In vitro comparison of the adsorption of inflammatory mediators by blood purification devices

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Abstract

Background

Septic shock, a leading cause of acute kidney injury, induces release of pro-/anti-inflammatory mediators, leading to increased mortality and poor renal recovery. This is the first in vitro study directly comparing three single-use blood purification devices in terms of removing sepsis-associated mediators and endotoxins.

Methods

In vitro hemoperfusion was performed using oXiris ^®, CytoSorb ^®, and Toraymyxin ^®. Heparinized human plasma from healthy volunteers was pre-incubated with pathologic quantities of inflammatory mediators and filtered in a closed-loop circulation model for 2 h. For each device, the removal of 27 inflammatory mediators was measured over time. Endotoxin removal mediated by oXiris and Toraymyxin was assessed using hemoperfusion over 6 h.

Results

Endotoxin (lipopolysaccharide) removal was most rapid with Toraymyxin; mean adsorptive clearance over the first 30 min was ~ 20 ml/min vs ~ 8 ml/min with oXiris ( p < 0.05). There was minimal endotoxin removal with CytoSorb (1 ml/min). At 120 min, there was no significant difference between the endotoxin removal rates using oXiris (mean ± standard deviation, 68.0 ± 4.4%) and Toraymyxin (83.4 ± 3.8%); both were significantly higher vs CytoSorb (− 6.3 ± 4.9%; p < 0.05). Total removal with oXiris was 6.9 μg vs 9.7 μg for Toraymyxin, where the total lipopolysaccharide quantity introduced was approximately 15.8 μg. Removal rates of pro-/anti-inflammatory cytokines and other inflammatory mediators were similar between oXiris and CytoSorb and were higher with CytoSorb and oXiris vs Toraymyxin. Granulocyte colony-stimulating factor was only effectively adsorbed by CytoSorb (99.4%). Differences were detected between the adsorption mechanism of the devices; binding to oXiris was mainly ionic, while CytoSorb was hydrophobic. No specific protein adsorption was found qualitatively with Toraymyxin.

Conclusions

Adsorption rate kinetics varied for individual inflammatory mediators using the three blood purification devices. Mechanisms of adsorption differed between the devices. oXiris was the only device tested that showed both endotoxin and cytokine removal. oXiris showed similar endotoxin adsorption to Toraymyxin and similar adsorption to CytoSorb for the removal of other inflammatory mediators. Differences in device removal capacities could enable treatment to be more tailored to patients.

Electronic supplementary material

The online version of this article (10.1186/s40635-018-0177-2) contains supplementary material, which is available to authorized users.

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Most cited references 20

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Sepsis and acute kidney injury.

Abolfazl Zarjou, Anupam Agarwal (2011)

Sepsis is a severe and dysregulated inflammatory response to infection characterized by end-organ dysfunction distant from the primary site of infection. Development of acute kidney injury (AKI) during sepsis increases patient morbidity, predicts higher mortality, has a significant effect on multiple organ functions, is associated with an increased length of stay in the intensive care unit, and hence consumes considerable healthcare resources. When compared with AKI of nonseptic origin, septic AKI is characterized by a distinct pathophysiology and therefore requires a different approach. Despite impressive advances in several fields of medicine, the pathophysiology, diagnostic procedures, and appropriate therapeutic interventions in sepsis are still highly debatable. Numerous immunomodulatory agents showing promise in preclinical studies fail to reduce the overwhelmingly high mortality rate of sepsis and provoke AKI when compared with other critically ill patients. Major impediments to progress in understanding, early diagnosis, and application of appropriate therapeutic modalities in sepsis-induced AKI include limited histopathologic information, few animal models that closely mimic human sepsis, and a relative shortage of specific diagnostic tools. Here we discuss the most recent advances in understanding the fundamental mechanisms of sepsis-induced AKI, characteristics of relevant animal models available, and potential therapies.

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Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial

Didier M. Payen, Joëlle Guilhot, Yoann Launey … (2015)

Purpose To test whether the polymyxin B hemoperfusion (PMX HP) fiber column reduces mortality and organ failure in peritonitis-induced septic shock (SS) from abdominal infections. Method Prospective, multicenter, randomized controlled trial in 18 French intensive care units from October 2010 to March 2013, enrolling 243 patients with SS within 12 h after emergency surgery for peritonitis related to organ perforation. The PMX HP group received conventional therapy plus two sessions of PMX HP. Primary outcome was mortality on day 28; secondary outcomes were mortality on day 90 and a reduction in the severity of organ failures based on Sequential Organ Failure Assessment (SOFA) scores. Results Primary outcome: day 28 mortality in the PMX HP group (n = 119) was 27.7 versus 19.5 % in the conventional group (n = 113), p = 0.14 (OR 1.5872, 95 % CI 0.8583–2.935). Secondary endpoints: mortality rate at day 90 was 33.6 % in PMX-HP versus 24 % in conventional groups, p = 0.10 (OR 1.6128, 95 % CI 0.9067–2.8685); reduction in SOFA score from day 0 to day 7 was −5 (−11 to 6) in PMX-HP versus −5 (−11 to 9), p = 0.78. Comparable results were observed in the predefined subgroups (presence of comorbidity; adequacy of surgery, <2 sessions of hemoperfusion) and for SOFA reduction from day 0 to day 3. Conclusion This multicenter randomized controlled study demonstrated a non-significant increase in mortality and no improvement in organ failure with PMX HP treatment compared to conventional treatment of peritonitis-induced SS. Electronic supplementary material The online version of this article (doi:10.1007/s00134-015-3751-z) contains supplementary material, which is available to authorized users.

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Sepsis-induced acute kidney injury revisited: pathophysiology, prevention and future therapies.

Alexander Zarbock, Hernando Gómez, John A. Kellum (2014)

Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with increased morbidity and mortality. Sepsis is the most common cause of AKI. Considerable evidence now suggests that the pathogenic mechanisms of sepsis-induced AKI are different from those seen in other causes of AKI. This review focuses on the recent advances in this area and discusses possible therapeutic interventions that might derive from these new insights into the pathogenesis of sepsis-induced AKI.

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Author and article information

Contributors

Benjamin Malard:

ORCID: http://orcid.org/0000-0002-8146-926X

+33 4 72 45 39 01 , benjamin_malard@baxter.com

Corine Lambert: corine_lambert@baxter.com

John A. Kellum: kellum@pitt.edu

Journal

Journal ID (nlm-ta): Intensive Care Med Exp

Journal ID (iso-abbrev): Intensive Care Med Exp

Title: Intensive Care Medicine Experimental

Publisher: Springer International Publishing (Cham )

ISSN (Electronic): 2197-425X

Publication date (Electronic): 4 May 2018

Publication date PMC-release: 4 May 2018

Publication date Collection: December 2018

Volume: 6

Electronic Location Identifier: 12

Affiliations

[1 ]GRID grid.487322.8, R&D Department, Gambro Industries, ; 7 avenue Lionel Terray, 69330 Meyzieu, France

[2 ]ISNI 0000 0004 1936 9000, GRID grid.21925.3d, Center for Critical Care Nephrology, Department of Critical Care Medicine, , University of Pittsburgh, ; 604 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261 USA

Author information

Benjamin Malard http://orcid.org/0000-0002-8146-926X

Article

Publisher ID: 177

DOI: 10.1186/s40635-018-0177-2

PMC ID: 5935601

PubMed ID: 29728790

SO-VID: 187aaa7d-928a-4823-a889-e2a24da6757c

License:

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.

History

Date received : 15 February 2018

Date accepted : 13 April 2018

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100004702, Baxter International;

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Keywords: adsorption,blood purification,cytokines,endotoxins,oxiris,septic shock,removal rate

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Keywords: adsorption, blood purification, cytokines, endotoxins, oxiris, septic shock, removal rate

In vitro comparison of the adsorption of inflammatory mediators by blood purification devices

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Biomarkers for Inflammatory Lung Disease

Most cited references 20

Sepsis and acute kidney injury.

Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial

Sepsis-induced acute kidney injury revisited: pathophysiology, prevention and future therapies.

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