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Optimal plateau pressure for patients with acute respiratory distress syndrome: a protocol for a systematic review and meta-analysis with meta-regression.

ABSTRACT: INTRODUCTION:Lower tidal volume ventilation in patients with acute respiratory distress syndrome (ARDS) is a strategy to reduce the plateau pressure and driving pressure to limit ventilator-induced lung injury (VILI). Several randomised controlled trials (RCTs) and meta-analyses showed that limiting both the plateau pressure and the tidal volume decreased mortality, but the optimal plateau pressure to demonstrate a benefit is uncertain. The aim of this systematic review is to investigate the optimal upper limit of plateau pressure in patients with ARDS to prevent VILI and improve clinical outcomes using meta-analysis with and without meta-regression. METHODS AND ANALYSIS:RCTs comparing two mechanical ventilation strategies will be included, with lower plateau pressure and with higher plateau pressure, among patients with ARDS and acute lung injury. Data sources include MEDLINE via the NCBI Entrez system, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and Ichushi, a database of papers in Japanese. Two of three physicians will independently screen trials obtained by search for eligibility, and extract data from included studies onto standardised data recording forms. For each included trial, the risk of bias and the quality of evidence will be evaluated using the Grading of Recommendation Assessment Development and Evaluation system. ETHICS AND DISSEMINATION:This study does not require ethical approval. The results of this systematic review and meta-analysis with and without meta-regression will be disseminated through conference presentation and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER:CRD42016041924.

SUBMITTER: Yasuda H

PROVIDER: S-EPMC5730008 | biostudies-other | 2017 May

REPOSITORIES: biostudies-other

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Optimal plateau pressure for patients with acute respiratory distress syndrome: a protocol for a systematic review and meta-analysis with meta-regression.

Yasuda Hideto H Nishimura Tetsuro T Kamo Tetsuro T Sanui Masamitsu M Nango Eishu E Abe Takayuki T Takebayashi Toru T Lefor Alan Kawarai AK Hashimoto Satoru S

BMJ open 20170529 5

<h4>Introduction</h4>Lower tidal volume ventilation in patients with acute respiratory distress syndrome (ARDS) is a strategy to reduce the plateau pressure and driving pressure to limit ventilator-induced lung injury (VILI). Several randomised controlled trials (RCTs) and meta-analyses showed that limiting both the plateau pressure and the tidal volume decreased mortality, but the optimal plateau pressure to demonstrate a benefit is uncertain. The aim of this systematic review is to investigate ...[more]

PMID: 28554924

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Project description:BackgroundThe effects of plateau pressure during the initial days of mechanical ventilation on outcomes for patients with acute respiratory distress syndrome have not been fully examined. We conducted meta-regression analysis of plateau pressure during the first 7 days using randomized control trials to investigate the optimal upper limits of plateau pressure on different days of mechanical ventilation.MethodsRandomized controlled trials comparing two mechanical ventilation strategies with lower and higher plateau pressures in patients with acute respiratory distress syndrome were included. Meta-regression analysis was performed to determine the association of plateau pressure with mortality on days 1, 3, and 7 of mechanical ventilation.ResultsAfter evaluation of 2,975 citations from a comprehensive search across electronic databases, 14 studies were included in the final qualitative analysis. A total of 4,984 patients were included in the quantitative analysis. As a result of the pairwise comparison, overall short-term mortality was significantly higher for patients with plateau pressures over 32 cm H2O during the first 3 days after intensive care unit (ICU) admission (day 1: relative risk (RR), 0.77; 95% confidence interval (CI), 0.66 - 0.89; I2 = 0%; day 3: RR, 0.76; 95% CI, 0.64 - 0.90; I2 = 0%), but not on day 7 (RR, 0.82; 95% CI, 0.65 - 1.04; I2 = 16%). Plateau pressures below 27 cm H2O and 30 cm H2O were not associated with an absolute risk reduction of short-term mortality. According to univariable meta-regression analysis, mortality was significantly associated with plateau pressure on day 1 (β = 0.01 (95% CI, 0.002 - 0.024), P = 0.02). On days 3 and 7, however, no significant difference was detected. When the cutoffs were set at 27, 30 and 32 cm H2O on day 1, which showed a significant difference, plateau pressure tended to be associated with increased mortality at pressures above the cut-off values, and there were no significant differences at pressures below the cut-off values, regardless of the cutoff used.ConclusionsThis study suggests that the optimal cut-off value for plateau pressure may be 27 cm H2O especially during the initial period of mechanical ventilation, although this association may not continue during the latter period of mechanical ventilation.

Project description:IntroductionSeveral systematic reviews and meta-analyses have demonstrated that prolonged (≥16 hours) prone positioning can reduce the mortality associated with acute respiratory distress syndrome (ARDS). However, the effectiveness and optimal duration of prone positioning was not fully evaluated. To fill these gaps, we will first investigate the effectiveness of prone positioning compared with the conventional management of patients with ARDS, regarding outcomes using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Second, if statistical heterogeneity in effectiveness with regard to short-term mortality (intensive care unit death or ≤30-day mortality) is shown, we will conduct a meta-regression analysis to explore the association between duration and effectiveness, and determine the optimal duration of prone positioning.Method and analysisRelevant studies are collected using PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials and the WHO International Clinical Trials Platform Search Portal. Randomised controlled trials comparing prone and supine positioning in adults with ARDS will be included in the meta-analysis. Two independent investigators will screen trials obtained by search eligibility and extract data from selected studies to standardised data recording forms. For each selected trial, the risk of bias and quality of evidence will be evaluated using the GRADE system. Meta-regression analyses will be performed to identify the most important factors associated with short-term mortality, and subgroup analysis will be used to analyse the following: duration of mechanical ventilation in the prone position per day, patient severity, tidal volume and cause of ARDS. If heterogeneity or inconsistency among the studies is detected, subgroup analysis will be conducted on factors that may cause heterogeneity.Ethics and disseminationThis study requires no ethical approval. The results obtained from this systematic review and meta-analysis will be disseminated through international conference presentations and publication in a peer-reviewed journal.Prospero registration numberCRD42017078340.

Project description:ObjectiveTo determine whether neuromuscular blocking agents (NMBAs) can decrease the mortality of patients with acute respiratory distress syndrome (ARDS) and improve their clinical outcomes.DesignSystematic review, meta-analysis and meta-regression.Data sourcesPubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov.MethodsRandomised controlled trials (RCTs) comparing the treatment effect of NMBAs with that of placebo (or traditional treatment) in patients with ARDS were carefully selected. The primary outcome was 90-day mortality. The secondary outcomes were 21-28 days mortality, NMBA-related complications (barotrauma, pneumothorax and intensive care unit (ICU)-acquired muscle weakness), days free of ventilation and days not in the ICU by day 28, Medical Research Council score, Acute Physiology and Chronic Health Evaluation II score and arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) (at 48 hours and 72 hours). Random-effects meta-regression was used to explore models involving potential moderators. Trial sequential analysis was performed to estimate the cumulative effect on mortality across RCTs.ResultsNMBAs were not associated with reduced 90-day mortality (risk ratio (RR) 0.85; 95% CI 0.66 to 1.09; p=0.20). However, they decreased the 21-28 days mortality (RR 0.71; 95% CI 0.53 to 0.96; p=0.02) and the rates of pneumothorax (RR 0.46; 95% CI 0.28 to 0.77; p=0.003) and barotrauma (RR 0.56; 95% CI 0.37 to 0.86; p=0.008). In addition, NMBAs increased PaO2/FiO2 at 48 hours (mean difference (MD) 18.91; 95% CI 4.29 to 33.53; p=0.01) and 72 hours (MD 12.27; 95% CI 4.65 to 19.89; p=0.002). Meta-regression revealed an association between sample size (p=0.042) and short-term mortality. Publication year (p=0.050), sedation strategy (p=0.047) and sample size (p=0.046) were independently associated with PaO2/FiO2 at 48 hours.ConclusionsIn summary, the results suggested that use of NMBAs might reduce 21-28 days mortality, NMBA-related complications and oxygenation. However, NMBAs did not reduce the 90-day mortality of patients with ARDS, which contradicts a previous meta-analysis.Prospero registration numberCRD42019139440.

Project description:Subphenotypes were recently reported within clinical acute respiratory distress syndrome (ARDS), with distinct outcomes and therapeutic responses. Experimental models have long been used to mimic features of ARDS pathophysiology, but the presence of distinct subphenotypes among preclinical ARDS remains unknown. This review will investigate whether: 1) subphenotypes can be identified among preclinical ARDS models; 2) such subphenotypes can identify some responsive traits. We will include comparative preclinical (in vivo and ex vivo) ARDS studies published between 2009 and 2019 in which pre-specified therapies were assessed (interleukin (IL)-10, IL-2, stem cells, beta-agonists, corticosteroids, fibroblast growth factors, modulators of the receptor for advanced glycation end-products pathway, anticoagulants, and halogenated agents) and outcomes compared to a control condition. The primary outcome will be a composite of the four key features of preclinical ARDS as per the American Thoracic Society consensus conference (histologic evidence of lung injury, altered alveolar-capillary barrier, lung inflammatory response, and physiological dysfunction). Secondary outcomes will include the single components of the primary composite outcome, net alveolar fluid clearance, and death. MEDLINE, Embase, and Cochrane databases will be searched electronically and data from eligible studies will be extracted, pooled, and analyzed using random-effects models. Individual study reporting will be assessed according to the Animal Research: Reporting of In Vivo Experiments guidelines. Meta-regressions will be performed to identify subphenotypes prior to comparing outcomes across subphenotypes and treatment effects. This study will inform on the presence and underlying pathophysiological features of subphenotypes among preclinical models of ARDS and should help to determine whether sufficient evidence exists to perform preclinical trials of subphenotype-targeted therapies, prior to potential clinical translation. PROSPERO (ID: CRD42019157236).

Project description:PURPOSE:Recruitment of lung volume is often cited as the reason for using positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS) patients. We performed a systematic review on PEEP-induced recruited lung volume measured from inspiratory volume-pressure (VP) curves in ARDS patients to assess the prevalence of patients with PEEP-induced recruited lung volume and the mortality in recruiters and non-recruiters. METHODS:We conducted a systematic search of PubMed to identify studies including ARDS patients in which the intervention of an increase in PEEP was accompanied by measurement of the recruited volume (Vrec increase versus no increase) using the VP curve in order to assess the relation between Vrec and mortality at ICU discharge. We first analysed the pooled data from the papers identified and then analysed individual patient level data received from the authors via personal contact. The risk of bias of the included papers was assessed using the quality in prognosis studies tool and the certainty of the evidence regarding the relationship of mortality to Vrec by the GRADE approach. Recruiters were defined as patients with a Vrec?>?150 ml. A random effects model was used for the pooled data. Multivariable logistic regression analysis was used for individual patient data. RESULTS:We identified 16 papers with a total of 308 patients for the pooled data meta-analysis and 14 papers with a total of 384 patients for the individual data analysis. The quality of the articles was moderate. In the pooled data, the prevalence of recruiters was 74% and the mortality was not significantly different between recruiters and non-recruiters (relative risk 1.20 [95% confidence intervals 0.88-1.63]). The certainty of the evidence regarding this association was very low and publication bias evident. In the individual data, the prevalence of recruiters was 70%. In the multivariable logistic regression, Vrec was not associated with mortality but Simplified Acute Physiology Score II and driving pressure at PEEP of 5 cmH2O were. CONCLUSION:After a PEEP increment, most patients are recruiters. Vrec was not associated with ICU mortality. The presence of similar findings in the individual patient level analysis and the driving pressure at PEEP of 5 cmH2O was associated with mortality as previously reported validate our findings. Publication bias and the lack of prospective studies suggest more research is required.

Project description:BackgroundWith the development of new techniques to easily obtain lower respiratory tract specimens, bronchoalveolar lavage fluid and other lung fluids are gaining importance in pulmonary disease diagnosis. We aimed to review and summarize lung fluid biomarkers associated with acute respiratory distress syndrome diagnosis and mortality.MethodsAfter searching PubMed, Embase, Web of Science, and the Cochrane Library for articles published prior to January 11, 2018, we performed a meta-analysis on biomarkers for acute respiratory distress syndrome diagnosis in at-risk patients and those related to disease mortality. From the included studies, we then extracted the mean and standard deviation of the biomarker concentrations measured in the lung fluid, acute respiratory distress syndrome etiologies, sample size, demographic variables, diagnostic criteria, mortality, and protocol for obtaining the lung fluid. The effect size was measured by the ratio of means, which was then synthesized by the inverse-variance method using its natural logarithm form and transformed to obtain a pooled ratio and 95% confidence interval.ResultsIn total, 1156 articles were identified, and 49 studies were included. Increases in total phospholipases A2 activity, total protein, albumin, plasminogen activator inhibitor-1, soluble receptor for advanced glycation end products, and platelet activating factor-acetyl choline were most strongly associated with acute respiratory distress syndrome diagnosis. As for biomarkers associated with acute respiratory distress syndrome mortality, interleukin-1?, interleukin-6, interleukin-8, Kerbs von Lungren-6, and plasminogen activator inhibitor-1 were significantly increased in the lung fluid of patients who died. Decreased levels of Club cell protein and matrix metalloproteinases-9 were associated with increased odds for acute respiratory distress syndrome diagnosis, whereas decreased levels of Club cell protein and interleukin-2 were associated with increased odds for acute respiratory distress syndrome mortality.ConclusionsThis meta-analysis provides a ranking system for lung fluid biomarkers, according to their association with diagnosis or mortality of acute respiratory distress syndrome. The performance of biomarkers among studies shown in this article may help to improve acute respiratory distress syndrome diagnosis and outcome prediction.

Dataset Information

Optimal plateau pressure for patients with acute respiratory distress syndrome: a protocol for a systematic review and meta-analysis with meta-regression.

Publications

Optimal plateau pressure for patients with acute respiratory distress syndrome: a protocol for a systematic review and meta-analysis with meta-regression.

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