Cytokine adsorption in severe, refractory septic shock.
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SUBMITTER: Wendel Garcia PD
PROVIDER: S-EPMC8409473 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundEndotoxin adsorption is a promising but controversial therapy in severe, refractory septic shock and conflicting results exist on the effective capacity of available devices to reduce circulating endotoxin and inflammatory cytokine levels.MethodsMultiarm, randomized, controlled trial in two Swiss intensive care units, with a 1:1:1 randomization of patients suffering severe, refractory septic shock with high levels of endotoxemia, defined as an endotoxin activity ≥ 0.6, a vasopressor dependency index ≥ 3, volume resuscitation of at least 30 ml/kg/24 h and at least single organ failure, to a haemoadsorption (Toraymyxin), an enhanced adsorption haemofiltration (oXiris) or a control intervention. Primary endpoint was the difference in endotoxin activity at 72-h post-intervention to baseline. In addition, inflammatory cytokine, vasopressor dependency index and SOFA-Score dynamics over the initial 72 h were assessed inter alia.ResultsIn the 30, out of 437 screened, randomized patients (10 Standard of care, 10 oXiris, 10 Toraymyxin), endotoxin reduction at 72-h post-intervention-start did not differ among interventions (Standard of Care: 12 [1-42]%, oXiris: 21 [10-51]%, Toraymyxin: 23 [10-36]%, p = 0.82). Furthermore, no difference between groups could be observed neither for reduction of inflammatory cytokine levels (p = 0.58), nor for vasopressor weaning (p = 0.95) or reversal of organ injury (p = 0.22).ConclusionsIn a highly endotoxemic, severe, refractory septic shock population neither the Toraymyxin adsorber nor the oXiris membrane could show a reduction in circulating endotoxin or cytokine levels over standard of care. Trial registration ClinicalTrials.gov. NCT01948778. Registered August 30, 2013. https://clinicaltrials.gov/study/NCT01948778.
| S-EPMC10721780 | biostudies-literature
Project description:BackgroundExtracorporeal cytokine adsorption is an option in septic shock as an additional measure to treat a pathological immune response. Purpose of this study was to investigate the effects of extracorporeal cytokine adsorption on hemodynamic parameters in patients with acute kidney injury (AKI) on continuous renal replacement therapy (CRRT) and septic shock after cardiac surgery.MethodsIn this retrospective study, a total of 98 patients were evaluated. Hemoadsorption was performed by the CytoSorb® adsorber. In all patients cytokine adsorption was applied for at least 15 hours and at least one adsorber was used per patient. To compare cumulative inotrope need in order to maintain a mean arterial pressure (MAP) of ≥ 65 mmHg, we applied vasoactive score (VAS) for each patient before and after cytokine adsorption. A paired t-test has been performed to determine statistical significance.ResultsBefore cytokine adsorption the mean VAS was 56.7 points. This was statistically significant decreased after cytokine adsorption (27.7 points, p< 0.0001). Before cytokine adsorption, the mean noradrenalin dose to reach a MAP of ≥ 65 mmHg was 0.49 μg/kg bw/min, the mean adrenalin dose was 0.12 μg/kg bw/min. After cytokine adsorption, significantly reduced catecholamine doses were necessary to maintain a MAP of ≥ 65 mmHg (0.24 μg/kg bw/min noradrenalin; p< 0.0001 and 0.07 μg/kg bw/min adrenalin; p < 0.0001). Moreover, there was a significant reduction of serum lactate levels after treatment (p< 0.0001). The mean SOFA-score for these patients with septic shock and AKI before cytokine adsorption was 16.7 points, the mean APACHE II-score was 30.2 points. The mean predicted in-hospital mortality rate based on this SOFA-score of 16.7 points was 77,0%, respectively 73,0% on APACHE II-score, while the all-cause in-hospital mortality rate of the patients in this study was 59.2%.ConclusionIn patients with septic shock and AKI undergoing cardiac surgery, extracorporeal cytokine adsorption could significantly lower the need for postoperative inotropes. Additionally, observed versus SOFA- and APACHE II-score predicted in-hospital mortality rate was decreased.
| S-EPMC7870055 | biostudies-literature
Project description:Refractory septic shock is associated with high morbidity and mortality. Hydroxocobalamin is used to treat postoperative vasoplegia; however, data supporting its use in the setting of refractory septic shock is limited and restricted to case reports. This study evaluates the effect of hydroxocobalamin on mean arterial pressure and vasopressor requirements in a series of patients with refractory septic shock.DesignSingle-center, retrospective analysis.SettingUrban, tertiary-care ICU.PatientsAdult ICU patients with refractory septic shock treated with hydroxocobalamin between August 2018 and January 2020.InterventionsHydroxocobalamin 5 g IV infusion.Measurements and main resultsTwenty-six patients were included for the analysis. Administration of hydroxocobalamin was associated with an increase in mean arterial pressure at 1, 6, and 24 hours postdose (+16.3, +14.3, and +16.3 mm Hg, respectively; p < 0.001). Increase in mean arterial pressure from baseline remained statistically significant when controlling for sex, age, and comorbid conditions. There was no change in the norepinephrine equivalents patients required 1 hour following hydroxocobalamin administration, but a statistically significant decrease in norepinephrine equivalent was observed at 6 and 24 hours postdose (p < 0.001).ConclusionsHydroxocobalamin provides sustained hemodynamic benefit at 24 hours in patients with refractory septic shock.
| S-EPMC8078293 | biostudies-literature
Project description:Morbidity and mortality from sepsis remains unacceptably high. Large variability in clinical practice, plus the increasing awareness that certain processes of care associated with improved critical care outcomes, has led to the development of clinical practice guidelines in a variety of areas related to infection and sepsis. The Surviving Sepsis Guidelines for Management of Severe Sepsis and Septic Shock were first published in 2004, revised in 2008, and recently revised again and published in 2013. The first part of this manuscript is a summary of the 2013 guidelines with some editorial comment. The second part of the manuscript characterizes hospital based sepsis performance improvement programs and highlights the sepsis bundles from the Surviving Sepsis Campaign as a key component of such a program.
| S-EPMC3916373 | biostudies-literature
Project description:Background: Vasopressin is one of the strong vasopressor agents associated with ischemic events. Responses to the administration of vasopressin differ among patients with septic shock. Although the administration of a high dose of vasopressin needs to be avoided, the effects of bolus loading have not yet been examined. Since the half-life of vasopressin is longer than that of catecholamines, we hypothesized that vasopressin loading may be effective for predicting responses to its continuous administration. Methods: We retrospectively analyzed consecutive cases of septic shock for which vasopressin was introduced with loading under noradrenaline at >0.2 μg/kg/min during the study period. Vasopressin was administered in a 1 U bolus followed by its continuous administration at 1 U/h. The proportion of patients with a negative catecholamine index (CAI) change 6 h after the introduction of vasopressin was set as the primary outcome. We defined non-responders for exploration as those with a mean arterial pressure change <18 mmHg 1 min after vasopressin loading, among whom none had a change in CAI <0. Results: Twenty-one consecutive cases were examined in the present study, and included 14 responders and 7 non-responders. The primary outcome accounted for 71.4% of responders and 0% of non-responders, with a significant difference (p = 0.0039). Median CAI changes 2, 4, and 6 h after the administration of vasopressin were 0, -5, and -10 in responders and +20, +10, and +10 in non-responders, respectively. CAI was not reduced in any non-responder. Outcomes including mortality were not significantly different between responders and non-responders. Digital ischemia (1/21) and mesenteric ischemia (1/21) were observed. Conclusions: Vasopressin loading may predict responses to its continuous administration in septic shock patients. Further investigations involving a safety analysis are needed.
| S-EPMC8129171 | biostudies-literature
Project description:BackgroundVasopressin is a second-line vasoactive agent for refractory septic shock. Vasopressin loading is not generally performed because of the lack of evidence for its effects and safety. However, based on our previous findings, we hypothesized it can predict the responsibility to vasopressin infusion with safety, and prospectively examined it in the present study.MethodsVasopressin loading was performed via the intravenous administration of a bolus of 1 U, followed by its continuous infusion at 1U/h in patients with septic shock treated with ≥ 0.2 μg/kg/min noradrenaline. An arterial pressure wave analysis was conducted, and endocrinological tests were performed immediately prior to vasopressin loading. We classified patients into responders/non-responders based on mean arterial pressure (MAP) changes after vasopressin loading. Based on our previous findings, the lower tertile of MAP changes was selected as the cut-off. The change in the catecholamine index (CAI) after 6 h was assigned as the primary outcome. Digital ischemia, mesenteric ischemia, and myocardial ischemia during the admission period were prospectively and systematically recorded as adverse events.ResultsNinety-two patients were registered during the study period and examined. Sixty-two patients with a MAP change > 22 mmHg were assigned as responders and the others as non-responders. Blood adrenocorticotropic hormone levels were significantly higher in non-responders. Stroke volume variations were higher in responders before loading, while stroke volume and dP/dtmax were higher in responders after loading. Median CAI changes were - 10 in responders and 0 in non-responders, which was significantly lower in the former (p < 0.0001). AUROC of MAP change with vasopressin loading to predict CAI change < 0 after continuous infusion was 0.843 with sensitivity of 0.92 and specificity of 0.77. Ischemia events were observed in 5 cases (5.4%).ConclusionsVasopressin loading may be safely introduced for septic shock. Vasopressin loading may be used to predict responses to its continuous infusion and select appropriate strategies to increase blood pressure.
| S-EPMC10362561 | biostudies-literature
Project description:The role of recombinant activated protein C (aPC) during sepsis is still controversial. It showed anti-inflammatory effect and improved the microvascular perfusion in experimental models of septic shock. The present study was aimed at testing the hypothesis that recombinant aPC therapy improves the microcirculation during severe sepsis.Prospective observational study on patients admitted in a 12-beds intensive care unit of a university hospital from July 2010 to December 2011, with severe sepsis and at least two sepsis-induced organ failures occurring within 48 hours from the onset of sepsis, who received an infusion of aPC (24 mcg/kg/h for 96 hours) (aPC group). Patients with contraindications to aPC administration were also monitored (no-aPC group).At baseline (before starting aPC infusion, T0), after 24 hours (T1a), 48 hours (T1b), 72 hours (T1c) and 6 hours after the end of aPC infusion (T2), general clinical and hemodynamic parameters were collected and the sublingual microcirculation was evaluated with sidestream dark-field imaging. Total vessel density (TVD), perfused vessel density (PVD), De Backer score, microvascular flow index (MFIs), the proportion of perfused vessels (PPV) and the flow heterogeneity index (HI) were calculated for small vessels. The perfused boundary region (PBR) was measured as an index of glycocalyx damage. Variables were compared between time points and groups using non parametric or parametric statistical tests, as appropriate.In the 13 aPC patients mean arterial pressure (MAP), base excess, lactate, PaO2/FiO2 and the Sequential Organ Failure Assessment (SOFA) score significantly improved over time, while CI and ITBVI did not change. MFIs, TVD, PVD, PPV significantly increased over time and the HI decreased (p?<?0.05 in all cases), while the PBR did not change. No-aPC patients (n?=?9) did not show any change in the microcirculation over time. A positive correlation was found between MFIs and MAP. TVD, PVD and De Backer score negatively correlated with norepinephrine dose, and the SOFA score negatively correlated with MFIs, TVD and PVD.aPC significantly improves the microcirculation in patients with severe sepsis/septic shock.NCT01806428.
| S-EPMC3848895 | biostudies-literature
Project description:IntroductionAlthough metabolic alkalosis is a common occurrence in intensive care units (ICUs), no study has evaluated its prevalence or outcomes in patients with severe sepsis or septic shock.MethodsThis is a retrospective cohort study of critically ill patients suffering from severe sepsis and septic shock admitted to the ICUs of Halmstad and Varberg County hospitals. From 910 patient records, 627 patients met the inclusion criteria. We investigated the relationship between metabolic alkalosis and mortality. Further, we studied the relationship between metabolic alkalosis and ICU length of stay (LOS).ResultsMetabolic alkalosis was associated with decreased 30-day and 12-month mortalities. This effect was however lost when a multivariate analysis was conducted, correcting for age, gender, pH on admission, base excess (BE) on admission, Simplified Acute Physiology Score III (SAPS III) and acute kidney injury (AKI). We then analyzed for any dose-response effect between the severity of metabolic alkalosis and mortality and found no relationship. Bivariate analysis showed that metabolic alkalosis had a significant effect on the length of ICU stay. When adjusting for age, sex, pH at admission, BE at admission, SAPS III and AKI in a multivariate analysis, metabolic alkalosis significantly contributed to prolonged ICU length of stay. In two separate sensitivity analyses pure metabolic alkalosis and late metabolic alkalosis (time of onset >48 hours) were the only significant predictor of increased ICU length of stay.ConclusionMetabolic alkalosis did not have any effect on 30-day and 12-month mortalities after adjusting for age, sex, SAPS III-score, pH and BE on admission and AKI in a multivariate analysis. The presence of metabolic alkalosis was independently associated with an increased ICU length of stay.
| S-EPMC5207677 | biostudies-literature
Project description:Risk factors for mortality in children with refractory pediatric septic shock who are supported with extracorporeal life support (ECLS) are largely unknown. Therefore, we performed univariable and multivariable analyses to determine risk factors for mortality among children (<19 years) who underwent an ECLS run between January 2012 and September 2014 at eight tertiary pediatric hospitals, and who had septic shock based on 2005 International Consensus Criteria. Of the 514 children treated with ECLS during the study period, 70 were identified with septic shock. The mortality rate was similar between those with (54.3%) and without septic shock (43.7%). Among those with septic shock, significant risk factors for mortality included cardiac failure or extracorporeal cardiopulmonary resuscitation (ECPR) as indication for ECLS cannulation compared with respiratory failure (P = 0.003), having a new neurologic event following cannulation (P = 0.032), acquiring a new infection following cannulation (P = 0.005), inability to normalize pH in the 48 hours following ECLS cannulation (P = 0.010), and requiring higher daily volume of platelet transfusions (P = 0.005). These findings can be used to help guide clinical decision making for children with septic shock that is refractory to medical management.
| S-EPMC7773130 | biostudies-literature
Project description:OBJECTIVES:Coupled Plasma Filtration and Adsorption (CPFA) use in septic shock remains controversial. The objective is to clarify whether the application of high doses of CPFA in addition to the current clinical practice could reduce hospital mortality in septic shock patients in Intensive Care Units at 28 days and at 90 days follow-up. DESIGN:We designed a prospective randomised clinical trial, Reducción de la Mortalidad Plasma-Adsorción (ROMPA), to demonstrate an absolute mortality reduction of 20% (?=0.05; 1-?=0.8; n=190 (95×2)). SETTING:Being aware of the pitfalls associated with previous medical device trials, we developed a training programme to improve CPFA use (especially clotting problems). The protocol was approved by the ethics committees of all participating centres. Circumstances beyond our control produced a change in recruitment conditions unacceptable to ROMPA researchers and the trial was discontinued. PARTICIPANTS:By closure, five centres from an initial 10 fulfilled the necessary trial criteria, with 49 patients included, 30 in the control group (CG) and 19 in the intervention group (IG). INTERVENTION:CPFA. MAIN OUTCOME MEASURES:Hospital mortality at 28 days and 90 days follow-up. RESULTS:After 28 days, 14 patients died (46.7%) from the CG and 11 (57.9%) from the IG, not reaching statistical significance (p=0.444). At 90 days, 19 patients had died (63.3%) from the CG and 11 patients (57.9%) from the IG, (p=0.878). The adjustment by propensity score or the use of the Kaplan-Meier technique failed to achieve statistical difference, neither by Intention to Treat nor by the Actual Intervention Received. CONCLUSION:We herewith present the results gained from the prematurely closed trial. The results are inconclusive due to low statistical power but we consider that this data is of interest for the scientific community and potentially necessary for any ensuing debate. REGISTER:NCT02357433 in clinicaltrials.gov.
| S-EPMC6924739 | biostudies-literature