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Renin-angiotensin-system, a potential pharmacological candidate, in acute respiratory distress syndrome during mechanical ventilation.

ABSTRACT: While effective treatments for acute respiratory distress syndrome (ARDS) are lacking, mechanical lung ventilation can sustain adequate gas exchange in critically ill patients with respiratory failure due to ARDS. However, as a result of the phenomenon of ventilator-induced lung injury (VILI), there is an increasing need to seek beneficial pharmacological therapies for ARDS. Recent studies have suggested the renin-angiotensin system (RAS), which consists of the ACE/Ang-II/AT1R axis and ACE2/Ang-(1-7)/MasR axis, plays a dual role in the pathogenesis of ARDS and VILI. This review highlights the deleterious action of ACE/Ang-II/AT1R axis and the beneficial role of ACE2/Ang-(1-7)/MasR axis, as well as AT2R, in VILI and ARDS, and also discusses the possibility of targeting RAS components with pharmacological interventions to improve outcomes in ARDS.

SUBMITTER: Wang D

PROVIDER: S-EPMC7110665 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Renin-angiotensin-system, a potential pharmacological candidate, in acute respiratory distress syndrome during mechanical ventilation.

Wang Di D Chai Xiao-Qing XQ Magnussen Costan G CG Zosky Graeme R GR Shu Shu-Hua SH Wei Xin X Hu Shan-Shan SS

Pulmonary pharmacology & therapeutics 20190801

While effective treatments for acute respiratory distress syndrome (ARDS) are lacking, mechanical lung ventilation can sustain adequate gas exchange in critically ill patients with respiratory failure due to ARDS. However, as a result of the phenomenon of ventilator-induced lung injury (VILI), there is an increasing need to seek beneficial pharmacological therapies for ARDS. Recent studies have suggested the renin-angiotensin system (RAS), which consists of the ACE/Ang-II/AT1R axis and ACE2/Ang- ...[more]

PMID: 31376462

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Project description:BackgroundRecruitment manoeuvres involve transient elevations in airway pressure applied during mechanical ventilation to open ('recruit') collapsed lung units and increase the number of alveoli participating in tidal ventilation. Recruitment manoeuvres are often used to treat patients in intensive care who have acute respiratory distress syndrome (ARDS), but the effect of this treatment on clinical outcomes has not been well established. This systematic review is an update of a Cochrane review originally published in 2009.ObjectivesOur primary objective was to determine the effects of recruitment manoeuvres on mortality in adults with acute respiratory distress syndrome.Our secondary objective was to determine, in the same population, the effects of recruitment manoeuvres on oxygenation and adverse events (e.g. rate of barotrauma).Search methodsFor this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), Embase (OVID), the Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCO), Latin American and Caribbean Health Sciences (LILACS) and the International Standard Randomized Controlled Trial Number (ISRCTN) registry from inception to August 2016.Selection criteriaWe included randomized controlled trials (RCTs) of adults who were mechanically ventilated that compared recruitment manoeuvres versus standard care for patients given a diagnosis of ARDS.Data collection and analysisTwo review authors independently assessed trial quality and extracted data. We contacted study authors for additional information.Main resultsTen trials met the inclusion criteria for this review (n = 1658 participants). We found five trials to be at low risk of bias and five to be at moderate risk of bias. Six of the trials included recruitment manoeuvres as part of an open lung ventilation strategy that was different from control ventilation in aspects other than the recruitment manoeuvre (such as mode of ventilation, higher positive end-expiratory pressure (PEEP) titration and lower tidal volume or plateau pressure). Six studies reported mortality outcomes. Pooled data from five trials (1370 participants) showed a reduction in intensive care unit (ICU) mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.72 to 0.97, P = 0.02, low-quality evidence), pooled data from five trials (1450 participants) showed no difference in 28-day mortality (RR 0.86, 95% CI 0.74 to 1.01, P = 0.06, low-quality evidence) and pooled data from four trials (1313 participants) showed no difference in in-hospital mortality (RR 0.88, 95% CI 0.77 to 1.01, P = 0.07, low-quality evidence). Data revealed no differences in risk of barotrauma (RR 1.09, 95% CI 0.78 to 1.53, P = 0.60, seven studies, 1508 participants, moderate-quality evidence).Authors' conclusionsWe identified significant clinical heterogeneity in the 10 included trials. Results are based upon the findings of several (five) trials that included an "open lung ventilation strategy", whereby the intervention group differed from the control group in aspects other than the recruitment manoeuvre (including co-interventions such as higher PEEP, different modes of ventilation and higher plateau pressure), making interpretation of the results difficult. A ventilation strategy that included recruitment manoeuvres in participants with ARDS reduced intensive care unit mortality without increasing the risk of barotrauma but had no effect on 28-day and hospital mortality. We downgraded the quality of the evidence to low, as most of the included trials provided co-interventions as part of an open lung ventilation strategy, and this might have influenced results of the outcome.

Project description:To determine the frequency of low-tidal volume ventilation in pediatric acute respiratory distress syndrome and assess if any demographic or clinical factors improve low-tidal volume ventilation adherence.Descriptive post hoc analysis of four multicenter pediatric acute respiratory distress syndrome studies.Twenty-six academic PICU.Three hundred fifteen pediatric acute respiratory distress syndrome patients.All patients who received conventional mechanical ventilation at hours 0 and 24 of pediatric acute respiratory distress syndrome who had data to calculate ideal body weight were included. Two cutoff points for low-tidal volume ventilation were assessed: less than or equal to 6.5?mL/kg of ideal body weight and less than or equal to 8?mL/kg of ideal body weight. Of 555 patients, we excluded 240 for other respiratory support modes or missing data. The remaining 315 patients had a median PaO2-to-FIO2 ratio of 140 (interquartile range, 90-201), and there were no differences in demographics between those who did and did not receive low-tidal volume ventilation. With tidal volume cutoff of less than or equal to 6.5?mL/kg of ideal body weight, the adherence rate was 32% at hour 0 and 33% at hour 24. A low-tidal volume ventilation cutoff of tidal volume less than or equal to 8?mL/kg of ideal body weight resulted in an adherence rate of 58% at hour 0 and 60% at hour 24. Low-tidal volume ventilation use was no different by severity of pediatric acute respiratory distress syndrome nor did adherence improve over time. At hour 0, overweight children were less likely to receive low-tidal volume ventilation less than or equal to 6.5?mL/kg ideal body weight (11% overweight vs 38% nonoverweight; p = 0.02); no difference was noted by hour 24. Furthermore, in the overweight group, using admission weight instead of ideal body weight resulted in misclassification of up to 14% of patients as receiving low-tidal volume ventilation when they actually were not.Low-tidal volume ventilation is underused in the first 24 hours of pediatric acute respiratory distress syndrome. Age, Pediatric Risk of Mortality-III, and pediatric acute respiratory distress syndrome severity were not associated with improved low-tidal volume ventilation adherence nor did adherence improve over time. Overweight children were less likely to receive low-tidal volume ventilation strategies in the first day of illness.

Project description:ObjectivesBlood products are often transfused in critically ill children, although recent studies have recognized their potential for harm. Translatability to pediatric acute respiratory distress syndrome is unknown given that hypoxemia has excluded pediatric acute respiratory distress syndrome patients from clinical trials. We aimed to determine whether an association exists between blood product transfusion and survival or duration of ventilation in pediatric acute respiratory distress syndrome.DesignRetrospective analysis of prospectively enrolled cohort.SettingLarge, academic PICU.PatientsInvasively ventilated children meeting Berlin Acute Respiratory Distress Syndrome and Pediatric Acute Lung Injury Consensus Conference Pediatric Acute Respiratory Distress Syndrome criteria from 2011 to 2015.InterventionsWe recorded transfusion of RBC, fresh frozen plasma, and platelets within the first 3 days of pediatric acute respiratory distress syndrome onset. Each product was tested for independent association with survival (Cox) and duration of mechanical ventilation (competing risk regression with extubation as primary outcome and death as competing risk). A sensitivity analysis using 1:1 propensity matching was also performed.Measurements and main resultsOf 357 pediatric acute respiratory distress syndrome patients, 155 (43%) received RBC, 82 (23%) received fresh frozen plasma, and 92 (26%) received platelets. Patients who received RBC, fresh frozen plasma, or platelets had higher severity of illness score, lower PaO2/FIO2, and were more often immunocompromised (all p < 0.05). Patients who received RBC, fresh frozen plasma, or platelets had worse survival and longer duration of ventilation by univariate analysis (all p < 0.05). After multivariate adjustment for above confounders, no blood product was associated with survival. After adjustment for the same confounders, RBC were associated with decreased probability of extubation (subdistribution hazard ratio, 0.65; 95% CI, 0.51-0.83). The association between RBC and prolonged ventilation was confirmed in propensity-matched subgroup analysis.ConclusionsRBC transfusion was independently associated with longer duration of mechanical ventilation in pediatric acute respiratory distress syndrome. Hemoglobin transfusion thresholds should be tested specifically within pediatric acute respiratory distress syndrome to establish whether a more restrictive transfusion strategy would improve outcomes.

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Renin-angiotensin-system, a potential pharmacological candidate, in acute respiratory distress syndrome during mechanical ventilation.

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Renin-angiotensin-system, a potential pharmacological candidate, in acute respiratory distress syndrome during mechanical ventilation.

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