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      Hemoadsorption with CytoSorb shows a decreased observed versus expected 28-day all-cause mortality in ICU patients with septic shock: a propensity-score-weighted retrospective study

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          Abstract

          Background and aims

          Innovative treatment modalities have not yet shown a clinical benefit in patients with septic shock. To reduce severe cytokinaemia, CytoSorb as an add-on to continuous renal replacement therapy (CRRT) showed promising results in case reports. However, there are no clinical trials investigating outcomes.

          Methods

          In this investigator-initiated retrospective study, patients with septic shock were treated with CRRT + CytoSorb ( n = 67) or CRRT alone ( n = 49). The primary outcome was the 28-day all-cause mortality rate. Patients were weighted by stabilized inverse probability of treatment weights (sIPTW) to overcome differences in baseline characteristics.

          Results

          At the start of therapy, CytoSorb-treated patients had higher lactate levels ( p < 0.001), lower mean arterial pressure ( p = 0.007) and higher levels of noradrenaline ( p < 0.001) compared to the CRRT group. For CytoSorb, the mean predicted mortality rate based on a SOFA of 13.8 ( n = 67) was 75% (95%CI 71–79%), while the actual 28-day mortality rate was 48% (mean difference − 27%, 95%CI − 38 to − 15%, p < 0.001). For CRRT, based on a SOFA of 12.8 ( n = 49), the mean predicted versus observed mortality was 68% versus 51% (mean difference − 16.9% [95%CI − 32.6 to − 1.2%, p = 0.035]). By sIPTW analysis, patients treated with CytoSorb had a significantly lower 28-day mortality rate compared to CRRT alone (53% vs. 72%, respectively, p = 0.038). Independent predictors of 28-day mortality in the CytoSorb group were the presence of pneumosepsis (adjusted odds ratio [aOR] 5.47, p = 0.029), higher levels of lactate at the start of CytoSorb (aOR 1.15, p = 0.031) and older age (aOR per 10 years 1.67, p = 0.034).

          Conclusions

          CytoSorb was associated with a decreased observed versus expected 28-day all-cause mortality. By IPTW analysis, intervention with CytoSorb may be associated with a decreased all-cause mortality at 28 days compared to CRRT alone.

          Electronic supplementary material

          The online version of this article (10.1186/s13054-019-2588-1) contains supplementary material, which is available to authorized users.

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          Most cited references 21

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          Propensity score techniques and the assessment of measured covariate balance to test causal associations in psychological research.

          There is considerable interest in using propensity score (PS) statistical techniques to address questions of causal inference in psychological research. Many PS techniques exist, yet few guidelines are available to aid applied researchers in their understanding, use, and evaluation. In this study, the authors give an overview of available techniques for PS estimation and PS application. They also provide a way to help compare PS techniques, using the resulting measured covariate balance as the criterion for selecting between techniques. The empirical example for this study involves the potential causal relationship linking early-onset cannabis problems and subsequent negative mental health outcomes and uses data from a prospective cohort study. PS techniques are described and evaluated on the basis of their ability to balance the distributions of measured potentially confounding covariates for individuals with and without early-onset cannabis problems. This article identifies the PS techniques that yield good statistical balance of the chosen measured covariates within the context of this particular research question and cohort.
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            Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study.

            Mortality from severe sepsis and septic shock differs across continents, countries, and regions. We aimed to use data from the Surviving Sepsis Campaign (SSC) to compare models of care and outcomes for patients with severe sepsis and septic shock in the USA and Europe. The SSC was introduced into more than 200 sites in Europe and the USA. All patients identified with severe sepsis and septic shock in emergency departments or hospital wards and admitted to intensive care units (ICUs), and those with sepsis in ICUs were entered into the SSC database. Patients entered into the database from its launch in January, 2005, through January, 2010, in units with at least 20 patients and 3 months of enrolment of patients were included in this analysis. Patients included in the cohort were limited to those entered in the first 4 years at every site. We used random-effects logistic regression to estimate the hospital mortality odds ratio (OR) for Europe relative to the USA. We used random-effects linear regression to find the relation between lengths of stay in hospital and ICU and geographic region. 25 375 patients were included in the cohort. The USA included 107 sites with 18 766 (74%) patients, and Europe included 79 hospital sites with 6609 (26%) patients. In the USA, 12 218 (65·1%) were admitted to the ICU from the emergency department whereas in Europe, 3405 (51·5%) were admitted from the wards. The median stay on the hospital wards before ICU admission was longer in Europe than in the USA (1·0 vs 0·1 days, difference 0·9, 95% CI 0·8-0·9). Raw hospital mortality was higher in Europe than in the USA (41·1%vs 28·3%, difference 12·8, 95% CI 11·5-14·7). The median length of stay in ICU (7·8 vs 4·2 days, 3·6, 3·3-3·7) and hospital (22·8 vs 10·5 days, 12·3, 11·9-12·8) was longer in Europe than in the USA. Adjusted mortality in Europe was not significantly higher than that in the USA (32·3%vs 31·3%, 1·0, -1·7 to 3·7, p=0·468). Complete compliance with all applicable elements of the sepsis resuscitation bundle was higher in the USA than in Europe (21·6%vs 18·4%, 3·2, 2·2-4·4). The significant difference in unadjusted mortality and the fact that this difference disappears with severity adjustment raise important questions about the effect of the approach to critical care in Europe compared with that in the USA. The effect of ICU bed availability on outcomes in patients with severe sepsis and septic shock requires further investigation. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Clinical review: Blood purification for sepsis

              Sepsis is the primary cause of death in the intensive care unit. Extracorporeal blood purification therapies have been proposed for patients with sepsis in order to improve outcomes since these therapies can alter the host inflammatory response by non-selective removal of inflammatory mediators or bacterial products or both. Recent technological progress has increased the number of techniques available for blood purification and their performance. In this overview, we report on the latest advances in blood purification for sepsis and how they relate to current concepts of disease, and we review the current evidence for high-volume hemofiltration, cascade hemofiltration, hemoadsorption, coupled plasma filtration adsorption, high-adsorption hemofiltration, and high-cutoff hemofiltration/hemodialysis. Promising results have been reported with all of these blood purification therapies, showing that they are well tolerated, effective in clearing inflammatory mediators or bacterial toxins (or both) from the plasma, and efficacious for improvement of various physiologic outcomes (for example, hemodynamics and oxygenation). However, numerous questions, including the timing, duration, and frequency of these therapies in the clinical setting, remain unanswered. Large multicenter trials evaluating the ability of these therapies to improve clinical outcomes (that is, mortality or organ failure), rather than surrogate markers such as plasma mediator clearance or transient improvement in physiologic variables, are required to define the precise role of blood purification in the management of sepsis.
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                Author and article information

                Contributors
                w.p.brouwer@erasmusmc.nl
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                18 September 2019
                18 September 2019
                2019
                : 23
                Affiliations
                [1 ]ISNI 000000040459992X, GRID grid.5645.2, Department of Gastroenterology and Hepatology, , Erasmus MC, University Medical Center Rotterdam, ; Dr Molewaterplein 15, Building NA-6, 3015 CE Rotterdam, The Netherlands
                [2 ]ISNI 0000 0004 0460 0556, GRID grid.416213.3, Department of Internal Medicine, , Maasstad Ziekenhuis, ; Rotterdam, The Netherlands
                [3 ]ISNI 0000 0004 0460 0556, GRID grid.416213.3, Department of Intensive Care Medicine, , Maasstad Ziekenhuis, ; Rotterdam, The Netherlands
                [4 ]ISNI 0000 0004 0460 0556, GRID grid.416213.3, Science board, , Maasstad Ziekenhuis, ; Rotterdam, The Netherlands
                [5 ]ISNI 000000040459992X, GRID grid.5645.2, Department of Intensive Care Medicine, , Erasmus MC, University Medical Center Rotterdam, ; Rotterdam, The Netherlands
                Article
                2588
                10.1186/s13054-019-2588-1
                6749645
                31533846
                © The Author(s). 2019

                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.

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