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      Extracorporeal carbon dioxide removal for patients with acute respiratory failure secondary to the acute respiratory distress syndrome: a systematic review

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          Abstract

          Acute respiratory distress syndrome (ARDS) continues to have significant mortality and morbidity. The only intervention proven to reduce mortality is the use of lung-protective mechanical ventilation strategies, although such a strategy may lead to problematic hypercapnia. Extracorporeal carbon dioxide removal (ECCO 2R) devices allow uncoupling of ventilation from oxygenation, thereby removing carbon dioxide and facilitating lower tidal volume ventilation. We performed a systematic review to assess efficacy, complication rates, and utility of ECCO 2R devices. We included randomised controlled trials (RCTs), case–control studies and case series with 10 or more patients. We searched MEDLINE, Embase, LILACS (Literatura Latino Americana em Ciências da Saúde), and ISI Web of Science, in addition to grey literature and clinical trials registries. Data were independently extracted by two reviewers against predefined criteria and agreement was reached by consensus. Outcomes of interest included mortality, intensive care and hospital lengths of stay, respiratory parameters and complications. The review included 14 studies with 495 patients (two RCTs and 12 observational studies). Arteriovenous ECCO 2R was used in seven studies, and venovenous ECCO 2R in seven studies. Available evidence suggests no mortality benefit to ECCO 2R, although post hoc analysis of data from the most recent RCT showed an improvement in ventilator-free days in more severe ARDS. Organ failure-free days or ICU stay have not been shown to decrease with ECCO 2R. Carbon dioxide removal was widely demonstrated as feasible, facilitating the use of lower tidal volume ventilation. Complication rates varied greatly across the included studies, representing technological advances. There was a general paucity of high-quality data and significant variation in both practice and technology used among studies, which confounded analysis. ECCO 2R is a rapidly evolving technology and is an efficacious treatment to enable protective lung ventilation. Evidence for a positive effect on mortality and other important clinical outcomes is lacking. Rapid technological advances have led to major changes in these devices and together with variation in study design have limited applicability of analysis. Further well-designed adequately powered RCTs are needed.

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          Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial.

          Studies have shown that an inflammatory response may be elicited by mechanical ventilation used for recruitment or derecruitment of collapsed lung units or to overdistend alveolar regions, and that a lung-protective strategy may reduce this response. To test the hypothesis that mechanical ventilation induces a pulmonary and systemic cytokine response that can be minimized by limiting recruitment or derecruitment and overdistention. Randomized controlled trial in the intensive care units of 2 European hospitals from November 1995 to February 1998, with a 28-day follow-up. Forty-four patients (mean [SD] age, 50 [18] years) with acute respiratory distress syndrome were enrolled, 7 of whom were withdrawn due to adverse events. After admission, volume-pressure curves were measured and bronchoalveolar lavage and blood samples were obtained. Patients were randomized to either the control group (n = 19): tidal volume to obtain normal values of arterial carbon dioxide tension (35-40 mm Hg) and positive end-expiratory pressure (PEEP) producing the greatest improvement in arterial oxygen saturation without worsening hemodynamics; or the lung-protective strategy group (n = 18): tidal volume and PEEP based on the volume-pressure curve. Measurements were repeated 24 to 30 and 36 to 40 hours after randomization. Pulmonary and systemic concentrations of inflammatory mediators approximately 36 hours after randomization. Physiological characteristics and cytokine concentrations were similar in both groups at randomization. There were significant differences (mean [SD]) between the control and lung-protective strategy groups in tidal volume (11.1 [1.3] vs 7.6 [1.1] mL/kg), end-inspiratory plateau pressures (31.0 [4.5] vs 24.6 [2.4] cm H2O), and PEEP (6.5 [1.7] vs 14.8 [2.7] cm H2O) (P<.001). Patients in the control group had an increase in bronchoalveolar lavage concentrations of interleukin (IL) 1beta, IL-6, and IL-1 receptor agonist and in both bronchoalveolar lavage and plasma concentrations of tumor necrosis factor (TNF) alpha, IL-6, and TNF-alpha, receptors over 36 hours (P<.05 for all). Patients in the lung-protective strategy group had a reduction in bronchoalveolar lavage concentrations of polymorphonuclear cells, TNF-alpha, IL-1beta, soluble TNF-alpha receptor 55, and IL-8, and in plasma and bronchoalveolar lavage concentrations of IL-6, soluble TNF-alpha receptor 75, and IL-1 receptor antagonist (P<.05). The concentration of the inflammatory mediators 36 hours after randomization was significantly lower in the lung-protective strategy group than in the control group (P<.05). Mechanical ventilation can induce a cytokine response that may be attenuated by a strategy to minimize overdistention and recruitment/derecruitment of the lung. Whether these physiological improvements are associated with improvements in clinical end points should be determined in future studies.
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            A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial.

            Standard treatment of critically ill patients undergoing mechanical ventilation is continuous sedation. Daily interruption of sedation has a beneficial effect, and in the general intesive care unit of Odense University Hospital, Denmark, standard practice is a protocol of no sedation. We aimed to establish whether duration of mechanical ventilation could be reduced with a protocol of no sedation versus daily interruption of sedation. Of 428 patients assessed for eligibility, we enrolled 140 critically ill adult patients who were undergoing mechanical ventilation and were expected to need ventilation for more than 24 h. Patients were randomly assigned in a 1:1 ratio (unblinded) to receive: no sedation (n=70 patients); or sedation (20 mg/mL propofol for 48 h, 1 mg/mL midazolam thereafter) with daily interruption until awake (n=70, control group). Both groups were treated with bolus doses of morphine (2.5 or 5 mg). The primary outcome was the number of days without mechanical ventilation in a 28-day period, and we also recorded the length of stay in the intensive care unit (from admission to 28 days) and in hospital (from admission to 90 days). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00466492. 27 patients died or were successfully extubated within 48 h, and, as per our study design, were excluded from the study and statistical analysis. Patients receiving no sedation had significantly more days without ventilation (n=55; mean 13.8 days, SD 11.0) than did those receiving interrupted sedation (n=58; mean 9.6 days, SD 10.0; mean difference 4.2 days, 95% CI 0.3-8.1; p=0.0191). No sedation was also associated with a shorter stay in the intensive care unit (HR 1.86, 95% CI 1.05-3.23; p=0.0316), and, for the first 30 days studied, in hospital (3.57, 1.52-9.09; p=0.0039), than was interrupted sedation. No difference was recorded in the occurrences of accidental extubations, the need for CT or MRI brain scans, or ventilator-associated pneumonia. Agitated delirium was more frequent in the intervention group than in the control group (n=11, 20%vs n=4, 7%; p=0.0400). No sedation of critically ill patients receiving mechanical ventilation is associated with an increase in days without ventilation. A multicentre study is needed to establish whether this effect can be reproduced in other facilities. Danish Society of Anesthesiology and Intensive Care Medicine, the Fund of Danielsen, the Fund of Kirsten Jensa la Cour, and the Fund of Holger og Ruth Hess. Copyright 2010 Elsevier Ltd. All rights reserved.
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              Has mortality from acute respiratory distress syndrome decreased over time?: A systematic review.

              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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                Author and article information

                Contributors
                Journal
                Crit Care
                Crit Care
                Critical Care
                BioMed Central
                1364-8535
                1466-609X
                2014
                15 May 2014
                15 May 2015
                : 18
                : 3
                : 222
                Affiliations
                [1 ]Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7AE, UK
                Article
                cc13875
                10.1186/cc13875
                4056779
                25033302
                506cabae-7ac1-445f-bf30-803500339a89
                Copyright © 2014 Fitzgerald et al.; licensee BioMed Central Ltd.

                The licensee has exclusive rights to distribute this article, in any medium, for 12 months following its publication. After this time, the article is available under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Review

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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