Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study

Abstract Objectives The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To under...

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Main Authors: Vaclav Tegl, Jan Horak, Lukas Nalos, Michala Horakova, Milan Stengl, Martin Matejovic, Jan Benes
Format: Article
Language:English
Published: SpringerOpen 2024-04-01
Series:Intensive Care Medicine Experimental
Subjects:
Online Access:https://doi.org/10.1186/s40635-024-00622-x
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author Vaclav Tegl
Jan Horak
Lukas Nalos
Michala Horakova
Milan Stengl
Martin Matejovic
Jan Benes
author_facet Vaclav Tegl
Jan Horak
Lukas Nalos
Michala Horakova
Milan Stengl
Martin Matejovic
Jan Benes
author_sort Vaclav Tegl
collection DOAJ
description Abstract Objectives The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment. Design Prospective randomized large-animal peritoneal septic shock experiment. Setting Laboratory investigation. Subjects Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 μg/kg/min (LATE, n = 8). Interventions Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse. Measurements and main results Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia. Conclusions In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.
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spelling doaj.art-2c3d9c4cd7f141d59b9b3520bb67950e2024-04-21T11:03:49ZengSpringerOpenIntensive Care Medicine Experimental2197-425X2024-04-0112111110.1186/s40635-024-00622-xIneffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine studyVaclav Tegl0Jan Horak1Lukas Nalos2Michala Horakova3Milan Stengl4Martin Matejovic5Jan Benes6Laboratory of Experimental Intensive Care Medicine, Biomedical Center, Faculty of Medicine in Pilsen, Charles UniversityLaboratory of Experimental Intensive Care Medicine, Biomedical Center, Faculty of Medicine in Pilsen, Charles UniversityLaboratory of Experimental Intensive Care Medicine, Biomedical Center, Faculty of Medicine in Pilsen, Charles UniversityLaboratory of Experimental Intensive Care Medicine, Biomedical Center, Faculty of Medicine in Pilsen, Charles UniversityDepartment of Physiology, Faculty of Medicine in Pilsen, Charles UniversityLaboratory of Experimental Intensive Care Medicine, Biomedical Center, Faculty of Medicine in Pilsen, Charles UniversityLaboratory of Experimental Intensive Care Medicine, Biomedical Center, Faculty of Medicine in Pilsen, Charles UniversityAbstract Objectives The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment. Design Prospective randomized large-animal peritoneal septic shock experiment. Setting Laboratory investigation. Subjects Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 μg/kg/min (LATE, n = 8). Interventions Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse. Measurements and main results Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia. Conclusions In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.https://doi.org/10.1186/s40635-024-00622-xSepsisSeptic shockAdsorptionInvestigational therapiesHemoperfusion
spellingShingle Vaclav Tegl
Jan Horak
Lukas Nalos
Michala Horakova
Milan Stengl
Martin Matejovic
Jan Benes
Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study
Intensive Care Medicine Experimental
Sepsis
Septic shock
Adsorption
Investigational therapies
Hemoperfusion
title Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study
title_full Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study
title_fullStr Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study
title_full_unstemmed Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study
title_short Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study
title_sort ineffectiveness of hemoadsorption in large animals with abdominal sepsis a randomized controlled porcine study
topic Sepsis
Septic shock
Adsorption
Investigational therapies
Hemoperfusion
url https://doi.org/10.1186/s40635-024-00622-x
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