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      Corticosteroids for the prevention of ventilator-induced lung injury? Translated title: Corticosteroides para prevenir lesão pulmonar induzida por ventilação mecânica?

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          Abstract

          Numerous pharmacological therapies for acute respiratory distress syndrome (ARDS) have failed to demonstrate a benefit in multicenter clinical trials. 1 Given that dysregulated inflammation is a prominent feature of ARDS, systemic corticosteroids are thought to represent a potentially beneficial therapy. 2 Meta-analyses of the use of corticosteroid therapy in ARDS have yielded inconsistent conclusions. That is primarily because ARDS is a heterogeneous disease with various etiologies and clinical courses. Other factors include different outcome measures and the fact that patients are usually enrolled within 48 h after meeting the criteria for a diagnosis of ARDS, while already on mechanical ventilation, which could delay the initiation of treatment until several days after the onset of lung injury. 2 In this issue of the JBP, Reis et al. 3 publish a very well-designed experimental study that assessed the effects of dexamethasone pre-treatment on ventilator-induced lung injury (VILI), a well-recognized and important aspect of the physiopathology of ARDS. Experimental VILI was induced in Wistar rats by means of mechanical ventilation at a high tidal volume. The rats were divided into two groups according to the previous intraperitoneal administration of dexamethasone or saline at 30 min before VILI induction. The main result of the study was that dexamethasone administration was able to attenuate the inflammatory response caused by VILI, as measured by a histopathological lung injury score, by counting the leukocytes and neutrophils in the BAL fluid, and by assessing its impact on oxygenation at 4 h and 24 h after the initial insult (injurious ventilation). One drawback of the investigation is the lack of data on the molecular mechanisms involved in the dexamethasone-induced attenuation of experimental VILI. 4 Corticosteroids continue to be one of the most widely investigated pharmacological treatments for ARDS. One recent publication showed that short-term, low-dose corticosteroid therapy can have an impact on survival in aspiration-related ARDS. 5 It is plausible that the timing (either prophylactic or after the initial insult), the dose, and the duration of the therapy, as well as the etiology of the lung injury, are all important factors in determining the response of patients with ARDS to the administration of systemic corticosteroids. Future clinical trials must take all of these issues into account. The controversy regarding the possible benefits of this class of drugs in ARDS is therefore still "alive and kicking". The work of Reis et al. 3 generates even more interest in pharmacological approaches to prevent or treat VILI, especially in the role of corticosteroids in such injury, mainly as a preventive measure in patients at risk for ARDS.

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          Exploring the heterogeneity of effects of corticosteroids on acute respiratory distress syndrome: a systematic review and meta-analysis

          Introduction The effectiveness of corticosteroid therapy on the mortality of acute respiratory distress syndrome (ARDS) remains under debate. We aimed to explore the grounds for the inconsistent results in previous studies and update the evidence. Methods We searched MEDLINE, Cochrane Central Register of Controlled Trials and Web of Science up to December 2013. Eligible studies included randomized clinical trials (RCTs) and cohort studies that reported mortality and that had corticosteroid nonusers for comparison. The effect of corticosteroids on ARDS mortality was assessed by relative risk (RR) and risk difference (RD) for ICU, hospital, and 60-day mortality using a random-effects model. Results Eight RCTs and 10 cohort studies were included for analysis. In RCTs, corticosteroids had a possible but statistically insignificant effect on ICU mortality (RD, −0.28; 95% confidence interval (CI), −0.53 to −0.03 and RR, 0.55; 95% CI, 0.24 to 1.25) but no effect on 60-day mortality (RD, −0.01; 95% CI, −0.12 to 0.10 and RR, 0.97; 95% CI, 0.75 to 1.26). In cohort studies, corticosteroids had no effect on ICU mortality (RR, 1.05; 95% CI, 0.74 to 1.49) but non-significantly increased 60-day mortality (RR, 1.30; 95% CI, 0.96 to 1.78). In the subgroup analysis by ARDS etiology, corticosteroids significantly increased mortality in influenza-related ARDS (three cohort studies, RR, 2.45, 95% CI, 1.40 to 4.27). Conclusions The effects of corticosteroids on the mortality of ARDS differed by duration of outcome measures and etiologies. Corticosteroids did not improve longer-term outcomes and may cause harm in certain subgroups. Current data do not support routine use of corticosteroids in ARDS. More clinical trials are needed to specify the favorable and unfavorable subgroups for corticosteroid therapy.
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            Clinical review: Early treatment of acute lung injury - paradigm shift toward prevention and treatment prior to respiratory failure

            Acute lung injury (ALI) remains a major cause of morbidity and mortality in critically ill patients. Despite improved understanding of the pathogenesis of ALI, supportive care with a lung protective strategy of mechanical ventilation remains the only treatment with a proven survival advantage. Most clinical trials in ALI have targeted mechanically ventilated patients. Past trials of pharmacologic agents may have failed to demonstrate efficacy in part due to the resultant delay in initiation of therapy until several days after the onset of lung injury. Improved early identification of at-risk patients provides new opportunities for risk factor modification to prevent the development of ALI and novel patient groups to target for early treatment of ALI before progression to the need for mechanical ventilation. This review will discuss current strategies that target prevention of ALI and some of the most promising pharmacologic agents for early treatment of ALI prior to the onset of respiratory failure that requires mechanical ventilation.
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              Dexamethasone Attenuates VEGF Expression and Inflammation but Not Barrier Dysfunction in a Murine Model of Ventilator–Induced Lung Injury

              Background Ventilator–induced lung injury (VILI) is characterized by vascular leakage and inflammatory responses eventually leading to pulmonary dysfunction. Vascular endothelial growth factor (VEGF) has been proposed to be involved in the pathogenesis of VILI. This study examines the inhibitory effect of dexamethasone on VEGF expression, inflammation and alveolar–capillary barrier dysfunction in an established murine model of VILI. Methods Healthy male C57Bl/6 mice were anesthetized, tracheotomized and mechanically ventilated for 5 hours with an inspiratory pressure of 10 cmH2O (“lower” tidal volumes of ∼7.5 ml/kg; LVT) or 18 cmH2O (“higher” tidal volumes of ∼15 ml/kg; HVT). Dexamethasone was intravenously administered at the initiation of HVT–ventilation. Non–ventilated mice served as controls. Study endpoints included VEGF and inflammatory mediator expression in lung tissue, neutrophil and protein levels in bronchoalveolar lavage fluid, PaO2 to FiO2 ratios and lung wet to dry ratios. Results Particularly HVT–ventilation led to alveolar–capillary barrier dysfunction as reflected by reduced PaO2 to FiO2 ratios, elevated alveolar protein levels and increased lung wet to dry ratios. Moreover, VILI was associated with enhanced VEGF production, inflammatory mediator expression and neutrophil infiltration. Dexamethasone treatment inhibited VEGF and pro–inflammatory response in lungs of HVT–ventilated mice, without improving alveolar–capillary permeability, gas exchange and pulmonary edema formation. Conclusions Dexamethasone treatment completely abolishes ventilator–induced VEGF expression and inflammation. However, dexamethasone does not protect against alveolar–capillary barrier dysfunction in an established murine model of VILI.
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                Author and article information

                Journal
                J Bras Pneumol
                J Bras Pneumol
                jbpneu
                Jornal Brasileiro de Pneumologia
                Sociedade Brasileira de Pneumologia e Tisiologia
                1806-3713
                1806-3756
                May-Jun 2016
                May-Jun 2016
                : 42
                : 3
                : 163
                Affiliations
                [1 ]. Departamento de Medicina Clínica, Universidade Federal do Ceará, Fortaleza (CE) Brasil.
                Article
                10.1590/S1806-37562016000300001
                5569614
                27383925
                9d5f080a-ad10-4baa-bd26-f9dcc1e13301

                This is an open-access article distributed under the terms of the Creative Commons Attribution License

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