The Potential Role of Extracorporeal Cytokine Removal in Hemodynamic Stabilization in Hyperinflammatory Shock (original) (raw)
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Journal of Critical Care
Background: The aim of this proof of concept, prospective, randomized pilot trial was to investigate the effects of extracorporeal cytokine removal (CytoSorb®) applied as a standalone treatment in patients with septic shock. Methods: 20 patients with early (b24 h) onset of septic shock of medical origin, on mechanical ventilation, norepinephrineN10 μg/min, procalcitonin (PCT) N 3 ng/mL without the need for renal replacement therapy were randomized into CytoSorb (n = 10) and Control groups (n = 10). CytoSorb therapy lasted for 24 h. Clinical and laboratory data were recorded at baseline (T 0), T 12 , T 24 , and T 48 hours. Results: Overall SOFA scores did not differ between the groups. In the CytoSorb-group norepinephrine requirements and PCT concentration decreased significantly
Scientific Reports, 2023
Extracorporeal cytokine adsorption aims to reduce cytokine levels in critically ill patients. However, little convincing data exist to support its widespread use. This retrospective study compared interleukin-6 (IL-6) levels in patients treated with or without cytokine adsorber (CytoSorb®). Intensive care patients between Jan 2017 and Dec 2021 who had at least two IL-6 measurements were included. They were divided into an adsorber group and a standard of care group. We screened 3865 patients and included 52 patients in the adsorber group and 94 patients in the standard of care group. Matching was performed and the groups were compared regarding IL-6, lactate, CRP, procalcitonin, vasopressor requirement, and mortality rate. After matching, there were 21 patients in each group. Patients had similar age, ECMO and renal replacement therapy use, baseline noradrenaline requirement, serum lactate, pH, CRP, and IL-6 levels. There were no significant differences in the time course of IL-6, lactate, CRP, procalcitonin and noradrenaline requirement between groups. Two-day and ICU mortality and Kaplan-Meier estimated survival were also comparable. In this matched case-control study no difference in IL-6, inflammatory parameters, noradrenaline requirement or mortality was observed between patients treated with adsorber or standard of care.
2021
Introduction Sepsis and septic shock have mortality rates between 20% and 50%. In sepsis, the immune response becomes dysregulated, which leads to an imbalance between proinflammatory and anti-inflammatory mediators. When standard therapeutic measures fail to improve patients’ condition, additional therapeutic alternatives are applied to reduce morbidity and mortality. One of the most recent alternatives is extracorporeal cytokine adsorption with a device called CytoSorb. This study aims to compare the efficacy of standard medical therapy and continuous extracorporeal cytokine removal with CytoSorb therapy in patients with early refractory septic shock. Furthermore, we compare the dosing of CytoSorb adsorber device changed every 12 or 24 hours. Methods and analysis It is a prospective, randomised, controlled, open-label, international, multicentre, phase III study. Patients fulfilling the inclusion criteria will be randomly assigned to receive standard medical therapy (group A) or—i...
Dysregulated response of cytokines can result in hyper-inflammatory conditions called cytokine storm,commonly seen in sepsis and septic shock..The current study assessed hemoadsorption device-CytoSorb® for its efficiency as an adjuvant in treating patients suffering from septic shock. Total 8 patients enrolled were subjected to hemoadsorption therapy along with the standard treatment.The results of the study revealed significant improvement in clinical and haemodynamic parameters before and after initiation of CytoSorb® therapy. Out of 8 patients, 6 showed a positive outcome while 2 did not survive.The results of this study show that the use of hemoadsorption therapy can be considered in critically ill ICU patients as a safe and effective adjuvant therapy along with the standard treatment for a better outcome in patients.
Cytokine Adsorption in Critically Ill Patients Requiring ECMO Support
Frontiers in Cardiovascular Medicine
Systemic inflammation is a key characteristic of sepsis but also also in non-infectious conditions such as post-cardiac arrest syndrome. Cytokine adsorption and extracorporeal membrane oxygenation are emerging therapies applied in these critically ill patients, but the experience with their concurrent use is limited. We evaluated cytokine adsorption in critically ill patients requiring support with either veno-venous (vv) or veno-arterial (va) extracorporeal membrane oxygenation (ECMO) support and hypothesized that adsorber incorporation into the ECMO circuit was technically feasible and not associated with imminent risk. We analyzed data from the first six cases of a prospective single-center registry of patients undergoing veno-venous (vv) or veno-arterial (va) ECMO therapy. While in most published cases cytokine adsorbers were inserted into a hemofiltration circuit, we directly incorporated the adsorber into the ECMO circuit without interruption of continuous ECMO support. We observed no relevant side effects attributable to cytokine adsorption. Thirty-day mortality was 83% (predicted mortality 87%), indicating that the decision for adding cytokine adsorption may have been considered as an ultima ratio decision in severe cases with poor prognosis. Vasopressor or inotrope use, lactate level, and fluid balance did not change significantly when comparing pre-vs. post-cytokine adsorption values. Interestingly, the real-time course of the mentioned three surrogate parameters remained unaltered in all but two cases, regardless of cytokine removal. Beneficial effects of cytokine adsorption are plausible in two va-ECMO-treated patient, where increasing lactate began to drop after initiation of cytokine adsorption. Taken together, these data suggest that incorporation of cytokine adsorption into the management of critically ill patients requiring continued ECMO support is feasible and easy to handle. Whether cytokine removal improves clinical outcome in ECMO-treated patients should now be investigated in randomized controlled trials.
American Journal of Respiratory and Critical Care Medicine, 2013
Rationale: Changes in plasma cytokine levels may predict mortality, and therapies (vasopressin versus norepinephrine) could change plasma cytokine levels in early septic shock. Objectives: Our hypotheses were that changes in plasma cytokine levels over 24 hours differ between survivors and nonsurvivors, and that there are different effects of vasopressin and norepinephrine on plasma cytokine levels in septic shock. Methods: We studied 394 patients in a randomized, controlled trial of vasopressin versus norepinephrine in septic shock. We used hierarchical clustering and principal components analysis of the baseline cytokine concentrations to subgroup cytokines; we then compared survivors to nonsurvivors (28 d) and compared vasopressin-versus norepinephrine-induced changes in cytokine levels over 24 hours. Measurements and Main Results: A total of 39 plasma cytokines were measured at baseline and at 24 hours. Hierarchical clustering and principal components analysis grouped cytokines similarly. Survivors (versus nonsurvivors) had greater decreases of overall cytokine levels (P , 0.001). Vasopressin decreased overall 24-hour cytokine concentration compared with norepinephrine (P ¼ 0.037). In less severe septic shock, the difference in plasma cytokine reduction over 24 hours between survivors and nonsurvivors was less pronounced than that seen in more severe septic shock. Furthermore, vasopressin decreased interferon-inducible protein 10 and granulocyte colonystimulating factor more than did norepinephrine in less severe septic shock, whereas vasopressin decreased granulocyte-macrophage colony-stimulating factor in patients who had more severe shock. Conclusions: Survivors of septic shock had greater decreases of cytokines, chemokines and growth factors in early septic shock. Vasopressin decreased 24-hour plasma cytokine levels more than did norepinephrine. The vasopressin-associated decrease of cytokines differed according to severity of shock. Clinical trial registered with www.controlled-trials.com (ISRCTN94845869).
Wiener klinische Wochenschrift, 2014
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Early Use of Norepinephrine Improves Survival in Septic Shock: Earlier than Early
Archives of Medical Research, 2019
Background. The timing of initiation of Norepinephrine (NEP) in septic shock is controversial. Aim of the study. We evaluated the impact of early NEP simultaneously with fluids in those patients. Methods. We randomized 101 patients admitted to the emergency department with septic shock to early NEP simultaneously with IV fluids (early group) or after failed fluids trial (late group). The primary outcome was the in-hospital survival while the secondary outcomes were the time to target mean arterial pressure (MAP) of 65 mmHg, lactate clearance and resuscitation volumes. Results. There was no significant difference between the two groups regarding the baseline characteristics. NEP infusion started after 25 (20e30) and 120 (120e180) min in the early and late groups (p 5 0.000). MAP of 65 mmHg was achieved faster in the early group (2 [1e3.5] h vs. 3 [2e4.75] h, p 5 0.003). Serum lactate was decreased by 37.8 (24e49%) and 22.2 (3.3e38%) in both groups respectively (p 5 0.005). Patients with early NEP were resuscitated by significantly lower volume of fluids (25 [18.8e28.7] mL/kg vs. 32.5 [24.4e34.6] mL/kg) in the early and late groups (p 5 0.000). The early group had survival rate of 71.9% compared to 45.5% in the late group (p 5 0.007). NEP started after 30 (20e120 min) in survivors vs. 120 (30e165 min) in non-survivors (p 5 0.013). Conclusions. We concluded that early Norepinephrine in septic shock might cause earlier restoration of blood pressure, better lactate clearance and improve in-hospital survival.
Potentially Inadvertent Immunomodulation: Norepinephrine Use in Sepsis
American journal of respiratory and critical care medicine, 2016
Septic shock is a major cause of death worldwide and a considerable healthcare burden in the twenty-first century. Attention has shifted from damaging effects of the proinflammatory response to the detrimental role of antiinflammation, a phenomenon known as sepsis-induced immunoparalysis. Sepsis-induced immunoparalysis may render patients vulnerable to secondary infections and is associated with impaired outcome. The immunoparalysis hypothesis compels us to reevaluate the current management of septic shock and to assess whether we are inadvertently compromising or altering the host immune response. In this perspective, we discuss the potential detrimental role of norepinephrine, the cornerstone treatment for septic shock, in sepsis-induced immunoparalysis. We provide a short overview of the current understanding of the immunologic pathophysiology of sepsis, followed by a detailed description of the immunomodulatory effects of norepinephrine and alternative vasopressors. We conclude ...
Cytokine Removal by Plasma Exchange with Continuous Hemodiafiltration in Critically Ill Patients
Therapeutic Apheresis and Dialysis, 2002
The effectiveness of plasma exchange (PE) with continuous hemodiafiltration (CHDF) in the treatment of critically ill patients was evaluated based on changes in cytokine levels. Twenty-six patients with acute hepatic failure were treated with PE (PE group) or PE and CHDF (PE+CHDF group), and the levels of cytokines such as tumor necrosis factor (TNF)-␣, interleukin (IL)-6, and IL-8 were determined before and after treatment. Bilirubin levels were significantly lower after treatment in both the PE and PE+CHDF groups. There were no significant differences in TNF-␣ levels before and after treatment in the PE group, but the TNF-␣ level was significantly lower after treatment in the PE+CHDF group. There were no significant differences in the IL-6 levels before and after treatment in both the PE and PE+CHDF groups. There were no significant differences in IL-8 levels before and after treatment in the PE group, but the IL-8 level was significantly lower after treatment in the PE+CHDF group. PE with CHDF therapy was given to 5 patients with acutely aggravated autoimmune diseases, 2 patients with hemorrhagic shock and encephalopathy syndrome, and 3 patients with thrombotic microangiopathy. The results suggested that PE with CHDF therapy are useful in critically ill patients with suspected hypercytokinemia.