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      Effect of Renin-Angiotensin System Blockage in Patients with Acute Respiratory Distress Syndrome: A Retrospective Case Control Study

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          Abstract

          Background

          Acute respiratory distress syndrome (ARDS) remains a life-threatening disease. Many patients with ARDS do not recover fully, and progress to terminal lung fibrosis. Angiotensin-converting enzyme (ACE) inhibitor is known to modulate the neurohormonal system to reduce inflammation and to prevent tissue fibrosis. However, the role of ACE inhibitor in the lungs is not well understood. We therefore conducted this study to elucidate the effect of renin-angiotensin system (RAS) blockage on the prognosis of patients with ARDS.

          Methods

          We analyzed medical records of patients who were admitted to the medical intensive care unit (ICU) at a tertiary care hospital from January 2005 to December 2010. ARDS was determined using the Berlin definition. The primary outcome was the mortality rate of ICU. Survival analysis was performed after adjustment using propensity score matching.

          Results

          A total of 182 patients were included in the study. Thirty-seven patients (20.3%) took ACE inhibitor or angiotensin receptor blocker (ARB) during ICU admission, and 145 (79.7%) did not; both groups showed similar severity scores. In the ICU, mortality was 45.9% in the RAS inhibitor group and 58.6% in the non-RAS inhibitor group (P = 0.166). The RAS inhibitor group required a longer duration of mechanical ventilation (29.5 vs. 19.5, P = 0.013) and longer ICU stay (32.1 vs. 20.2 days, P < 0.001). In survival analysis, the RAS inhibitor group showed better survival rates than the non-RAS group (P < 0.001).

          Conclusions

          ACE inhibitor or ARB may have beneficial effect on ARDS patients.

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          Most cited references38

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          Has mortality from acute respiratory distress syndrome decreased over time?: A systematic review.

          Jason Phua, Joan Badia, Neill K. J. Adhikari … (2009)
          It is commonly stated that mortality from acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) is decreasing. To systematically review the literature assessing ARDS mortality over time and to determine patient- and study-level factors independently associated with mortality. We searched multiple databases (MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL) for prospective observational studies or randomized controlled trials (RCTs) published during the period 1984 to 2006 that enrolled 50 or more patients with ALI/ARDS and reported mortality. We pooled mortality estimates using random-effects meta-analysis and examined mortality trends before and after 1994 (when a consensus definition of ALI/ARDS was published) and factors associated with mortality using meta-regression models. Of 4,966 studies, 89 met inclusion criteria (53 observational, 36 RCTs). There was a total of 18,900 patients (mean age 51.6 years; 39% female). Overall pooled weighted mortality was 44.3% (95% confidence interval [CI], 41.8-46.9). Mortality decreased with time in observational studies conducted before 1994; no temporal associations with mortality were demonstrated in RCTs (any time) or observational studies (after 1994). Pooled mortality from 1994 to 2006 was 44.0% (95% CI, 40.1-47.5) for observational studies, and 36.2% (95% CI, 32.1-40.5) for RCTs. Meta-regression identified study type (observational versus RCT, odds ratio, 1.36; 95% CI, 1.08-1.73) and patient age (odds ratio per additional 10 yr, 1.27; 95% CI, 1.07-1.50) as the only factors associated with mortality. A decrease in ARDS mortality was only seen in observational studies from 1984 to 1993. Mortality did not decrease between 1994 (when a consensus definition was published) and 2006, and is lower in RCTs than observational studies.
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            Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time.

            G Köhler, E. Tolley, K Leeper … (1995)
            Inflammatory cytokines have been related to the development of adult respiratory distress syndrome (ARDS), shock, and multiple organ dysfunction syndrome (MODS). We tested the hypothesis that unfavorable outcome in patients with ARDS is related to the presence of a persistent inflammatory response. For this purpose, we evaluated the behavior of inflammatory cytokines during progression of ARDS and the relationship of plasma inflammatory cytokines with clinical variables and outcome. We prospectively studied 27 consecutive patients with severe medical ARDS. Plasma levels of tumor necrosis factor alpha (TNF-alpha) and interleukins (ILs) 1 beta, 2, 4, 6, and 8 were measured (enzyme-linked immunosorbent assay [ELISA] method) on days 1, 2, 3, 5, 7, 10, and 12 of ARDS and every third day thereafter while patients were receiving mechanical ventilation. Subgroups of patients were identified based on outcome, cause of ARDS, presence or absence of sepsis, shock, and MODS at the time ARDS developed. Subgroups were compared for levels of plasma inflammatory cytokines on day 1 of ARDS and over time. Of the 27 patients, 13 survived ICU admission and 14 died (a mortality rate of 52%). Overall mortality was higher in patients with sepsis (86 vs 38%, p 200 pg/mL lost its usefulness after the first 48 h. A plasma IL-1 beta or IL-6 level > 400 pg/mL on any day in the first week of ARDS was associated with a low likelihood of survival. Our findings indicate that unfavorable outcome in acute lung injury is related to the degree of inflammatory response at the onset and during the course of ARDS. Patients with higher plasma levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 on day 1 of ARDS had persistent elevation of these inflammatory cytokines over time and died. Survivors had lesser elevations of plasma inflammatory cytokines on day 1 of ARDS and a rapid reduction over time. Plasma IL-1 beta and IL-6 levels were consistent and efficient predictors of outcome.
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              The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance.

              G Downey, Marc Moss, David Riches … (2013)
              Acute respiratory distress syndrome (ARDS) continues to be a major healthcare problem, affecting >190,000 people in the USA annually, with a mortality of 27-45%, depending on the severity of the illness and comorbidities. Despite advances in clinical care, particularly lung protective strategies of mechanical ventilation, most survivors experience impaired health-related quality of life for years after the acute illness. While most patients survive the acute illness, a subset of ARDS survivors develops a fibroproliferative response characterised by fibroblast accumulation and deposition of collagen and other extracellular matrix components in the lung. Historically, the development of severe fibroproliferative lung disease has been associated with a poor prognosis with high mortality and/or prolonged ventilator dependence. More recent studies also support a relationship between the magnitude of the fibroproliferative response and long-term health-related quality of life. The factors that determine which patients develop fibroproliferative ARDS and the cellular mechanisms responsible for this pathological response are not well understood. This article reviews our current understanding of the contribution of pulmonary dysfunction to mortality and to quality of life in survivors of ARDS, the mechanisms driving pathological fibroproliferation and potential therapeutic approaches to prevent or attenuate fibroproliferative lung disease.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Korean J Crit Care Med
                Journal ID (iso-abbrev): Korean J Crit Care Med
                Journal ID (publisher-id): KJCCM
                Title: Korean Journal of Critical Care Medicine
                Publisher: Korean Society of Critical Care Medicine
                ISSN (Print): 2383-4870
                ISSN (Electronic): 2383-4889
                Publication date (Print): May 2017
                Publication date (Electronic): 31 May 2017
                Volume: 32
                Issue: 2
                Pages: 154-163
                Affiliations
                [1 ]Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
                [2 ]Seoul National University Hospital and Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
                Author notes
                Correspondence to: Sang-Min Lee, Seoul National University Hospital and Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-0833, Fax: +82-2-762-9662, E-mail: sangmin2@ 123456snu.ac.kr
                Author information
                http://orcid.org/0000-0002-1461-4850
                http://orcid.org/0000-0002-1388-9318
                Article
                Publisher ID: kjccm-2016-00976
                DOI: 10.4266/kjccm.2016.00976
                PMC ID: 6786717
                SO-VID: 35ffb3ac-934e-45be-b66e-a8a7723c11fc
                Copyright © Copyright © 2017 The Korean Society of Critical Care Medicine
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 3 December 2016
                Date revision received : 15 May 2017
                Date accepted : 15 May 2017
                Categories
                Subject: Original Article

                Keywords: acute respiratory distress syndrome,angiotensin-converting enzyme inhibitors,angiotensin receptor antagonists,mortality,renin-angiotensin system
                Data availability:
                Keywords: acute respiratory distress syndrome, angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, mortality, renin-angiotensin system

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