Cytokine Hemoadsorption During Cardiac Surgery Versus Standard Surgical Care for Infective Endocarditis (REMOVE): Results From a Multicenter Randomized Controlled Trial
Authors: Diab Mahmoud , Lehmann Thomas , Bothe Wolfgang , Akhyari Payam , Platzer Stephanie , Wendt Daniel , Deppe Antje-Christin , Strauch Justus , Hagel Stefan , Günther Albrecht , Faerber Gloria , Sponholz Christoph , Franz Marcus , Scherag André , Velichkov Ilia , Silaschi Miriam , Fassl Jens , Hofmann Britt , Lehmann Sven , Schramm Rene , Fritz Georg , Szabo Gabor , Wahlers Thorsten , Matschke Klaus , Lichtenberg Artur , Pletz Mathias W. , Gummert Jan F. , Beyersdorf Friedhelm , Hagl Christian , Borger Michael A. , Bauer Michael , Brunkhorst Frank M. , Doenst Torsten , Diab Mahmoud , Lehmann Thomas , Bothe Wolfgang , Akhyari Payam , Platzer Stephanie , Wendt Daniel , Deppe Antje-Christin , Strauch Justus , Hagel Stefan , Günther Albrecht , Faerber Gloria , Sponholz Christoph , Franz Marcus , Scherag André , Velichkov Ilia , Silaschi Miriam , Fassl Jens , Hofmann Britt , Lehmann Sven , Schramm Rene , Fritz Georg , Szabo Gabor , Wahlers Thorsten , Matschke Klaus , Lichtenberg Artur , Pletz Mathias W. , Gummert Jan F , Hagl Christian , Borger Michael A. , Bauer Michael , Brunkhorst Frank M. , Doenst Torsten , Schiller Isabella , Winter Marcus , Eichhorn Cornelia , Helbig Aicko , Rißner Florian , Abdyvasiev Kubanychbek , Moschovas Alexandros , Freiburger Sebastian , Safarov Rauf , Bargenda Steffen , Kirov Hristo , Richter Markus , Sandhaus Tim , Zeynalov Natig , Kaluza Mirko , Bösemann Denis , Boog Swen , Ostermann Romanus , Christian Schulze P. , Hamadanchi Ali , Musleh Rita , Witte Otto W. , Bloos Petra , Schwope Katrin , Kolanos Steffi , Knuhr-Kohlberg Karina , Haucke Anja , Lehmann-Pohl Katja , Weber Carolyn , Cizmic Amila , Grathwohl Corinna , Sindhu Dirk , Schaschek Markus , Baier Axel , Schaub Sebastian , Großkurth Uwe , Sone Herré Eranya , Vlasov Andrey , Podanev Dimitry , Plettenberg Tobias , Mühlbauer Thomas , Tunggal Irawati , Eichler Madlen , Cosic Jasmina , Wolf Vera , Krause Petra , Krischer Stephanie , Thielmann Matthias , Wiese Ingo , Hillmer Tobias , von Manstein Jörg , Deus Markus , Ljesic Dusko , Roloff Daniel , Alabowicz Wolfgang Ristau Tim , Spangel Gina , Kroll Johannes , Ballazhi Fatos , Kondov Stoyan , Siepe Matthias , Rylski Bartosz , Scheumann Johannes , D’Inka Matthias , Eschenhagen Matthias , Al-Hamami Yasir , Bauer Nils , Thoma Martin , Rambach Albena , Ziemann Christian , Fernandez Baca Garcia Gustavo , Morlock Julia , Benk Christoph , Klink Alina , Maltes Christoph , Lechner Gabriele , Blümel Veronika , Heizmann Ulrike , Kotzjan Priscilla , Haldenwang Peter , Elghannam Mahmoud , Useini Dritan , Buchwald Dirk , Buchwald Bärbel , Schröter Thomas , Binner Christian , Hartung Philipp , Holzhey David , Misfeld Martin , Etz Christian , Davierwala Piroze , Leontyev Sergey , Pfannmüller Bettina , Garbade Jens , von Aspern Konstantin , Saeed Diyar , Aydin Muhammed , Herzfeld Jonathan , Feder Stefan , Kiefer Philipp , Meyer Anna , Seeburger Joerg , Münch Philipp , Prehl Jörg , Ginther René , Koch Josephine , Hecht Salome , Winkler Hannes , Fritzsche Berit , Winata Johann , Schmidt Julia , Labus Jakob , Frei Isabell , Schmidt Volker , Plötze Katrin , Schal Susanne , Immohr Moritz , Sugimura Yukiharu , Gietmann Anne , Simm Andreas , Höpfner Florian , Stiller Markus , Ludwig Kathrin , Helms Sven , Sunavsky Jakub , Götte Julia , Rudloff Markus , Schönbrodt Andrea , Fink Swetlana , Albrecht Ina-Maria , Minko Nnanga Alice Huguette , Schneider Carola , Schilling Heike , Maier Tanja , Kühnel Ralf-Uwe , Ioannou Stelios , Necaev Anna-Maria , Müller Torsten , Bienek Ralph , Treede Hendrik , Kohistani Zaki , Ahmadpour Touraj , Friese Sonja , Oberbach Andreas , Luehr Maximilian , Joskowiak Dominik , Büch Joscha 
Published: February 2022

Background:
Cardiac surgery often represents the only treatment option in patients with infective endocarditis (IE). However, IE surgery may lead to a sudden release of inflammatory mediators, which is associated with postoperative organ dysfunction. We investigated the effect of hemoadsorption during IE surgery on postoperative organ dysfunction.

Methods:
This multicenter, randomized, nonblinded, controlled trial assigned patients undergoing cardiac surgery for IE to hemoadsorption (integration of CytoSorb to cardiopulmonary bypass) or control. The primary outcome (change in sequential organ failure assessment score [ΔSOFA]) was defined as the difference between the mean total postoperative SOFA score, calculated maximally to the 9th postoperative day, and the basal SOFA score. The analysis was by modified intention to treat. A predefined intergroup comparison was performed using a linear mixed model for ΔSOFA including surgeon and baseline SOFA score as fixed effect covariates and with the surgical center as random effect. The SOFA score assesses dysfunction in 6 organ systems, each scored from 0 to 4. Higher scores indicate worsening dysfunction. Secondary outcomes were 30-day mortality, duration of mechanical ventilation, and vasopressor and renal replacement therapy. Cytokines were measured in the first 50 patients.

Results:

Between January 17, 2018, and January 31, 2020, a total of 288 patients were randomly assigned to hemoadsorption (n=142) or control (n=146). Four patients in the hemoadsorption and 2 in the control group were excluded because they did not undergo surgery. The primary outcome, ΔSOFA, did not differ between the hemoadsorption and the control group (1.79±3.75 and 1.93±3.53, respectively; 95% CI, –1.30 to 0.83;
P
=0.6766). Mortality at 30 days (21% hemoadsorption versus 22% control;
P
=0.782), duration of mechanical ventilation, and vasopressor and renal replacement therapy did not differ between groups. Levels of interleukin-1β and interleukin-18 at the end of integration of hemoadsorption to cardiopulmonary bypass were significantly lower in the hemoadsorption than in the control group.

Conclusions:
This randomized trial failed to demonstrate a reduction in postoperative organ dysfunction through intraoperative hemoadsorption in patients undergoing cardiac surgery for IE. Although hemoadsorption reduced plasma cytokines at the end of cardiopulmonary bypass, there was no difference in any of the clinically relevant outcome measures.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03266302.