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: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: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: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
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:High serum lactate is associated with increased mortality in septic shock patients. Metformin alters lactate metabolism, and may affect its prognostic value. We compared, between metformin users and nonusers, the prognosis of extremely elevated plasma lactate levels in patients with septic shock.The electronic medical records (EMR) of patients admitted to the emergency room between January 2011 and June 2013 were reviewed. The study cohort comprised patients with an initial diagnosis of septic shock and blood lactate higher than 10 mmol/L. The selected population was divided into two groups: metformin users (exposed) and metformin nonusers (unexposed). The primary outcome measured was inhospital mortality.The study included 44 metformin users and 118 nonusers. Metformin users were similar to nonusers with respect to levels of lactate, HCO3, and blood pH; however, they were older and had higher incidence rates of cardiovascular disease and acute kidney injury at admission, compared to nonusers. Inhospital mortality rates were significantly lower in the metformin-treated group, 56.8 % vs. 88.1 %, p <0.0001.Though high lactate concentration indicates poor prognosis in septic patients, mortality rate was found to be significantly lower in those who were treated with metformin. This finding may help clinicians in deciding treatment for these patients, who could otherwise be considered too ill for real treatment benefit.
| S-EPMC4715304 | biostudies-other
Project description:In an ongoing translational research program involving microarray-based expression profiles in pediatric septic shock, we have now conducted longitudinal studies focused on the temporal expression profiles of canonical signaling pathways and gene networks. Genome-level expression profiles were generated from whole blood-derived RNA samples of children with septic shock (n = 30 individual patients) corresponding to days 1 and 3 of admission to the pediatric intensive care unit. Based on sequential statistical and expression filters, day 1 and day 3 of septic shock were characterized by differential regulation of 2,142 and 2,504 gene probes, respectively, relative to normal control patients. Venn analysis demonstrated 239 unique genes in the day 1 data set, 598 unique genes in the day 3 data set, and 1,906 genes common to both data sets. Analyses targeted toward derivation of biological function from these data sets demonstrated time-dependent, differential regulation of genes involved in multiple canonical signaling pathways and gene networks primarily related to immunity and inflammation. Notably, multiple and distinct gene networks involving T cell- and MHC antigen-related biological processes were persistently downregulated from day 1 to day 3. Further analyses demonstrated large scale and persistent downregulation of genes corresponding to functional annotations related to zinc homeostasis. These data represent the largest reported cohort of patients with septic shock, which has undergone longitudinal genome-level expression profiling. The data further advance our genome-level understanding of pediatric septic shock and support novel hypotheses that can be readily tested at both the experimental and translational levels. Keywords: Inflammation; sepsis; innate immunity; T cells; MHC antigen Keywords: to be updated
2007-06-14 | GSE8121 | GEO