Effect of extracorporeal cytokine removal on vascular barrier function in a septic shock patient

Abstract

BackgroundSepsis and septic shock are major healthcare problems, affecting millions of individuals around the world each year. Pathophysiologically, septic multiple organ dysfunction (MOD) is a life-threatening condition caused by an overwhelming systemic inflammatory response of the host’s organism to an infection. We experimentally tested if high circulating cytokine levels might increase vascular permeability—a critical hallmark of the disease—and if this phenomenon can be reversed by therapeutic cytokine removal (CytoSorb®) in an exemplary patient.Case presentationA 32-year-old Caucasian female presented with septic shock and accompanying acute kidney injury (Sequential Organ Failure Assessment (SOFA) = 18) to our ICU. In spite of a broad anti-infective regimen, adequate fluid resuscitation, and high doses of inotropics and catecholamines, she remained refractory hypotensive. The extraordinary severity of septic shock suggested an immense overwhelming host response assumingly accompanied by a notable cytokine storm such as known from patients with toxic shock syndrome. Thus, a CytoSorb® filter was added to the dialysis circuit to remove excess shock-perpetuating cytokines. To analyze the endothelial phenotype in vitro before and after extracorporeal cytokine removal, we tested the septic shock patient’s serum on human umbilical vein endothelial cells (HUVECs). The effect on endothelial integrity was assessed both on the morphological (fluorescent immunocytochemistry for VE-cadherin and F-actin) and functional (transendothelial electrical resistance (TER)) level that was recorded in real time with an “electric cell-substrate impedance sensing” (ECIS) system (ibidi). We found (1) severe alterations of cell-cell contacts and the cytoskeletal architecture and (2) profound functional permeability changes, the putative cellular correlate of the clinical vascular leakage syndrome. However, the endothelial barrier was protected from these profound adverse effects when HUVECs were challenged with septic shock serum that was collected after extracorporeal cytokine removal.ConclusionsBeneficial observations of extracorporeal cytokine removal in septic shock patients might—at least in part—be promoted via protection of vascular barrier function.

Removal of focal segmental glomerulosclerosis (FSGS) factor suPAR using CytoSorb

“…The clearance of suPAR and CLCF‐1 could display a preemptive treatment strategy as opposed to current treatment options. Recently, first evidence of the positive effects of CytoSorb hemoadsorption based removal of soluble factors on the therapeutic reorganization of the cytoskeleton was published supporting its potential in the FSGS treatment . However, the efficient size‐dependent clearance by CytoSorb hemoadsorption is very likely to influence serum concentrations of administered pharmaceuticals either for the underlying kidney or other comorbidities …”

“…30 However, the efficient size-dependent clearance by CytoSorb hemoadsorption is very likely to influence serum concentrations of administered pharmaceuticals either for the underlying kidney or other comorbidities. 30…”

Application of Hemoadsorption in Neonatal and Pediatric Hyperinflammatory States: A Case Series

“…nitric oxide production via iNOS) resulting in stabilization of the vascular tone and a reduction in vasoplegia. Moreover, there is evidence, mainly from case reports, that hemoadsorption may have a positive impact on vascular barrier integrity and therefore indirectly on capillary leakage syndrome, which might also be part of the beneficial effects of CytoSorb therapy on hemodynamics [21][22][23].…”

The answer is blowing in the wind: an uncommon cause for severe ARDS accompanied by circulatory insufficiency requiring extracorporeal membrane oxygenation

“…Although the role of TPE in modern sepsis therapy remains unclear, several case series and small randomised controlled trials suggest that TPE improves coagulation, haemodynamics and possibly survival in severe sepsis 34. Removal of cytokines using the Cytosorb device would have represented an alternative treatment, yet we deliberately chose to perform TPE using fresh frozen plasma, as we aimed to combine removal of cytokines with the replenishment of plasma components such as ADAMTS-13 whose decrease had been shown to be associated with poor prognosis in sepsis-induced organ failure 35 36…”