was the most common cause of AHRF in seven trials (53.8%) [ 7 , 24 , 26 – 28 , 31 , 32 ]. Table 2 shows the data for the risk of bias; all studies were judged to have major biased concerns for outcomes and high overall risk of bias. Table 1 Summary of characteristics of the studies included in the network meta-analysis. Source Funding Total No. of patients Main reason for hypoxemic respiratory failure (main baseline risk factor) Age, y P/F RR, /min PaCO 2 , mmHg Main exposure interface, NIV mode Comparator Outcomes of interest assessed Antolnelli et al., 1998 [ 23 ]. Undisclosed 64 Mixed ARF (CPO 19%, atelectasis 25%) 54 120 39 40 noninvasive ventilation (N = 32) face mask, pressure support Invasive ventilation, tidal volume 10 ml/kg (N = 32) Hospital mortality Confalonieri et al., 1999 [ 24 ]. Undisclosed 56 CAP 64 175 37 49 noninvasive ventilation (N = 28) face mask, pressure support standard oxygen (N = 28) 2-month mortality, intubation Antonelli et al., 2000 [ 25 ]. Undisclosed 40 Mixed ARF (ARDS 37.5%, atelectasis 25%) 67 NA NA 40 noninvasive ventilation (N = 20) face mask, pressure support standard oxygen (N = 20) Hospital mortality, intubation Delcaux et al., 2000 [ 26 ]. Vital Signs Inc 123 Mixed ARF (CAP 54.5%) 58 a 144 a 33 36 a noninvasive ventilation (N = 62) face mask, CPAP standard oxygen (N = 61) Hospital mortality, intubation Hilbert et al., 2001 [ 27 ]. Undisclosed 52 CAP in immunocompromised patients 49 139 36 38 noninvasive ventilation (N = 26) face mask, pressure support standard oxygen (N = 26) Hospital mortality, intubation Ferrer et al., 2003 [ 28 ]. Red GIRA, Red Respira, and Carburos Metalicos SA 105 Mixed ARF (CAP 32.4%, CPE 28.6%) 62 103 37 37 noninvasive ventilation (N = 51) face mask, pressure support standard oxygen (N = 54) ICU mortality, intubation Squadrone et al., 2010 [ 29 ]. Regione Piemonte (CEP AN RAN 07) and Ministero dell’Università (PRIN RANI 07) 40 Mixed ARF in immunocompromised patients 49 269 30 36 noninvasive ventilation (N = 20) helmet, CPAP standard oxygen (N = 20) Hospital mortality, intubation Zhan et al., 2012 [ 30 ]. Beijing Municipal Science and Technology Commission Program 40 ALI (immunocompromised 30%) 46 230 20 32 noninvasive ventilation (N = 21) face mask, pressure support standard oxygen (N = 19) Hospital mortality, intubation Frat et al., 2015 [ 7 ]. French Ministry of Health 310 Mixed ARF (CAP 63.5%) 60 155 33 35 noninvasive ventilation (N = 110) face mask, pressure support high-flow nasal oxygen (N = 106); standard oxygen (N = 94) 90-day mortality, intubation Muncharaz et al., 2017 [ 31 ]. Undisclosed 65 Mixed ARF (CAP 63.1%) 62 a 97 36 44 noninvasive ventilation (N = 34) face mask, pressure support invasive ventilation, tidal volume 8–10 ml/kg (PBW), Ppl < 35 (N = 31) Hospital mortality He et al., 2019 [ 32 ]. National Natural Science Foundation of China 200 CAP 55 231 25 34 noninvasive ventilation (N = 102) face mask, pressure support standard oxygen (N = 98) Hospital mortality, intubation Awadallah et al., 2021 [ 33 ]. None 52 ARDS (pulmonary ARDS 50%) 52 94.5 NA 33 noninvasive ventilation (N = 26) face mask, pressure support invasive ventilation, tidal volume 6-7ml/kg (PBW), Ppl < 30 (N = 26) Hospital mortality Grieco et al., 2021 [ 34 ]. 2017 Merck Sharp & Dohme SRL award 107 ARF in COVID-19 patients 65 a 102 a 28 a 34 a noninvasive ventilation (N = 54) helmet, pressure support high-flow nasal oxygen (N = 55) 60-day mortality, intubation a. Age was reported as median. Abbreviations: ALI, acute lung injury; ARDS, acute respiratory distress syndrome; ARF, acute respiratory failure; CAP, community-acquired pneumonia; CPAP, continuous positive airway pressure; CPO, cardiopulmonary oedema; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; ICU, intensive care unit; NA, not available; NIV, noninvasive ventilation; P/F ratio, ratio of arterial oxygen partial pressure to fractional inspired oxygen; PaCO 2 , partial pressure of arterial carbon dioxide; Ppl, plateau pressure; PBW, predicted body weight; RR, respiratory rate. Table 2 Summary of risk of bias of the studies included in the network meta-analysis. Pneumonia Source Bias arising from the randomization process Bias due to deviations from intended interventions Bias due to missing outcome data Bias in measurement of the outcome Bias in selection of the reported result Overall risk of bias a) Pneumonia Antolnelli et al., 1998 [ 22 ]. Some concerns Some concerns Low High Low High Confalonieri et al., 1999 [ 23 ]. Low Some concerns Low High Low High Antonelli et al., 2000 [ 24 ]. Low Some concerns Low High Low High Delcaux et al., 2000 [ 25 ]. Low Some concerns Some concerns High Low High Hilbert et al., 2001 [ 26 ]. Low Some concerns Low High Low High Ferrer et al., 2003 [ 27 ]. Low Some concerns Low High Low High Squadrone et al., 2010 [ 28 ]. Low Some concerns Low High Low High Zhan et al., 2012 [ 29 ]. Low Some concerns Low High Low High Frat et al., 2015 [ 7 ]. Low Some concerns Low High Low High Muncharaz et al., 2017 [ 30 ]. Low Some concerns Low High Low High He et al., 2019 [ 31 ]. Low Some concerns Low High Low High Awadallah et al., 2021 [ 32 ]. Some concerns Some concerns Low High Low High Grieco et al., 2021 [ 33 ]. Low Some concerns Low High Low High b) Ventilator-associated pneumonia Antolnelli et al., 1998 [ 22 ]. Some concerns Some concerns Low High Low High Confalonieri et al., 1999 [ 23 ]. Low Some concerns Low High Low High Antonelli et al., 2000 [ 24 ]. Low Some concerns Low High Low High Hilbert et al., 2001 [ 26 ]. Low Some concerns Low High Low High Zhan et al., 2012 [ 29 ]. Low Some concerns Low High Low High Muncharaz et al., 2017 [ 30 ]. Low Some concerns Low High Low High Awadallah et al., 2021 [ 32 ]. Some concerns Some concerns Low High Low High Grieco et al., 2021 [ 33 ]. Low Some concerns Low High Low High Risk of pneumonia Thirteen trials (1,254 patients) were included in the risk of pneumonia analysis. We did not rate down due to publication bias (funnel plot shown in Figure 3). However, we rated down considering heterogeneity and/or imprecision in the comparisons of HFNO vs. SOT, IMV vs. SOT, and NPPV vs. HFNO (Table 3). We also rated down in all comparisons because of the very serious risk of bias. Table 3 Summary of the network meta-analysis and network estimate rating of pneumonia and ventilator-associated pneumonia. Comparison Direct estimate (95% CI) Indirect estimate (95% CI) P value Network estimate (95% CI) Rating NPPV vs SOT 0.57 (0.37–0.88) 0.12 (0.01–1.93) 0.233 0.55 (0.35–0.84) ⨁⨁⨁◯ Moderate a), b) HFNO vs SOT 0.44 (0.13–1.53) 0.62 (0.26–1.48) 0.233 0.55 (0.27–1.13) ⨁⨁◯◯ Low a), b), c) IMV vs SOT NA 2.33 (0.96–5.61) 0.233 2.33 (0.96–5.61) ⨁⨁◯◯ Low a), b), c) NPPV vs IMV 0.23 (0.11–0.51) NA 0.233 0.23 (0.11–0.51) ⨁⨁⨁◯ Moderate a) HFNO vs IMV NA 0.24 (0.09–0.64) 0.233 0.24 (0.09–0.64) ⨁⨁⨁◯ Moderate a) NPPV vs HFNO 1.03 (0.55–1.92) 0.28 (0.01–7.30) 0.233 0.98 (0.53–1.81) ⨁⨁◯◯ Low a), d) a) Very serious risk of bias, b) Serious heterogeneity, c) Serious imprecision, d) Very serious imprecision. CI, confidence interval; HFNO, high-flow nasal oxygenation; IMV, invasive mechanical ventilation; NA, not applicable; NPPV, non-invasive positive pressure ventilation; SOT, standard oxygen therapy In the current NMA, using SOT as the reference, NPPV (RR, 0.55; 95% CI, 0.35–0.84; moderate certainty) was significantly associated with a lower risk of pneumonia, while HFNO (RR, 0.55; 95% CI, 0.27–1.13; low certainty) was not associated with a statistically significant lower risk of pneumonia (Figure 4). Compared with IMV, NPPV (RR, 0.23; 95% CI, 0.11–0.51; moderate certainty) and HFNO (RR, 0.24; 95% CI, 0.09–0.64; moderate certainty) were associated with a significantly lower risk of pneumonia (Figure 4). There were no significant differences in the additional comparisons. The ranking analysis revealed the following hierarchy regarding efficacy in reducing pneumonia: NPPV (SUCRA 87.3), followed by HFNO (SUCRA 70.5) and SOT (SUCRA 41.8), and finally, IMV (SUCRA 0.4) (Table 4). In summary, the probability of being the best strategy of reducing pneumonia among all the possible interventions was highest for NPPV, followed by HFNO. Table 4 Results of network rank test for pneumonia in the network meta-analysis. NPPV HFNO IMV SOT Best 65.3% 31.6% 0.0% 3.1% 2nd 31.3% 48.6% 0.1% 20.0% 3rd 3.4% 19.5% 0.9% 76.2% Worst 0.0% 0.3% 99.0% 0.7% Mean rank 1.4 1.9 4.0 2.7 SUCRA 87.3 70.5 0.4 41.8 HFNO, high-flow nasal oxygenation; IMV, invasive mechanical ventilation; NPPV, non-invasive positive pressure ventilation; SUCRA, surface under the cumulative ranking; SOT, standard oxygen therapy Risk of ventilator-associated pneumonia Eight trials (476 patients) were included in the risk of VAP analysis. We did not rate down due to publication bias (funnel plot shown in Figure 5). However, very serious heterogeneity and/or imprecision was observed in several comparisons (Table 5). A very serious risk of bias and incoherence was observed for all comparisons, resulting in a rating down. Table 5 Summary of the network meta-analysis and network estimate rating of ventilator-associated pneumonia. Comparison Direct estimate (95%CI) Indirect estimate (95%CI) P value Network estimate (95%CI) Rating NPPV vs SOT 0.37 (0.14–0.97) NA NA 0.37 (0.14–0.97) ⨁◯◯◯ Very Low a), b), c) HFNO vs SOT NA 0.46 (0.15–1.44) NA 0.46 (0.15–1.44) ⨁◯◯◯ Very Low a), c), d) IMV vs SOT NA 1.58 (0.48–5.26) NA 1.58 (0.48–5.26) ⨁◯◯◯ Very Low a), c), d) NPPV vs IMV 0.23 (0.11–0.47) NA NA 0.23 (0.11–0.47) ⨁⨁◯◯ Low a), c) HFNO vs IMV NA 0.29 (0.12–0.73) NA 0.29 (0.12–0.73) ⨁⨁◯◯ Low a), c), e) NPPV vs HFNO 0.79 (0.44–1.43) NA NA 0.79 (0.44–1.43) ⨁◯◯◯ Very low a), c), d) a) Very serious risk of bias, b) Very serious heterogeneity, c) Very serious inconsistency, d) Very serious imprecision, e) Serious heterogeneity. CI, confidence interval; HFNO, high-flow nasal oxygenation; IMV, invasive mechanical ventilation; NA, not applicable; NPPV, non-invasive positive pressure ventilation; SOT, standard oxygen therapy In the current NMA, using SOT as the reference, NPPV (RR, 0.37; 95% CI, 0.14–0.97; low certainty) was significantly associated with a lower risk of VAP, while HFNO (RR, 0.46; 95% CI 0.15–1.44; low certainty) was not associated with a statistically significant lower risk of VAP (Figure 6). Compared with IMV, NPPV (RR, 0.23; 95% CI, 0.11–0.47; very low certainty) and HFNO (RR, 0.29; 95% CI, 0.12–0.73; very low certainty) were associated with a statistically significant lower risk of VAP (Figure 6). There were no significant differences in the additional comparisons. The ranking analysis revealed the following hierarchy regarding efficacy in reducing VAP: NPPV (SUCRA 91.7), followed by HFNO (SUCRA 70.6), SOT (SUCRA 30.1), and IMV (SUCRA 7.7) (Table 3 and S3 Fig). As well the risk of pneumonia, the probability of being the best in reducing VAP among all the possible interventions was highest for NPPV, followed by HFNO. Table 6 Results of network rank test for ventilator- associated pneumonia in the network meta-analysis. NPPV HFNO IMV SOT Best 75.5% 22.4% 0.0% 2.1% 2nd 24.0% 66.9% 0.1% 9.0% 3rd 0.5% 10.7% 22.9% 65.9% Worst 0.0% 0.0% 77.0% 23.0% Mean rank 1.2 1.9 3.8 3.1 SUCRA 91.7 70.6 7.7 30.1 HFNO, high-flow nasal oxygenation; IMV, invasive mechanical ventilation; NPPV, non-invasive positive pressure ventilation; SUCRA, surface under the cumulative ranking; SOT, standard oxygen therapy Discussion The current NMA of RCTs for adults with AHRF revealed that, compared with SOT, NPPV decreased the risk of pneumonia and VAP. Using IMV as the reference, both NPPV and HFNO were associated with a lower risk of pneumonia and VAP. The ranking analyses suggested that NPPV was the best strategy for reducing pneumonia. This NMA is the first study to demonstrate that NPPV and HFNO can reduce the risk of pneumonia in patients with AHRF. In various previous trials, including observational studies, the incidence of nosocomial infections such as VAP was lower in NPPV than in IMV for AHRF due to various etiologies. Gay performed a meta-analysis of 12 studies and reviewed the risk of pneumonia in patients with NPPV [35]. In this meta-analysis, the pneumonia rate was lower in NPPV than that in IMV and SOT, consistent with our results. Moreover, in three studies that included patients who initially failed NPPV and were then intubated, the pneumonia rate was lower in those who initially received NPPV than in those with immediate intubation. Regarding the risk reduction of pneumonia, the use of NPPV for AHRF in adults may be superior to IMV or SOT as initial therapy. We found that using HFNO for AHRF may reduce the incidence of pneumonia compared to IMV. Although the sample size was inadequate due to the lack of RCTs that directly compared HFNO and IMV, we could evaluate the effects of HFNO versus those of IMV with indirect comparisons, complementing the limitations of the existing studies. This finding indicates the effectiveness of non-invasive oxygenation strategies compared to endotracheal intubation management. On the other hand, HFNO did not show the significant reduction of pneumonia when compared with SOT. This result is consistent with a recent systematic review by Lewis et al. [36], which included four studies (three of which did not overlap with the current NMA) that compared HFNO with SOT. Further evaluation is needed to provide conclusive recommendations, although HFNO is recommended for patients with AHRF compared with SOT [5]. NPPV has been proposed for the management of AHRF, with conflicting results [4,7,23,27,28]. Therefore, recent guidelines have been unable to provide conclusive recommendations regarding the use of NPPV in patients with de novo AHRF [3,37], while the use of HFNO is encouraged [5]. In our NMA, HFNO did not show a reduction in the rate of pneumonia and VAP compared with NPPV, consistent with a recent systematic review by Lewis comparing HFNO and NPPV [36]. Interestingly, ranking analyses using SUCRA suggested that NPPV was the best non-invasive oxygenation strategy for reducing pneumonia. In 2020, Ferreyro et al. reported an NMA in which the efficacy of non-invasive respiratory managements was compared with that of SOT among adult patients with AHRF, and helmet non-invasive ventilation was associated with a lower risk of mortality and intubation compared with HFNO [8]. While HFNO may be both acceptable and feasible to implement, compared to NPPV [5], it is necessary to verify which intervention has more clinical benefit especially for patients with de novo AHRF. This study has several limitations. First, we included studies with patients with cardiopulmonary edema and COPD who had a low risk of NPPV failure. This may have contributed to the overestimate of the treatment effect of NPPV. The NMA assumption is that individual trials enrol similar populations, and the intervention protocol is similar across different studies. We excluded studies in which more than half of the patients had cardiopulmonary edema or COPD, as reported in the previous NMA [8]. Second, there was a concern about the primary studies included in our review regarding the lack of blinding of the treatment groups. Although this was unlikely to bias the assessment of hard outcomes, it may have contributed to performance bias. Third, network RR was estimated using only indirect evidence in some comparisons. Specifically, few studies have compared HFNO with other interventions. Further studies are required to obtain a higher certainty of evidence. Finally, ranking results should be evaluated with caution because they do not consider the certainty of the evidence. Although NPPV seemed to be the best strategy considering ranking probabilities, this result dose not imply a significant clinical difference between NPPV and HFNO. Conclusions This NMA demonstrates that NPPV and HFNO were significantly associated with a lower incidence of pneumonia, compared to IMV, and NPPV but not HFNO was significantly associated with a lower incidence of pneumonia, compared to SOT. Our findings imply that NPPV and HFNO may be better strategies for the primary respiratory management of adult patients with AHRF to reduce pneumonia. Further studies are required to obtain a higher certainty of evidence, particularly with HFNO as a comparator. Abbreviations AHRF acute hypoxemic respiratory failure ARDS acute respiratory distress syndrome CI confidence interval COPD chronic obstructive pulmonary disease HFNO high-flow nasal oxygen IMV invasive mechanical ventilation NMA network meta-analysis RCT Randomized controlled trial RR risk ratio SOT standard oxygen therapy SUCRA Surface under the cumulative ranking curve VAP ventilator-associated pneumonia. Declarations Author contributions: MS, SK, and SH designed the study, acquired data, performed statistical analyses, and interpreted the data. HO and TM conceived the study and acquired and interpreted the data. SK and SH conceived the acquisition of data. The first draft of the manuscript was written by SH, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgements We would thank all the members of the Japanese ARDS clinical practice guideline committee from the Japan Society for Respiratory Care and Rehabilitation, the Japanese Respiratory Society, and the Japanese Society of Intensive Care Medicine. We also appreciate the librarian Takaaki Suzuki at the Nara Medical University Library, the librarians at the Kyoto Prefectural University of Medicine for supporting our search strategies, and Editage ( www.editage.com ) for English language editing. References Vincent JL, Akça S, De Mendonça A et al (2002) The epidemiology of acute respiratory failure in critically ill patients(*). Chest 121:1602–1609. 10.1378/chest.121.5.1602 Berbenetz N, Wang Y, Brown J et al (2019) Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema. 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JAMA 320:2099–2107. 10.1001/jama.2018.14282 Frat JP, Thille AW, Mercat A et al (2015) High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 372:2185–2196. 10.1056/NEJMoa1503326 Ferreyro BL, Angriman F, Munshi L et al (2020) Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-analysis. JAMA 324:57–67. 10.1001/jama.2020.9524 Hutton B, Salanti G, Caldwell DM et al (2015) The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 162:777–784. 10.7326/m14-2385 Hokari S, Kimata S, Sakuraya M, Okano H, Masuyama T (2021) Pneumonia Associated with Invasive and Noninvasive Oxygenation Strategies for Acute Hypoxemic Respiratory Failure in Adults: A Systematic Review and Network Meta-analysis Protocol. Protocolsio https://dx.doi.org/10.17504/protocols.io.bup17505nvq17506. dx.doi.org/10.17504/protocols.io.bup5nvq6 Tasaka S, Ohshimo S, Takeuchi M et al (2022) ARDS clinical practice guideline 2021. Respiratory Invest 60:446–495. 10.1016/j.resinv.2022.05.003 Papakonstantinou T, Nikolakopoulou A, Higgins J, Egger M, Salanti G (2020) CINeMA: Software for semiautomated assessment of the confidence in the results of network meta-analysis. Campbell Syst Reviews 16:e1080. 10.1002/cl2.1080 Sterne JAC, Savović J, Page MJ et al (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 366:l4898. 10.1136/bmj.l4898 RevMan 5 Download and installation. Secondary RevMan 5 download and installation (2014) Accessed: 23 April, 2021: https://community.cochrane.org/help/tools-and-software/revman-5/revman-5-download/installation Chaimani A, Salanti G (2012) Using network meta-analysis to evaluate the existence of small-study effects in a network of interventions. Res synthesis methods 3:161–176. 10.1002/jrsm.57 Nikolakopoulou A, Higgins JPT, Papakonstantinou T et al (2020) CINeMA: An approach for assessing confidence in the results of a network meta-analysis. PLoS Med 17:e1003082. 10.1371/journal.pmed.1003082 Yepes-Nuñez JJ, Li SA, Guyatt G et al (2019) Development of the summary of findings table for network meta-analysis. J Clin Epidemiol 115:1–13. 10.1016/j.jclinepi.2019.04.018 Salanti G, Ades AE, Ioannidis JP (2011) Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol 64:163–171. 10.1016/j.jclinepi.2010.03.016 Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G (2013) Graphical tools for network meta-analysis in STATA. PLoS ONE 8:e76654. 10.1371/journal.pone.0076654 Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558. 10.1002/sim.1186 Higgins JP, Jackson D, Barrett JK, Lu G, Ades AE, White IR (2012) Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies. Res synthesis methods 3:98–110. 10.1002/jrsm.1044 Guyatt GH, Oxman AD, Kunz R et al (2011) GRADE guidelines 6. Rating the quality of evidence–imprecision. J Clin Epidemiol 64:1283–1293. 10.1016/j.jclinepi.2011.01.012 Antonelli M, Conti G, Rocco M et al (1998) A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med 339:429–435. 10.1056/nejm199808133390703 Confalonieri M, Potena A, Carbone G, Porta RD, Tolley EA, Umberto Meduri G (1999) Acute respiratory failure in patients with severe community-acquired pneumonia. A prospective randomized evaluation of noninvasive ventilation. Am J Respir Crit Care Med 160:1585–1591. 10.1164/ajrccm.160.5.9903015 Antonelli M, Conti G, Bufi M et al (2000) Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial. JAMA 283:235–241. 10.1001/jama.283.2.235 Delclaux C, L'Her E, Alberti C et al (2000) Treatment of acute hypoxemic nonhypercapnic respiratory insufficiency with continuous positive airway pressure delivered by a face mask: A randomized controlled trial. JAMA 284:2352–2360. 10.1001/jama.284.18.2352 Hilbert G, Gruson D, Vargas F et al (2001) Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med 344:481–487. 10.1056/nejm200102153440703 Ferrer M, Esquinas A, Leon M, Gonzalez G, Alarcon A, Torres A (2003) Noninvasive ventilation in severe hypoxemic respiratory failure: a randomized clinical trial. Am J Respir Crit Care Med 168:1438–1444. 10.1164/rccm.200301-072OC Squadrone V, Massaia M, Bruno B et al (2010) Early CPAP prevents evolution of acute lung injury in patients with hematologic malignancy. Intensive Care Med 36:1666–1674. 10.1007/s00134-010-1934-1 Zhan Q, Sun B, Liang L et al (2012) Early use of noninvasive positive pressure ventilation for acute lung injury: a multicenter randomized controlled trial. Crit Care Med 40:455–460. 10.1097/CCM.0b013e318232d75e Muncharaz AB, Bort MC, Asensio DB et al (2017) Non-invasive ventilation versus invasive mechanical ventilation in patients with hypoxemic acute respiratory failure in an intensive care unit. a randomized controlled study. Minerva Pneumologica 56:1–10. 10.23736/S0026-4954.16.01770-3 He H, Sun B, Liang L et al (2019) A multicenter RCT of noninvasive ventilation in pneumonia-induced early mild acute respiratory distress syndrome. Crit Care 23:300. 10.1186/s13054-019-2575-6 Awadallah M, Taha A, Sarhan T (2021) Cardiorespiratory changes and outcome during noninvasive and invasive mechanical ventilation in ARDS: a comparative study. Res Opin Anesth Intensive Care 8:6–12. 10.4103/roaic.roaic_15_19 Grieco DL, Menga LS, Cesarano M et al (2021) Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory Failure: The HENIVOT Randomized Clinical Trial. JAMA 325:1731–1743. 10.1001/jama.2021.4682 Gay PC (2009) Complications of noninvasive ventilation in acute care. Respir Care 54:246–257 Lewis SR, Baker PE, Parker R, Smith AF (2021) High-flow nasal cannulae for respiratory support in adult intensive care patients. Cochrane Database Syst Rev 3(Cd010172). 10.1002/14651858.CD010172.pub3 Akashiba T, Ishikawa Y, Ishihara H et al (2017) The Japanese Respiratory Society Noninvasive Positive Pressure Ventilation (NPPV) Guidelines (second revised edition). Respiratory Invest 55:83–92. 10.1016/j.resinv.2015.11.007 Additional Declarations The authors declare no competing interests. Supplementary Files Additionalfile1.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5069185","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":360215079,"identity":"2d1ea9f5-1696-43ba-84b2-423ee19312dc","order_by":0,"name":"Satoshi Hokari","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIiWNgGAWjYDACZoYEBoYDDAz8DIwNH4jTwg7VItnA2DjjAFFa+EEEUKnBAQZG4rTIOzM8fPDjjE3i5tvNjc0f2xjk+cUIaDQ8zJBs2HMjLXHbnYONDQfbGAxnzk4goKWZIU2a4cPhxG03EtsfALUkGNwmTsv/xM0zEsG2ENYizwzScuNA4gYJYrUYMIP8cibZeMYNoJYz5yQI+0W+/0zigx/H7GT7Z6Q/bKgos5HnlyZkywEesArHBhDJyCaBXznYlgb2AyDaHsL9Q1jHKBgFo2AUjDwAAK+cT7swX2taAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-4129-6368","institution":"Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences","correspondingAuthor":true,"prefix":"","firstName":"Satoshi","middleName":"","lastName":"Hokari","suffix":""},{"id":360215345,"identity":"5547abff-1576-420c-a24b-2150417d4338","order_by":1,"name":"Shunsuke Kimata","email":"","orcid":"","institution":"Department of Preventive Services, School of Public Health, Kyoto University","correspondingAuthor":false,"prefix":"","firstName":"Shunsuke","middleName":"","lastName":"Kimata","suffix":""},{"id":360215346,"identity":"ab5055c4-d147-4ba0-9fe7-87060e5bf337","order_by":2,"name":"Masaaki Sakuraya","email":"","orcid":"https://orcid.org/0000-0002-7695-4340","institution":"Department of Emergency and Intensive Care Medicine","correspondingAuthor":false,"prefix":"","firstName":"Masaaki","middleName":"","lastName":"Sakuraya","suffix":""},{"id":360215347,"identity":"342d3b15-9a90-4803-a056-9edac6c67929","order_by":3,"name":"Hiromu Okano","email":"","orcid":"https://orcid.org/0000-0002-2116-0455","institution":"Department of Critical care Medicine and Emergency Medicine, National Hospital Organization Yokohama Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Hiromu","middleName":"","lastName":"Okano","suffix":""},{"id":360215348,"identity":"d431789f-2eb8-422b-9c2f-1f3b04632c5d","order_by":4,"name":"Tomoyuki Masuyama","email":"","orcid":"https://orcid.org/0000-0003-2148-5556","institution":"Department of Emergency and Critical Care Medicine, Misato Kenwa Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tomoyuki","middleName":"","lastName":"Masuyama","suffix":""}],"badges":[],"createdAt":"2024-09-11 07:49:45","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5069185/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5069185/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":65782046,"identity":"c73ec164-720b-4a07-aeaa-a8e764db06e1","added_by":"auto","created_at":"2024-10-02 15:20:36","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":342213,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow diagram of studies included in this review.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e*\u003c/sup\u003eIchushi is a database of Japanese research papers\u003c/p\u003e\n\u003cp\u003eCENTRAL, Cochrane Central Register of Controlled Trials; HFNO, high-flow nasal oxygen; IMV, invasive mechanical ventilation; NPPV, non-invasive positive pressure ventilation; SOT, standard oxygen therapy\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5069185/v1/f3add9a76880e8894c422e52.jpg"},{"id":65782047,"identity":"9bb544da-9497-45a5-a499-f63180389bb9","added_by":"auto","created_at":"2024-10-02 15:20:36","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":73539,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNetwork plot showing non-invasive respiratory management strategies for adults with acute hypoxemic respiratory failure.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhen randomized controlled trials for direct comparisons exist, this is shown by the connections between the nodes. The size of the node represents the number of participants who received the intervention. The thickness of the lines connecting the nodes represents the number of trials for that comparison.\u003c/p\u003e\n\u003cp\u003eHFNO, high-flow nasal oxygen; IMV, invasive mechanical ventilation; NPPV, non-invasive positive pressure ventilation; RCT, randomized controlled trial; SOT, standard oxygen therapy\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5069185/v1/c59cf09c4148a5433e1179b5.jpg"},{"id":65782048,"identity":"241df731-4e55-46e0-8b63-88b8ae12762e","added_by":"auto","created_at":"2024-10-02 15:20:36","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":186463,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison adjusted funnel plot for the network meta-analysis of pneumonia.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHFNO, high-flow nasal oxygenation; IMV, invasive mechanical ventilation; NPPV, non-invasive positive pressure ventilation; SOT, standard oxygen therapy\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5069185/v1/c8d7d419dda9f3c1a6acda9e.jpg"},{"id":65782049,"identity":"44a37726-5898-43dc-b710-e144a74df4c1","added_by":"auto","created_at":"2024-10-02 15:20:36","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":94339,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eForest plots showing the association of non-invasive respiratory managements with the incidence rate of pneumonia.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll outcomes are reported as network risk ratios with 95% CIs.\u003c/p\u003e\n\u003cp\u003eCI, confidence interval; HFNO, high-flow nasal oxygen; IMV, invasive mechanical ventilation; NPPV, non-invasive positive pressure ventilation; RR, risk ratio; SOT, standard oxygen therapy\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5069185/v1/0b9c9139d9a95fc7e8fb4cff.jpg"},{"id":65782051,"identity":"90ab1b6d-1fae-4efb-99a7-a2af859052eb","added_by":"auto","created_at":"2024-10-02 15:20:37","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":178246,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison adjusted funnel plot for the network meta-analysis of ventilator-associated pneumonia.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHFNO, high-flow nasal oxygenation; IMV, invasive mechanical ventilation; NPPV, non-invasive positive pressure ventilation; SOT, standard oxygen therapy\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5069185/v1/461eca738d4665473d30cba4.jpg"},{"id":65782050,"identity":"2fc2369b-521d-4e38-ab8b-d8c7c62f2289","added_by":"auto","created_at":"2024-10-02 15:20:37","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":82393,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eForest plots showing the association of non-invasive respiratory managements with the incidence rate of ventilator-associated pneumonia.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll outcomes are reported as network risk ratios with 95% CIs.\u003c/p\u003e\n\u003cp\u003eCI, confidence interval; HFNO, high-flow nasal oxygen; IMV, invasive mechanical ventilation; NPPV, non-invasive positive pressure ventilation; RR, risk ratio; SOT, standard oxygen therapy\u003c/p\u003e","description":"","filename":"Figure6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5069185/v1/22baf64b30e4c22763bf9775.jpg"},{"id":65783358,"identity":"5db8ecc5-000d-4cee-ad9c-d6f95d7a31d0","added_by":"auto","created_at":"2024-10-02 15:28:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2108310,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5069185/v1/17219dd2-c38d-4366-8ce7-6b5229aa2925.pdf"},{"id":65782053,"identity":"e0bcb658-a609-4301-8589-ebd4120a5316","added_by":"auto","created_at":"2024-10-02 15:20:37","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1042874,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5069185/v1/5fe25fef0fa60700a6bc10e6.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eNon-invasive Oxygenation Strategies for Reducing the Incidence of Pneumonia in Adult Patients with Acute Hypoxemic Respiratory Failure: A Systematic Review and Network Meta-analysis\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute hypoxemic respiratory failure (AHRF) is frequently found in critically ill patients and associated with high in-hospital mortality [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. To reduce the complications associated with invasive mechanical ventilation (IMV), non-invasive oxygenation strategies, such as non-invasive positive pressure ventilation (NPPV) and high-flow nasal oxygen (HFNO), have been widely investigated in patients with AHRF. NPPV is recommended in patients with cardiogenic pulmonary edema [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] but not in patients with \u003cem\u003ede novo\u003c/em\u003e AHRF [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], which includes acute respiratory distress syndrome (ARDS) and pneumonia as major causes. In a previous large observational study, the usage of NPPV for patients with severe ARDS may be associated with higher intensive care unit mortality [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. On the other hand, although HFNO is preferred to manage patients with AHRF [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], the efficacy of HFNO has not been consistent among patients with \u003cem\u003ede novo\u003c/em\u003e AHRF [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Further research is required to understand the relative benefits and risks of each strategy.\u003c/p\u003e \u003cp\u003eA network meta-analysis (NMA) was recently conducted to compare the effectiveness of initial respiratory support in adult patients with \u003cem\u003ede novo\u003c/em\u003e AHRF [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This NMA revealed that non-invasive oxygenation strategies were associated with a lower risk of death compared with standard oxygen therapy (SOT). However, no such comparisons were made between IMV and non-invasive oxygenation strategies. Additionally, the risk of adverse events associated with each treatment strategy was unclear in the NMA.\u003c/p\u003e \u003cp\u003eIn this study, we aimed to identify the most optimum respiratory management strategy reducing pneumonia in patients with AHRF. We conducted an NMA to evaluate the associations of different respiratory management strategies (NPPV, HFNO, SOT, and IMV) with the incidence of pneumonia in adult patients with AHRF.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eProtocol and registration\u003c/h2\u003e \u003cp\u003eThis systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) extension statement for reviews incorporating network meta-analyses [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The protocol has been registered in protocols.io (Protocol integer ID 49629) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion criteria\u003c/h3\u003e\n\u003cp\u003eWe included randomized controlled trials (RCTs) reported in English and Japanese, comparing two of the following four strategies: SOT (nasal cannula, facemask, and venturi mask with limitless flow rate), NPPV (mask type, ventilation mode, and methods of weaning were not limited), HFNO (flow rate and fraction of inspired oxygen were not limited), and IMV (mechanical ventilation via endotracheal intubation, not tracheostomy).\u003c/p\u003e \u003cp\u003eThis review included adults (age\u0026thinsp;\u0026ge;\u0026thinsp;18 years) with AHRF, defined by any of the following criteria: new onset (\u0026lt;\u0026thinsp;7 days) of clinical signs (e.g., tachypnea), radiological signs (e.g. chest X-ray opacities), and hypoxemia. Hypoxemia was defined as the ratio of arterial oxygen partial pressure to fractional inspired oxygen below 300, arterial or percutaneous oxygen saturation\u0026thinsp;\u0026lt;\u0026thinsp;94% in room air, PaO\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;\u0026lt;\u0026thinsp;60 mmHg in room air, or \u0026lt;\u0026thinsp;80 mmHg with oxygen.\u003c/p\u003e \u003cp\u003eThe primary outcome was the incidence rate of pneumonia (ventilator-associated pneumonia (VAP), aspiration pneumonia, and nosocomial pneumonia were not limited). The secondary outcome was the incidence rate of VAP (VAP was defined in each study).\u003c/p\u003e\n\u003ch3\u003eExclusion criteria\u003c/h3\u003e\n\u003cp\u003eRandomized crossover, cluster-randomized, or quasi-experimental trials were excluded. The current meta-analysis excluded studies in which more than half of the patients had congestive heart failure, acute exacerbation of chronic obstructive pulmonary disease (COPD), asthma attack, hypercapnia (PaCO\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;\u0026gt;\u0026thinsp;50 mmHg), respiratory failure due to post-extubation or trauma, post-surgical status, or do-not-resuscitate orders. We also excluded the studies which had limited intervention in the emergency department or pre-hospital care.\u003c/p\u003e\n\u003ch3\u003eSearch strategy\u003c/h3\u003e\n\u003cp\u003eDatabases used for the search of eligible trials were The Cochrane Central Register of Controlled Trials, MEDLINE via PubMed, EMBASE, and Ichushi, a database of Japanese research papers. Because this systematic review was planned for ARDS clinical practice guidelines 2021 in Japan [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], we also included studies on clinical questions about non-invasive oxygenation strategies in the guideline, using manual search. A literature search was performed on May 30, 2021. The terms used for database search showed in Appendices.\u003c/p\u003e\n\u003ch3\u003eStudy selection and data extraction\u003c/h3\u003e\n\u003cp\u003eAt the first screening, two of the five reviewers (HO, TM, SH, SK, and MS) screened the title and abstract. At the second screening, the full text for relevant studies was analysed and data were independently extracted from the included studies into standardized data forms. Disagreements were resolved by discussing with one of the three reviewers not involved in screening the studies. We also asked the original authors for additional details when necessary. After identifying studies in the second screening, we extracted the following study characteristics: methods, participants, interventions, and outcomes.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eNetwork geometry\u003c/h2\u003e \u003cp\u003eNetwork diagrams were constructed using the Confidence In Network Meta-Analysis (CINeMA) web application [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], to show the number of studies and patients included in the meta-analysis. We represented network geometry that treatments by nodes and head-to-head comparisons by lines connecting these nodes. The size of the node is proportional to the number of patients, while the thickness of the lines is proportional to the number of studies evaluating each treatment.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eQuality assessment\u003c/h3\u003e\n\u003cp\u003eThe risk of bias of outcomes in the eligible studies was independently assessed by two of the five authors using the Cochrane Risk of Bias tool 2.0 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] for the following seven domains: (a) random sequence generation, (b) allocation concealment, (c) blinding of participants and personnel, (d) blinding of outcome assessors, (e) incomplete outcome data, (f) selective outcome reporting, and (g) other sources of bias. Each domain of bias was graded as either \u0026ldquo;low risk,\u0026rdquo; \u0026ldquo;unclear risk,\u0026rdquo; or \u0026ldquo;high risk.\u0026rdquo; If there was a discrepancy between the two reviewers, an agreement was reached through discussion. Discrepancy checks were resolved by discussion with a third reviewer, as necessary. Each domain was evaluated in three categories: high risk, low risk, and some concerns.\u003c/p\u003e\n\u003ch3\u003eMethods of direct comparison meta-analysis\u003c/h3\u003e\n\u003cp\u003eA pairwise meta-analysis was performed using Review Manager version 5.3 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Forest plots were used for meta-analysis, and the effect size was expressed as a risk ratio (RR) with 95% confidence interval (CI) for categorical data. Outcome measures were pooled using a random-effects model to analyse study-specific effects in the measures. A two-sided \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant for all analyses.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eMethods of network comparison meta-analysis\u003c/h2\u003e \u003cp\u003eAn NMA was performed using a frequentist-based approach with multivariate random-effects meta-analysis, and the effect size was expressed as the RR (95% CI) using the CINeMA web application [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. CINeMA is based on the framework that was developed by Salanti et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] and modified by Nikolakopoulou et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Six domains that influence the level of confidence of NMA results are: (a) within-study bias, (b) reporting bias, (c) indirectness, (d) imprecision, (e) heterogeneity, and (f) incoherence. The covariance between two estimates from the same study indicated the variance of data in the shared arm, as calculated in a multivariable meta-analysis performed for an NMA [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Transitivity was assessed in the incoherence domain using CINeMA. We constructed forest plots of the RR with 95% CI for each treatment strategy in the network.\u003c/p\u003e \u003cp\u003eRanking plots (rankograms) were constructed based on the probability that a given treatment had the highest event rate for each outcome. The surface under the cumulative ranking curve (SUCRA), which is a simple transformation of the mean rank, was used to determine the treatment hierarchy. We calculated values of the SUCRA statistic using the mvmeta command in Stata 15.1 (StataCorp LLC, College Station, TX, USA) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. SUCRA is a percentage that shows how much effectiveness a treatment archives in comparison with a theoretical treatment that is always the best. The larger the SUCRA value, the better the rank of the treatment [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eAssessments of the certainty of evidence\u003c/h2\u003e \u003cp\u003eWe evaluated the indirectness, classified as \u0026ldquo;no\u0026rdquo;, \u0026ldquo;some\u0026rdquo;, or \u0026ldquo;major\u0026rdquo; concern, of each study included in the NMA based on its relevance to the research question. The study-level judgments can be combined with a percentage contribution matrix. The approach to imprecision involved comparing the range of treatment effects included in the 95% CI with the range of equivalence. We assessed the heterogeneity of treatment effects for a clinically important risk ratio of \u0026lt;\u0026thinsp;0.8 or \u0026gt;\u0026thinsp;1.25 in prediction interval. Study heterogeneity among trials for each outcome was assessed by visually inspecting forest plots and with an I\u003csup\u003e2\u003c/sup\u003e statistic to quantify inconsistency [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Publication bias was visually assessed using a funnel plot [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The global inconsistency test with a fitting design-by-treatment model was used to identify the disagreement between the direct and indirect estimates as a measure of inconsistency [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The studies were categorized based on the \u003cem\u003ep\u003c/em\u003e-value of the global design-by-treatment interaction test: \u0026ldquo;major concerns\u0026rdquo; (\u0026lt;\u0026thinsp;0.05), \u0026ldquo;some concerns\u0026rdquo; (0.05\u0026ndash;0.10), and \u0026ldquo;no concerns\u0026rdquo; (\u0026gt;\u0026thinsp;0.10). Studies were also categorized as showing \u0026ldquo;major concerns\u0026rdquo; if the design-by-treatment interaction test statistic could not be computed due to the absence of closed loops in the network. The network estimate was rated considering the risk of bias, indirectness, imprecision, heterogeneity, publication bias, and inconsistency [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"Search results","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003cp\u003eThe search strategy identified 14,263 records. Based on the study selection process, 13 studies (1,254 participants; range, 40\u0026ndash;310 participants) [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e] were included in this NMA (Fig.\u0026nbsp;1).\u003c/p\u003e\n \u003cp\u003eThe included trials evaluated four different interventions. These included four out of six potential head-to-head comparisons for all types of pneumonia and three out of six potential head-to-head comparisons for VAP. Specifically, nine trials compared NPPV with SOT [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e], one trial compared HFNO with SOT [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e], three trials compared NPPV with IMV [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e], and two trials compared NPPV with HFNO [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e]. No studies compared HFNO with IMV (Fig.\u0026nbsp;2).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy characteristics and risk of bias assessment\u003c/h2\u003e\n \u003cp\u003eThe characteristics of each study included in the final meta-analysis dataset are summarized in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Three trials (23.1%) included immunocompromised patients [\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e]. Community-acquired pneumonia was the most common cause of AHRF in seven trials (53.8%) [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e]. Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e shows the data for the risk of bias; all studies were judged to have major biased concerns for outcomes and high overall risk of bias.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSummary of characteristics of the studies included in the network meta-analysis.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSource\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFunding\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal No.\u003c/p\u003e\n \u003cp\u003eof patients\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMain reason for hypoxemic respiratory failure\u003c/p\u003e\n \u003cp\u003e(main baseline risk factor)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge, y\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP/F\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRR, /min\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePaCO\u003csub\u003e2\u003c/sub\u003e, mmHg\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMain exposure\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003einterface, NIV mode\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eComparator\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOutcomes of interest assessed\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAntolnelli et al., 1998 [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUndisclosed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed ARF (CPO 19%, atelectasis 25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enoninvasive ventilation (N\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eface mask, pressure support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInvasive ventilation, tidal volume 10 ml/kg (N\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConfalonieri et al., 1999 [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUndisclosed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enoninvasive ventilation (N\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eface mask, pressure support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003estandard oxygen (N\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2-month mortality, intubation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAntonelli et al., 2000 [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUndisclosed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed ARF (ARDS 37.5%, atelectasis 25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enoninvasive ventilation (N\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eface mask, pressure support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003estandard oxygen (N\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital mortality, intubation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDelcaux et al., 2000 [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVital Signs Inc\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed ARF (CAP 54.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e144\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enoninvasive ventilation (N\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eface mask, CPAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003estandard oxygen (N\u0026thinsp;=\u0026thinsp;61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital mortality, intubation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHilbert et al., 2001 [\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUndisclosed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAP in immunocompromised patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enoninvasive ventilation (N\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eface mask, pressure support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003estandard oxygen (N\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital mortality, intubation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFerrer et al., 2003 [\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRed GIRA, Red Respira, and Carburos Metalicos SA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed ARF (CAP 32.4%, CPE 28.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enoninvasive ventilation (N\u0026thinsp;=\u0026thinsp;51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eface mask, pressure support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003estandard oxygen (N\u0026thinsp;=\u0026thinsp;54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eICU mortality, intubation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSquadrone et al., 2010 [\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRegione Piemonte (CEP AN RAN 07) and Ministero dell\u0026rsquo;Universit\u0026agrave; (PRIN RANI 07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed ARF in immunocompromised patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enoninvasive ventilation (N\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ehelmet, CPAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003estandard oxygen (N\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital mortality, intubation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZhan et al., 2012 [\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBeijing Municipal Science and Technology Commission Program\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eALI (immunocompromised 30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e230\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enoninvasive ventilation (N\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eface mask, pressure support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003estandard oxygen (N\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital mortality, intubation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFrat et al., 2015 [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFrench Ministry of Health\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e310\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed ARF (CAP 63.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enoninvasive ventilation (N\u0026thinsp;=\u0026thinsp;110)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eface mask, pressure support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ehigh-flow nasal oxygen (N\u0026thinsp;=\u0026thinsp;106); standard oxygen (N\u0026thinsp;=\u0026thinsp;94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90-day mortality, intubation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMuncharaz et al., 2017 [\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUndisclosed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed ARF (CAP 63.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enoninvasive ventilation (N\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eface mask, pressure support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003einvasive ventilation, tidal volume 8\u0026ndash;10 ml/kg (PBW), Ppl\u0026thinsp;\u0026lt;\u0026thinsp;35 (N\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHe et al., 2019 [\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNational Natural Science Foundation of China\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e231\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enoninvasive ventilation (N\u0026thinsp;=\u0026thinsp;102)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eface mask, pressure support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003estandard oxygen (N\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital mortality, intubation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAwadallah et al., 2021 [\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eARDS (pulmonary ARDS 50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e94.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enoninvasive ventilation (N\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eface mask, pressure support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003einvasive ventilation, tidal volume 6-7ml/kg (PBW), Ppl\u0026thinsp;\u0026lt;\u0026thinsp;30 (N\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHospital mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrieco et al., 2021 [\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2017 Merck Sharp \u0026amp; Dohme SRL award\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eARF in COVID-19 patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e102 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enoninvasive ventilation (N\u0026thinsp;=\u0026thinsp;54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ehelmet, pressure support\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ehigh-flow nasal oxygen (N\u0026thinsp;=\u0026thinsp;55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60-day mortality, intubation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003ea. Age was reported as median.\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\n \u003cp\u003eAbbreviations: ALI, acute lung injury; ARDS, acute respiratory distress syndrome; ARF, acute respiratory failure; CAP, community-acquired pneumonia; CPAP, continuous positive airway pressure; CPO, cardiopulmonary oedema; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; ICU, intensive care unit; NA, not available; NIV, noninvasive ventilation; P/F ratio, ratio of arterial oxygen partial pressure to fractional inspired oxygen; PaCO\u003csub\u003e2\u003c/sub\u003e, partial pressure of arterial carbon dioxide; Ppl, plateau pressure; PBW, predicted body weight; RR, respiratory rate.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSummary of risk of bias of the studies included in the network meta-analysis. Pneumonia\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr style=\"height: 72px;\"\u003e\n \u003cth style=\"height: 72px;\" align=\"left\"\u003e\n \u003cp\u003eSource\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 72px;\" align=\"left\"\u003e\n \u003cp\u003eBias arising from the randomization process\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 72px;\" align=\"left\"\u003e\n \u003cp\u003eBias due to deviations from intended interventions\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 72px;\" align=\"left\"\u003e\n \u003cp\u003eBias due to missing outcome data\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 72px;\" align=\"left\"\u003e\n \u003cp\u003eBias in measurement of the outcome\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 72px;\" align=\"left\"\u003e\n \u003cp\u003eBias in selection of the reported result\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 72px;\" align=\"left\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003cp\u003erisk of bias\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" colspan=\"7\" align=\"left\"\u003e\n \u003cp\u003ea) Pneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eAntolnelli et al., 1998 [\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eConfalonieri et al., 1999 [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eAntonelli et al., 2000 [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eDelcaux et al., 2000 [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHilbert et al., 2001 [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eFerrer et al., 2003 [\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSquadrone et al., 2010 [\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eZhan et al., 2012 [\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eFrat et al., 2015 [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eMuncharaz et al., 2017 [\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHe et al., 2019 [\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eAwadallah et al., 2021 [\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eGrieco et al., 2021 [\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" colspan=\"7\" align=\"left\"\u003e\n \u003cp\u003eb) Ventilator-associated pneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eAntolnelli et al., 1998 [\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eConfalonieri et al., 1999 [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eAntonelli et al., 2000 [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHilbert et al., 2001 [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eZhan et al., 2012 [\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eMuncharaz et al., 2017 [\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eAwadallah et al., 2021 [\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 48px;\"\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eGrieco et al., 2021 [\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eSome concerns\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 48px;\" align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ch2 class=\"colspec\" align=\"left\"\u003e\u003cstrong\u003eRisk of pneumonia\u003c/strong\u003e\u0026nbsp;\u003c/h2\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\n \u003cp\u003eThirteen trials (1,254 patients) were included in the risk of pneumonia analysis. We did not rate down due to publication bias (funnel plot shown in Figure 3). However, we rated down considering heterogeneity and/or imprecision in the comparisons of HFNO \u003cem\u003evs.\u003c/em\u003e SOT, IMV \u003cem\u003evs.\u003c/em\u003e SOT, and NPPV \u003cem\u003evs.\u003c/em\u003e HFNO (Table 3). We also rated down in all comparisons because of the very serious risk of bias.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSummary of the network meta-analysis and network estimate rating of pneumonia and ventilator-associated pneumonia.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eComparison\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDirect estimate (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIndirect estimate (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNetwork estimate (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRating\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNPPV vs SOT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.57 (0.37\u0026ndash;0.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.12 (0.01\u0026ndash;1.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.55 (0.35\u0026ndash;0.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e⨁⨁⨁◯\u003c/p\u003e\n \u003cp\u003eModerate \u003csup\u003ea), b)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHFNO vs SOT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44 (0.13\u0026ndash;1.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.62 (0.26\u0026ndash;1.48)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.55 (0.27\u0026ndash;1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e⨁⨁◯◯\u003c/p\u003e\n \u003cp\u003eLow \u003csup\u003ea), b), c)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIMV vs SOT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.33 (0.96\u0026ndash;5.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.33 (0.96\u0026ndash;5.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e⨁⨁◯◯\u003c/p\u003e\n \u003cp\u003eLow \u003csup\u003ea), b), c)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNPPV vs IMV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23 (0.11\u0026ndash;0.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.23 (0.11\u0026ndash;0.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e⨁⨁⨁◯\u003c/p\u003e\n \u003cp\u003eModerate \u003csup\u003ea)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHFNO vs IMV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.24 (0.09\u0026ndash;0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.24 (0.09\u0026ndash;0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e⨁⨁⨁◯\u003c/p\u003e\n \u003cp\u003eModerate \u003csup\u003ea)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNPPV vs HFNO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.03 (0.55\u0026ndash;1.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.28 (0.01\u0026ndash;7.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.98 (0.53\u0026ndash;1.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e⨁⨁◯◯\u003c/p\u003e\n \u003cp\u003eLow \u003csup\u003ea), d)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003ea) Very serious risk of bias, b) Serious heterogeneity, c) Serious imprecision, d) Very serious imprecision.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eCI, confidence interval; HFNO, high-flow nasal oxygenation; IMV, invasive mechanical ventilation; NA, not applicable; NPPV, non-invasive positive pressure ventilation; SOT, standard oxygen therapy\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\n \u003cp\u003eIn the current NMA, using SOT as the reference, NPPV (RR, 0.55; 95% CI, 0.35\u0026ndash;0.84; moderate certainty) was significantly associated with a lower risk of pneumonia, while HFNO (RR, 0.55; 95% CI, 0.27\u0026ndash;1.13; low certainty) was not associated with a statistically significant lower risk of pneumonia (Figure 4). Compared with IMV, NPPV (RR, 0.23; 95% CI, 0.11\u0026ndash;0.51; moderate certainty) and HFNO (RR, 0.24; 95% CI, 0.09\u0026ndash;0.64; moderate certainty) were associated with a significantly lower risk of pneumonia (Figure 4). There were no significant differences in the additional comparisons.\u003c/p\u003e\n \u003cp\u003eThe ranking analysis revealed the following hierarchy regarding efficacy in reducing pneumonia: NPPV (SUCRA 87.3), followed by HFNO (SUCRA 70.5) and SOT (SUCRA 41.8), and finally, IMV (SUCRA 0.4) (Table 4). In summary, the probability of being the best strategy of reducing pneumonia among all the possible interventions was highest for NPPV, followed by HFNO.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eResults of network rank test for pneumonia in the network meta-analysis.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eNPPV\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eHFNO\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eIMV\u003c/p\u003e\n \u003c/th\u003e\n \u003cth style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eSOT\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eBest\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e65.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e31.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e3.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e2nd\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e31.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e48.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e20.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003e3rd\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e3.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e19.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e76.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eWorst\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e99.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eMean rank\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr style=\"height: 35px;\"\u003e\n \u003ctd style=\"height: 35px;\" align=\"left\"\u003e\n \u003cp\u003eSUCRA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e87.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e70.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height: 35px;\" align=\"char\"\u003e\n \u003cp\u003e41.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr style=\"height: 26px;\"\u003e\n \u003ctd style=\"height: 26px;\" colspan=\"5\"\u003eHFNO, high-flow nasal oxygenation; IMV, invasive mechanical ventilation; NPPV, non-invasive positive pressure ventilation; SUCRA, surface under the cumulative ranking; SOT, standard oxygen therapy\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\n \u003ch3\u003e\u003cstrong\u003eRisk of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eventilator-associated pneumonia\u003c/strong\u003e\u003c/h3\u003e\n \u003cp\u003eEight trials (476 patients) were included in the risk of VAP analysis. We did not rate down due to publication bias (funnel plot shown in Figure 5). However, very serious heterogeneity and/or imprecision was observed in several comparisons (Table 5). A very serious risk of bias and incoherence was observed for all comparisons, resulting in a rating down.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSummary of the network meta-analysis and network estimate rating of ventilator-associated pneumonia.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eComparison\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDirect estimate (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIndirect estimate (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNetwork estimate (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRating\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNPPV vs SOT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.37 (0.14\u0026ndash;0.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.37 (0.14\u0026ndash;0.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e⨁◯◯◯\u003c/p\u003e\n \u003cp\u003eVery Low \u003csup\u003ea), b), c)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHFNO vs SOT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.46 (0.15\u0026ndash;1.44)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.46 (0.15\u0026ndash;1.44)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e⨁◯◯◯\u003c/p\u003e\n \u003cp\u003eVery Low \u003csup\u003ea), c), d)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIMV vs SOT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.58 (0.48\u0026ndash;5.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.58 (0.48\u0026ndash;5.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e⨁◯◯◯\u003c/p\u003e\n \u003cp\u003eVery Low \u003csup\u003ea), c), d)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNPPV vs IMV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23 (0.11\u0026ndash;0.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.23 (0.11\u0026ndash;0.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e⨁⨁◯◯\u003c/p\u003e\n \u003cp\u003eLow \u003csup\u003ea), c)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHFNO vs IMV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29 (0.12\u0026ndash;0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.29 (0.12\u0026ndash;0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e⨁⨁◯◯\u003c/p\u003e\n \u003cp\u003eLow \u003csup\u003ea), c), e)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNPPV vs HFNO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.79 (0.44\u0026ndash;1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.79 (0.44\u0026ndash;1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e⨁◯◯◯\u003c/p\u003e\n \u003cp\u003eVery low \u003csup\u003ea), c), d)\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003ea) Very serious risk of bias, b) Very serious heterogeneity, c) Very serious inconsistency, d) Very serious imprecision, e) Serious heterogeneity.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eCI, confidence interval; HFNO, high-flow nasal oxygenation; IMV, invasive mechanical ventilation; NA, not applicable; NPPV, non-invasive positive pressure ventilation; SOT, standard oxygen therapy\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003cbr\u003e\n \u003cp\u003eIn the current NMA, using SOT as the reference, NPPV (RR, 0.37; 95% CI, 0.14\u0026ndash;0.97; low certainty) was significantly associated with a lower risk of VAP, while HFNO (RR, 0.46; 95% CI 0.15\u0026ndash;1.44; low certainty) was not associated with a statistically significant lower risk of VAP (Figure 6). Compared with IMV, NPPV (RR, 0.23; 95% CI, 0.11\u0026ndash;0.47; very low certainty) and HFNO (RR, 0.29; 95% CI, 0.12\u0026ndash;0.73; very low certainty) were associated with a statistically significant lower risk of VAP (Figure 6). There were no significant differences in the additional comparisons.\u003c/p\u003e\n \u003cp\u003eThe ranking analysis revealed the following hierarchy regarding efficacy in reducing VAP: NPPV (SUCRA 91.7), followed by HFNO (SUCRA 70.6), SOT (SUCRA 30.1), and IMV (SUCRA 7.7) (Table 3 and S3 Fig). As well the risk of pneumonia, the probability of being the best in reducing VAP among all the possible interventions was highest for NPPV, followed by HFNO.\u003c/p\u003e\n \u003c/div\u003e\n \u003ctable id=\"Tab6\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eResults of network rank test for ventilator- associated pneumonia in the network meta-analysis.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNPPV\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHFNO\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIMV\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSOT\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBest\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e75.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2nd\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e66.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3rd\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e65.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWorst\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e77.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean rank\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSUCRA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e91.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e70.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eHFNO, high-flow nasal oxygenation; IMV, invasive mechanical ventilation; NPPV, non-invasive positive pressure ventilation; SUCRA, surface under the cumulative ranking; SOT, standard oxygen therapy\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe current NMA of RCTs for adults with AHRF revealed that, compared with SOT, NPPV decreased the risk of pneumonia and VAP. Using IMV as the reference, both NPPV and HFNO were associated with a lower risk of pneumonia and VAP. The ranking analyses suggested that NPPV was the best strategy for reducing pneumonia. This NMA is the first study to demonstrate that NPPV and HFNO can reduce the risk of pneumonia in patients with AHRF.\u003c/p\u003e\n\u003cp\u003eIn various previous trials, including observational studies, the incidence of nosocomial infections such as VAP was lower in NPPV than in IMV for AHRF due to various etiologies. Gay performed a meta-analysis of 12 studies and reviewed the risk of pneumonia in patients with NPPV [35]. In this meta-analysis, the pneumonia rate was lower in NPPV than that in IMV and SOT, consistent with our results. Moreover, in three studies that included patients who initially failed NPPV and were then intubated, the pneumonia rate was lower in those who initially received NPPV than in those with immediate intubation. Regarding the risk reduction of pneumonia, the use of NPPV for AHRF in adults may be superior to IMV or SOT as initial therapy.\u003c/p\u003e\n\u003cp\u003eWe found that using HFNO for AHRF may reduce the incidence of pneumonia compared to IMV. Although the sample size was inadequate due to the lack of RCTs that directly compared HFNO and IMV, we could evaluate the effects of HFNO versus those of IMV with indirect comparisons, complementing the limitations of the existing studies. This finding indicates the effectiveness of non-invasive oxygenation strategies compared to endotracheal intubation management. On the other hand, HFNO did not show the significant reduction of pneumonia when compared with SOT. This result is consistent with a recent systematic review by Lewis et al. [36], which included four studies (three of which did not overlap with the current NMA) that compared HFNO with SOT. Further evaluation is needed to provide conclusive recommendations, although HFNO is recommended for patients with AHRF compared with SOT [5].\u003c/p\u003e\n\u003cp\u003eNPPV has been proposed for the management of AHRF, with conflicting results [4,7,23,27,28]. Therefore, recent guidelines have been unable to provide conclusive recommendations regarding the use of NPPV in patients with \u003cem\u003ede novo\u003c/em\u003e AHRF [3,37], while the use of HFNO is encouraged [5]. In our NMA, HFNO did not show a reduction in the rate of pneumonia and VAP compared with NPPV, consistent with a recent systematic review by Lewis comparing HFNO and NPPV [36]. Interestingly, ranking analyses using SUCRA suggested that NPPV was the best non-invasive oxygenation strategy for reducing pneumonia. In 2020, Ferreyro et al. reported an NMA in which the efficacy of non-invasive respiratory managements was compared with that of SOT among adult patients with AHRF, and helmet non-invasive ventilation was associated with a lower risk of mortality and intubation compared with HFNO [8]. While HFNO may be both acceptable and feasible to implement, compared to NPPV [5], it is necessary to verify which intervention has more clinical benefit especially for patients with \u003cem\u003ede novo\u003c/em\u003e AHRF.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, we included studies with patients with cardiopulmonary edema and COPD who had a low risk of NPPV failure. This may have contributed to the overestimate of the treatment effect of NPPV. The NMA assumption is that individual trials enrol similar populations, and the intervention protocol is similar across different studies. We excluded studies in which more than half of the patients had cardiopulmonary edema or COPD, as reported in the previous NMA [8]. Second, there was a concern about the primary studies included in our review regarding the lack of blinding of the treatment groups. Although this was unlikely to bias the assessment of hard outcomes, it may have contributed to performance bias. Third, network RR was estimated using only indirect evidence in some comparisons. Specifically, few studies have compared HFNO with other interventions. Further studies are required to obtain a higher certainty of evidence. Finally, ranking results should be evaluated with caution because they do not consider the certainty of the evidence. Although NPPV seemed to be the best strategy considering ranking probabilities, this result dose not imply a significant clinical difference between NPPV and HFNO.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis NMA demonstrates that NPPV and HFNO were significantly associated with a lower incidence of pneumonia, compared to IMV, and NPPV but not HFNO was significantly associated with a lower incidence of pneumonia, compared to SOT. Our findings imply that NPPV and HFNO may be better strategies for the primary respiratory management of adult patients with AHRF to reduce pneumonia. Further studies are required to obtain a higher certainty of evidence, particularly with HFNO as a comparator.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAHRF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eacute hypoxemic respiratory failure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eARDS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eacute respiratory distress syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCOPD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003echronic obstructive pulmonary disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHFNO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehigh-flow nasal oxygen\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIMV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einvasive mechanical ventilation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNMA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enetwork meta-analysis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRandomized controlled trial\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003erisk ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSOT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003estandard oxygen therapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSUCRA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSurface under the cumulative ranking curve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVAP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eventilator-associated pneumonia.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor contributions:\u003c/h2\u003e \u003cp\u003eMS, SK, and SH designed the study, acquired data, performed statistical analyses, and interpreted the data. HO and TM conceived the study and acquired and interpreted the data. SK and SH conceived the acquisition of data. The first draft of the manuscript was written by SH, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003e We would thank all the members of the Japanese ARDS clinical practice guideline committee from the Japan Society for Respiratory Care and Rehabilitation, the Japanese Respiratory Society, and the Japanese Society of Intensive Care Medicine. 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Respiratory Invest 55:83\u0026ndash;92. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.resinv.2015.11.007\u003c/span\u003e\u003cspan address=\"10.1016/j.resinv.2015.11.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Niigata University Medical and Dental Hospital","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"acute hypoxemic respiratory failure, invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow nasal oxygen, pneumonia, network meta-analysis, ventilator-associated pneumonia","lastPublishedDoi":"10.21203/rs.3.rs-5069185/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5069185/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e In the current guidelines, the usage of non-invasive oxygenation strategies, such as non-invasive positive pressure ventilation (NPPV) and high-flow nasal oxygen (HFNO), for acute hypoxemic respiratory failure (AHRF) are unable to provide conclusive recommendations. We aimed to identify the most optimum respiratory management strategy reducing pneumonia in patients with AHRF.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe searched the four databases for eligible trials. Studies including adults with AHRF and randomized controlled trials comparing two different respiratory management methods (NPPV, HFNO, standard oxygen therapy [SOT], or invasive mechanical ventilation [IMV]) were reviewed. The primary outcome was the incidence of pneumonia. A network meta-analysis was performed a frequentist approach with a multivariate random-effects meta-analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e We identified 14,263 unique articles, reviewed 126 full-text articles, and finally included 13 studies. Using IMV as the reference, NPPV (risk ratio [RR], 0.23; 95% confidence interval [CI], 0.11–0.51; moderate certainty) and HFNO (RR, 0.24; 95% CI, 0.09–0.64; moderate certainty) were significantly associated with a lower incidence of pneumonia. Compared with SOT, NPPV (RR, 0.55; 95% CI, 0.35–0.84; moderate certainty) but not HFNO (RR, 0.55; 95% CI 0.27–1.13; low certainty) was significantly associated with a lower incidence of pneumonia. The probability of being the best in reducing the incidence of pneumonia among all interventions was higher for NPPV and HFNO, followed by SOT, whereas IMV was the worst.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Our findings imply that NPPV and HFNO may be the most effective strategies for primary respiratory management in adults with AHRF to reduce pneumonia.\u003c/p\u003e","manuscriptTitle":"Non-invasive Oxygenation Strategies for Reducing the Incidence of Pneumonia in Adult Patients with Acute Hypoxemic Respiratory Failure: A Systematic Review and Network Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-02 15:20:32","doi":"10.21203/rs.3.rs-5069185/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c56e81b1-f350-4442-88b3-93979c04c463","owner":[],"postedDate":"October 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":38325164,"name":"Pulmonology"}],"tags":[],"updatedAt":"2024-10-02T15:20:32+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-02 15:20:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5069185","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5069185","identity":"rs-5069185","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}