Systematic review with expert consensus on use of extracorporeal hemoadsorption in septic shock:An Indian perspective

BACKGROUND Septic shock is a severe form of sepsis characterised by deterioration in circulatory and cellular-metabolic parameters.Despite standard therapy,the outcomes are poor.Newer adjuvant therapy,such as CytoSorb®extracorporeal haemoadsorption device,has been investigated and shown promising outcome.However,there is a lack of some guidance to make clinical decisions on the use of CytoSorb®haemoadsorption as an adjuvant therapy in septic shock in Indian Setting.Therefore,this expert consensus was formulated.AIM To formulate/establish specific consensus statements on the use of CytoSorb®haemoadsorption treatment based on the best available evidence and contextualised to the Indian scenario.METHODS We performed a comprehensive literature on CytoSorb®haemoadsorption in sepsis,septic shock in PubMed selecting papers published between January 2011 and March 20232021 in English language.The statements for a consensus document were developed based on the summarised literature analysis and identification of knowledge gaps.Using a modified Delphi approach combining evidence appraisal and expert opinion,the following topics related to CytoSorb®in septic shock were addressed:need for adjuvant therapy,initiation timeline,need for Interleukin-6 levels,duration of therapy,change of adsorbers,safety,prerequisite condition,efficacy endpoints and management flowchart.Eleven expert members from critical care,emergency medicine,and the intensive care participated and voted on nine statements and one open-ended question.RESULTS Eleven expert members from critical care,emergency medicine,and the intensive care participated and voted on nine statements and one open-ended question.All 11 experts in the consensus group(100%)participated in the first,second and third round of voting.After three iterative voting rounds and adapting two statements,consensus was achieved on nine statements out of nine statements.The consensus expert panel also recognised the necessity to form an association or society that can keep a registry regarding the use of CytoSorb®for all indications in the open-ended question(Q10)focusing on“future recommendations for CytoSorb®therapy”.CONCLUSION This Indian perspective consensus statement supports and provides guidance on the use of CytoSorb®haemoadsorption as an adjuvant treatment in patients with septic shock to achieve optimal outcomes.

Experience with hemoadsorption (CytoSorb~?) in the management of septic shock patients

BACKGROUND Cytokines and inflammatory mediators are the hallmarks of sepsis.Extracorporeal cytokine hemoadsorption devices are the newer clinical support system to overcome the cytokine storm during sepsis.AIM To retrospectively evaluate the clinical outcomes of patients admitted in intensive care unit with septic shock with different etiologies.METHODS The laboratory parameters including biomarkers such as procalcitonin,serum lactate and C-reactive protein;and the hemodynamic parameters;mean arterial pressure,vasopressor doses,sepsis scores,cytokine levels and other vital parameters were evaluated.We evaluated these outcomes among survivors and non-survivors.RESULTS Of 100 patients evaluated,40 patients survived.Post treatment,the vasopressors dosage remarkably decreased though it was not statistically different;34.15%(P=0.0816)for epinephrine,20.5%for norepinephrine(P=0.3099)and 51%(P=0.0678)for vasopressin.In the survivor group,a remarkable reduction of biomarkers levels;procalcitonin(65%,P=0.5859),C-reactive protein(27%,P=0.659),serum lactate(27%,P=0.0159)and bilirubin(43.11%;P=0.0565)were observed from baseline after CytoSorb^® therapy.A significant reduction in inflammatory markers;interleukin 6 and interleukin 10;(87%and 92%,P<0.0001)and in tumour necrosis factor(24%,P=0.0003)was also seen.Overall,28(28%)patients who were given CytoSorb^® therapy less than 48 h after onset of septic shock survived and the maximum duration of stay for 70%of these patients in intensive care unit was less than 15 d.CONCLUSION CytoSorb^® is a safe and well tolerated rescue therapy option in patients with septic shock.However,early(preferably within<48 h after onset of septic shock)initiation could result in better clinical outcomes.Further randomized trials are needed to define the potential benefits of this new treatment modality.

Efficacy of HA330-II column hemoadsorption in Epstein-Barr virusassociated hemophagocytic lymphohistiocytosis combined with liver failure:A case report

BACKGROUND Hemophagocytic lymphohistiocytosis(HLH)is a severe and potentially deadly condition associated with extensive inflammation and immune activation.Cytokine adsorption may serve as a supportive treatment that can stabilize organ function in affected patients by reducing their circulating cytokines levels.To date,no descriptions of clinical experiences associated with the use of HA330-II column hemoadsorption for the treatment of children affected by HLH have been published.CASE SUMMARY We describe the case of an 11-year-old child with Epstein-Barr virus-associated HLH complicated by liver failure.She underwent HA330-II column hemoadsorption and chemotherapy and exhibited reductions in levels of inflammatory cytokines,including interleukin(IL),IL-6,IL-8,IL-10,and interferon-γ.The patient’s condition and laboratory parameters gradually improved with treatment.CONCLUSION Hemoadsorption may play an important role in cytokine storm elimination in children with HLH combined with liver failure and consequent multiple organ failure.

Preliminary study on the safety and efficacy of a new polymyxin B-immoblized resin column in treatment of LPS-induced sepsis beagles

Background:This study aims to assess the safety and efficacy of direct hemoperfu-sion using a new polymyxin B-immobilized resin column(disposable endotoxin ad-sorber,KCEA)in an endotoxin/lipopolysaccharide(LPS)-induced sepsis model.Methods:Eighteen beagles were randomized into 1 intervention group(KCEA group,n=6)and 2 control groups(sham group and model group,n=6 each).Sepsis was in-duced by continuous intravenous application of 0.5 mg/kg body weight of endotoxin for 60 min.An extracorporeal hemoperfusion device made with KCEA for endotoxin adsorption was used.Model group beagles received standard treatment with fluids and vasoactive drugs,KCEA group beagles received standard treatment and direct hemoperfusion of KCEA for 2 h,and sham group beagles were treated with standard treatment and direct hemoperfusion of a sham column for 2 h.Results:Good blood compatibility of KCEA was confirmed by assessing clinical pa-rameters.Blood endotoxin peak levels in the KCEA group were significantly lower,resulting in a significant suppression of IL-6,TNF-αand procalcitonin,which improved mean arterial pressure and significantly lowered vasopressor demand,thereby pro-tecting organ function and improving survival time and rate.In the KCEA group,MAP was significantly higher over 6 h than those recorded both in the sham group and model group.The 7-day survival rates of the KCEA,sham and model groups were 50%,0%and 0%,respectively.Conclusion:KCEA hemoadsorption was effective at detoxifying circulatory endotoxin and inflammatory mediators and contributed to the decreased mortality rate in the sepsis beagles.

Investigating Cytokine Binding Using a Previously Reported TNF-Specific Aptamer

Cytokines are of chief importance in the pathophysiology of sepsis and other systemic inflammatory response syndromes. We are designing and testing an extracorporeal cytokine adsorption device (CAD) that can remove cytokines via adsorption on biocompatible, microporous beads. The goal of this study was to determine whether a previously reported TNF binding DNA aptamer, 5’-GCGGCCGATA AGGTCTTTCC AAGCGAACGA ATTGAACCGC-3’, could be immobilized our hemoadsorption polymer surface to increase the removal rate of TNF. A reservoir consisting of horse serum spiked with a known concentration of TNF was perfused through our CAD packed with aptamer modified or unmodified (control) polymer beads. The binding affinity of the TNF aptamer was characterized using an enzyme-linked oligonucleotide assay (ELONA). As a positive control a well-established DNA aptamer that binds PDGF BB was also subjected to the same ELONA to validate the assay. TNF capture using the CAD showed no TNF removal over four hours for both the aptamer modified and unmodified control beads. Additionally, the results of the ELONA showed no binding of TNF to the reported aptamer;however the PDGF BB aptamer did bind PDGF BB. Based on these results we are able to conclude that the reported TNF specific aptamer does not bind TNF. These results will be of importance to other studies exploring aptamers for specific binding of TNF.