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      Current real-life use of vasopressors and inotropes in cardiogenic shock - adrenaline use is associated with excess organ injury and mortality

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          Abstract

          Background

          Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS.

          Methods

          The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling.

          Results

          Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan.

          Conclusion

          Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13054-016-1387-1) contains supplementary material, which is available to authorized users.

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          Most cited references28

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          A comparison of 12 algorithms for matching on the propensity score

          Propensity-score matching is increasingly being used to reduce the confounding that can occur in observational studies examining the effects of treatments or interventions on outcomes. We used Monte Carlo simulations to examine the following algorithms for forming matched pairs of treated and untreated subjects: optimal matching, greedy nearest neighbor matching without replacement, and greedy nearest neighbor matching without replacement within specified caliper widths. For each of the latter two algorithms, we examined four different sub-algorithms defined by the order in which treated subjects were selected for matching to an untreated subject: lowest to highest propensity score, highest to lowest propensity score, best match first, and random order. We also examined matching with replacement. We found that (i) nearest neighbor matching induced the same balance in baseline covariates as did optimal matching; (ii) when at least some of the covariates were continuous, caliper matching tended to induce balance on baseline covariates that was at least as good as the other algorithms; (iii) caliper matching tended to result in estimates of treatment effect with less bias compared with optimal and nearest neighbor matching; (iv) optimal and nearest neighbor matching resulted in estimates of treatment effect with negligibly less variability than did caliper matching; (v) caliper matching had amongst the best performance when assessed using mean squared error; (vi) the order in which treated subjects were selected for matching had at most a modest effect on estimation; and (vii) matching with replacement did not have superior performance compared with caliper matching without replacement. © 2013 The Authors. Statistics in Medicine published by John Wiley & Sons, Ltd.
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            Matching Methods for Causal Inference: A Review and a Look Forward

            (2010)
            When estimating causal effects using observational data, it is desirable to replicate a randomized experiment as closely as possible by obtaining treated and control groups with similar covariate distributions. This goal can often be achieved by choosing well-matched samples of the original treated and control groups, thereby reducing bias due to the covariates. Since the 1970s, work on matching methods has examined how to best choose treated and control subjects for comparison. Matching methods are gaining popularity in fields such as economics, epidemiology, medicine and political science. However, until now the literature and related advice has been scattered across disciplines. Researchers who are interested in using matching methods---or developing methods related to matching---do not have a single place to turn to learn about past and current research. This paper provides a structure for thinking about matching methods and guidance on their use, coalescing the existing research (both old and new) and providing a summary of where the literature on matching methods is now and where it should be headed.
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              Clinical picture and risk prediction of short-term mortality in cardiogenic shock.

              The aim of this study was to investigate the clinical picture and outcome of cardiogenic shock and to develop a risk prediction score for short-term mortality.
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                Author and article information

                Contributors
                +358 40 534 3955 , +358 9 471 71488 , tuukka.tarvasmaki@fimnet.fi
                johan.lassus@fimnet.fi
                marjut.varpula@hus.fi
                ASionis@santpau.cat
                reijo.sund@helsinki.fi
                lk@heart.dk
                jspinar@fnbrno.cz
                jparissis@yahoo.com
                m.banaszewski@eranet.pl
                silvacardoso30@hotmail.com
                valentina.carubelli@gmail.com
                salvatore.disomma@uniroma1.it
                alexandre.mebazaa@aphp.fr
                veli-pekka.harjola@hus.fi
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                4 July 2016
                4 July 2016
                2016
                : 20
                : 208
                Affiliations
                [ ]Emergency Medicine, University of Helsinki and Department of Emergency Medicine and Services, Helsinki University Hospital, PO Box 340, 00029 HUS Helsinki, Finland
                [ ]Division of Cardiology, Heart and Lung Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
                [ ]Intensive Cardiac Care Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
                [ ]Department of Social Research, Faculty of Social Sciences, Centre for Research Methods, University of Helsinki, Helsinki, Finland
                [ ]Rigshospitalet, Copenhagen University Hospital, Division of Heart Failure, Pulmonary Hypertension and Heart Transplantation, Copenhagen, Denmark
                [ ]Department of Internal Medicine and Cardiology, University Hospital Brno, Brno, Czech Republic
                [ ]Heart Failure Clinic and Secondary Cardiology Department, Attikon University Hospital, Athens, Greece
                [ ]Institute of Cardiology, Intensive Cardiac Therapy Clinic, Warsaw, Poland
                [ ]Department of Cardiology, University of Porto, CINTESIS, Porto Medical School, São João Hospital Center, Porto, Portugal
                [ ]Division of Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University and Civil Hospital of Brescia, Brescia, Italy
                [ ]Department of Medical Sciences and Translational Medicine, University of Rome Sapienza, Emergency Medicine Sant’Andrea Hospital, Rome, Italy
                [ ]INSERM U942, Hopital Lariboisiere, APHP and University Paris Diderot, Paris, France
                Author information
                http://orcid.org/0000-0003-3406-243X
                Article
                1387
                10.1186/s13054-016-1387-1
                4931696
                27374027
                b1b04756-0268-44a2-9862-8ac59e19ddd5
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 25 March 2016
                : 14 June 2016
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Emergency medicine & Trauma
                cardiogenic shock,vasoactive medication,vasopressors,inotropes,adrenaline,mortality,survival,propensity score

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