Extracorporeal cytokine adsorption in septic shock: A proof of concept randomized, controlled pilot study (original) (raw)
Related papers
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.
Biomedicines, 2021
Hemodynamic instability due to dysregulated host response is a life-threatening condition requiring vasopressors and vital organ support. Hemoadsorption with Cytosorb has proven to be effective in reducing cytokines and possibly in attenuating the devastating effects of the cytokine storm originating from the immune over-response to the initial insult. We reviewed the PubMed database to assess evidence of the impact of Cytosorb on norepinephrine needs in the critically ill. We further analyzed those studies including data on control cohorts in a comparative pooled analysis, defining a treatment effect as the standardized mean differences in relative reductions in vasopressor dosage at 24 h. The literature search returned 33 eligible studies. We found evidence of a significant reduction in norepinephrine requirement after treatment: median before, 0.55 (IQR: 0.39–0.90); after, 0.09 (0.00–0.25) μg/kg/min, p < 0.001. The pooled effect size at 24 h was large, though characterized by ...
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.
Prognostic values of serum cytokines in septic shock
Intensive Care Medicine, 1994
cantly associated with a favourable outcome. IL6 is certainly involved in the pathophysiology of septic shock but further studies are required to determine whether or not it is directly involved in the mediation of late and lethal complications of septic shock. Serum lactate levels and oxygen-derived variables were of less interest as prognostic factors.
The time course of adrenocortical hormones and cytokines in sepsis and/or septic shock
Critical Care, 2005
Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated with significant morbidity and mortality. The aim of this study was to evaluate conditions that could predict a poor outcome. Design Retrospective analyse of 69 patients admitted to the ICU from 1996 to 2003. Demographic data included age, sex and medical history. Etiologic agents, multiorgan dysfunction, nosocomial infections, SAPS II and PORT scores were recorded for each patient. For statistical analysis we used a t test, chi-square test and Mann-Whitney U test on SPSS ® . A value of P less than 0.05 was considered significant. Results Forty-seven patients were male and 22 patients were female. Mean age was 52 years. Sixty-seven percent had serious pre-morbid conditions including pulmonary disease (34.8%), cardiac problems (36.2%), diabetes (13%) and chronic liver disease (5.8%); 40.6% were smokers, drug abusers or alcohol dependents. Sixtyeight patients required invasive mechanical ventilation. The average length of ventilation was 13.5 days, median 8 days. The mean SAPS II score was 40.14 and the mean PORT score was 141. The mortality rate was 27.5% (SAPS II estimated mortality, 35%). Complications reported were ARDS (40.6%), septic shock (34.8%), acute renal failure (2.9%), cardiac arrest (8.7%) and nosocomial infeccions (46.4%). Mortality rates were higher for previous hepatic (75%) and metabolic (33%) diseases. We found a close association between crude mortality and SAPS II score (P = 0.003) and development of complications (P = 0.0028). Respiratory dysfunction (P = 0.006) and septic shock (P = 0.022) were most significantly related to mortality. No significant differences were founded regarding age, comorbidities, PORT score, etiologic agents, nosocomial infections and length of invasive mechanical ventilation. Conclusions Previous hepatic chronic disease was strictly related to higher mortality as well as isolation of MRSA. ARDS and septic shock predicted a poor outcome. SAPS II score was the best severity indicator of mortality.
Extracorporeal Cytokine Removal in Critically Ill COVID-19 Patients: A Case Series
Frontiers in Medicine, 2021
Introduction: Extracorporeal hemoadsorption (HA) is a potential adjunctive therapy in severe cases of COVID-19 associated pneumonia. In this retrospective study we report data from critically ill patients treated with HA during the first and second wave of the pandemic.Patients and Methods: All patients, who received HA therapy with CytoSorb within the first 96 h of intensive care unit (ICU) admission without hospital-acquired bacterial superinfection, were included. Clinical and laboratory data were collected: on admission, before (TB) and after (TA) HA therapy.Results: Out of the 367 COVID-19 cases, 13 patients were treated with CytoSorb, also requiring mechanical ventilation and renal replacement therapy. All patients were alive at the end of HA, but only 3 survived hospital stay. From TB-TA there was a tendency of decreasing norepinephrine requirement: 193.7 [IQR: 34.8–270.4] to 50.2 [6.5–243.5] ug/kg/day and increasing PaO2/FiO2 ratio 127.8 (95% CI: 96.0–159.6) to 155.0 (115.3–...
Trials, 2023
Background Sepsis is as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. The mortality of sepsis and particular of septic shock is very high. Treatment mostly focuses on infection control but a specific intervention that targets the underlying pathological host response is lacking to the present time. The investigators hypothesize that early therapeutic plasma exchange (TPE) will dampen the maladaptive host response by removing injurious mediators thereby limiting organ dysfunction and improving survival in patients with septic shock. Although small prospective studies demonstrated rapid hemodynamic stabilization under TPE, no adequately powered randomized clinical trial has investigated hard outcomes. Methods This is a randomized, prospective, multicenter, open-label, controlled, parallel-group interventional trial to test the adjunctive effect of TPE in patients with early septic shock. Patients with a refractory (defined as norepinephrine (NE) ≥ 0.4 μg/kg/min ≥ 30 min OR NE 0.3 μg/kg/min + vasopressin) and early (shock onset < 24 h) septic shock will be included. The intervention is a standard TPE with donor fresh frozen plasma (1.2 × individual plasma volume) performed within 6 h after randomization and will be compared to a standard of care (SOC) control arm. The primary endpoint is 28 days mortality for which the power analysis revealed a group size of 137 / arm (n = 274) to demonstrate a benefit of 15%. The key secondary objective will be to compare the extent of organ failure indicated by mean SOFA over the first 7 days as well as organ support-free days until day 28 following randomization. Besides numerous biological secondary, safety endpoints such as incidence of bleeding, allergic reactions, transfusion associated lung injury, severe thrombocytopenia, and other severe adverse events will be assessed during the first 7 days. For exploratory scientific analyses, biomaterial will be acquired longitudinally and multiple predefined scientific subprojects are planned. This study is an investigator-initiated trial supported by the German Research Foundation (DFG, DA 1209/7-1), in which 26 different centers in Germany, Switzerland, and Austria will participate over a duration of 33 months. Discussion This trial has substantial clinical relevance as it evaluates a promising adjunctive treatment option in refractory septic shock patients suffering from an extraordinary high mortality. A positive trial result could change the