Hemofiltration and Immune Response in Severe Sepsis

Hörner, Christian; Schuster, Silke; Plachky, J.; Hofer, Stefan; Martin, Eike; Weigand, Markus A.

doi:10.1016/j.jss.2006.09.019

Cited by 8 publications

(6 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Up-regulated surface expression of β 2 -integrin has been reported on freshly isolated PMN stimulated with blood plasma obtained from severe sepsis patients 24 hours after diagnosis [ 34 ]. Treatment of PMN with individual chemokines, such as IL-8, may also induce LFA-1- or Mac-1-dependent PMN adhesion [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Human severe sepsis cytokine mixture increases β2-integrin-dependent polymorphonuclear leukocyte adhesion to cerebral microvascular endothelial cells in vitro

et al. 2015

View full text Add to dashboard Cite

IntroductionSepsis-associated encephalopathy (SAE) is a state of acute brain dysfunction in response to a systemic infection. We propose that systemic inflammation during sepsis causes increased adhesion of leukocytes to the brain microvasculature, resulting in blood-brain barrier dysfunction. Thus, our objectives were to measure inflammatory analytes in plasma of severe sepsis patients to create an experimental cytokine mixture (CM), and to use this CM to investigate the activation and interactions of polymorphonuclear leukocytes (PMN) and human cerebrovascular endothelial cells (hCMEC/D3) in vitro.MethodsThe concentrations of 41 inflammatory analytes were quantified in plasma obtained from 20 severe sepsis patients and 20 age- and sex-matched healthy controls employing an antibody microarray. Two CMs were prepared to mimic severe sepsis (SSCM) and control (CCM), and these CMs were then used for PMN and hCMEC/D3 stimulation in vitro. PMN adhesion to hCMEC/D3 was assessed under conditions of flow (shear stress 0.7 dyn/cm2).ResultsEight inflammatory analytes elevated in plasma obtained from severe sepsis patients were used to prepare SSCM and CCM. Stimulation of PMN with SSCM led to a marked increase in PMN adhesion to hCMEC/D3, as compared to CCM. PMN adhesion was abolished with neutralizing antibodies to either β2 (CD18), αL/β2 (CD11α/CD18; LFA-1) or αM/β2 (CD11β/CD18; Mac-1) integrins. In addition, immune-neutralization of the endothelial (hCMEC/D3) cell adhesion molecule, ICAM-1 (CD54) also suppressed PMN adhesion.ConclusionsHuman SSCM up-regulates PMN pro-adhesive phenotype and promotes PMN adhesion to cerebrovascular endothelial cells through a β2-integrin-ICAM-1-dependent mechanism. PMN adhesion to the brain microvasculature may contribute to SAE.

show abstract

Section: Discussionmentioning

confidence: 99%

Human severe sepsis cytokine mixture increases β2-integrin-dependent polymorphonuclear leukocyte adhesion to cerebral microvascular endothelial cells in vitro

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Although early uncontrolled work suggested benefit to simple continuous peritoneal lavage after either gross peritoneal contamination in secondary peritonitis or in the setting of necrotizing pancreatitis [ 92 , 93 ], more structured studies could not confirm such benefits [ 94 – 96 ]. Thereafter, work focused upon using hemofiltration to remove inflammatory mediators from the blood which has been associated with reduced elevations of inflammatory cytokines (as assessed by blood IL-6 levels), early improvements of hemodynamic state, and decreased lactate levels [ 97 – 99 ]. In an attempt to comprehensively increase efficiency, the potential utility of adding extra-corporeal mediator removal through hemofiltration in addition to continuous peritoneal lavage have been entertained and studied in early models [ 91 ].…”

Section: Discussionmentioning

confidence: 99%

Closed Or Open after Source Control Laparotomy for Severe Complicated Intra-Abdominal Sepsis (the COOL trial): study protocol for a randomized controlled trial

et al. 2018

View full text Add to dashboard Cite

BackgroundSevere complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. Principles of treatment include early antibiotic administration and operative source control. A further therapeutic option may be open abdomen (OA) management with active negative peritoneal pressure therapy (ANPPT) to remove inflammatory ascites and ameliorate the systemic damage from SCIAS. Although there is now a biologic rationale for such an intervention as well as non-standardized and erratic clinical utilization, this remains a novel therapy with potential side effects and clinical equipoise.MethodsThe Closed Or Open after Laparotomy (COOL) study will constitute a prospective randomized controlled trial that will randomly allocate eligible surgical patients intra-operatively to either formal closure of the fascia or use of the OA with application of an ANPTT dressing. Patients will be eligible if they have free uncontained intra-peritoneal contamination and physiologic derangements exemplified by septic shock OR a Predisposition-Infection-Response-Organ Dysfunction Score ≥ 3 or a World-Society-of-Emergency-Surgery-Sepsis-Severity-Score ≥ 8. The primary outcome will be 90-day survival. Secondary outcomes will be logistical, physiologic, safety, bio-mediators, microbiological, quality of life, and health-care costs. Secondary outcomes will include days free of ICU, ventilation, renal replacement therapy, and hospital at 30 days from the index laparotomy. Physiologic secondary outcomes will include changes in intensive care unit illness severity scores after laparotomy. Bio-mediator outcomes for participating centers will involve measurement of interleukin (IL)-6 and IL-10, procalcitonin, activated protein C (APC), high-mobility group box protein-1, complement factors, and mitochondrial DNA. Economic outcomes will comprise standard costing for utilization of health-care resources.DiscussionAlthough facial closure after SCIAS is considered the current standard of care, many reports are suggesting that OA management may improve outcomes in these patients. This trial will be powered to demonstrate a mortality difference in this highly lethal and morbid condition to ensure critically ill patients are receiving the best care possible and not being harmed by inappropriate therapies based on opinion only.Trial registrationClinicalTrials.gov, NCT03163095.

show abstract

“…Furthermore, hemofiltration membranes per se may increase cytokine production by activating mononuclear cells. In 2007, Horner et al [23] concluded that plasma from septic patients contains substances mediating a substantially different immune response pattern compared with plasma from critically ill nonseptic patients. In an experimental study, Toft et al [24] showed that infusion of endotoxin in pigs induced a significant increase in IL-6 and IL-10 levels in peripheral blood, but there was no difference in cytokine levels between CVVH-treated and nontreated septic animals.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effect of Continuous Venovenous Hemofiltration during Sepsis: Preliminary Data

Servillo

Vargas

Pastore

et al. 2013

BioMed Research International

View full text Add to dashboard Cite

Introduction. Severe sepsis and septic shock are the primary causes of multiple organ dysfunction syndrome (MODS), which is the most frequent cause of death in intensive care unit patients. Many pro- and anti-inflammatory mediators, such as interleukin-6 (IL-6), play a strategic role in septic syndrome. Continuous renal replacement therapy (CRRT) removes in a nonselective way pro- and anti-inflammatory mediators. Objective. To investigate the effects of continuous venovenous hemofiltration (CVVH) as an immunomodulatory treatment of sepsis in a prospective clinical study. Methods. High flux hemofiltration (Qf = 60 ml/Kg/hr) was performed for 72 hr in thirteen critically ill patients suffering from severe sepsis or septic shock with acute renal failure (ARF). IL-6 gene expression was measured by real-time PCR analysis on RNA extracted from peripheral blood mononuclear cell before beginning of treatment (T0) and after 12, 24, 48, and 72 hours (T1–4). Results. Real-time PCR analysis demonstrated in twelve patients IL-6 mRNA reduction after 12 hours of treatment and a progressive increase after 24, 48, and 72 hours. Conclusions. We suggest that an immunomodulatory effect might exist during CVVH performed in critically ill patients with severe sepsis and septic shock. Our data show that the transcriptional activity of IL-6 increases during CVVH.

show abstract

Hemofiltration and Immune Response in Severe Sepsis

Cited by 8 publications

References 23 publications

Human severe sepsis cytokine mixture increases β2-integrin-dependent polymorphonuclear leukocyte adhesion to cerebral microvascular endothelial cells in vitro

Human severe sepsis cytokine mixture increases β2-integrin-dependent polymorphonuclear leukocyte adhesion to cerebral microvascular endothelial cells in vitro

Closed Or Open after Source Control Laparotomy for Severe Complicated Intra-Abdominal Sepsis (the COOL trial): study protocol for a randomized controlled trial

Immunomodulatory Effect of Continuous Venovenous Hemofiltration during Sepsis: Preliminary Data

Contact Info

Product

Resources

About