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      Options in extracorporeal support of multiple organ failure Translated title: Optionen der extrakorporalen Unterstützung bei Multiorganversagen

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          Abstract

          Multiorgan failure is among the most frequent reasons of death in critically ill patients. Based on extensive and long-term use of renal replacement therapy, extracorporeal organ support became available for other organ failures. Initially, most of these techniques (e.g. extracorporeal membrane oxygenation, extracorporeal CO 2 removal [ECCO2R] and extracorporeal liver support) were used as stand-alone single organ support systems. Considering multiple interactions between native organs (“crosstalk”), combined or integrated extracorporeal organ support (ECOS) devices are intriguing. The concept of multiple organ support therapy (MOST) providing simultaneous and combined support for different failing organs was described more than 15 years ago by Ronco and Bellomo. This concept also implicates overcoming the “compartmentalized” approach provided by different single organ specialized professionals by a multidisciplinary and multiprofessional strategy. The idea of MOST is supported by the failure of several recent studies on single organ support including liver and lung support. Improvement of outcome by ECOS necessarily depends on optimized patient selection, integrated organ support and limitation of its side effects. This implicates challenges for engineers, industry and healthcare professionals. From a technical viewpoint, modular combination of pre-existing technologies such as renal replacement, albumin-dialysis, ECCO2R and potentially cytokine elimination can be considered as a first step. While this allows for stepwise and individual combination of standard organ support facilities, it carries the disadvantage of large extracorporeal blood volume and surfaces as well as additive costs. The more intriguing next step is an integrated platform providing the capacity of multiple organ support within one device. (This article is freely available.)

          Translated abstract

          Das Multiorganversagen ist eine der häufigsten Todesursachen auf der Intensivstation. Die breite Anwendung der Nierenersatztherapie bei akutem und chronischem Nierenversagen ebnete den Weg für andere extrakorporale Organersatzverfahren. Diese wurden zunächst überwiegend als Einzelorganersatztherapien eingesetzt (extrakorporale Membranoxygenierung, extrakorporale CO 2-Entfernung [ECCO2R] sowie extrakorporaler Leberersatz). Im Hinblick auf multiple Interaktionen zwischen den Organsystemen („crosstalk“) sind kombinierte bzw. integrierte Organersatzverfahren von großem Interesse. Das Konzept der „multiple organ support therapy“ (MOST) mit kombiniertem Organersatz wurde vor über 15 Jahren von Ronco und Bellomo erstbeschrieben. Dieses Konzept ersetzt den Ansatz der „Kompartimentalisierung“ mit Ersatz einzelner Organversagen im Rahmen der jeweiligen speziellen Verfahren durch eine multidisziplinäre, multiprofessionelle Vorgehensweise. Die Strategie der MOST gewann nach dem Scheitern mehrerer jüngster Studien zum Einzelorganersatz (v. a. Leber- bzw. Lungenersatz) zunehmend an Bedeutung. Der zukünftige Erfolg dieses Konzepts des integrierten Organersatzes hängt dabei auch von einer optimierten Patientenauswahl und einer Limitierung von Nebenwirkungen des Verfahrens ab. Dies bringt zwangsläufig Herausforderungen für Ingenieure, Industrie und Heilberufe mit sich. Technisch ist eine bloße Kombination von vorbestehenden Verfahren wie Nieren- oder Leberersatz, CO 2-Entfernung und ggf. Zytokinelimination nur ein erster Schritt. Auch wenn dies eine schrittweise und individualisierte Kombination von vorhandenen Organunterstützungstherapien bedeutet, ergibt sich daraus der Nachteil eines hohen extrakorporalen Blutvolumens, großer künstlicher Oberflächen und additiver Kosten für die einzelnen Verfahren. Der notwendige nächste Schritt sind integrierte Verfahren, die einen Multiorganersatz in einem Gerät ermöglichen.

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          Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal carbon dioxide removal.

          Tidal hyperinflation may occur in patients with acute respiratory distress syndrome who are ventilated with a tidal volume (VT) of 6 ml/kg of predicted body weight develop a plateau pressure (PPLAT) of 28 < or = PPLAT < or = 30 cm H2O. The authors verified whether VT lower than 6 ml/kg may enhance lung protection and that consequent respiratory acidosis may be managed by extracorporeal carbon dioxide removal. PPLAT, lung morphology computed tomography, and pulmonary inflammatory cytokines (bronchoalveolar lavage) were assessed in 32 patients ventilated with a VT of 6 ml/kg. Data are provided as mean +/- SD or median and interquartile (25th and 75th percentile) range. In patients with 28 < or = PPLAT < or = 30 cm H2O (n = 10), VT was reduced from 6.3 +/- 0.2 to 4.2 +/- 0.3 ml/kg, and PPLAT decreased from 29.1 +/- 1.2 to 25.0 +/- 1.2 cm H2O (P < 0.001); consequent respiratory acidosis (Paco2 from 48.4 +/- 8.7 to 73.6 +/- 11.1 mmHg and pH from 7.36 +/- 0.03 to 7.20 +/- 0.02; P < 0.001) was managed by extracorporeal carbon dioxide removal. Lung function, morphology, and pulmonary inflammatory cytokines were also assessed after 72 h. Extracorporeal assist normalized Paco2 (50.4 +/- 8.2 mmHg) and pH (7.32 +/- 0.03) and allowed use of VT lower than 6 ml/kg for 144 (84-168) h. The improvement of morphological markers of lung protection and the reduction of pulmonary cytokines concentration (P < 0.01) were observed after 72 h of ventilation with VT lower than 6 ml/kg. No patient-related complications were observed. VT lower than 6 ml/Kg enhanced lung protection. Respiratory acidosis consequent to low VT ventilation was safely and efficiently managed by extracorporeal carbon dioxide removal.
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            Lower tidal volume strategy (≈3 ml/kg) combined with extracorporeal CO2 removal versus ‘conventional’ protective ventilation (6 ml/kg) in severe ARDS

            Background Acute respiratory distress syndrome is characterized by damage to the lung caused by various insults, including ventilation itself, and tidal hyperinflation can lead to ventilator induced lung injury (VILI). We investigated the effects of a low tidal volume (V T) strategy (V T ≈ 3 ml/kg/predicted body weight [PBW]) using pumpless extracorporeal lung assist in established ARDS. Methods Seventy-nine patients were enrolled after a ‘stabilization period’ (24 h with optimized therapy and high PEEP). They were randomly assigned to receive a low V T ventilation (≈3 ml/kg) combined with extracorporeal CO2 elimination, or to a ARDSNet strategy (≈6 ml/kg) without the extracorporeal device. The primary outcome was the 28-days and 60-days ventilator-free days (VFD). Secondary outcome parameters were respiratory mechanics, gas exchange, analgesic/sedation use, complications and hospital mortality. Results Ventilation with very low V T’s was easy to implement with extracorporeal CO2-removal. VFD’s within 60 days were not different between the study group (33.2 ± 20) and the control group (29.2 ± 21, p = 0.469), but in more hypoxemic patients (PaO2/FIO2 ≤150) a post hoc analysis demonstrated significant improved VFD-60 in study patients (40.9 ± 12.8) compared to control (28.2 ± 16.4, p = 0.033). The mortality rate was low (16.5 %) and did not differ between groups. Conclusions The use of very low V T combined with extracorporeal CO2 removal has the potential to further reduce VILI compared with a ‘normal’ lung protective management. Whether this strategy will improve survival in ARDS patients remains to be determined (Clinical trials NCT 00538928). Electronic supplementary material The online version of this article (doi:10.1007/s00134-012-2787-6) contains supplementary material, which is available to authorized users.
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              Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial.

              Acute-on-chronic liver failure (ACLF) is a frequent cause of death in cirrhosis. Albumin dialysis with the molecular adsorbent recirculating system (MARS) decreases retained substances and improves hemodynamics and hepatic encephalopathy (HE). However, its survival impact is unknown. In all, 189 patients with ACLF were randomized either to MARS (n=95) or to standard therapy (SMT) (n=94). Ten patients (five per group) were excluded due to protocol violations. In addition, 23 patients (MARS: 19; SMT: 4) were excluded from per-protocol (PP) analysis (PP population n=156). Up to 10 6-8-hour MARS sessions were scheduled. The main endpoint was 28-day ITT and PP survival. There were no significant differences at inclusion, although the proportion of patients with Model for Endstage Liver Disease (MELD) score over 20 points and with spontaneous bacterial peritonitis (SBP) as a precipitating event was almost significantly greater in the MARS group. The 28-day survival was similar in the two groups in the ITT and PP populations (60.7% versus 58.9%; 60% versus 59.2% respectively). After adjusting for confounders, a significant beneficial effect of MARS on survival was not observed (odds ratio [OR]: 0.87, 95% confidence interval [CI] 0.44-1.72). MELD score and HE at admission and the increase in serum bilirubin at day 4 were independent predictors of death. At day 4, a greater decrease in serum creatinine (P=0.02) and bilirubin (P=0.001) and a more frequent improvement in HE (from grade II-IV to grade 0-I; 62.5% versus 38.2%; P=0.07) was observed in the MARS group. Severe adverse events were similar.
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                Author and article information

                Contributors
                wolfgang.huber@tum.de
                Journal
                Med Klin Intensivmed Notfmed
                Med Klin Intensivmed Notfmed
                Medizinische Klinik, Intensivmedizin Und Notfallmedizin
                Springer Medizin (Heidelberg )
                2193-6218
                2193-6226
                24 February 2020
                24 February 2020
                2020
                : 115
                : Suppl 1
                : 28-36
                Affiliations
                [1 ]GRID grid.6936.a, ISNI 0000000123222966, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, , Technische Universität München, ; Ismaninger Str. 22, 81675 München, Germany
                [2 ]ADVITOS GmbH, München, Germany
                Author notes
                [Redaktion]

                M. Bauer; Jena

                M. Singer, London

                Article
                658
                10.1007/s00063-020-00658-3
                7220977
                32095838
                f06e5cc7-1a04-4b71-b7a2-d32f828f1d7f
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 27 December 2019
                : 14 January 2020
                Funding
                Funded by: Klinikum rechts der Isar der Technischen Universität München (8934)
                Categories
                Review Articles
                Custom metadata
                © Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2020

                extracorporeal organ support,renal replacement therapy,albumin dialysis,plasma separation,extracorporeal co2 removal,extrakorporaler organersatz,nierenersatztherapie,albumindialyse,plasmaseparation,extrakorporale co2-entfernung

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