Selective LPS Adsorption Using Polymyxin B-Immobilized Fiber Cartridges in Sepsis Patients Following Cardiac Surgery

Yaroustovsky, M.B.; Abramyan, Marina; Komardina, Ekaterina; Nazarova, Helen; Popov, D. A.; Plyushch, Marina; Soldatkina, Alina; Rogalskaya, Ekaterina

doi:10.1097/shk.0000000000001016

Cited by 9 publications

(6 citation statements)

References 32 publications

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“…We perform in silico investigations to explore the impact of interventions used in the clinical management of endotoxaemia: LPS adsorption, vasopressors and antipyretics. LPS adsorption is a therapy for reducing the endotoxin load (Yaroustovsky et al 2018). Our simulation results show that this treatment leads to HR normalization and relief of fever and pain.…”

Section: Discussionmentioning

confidence: 86%

“…LPS adsorption is a therapy for reducing the endotoxin load (Yaroustovsky et al . 2018). Our simulation results show that this treatment leads to HR normalization and relief of fever and pain.…”

Section: Discussionmentioning

confidence: 99%

“…This treatment is recommended as early intervention, within the first 6 hr of diagnosis for sepsis patients (Yaroustovsky et al . 2018). To capture the action of LPS adsorption, we increased the decay rate of LPS (

k_{E}

).…”

Section: Methodsmentioning

confidence: 99%

“…LPS adsorption is a therapeutic strategy used to clear endotoxin from the bloodstream through haemoperfusion. This treatment is recommended as early intervention, within the first 6 hr of diagnosis for sepsis patients (Yaroustovsky et al 2018). To capture the action of LPS adsorption, we increased the decay rate of LPS (k E ).…”

Section: Therapeutic Interventionsmentioning

confidence: 99%

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A physiological model of the inflammatory‐thermal‐pain‐cardiovascular interactions during an endotoxin challenge

Dobreva

Brady‐Nicholls

Larripa

et al. 2021

The Journal of Physiology

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Key points Inflammation in response to bacterial endotoxin challenge impacts physiological functions, including cardiovascular, thermal and pain dynamics, although the mechanisms are poorly understood. We develop an innovative mathematical model incorporating interaction pathways between inflammation and physiological processes observed in response to an endotoxin challenge. We calibrate the model to individual data from 20 subjects in an experimental study of the human inflammatory and physiological responses to endotoxin, and we validate the model against human data from an independent study. Using the model to simulate patient responses to different treatment modalities reveals that a multimodal treatment combining several therapeutic strategies gives the best recovery outcome. Abstract Uncontrolled, excessive production of pro‐inflammatory mediators from immune cells and traumatized tissues can cause systemic inflammatory conditions such as sepsis, one of the ten leading causes of death in the USA, and one of the three leading causes of death in the intensive care unit. Understanding how inflammation affects physiological processes, including cardiovascular, thermal and pain dynamics, can improve a patient's chance of recovery after an inflammatory event caused by surgery or a severe infection. Although the effects of the autonomic response on the inflammatory system are well‐known, knowledge about the reverse interaction is lacking. The present study develops a mathematical model analyzing the inflammatory system's interactions with thermal, pain and cardiovascular dynamics in response to a bacterial endotoxin challenge. We calibrate the model with individual data from an experimental study of the inflammatory and physiological responses to a one‐time administration of endotoxin in 20 healthy young men and validate it against data from an independent endotoxin study. We use simulation to explore how various treatments help patients exposed to a sustained pathological input. The treatments explored include bacterial endotoxin adsorption, antipyretics and vasopressors, as well as combinations of these. Our findings suggest that the most favourable recovery outcome is achieved by a multimodal strategy, combining all three interventions to simultaneously remove endotoxin from the body and alleviate symptoms caused by the immune system as it fights the infection.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

k_{E}

).…”

Section: Methodsmentioning

confidence: 99%

Section: Therapeutic Interventionsmentioning

confidence: 99%

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A physiological model of the inflammatory‐thermal‐pain‐cardiovascular interactions during an endotoxin challenge

Dobreva

Brady‐Nicholls

Larripa

et al. 2021

The Journal of Physiology

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“…"TORAY" in Japan developed optimal-sized cartridges for children weighing 10-30 kg, namely, Toraymyxin-PMX-05R, and for newborns, namely, Toraymyxin-PMX-01R. Single cases of hemoperfusion with such cartridges with PMX B-immobilized fibers have been reported in the literature for sepsis treatment in children [13][14][15][16][17] and in experimental studies [18,19].…”

Section: Introductionmentioning

confidence: 99%

Selective Polymyxin Hemoperfusion in Complex Therapy of Sepsis in Children after Cardiac Surgery

et al. 2020

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Background: To date, sepsis remains one of the main challenges of intensive care in pediatrics. Newborns with low birth weight and infants with chronic diseases and congenital disorders are particularly at risk. The incidence of infectious complications in pediatric cardiac surgery is known to be approximately 15–30%. The main etiological factor of sepsis is endotoxin. Aim: To evaluate the efficiency and safety of polymyxin (PMX) B-immobilized column-direct hemoperfusion in complex intensive therapy of sepsis in children after cardiac surgery with cardiopulmonary bypass. Design: Prospective cohort study. Methods: This study enrolled 15 children, aged 9–96 months, with congenital heart diseases and with body weights of 6.2–22.5 kg. The criteria for admission were body weight >6 kg and clinical and laboratory signs of sepsis (microbiological analysis, procalcitonin [PCT] >2 ng/mL, and endotoxin activity assay [ЕАА] >0.6). Intensive care included inotropic and vasopressor support, mechanical ventilation, broad-spectrum antibiotic therapy, and PMX hemoperfusion procedures. Extracorporeal therapy was initiated within 24 h following the sepsis diagnosis. Every patient underwent 2 hemoperfusion sessions with the use of a PMX B-immobilized column; the session duration was 180 min. Results: We noted improvements in hemodynamic parameters, oxygenation index, and laboratory signs of sepsis, with decreases in the endotoxin concentration according to the EAA, PCT, and presepsin levels. The 28-day survival of the patients in this severely affected group was 80%. Main Conclusion: The inclusion of extracorporeal methods of blood purification, aimed at the selective elimination of circulating endotoxin, in the treatment of sepsis increases the survival rates of children after open heart surgery. Second Conclusion: The obtained results of sepsis therapy with PMX hemoperfusion in children after cardiac surgery enable us to suggest the sufficient safety and efficiency of the procedures in this category of severely affected patients.

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Bacterial extracellular vesicles repress the vascular protective factor RNase1 in human lung endothelial cells

Laakmann,

Eckersberg,

Hapke

et al. 2024

64. Kongress Der Deutschen Gesellschaft Für Pneumologie Und Beatmungsmedizin E. V.

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Background Sepsis is one of the leading causes of death worldwide and characterized by blood stream infections associated with a dysregulated host response and endothelial cell (EC) dysfunction. Ribonuclease 1 (RNase1) acts as a protective factor of vascular homeostasis and is known to be repressed by massive and persistent inflammation, associated to the development of vascular pathologies. Bacterial extracellular vesicles (bEVs) are released upon infection and may interact with ECs to mediate EC barrier dysfunction. Here, we investigated the impact of bEVs of sepsisrelated pathogens on human EC RNase1 regulation.Methods bEVs from sepsis-associated bacteria were isolated via ultrafiltration and size exclusion chromatography and used for stimulation of human lung microvascular ECs combined with and without signaling pathway inhibitor treatments.Results bEVs from Escherichia coli, Klebsiella pneumoniae and Salmonella enterica serovar Typhimurium significantly reduced RNase1 mRNA and protein expression and activated ECs, while TLR2-inducing bEVs from Streptococcus pneumoniae did not. These effects were mediated via LPS-dependent TLR4 signaling cascades as they could be blocked by Polymyxin B. Additionally, LPS-free ClearColi ™ had no impact on RNase1. Further characterization of TLR4 downstream pathways involving NF-кB and p38, as well as JAK1/STAT1 signaling, revealed that RNase1 mRNA regulation is mediated via a p38-dependent mechanism. ConclusionBlood stream bEVs from gram-negative, sepsis-associated bacteria reduce the vascular protective factor RNase1, opening new avenues for therapeutical intervention of EC dysfunction via promotion of RNase1 integrity.

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Selective LPS Adsorption Using Polymyxin B-Immobilized Fiber Cartridges in Sepsis Patients Following Cardiac Surgery

Cited by 9 publications

References 32 publications

A physiological model of the inflammatory‐thermal‐pain‐cardiovascular interactions during an endotoxin challenge

A physiological model of the inflammatory‐thermal‐pain‐cardiovascular interactions during an endotoxin challenge

Selective Polymyxin Hemoperfusion in Complex Therapy of Sepsis in Children after Cardiac Surgery

Bacterial extracellular vesicles repress the vascular protective factor RNase1 in human lung endothelial cells

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