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Effect of ketamine on pro- and anti-inflammatory cytokine response in paediatric cardiac surgery: A prospective randomised controlled study.

ABSTRACT: Paediatric cardiac surgery with cardiopulmonary bypass (CPB) is associated with a marked inflammatory response and triggers release of inflammatory cytokines. The aim of this study was to study the effect of ketamine on the inflammatory response during correction of congenital cyanotic heart diseases.Sixty-six patients with congenital cyanotic heart diseases scheduled for cardiac surgery were randomised into three groups. Group A patients did not receive ketamine (control group), Group B patients received 2 mg/kg ketamine intravenous (IV) and Group C patients received ketamine 2 mg/kg IV and an IV infusion of ketamine (50 μg/kg/min). Interleukin (IL) levels for IL-6, IL-8, IL-10, C-reactive protein (CRP) and tumour necrosis factor-α (TNF-α) levels were examined in the three groups at four timings: pre-operative (baseline), intraoperative (after weaning off the CPB) and post-operative (6 and 24 h after weaning off CPB). Paired sample t-test and ANOVA test were used for statistical analysis and P < 0.05 was considered statistically significant.Within each group, the intra- and post-operative serum levels of IL-6, IL-8, IL-10 and CRP were significantly elevated from the baseline, however, TNF-α was not significantly elevated. There were no statistically significant differences in the IL, CRP or TNF-α levels between the three groups.Paediatric cardiac surgery for congenital cyanotic heart disease is a triggering factor for the inflammatory response, yet we could not detect any beneficial effect of ketamine on that response whether given either as an IV induction dose or continued as an IV infusion.

SUBMITTER: Ibrahim TH

PROVIDER: S-EPMC5530739 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Project description:IntroductionCardiac surgery-associated acute kidney injury (CS-AKI) occurs in up to 40%~60% of paediatric patients and increases postoperative morbidity and mortality. A goal-directed perfusion (GDP) strategy aimed at maintaining indexed oxygen delivery (DO2i) above the critical threshold (reported to be 260~300 mL/min/m2 in adults) during cardiopulmonary bypass (CPB), is effective in reducing the incidence of CS-AKI. However, no clear standards of paediatric critical DO2i exist. Our prior prospective cohort study exploring the critical DO2i threshold during paediatric CPB has found the nadir DO2i <353 mL/min/m2 was an independent risk predictor of CS-AKI. Based on this background, this trial is designed to further determine whether the implementation of the GDP initiative aimed at maintaining DO2i ≥360 mL/min/m2 would reduce the rate of CS-AKI in paediatrics and improve clinical outcome.Methods and analysisThis is a prospective, single-centre, randomised controlled trial. In total, 166 paediatric patients undergoing cardiac surgery will be randomly allocated to the GDP group or control group. Patients in the GDP arm will be treated with a GDP strategy during CPB aimed to maintain DO2i at ≥360 mL/min/m2 (to ensure safely above the risk DO2i threshold we found). The perfusion strategy for patients in the control arm will be factored on body surface area and temperature. The primary outcome is the rate of postoperative CS-AKI (it is defined according to paediatric Risk, Injury, Failure, Loss of renal function and End-stage renal disease criteria). The secondary end points include: (1) the other oxygen metabolism parameters during CPB; (2) major complication and all-cause mortality (in-hospital or within 30 days postoperatively); (3) short-term clinical outcomes (ie, time to extubation, mechanical ventilation time, hospital stay).Ethics and disseminationThe study has been approved by the Biomedical Research Ethics committee of West China Hospital of Sichuan University (approval number: 2019(863)). Results will be disseminated through peer-reviewed publications and conferences.Trial registration numberChiCTR2000029232.

Project description:IntroductionThe release of pro-inflammatory cytokines in critically ill patients with sepsis leads to endothelial dysfunction resulting in cardiocirculatory insufficiency. Their extracorporeal elimination using the cytokine adsorber CytoSorb® (CS) (adsorption of especially hydrophobic molecules < 60 kDa) might be promising, but data about the adsorption capacity as well as a potential harmful adsorption of anti-inflammatory cytokines are missing so far.MethodsThe prospective Cyto-SOLVE-study included 15 patients with sepsis or other hyperinflammatory conditions (interleukin 6 > 500 pg/ml), continuous kidney replacement therapy, and the application of CS. Various cytokines and chemokines were measured pre- and post-CS as well as in patients' blood at predefined timepoints. Significant changes in the concentrations were detected with the Wilcoxon test with associated samples. Clearance of the adsorber (ml/min) was calculated with: bloodflow∗concentrationpre-postconcentrationpre. RESULTS: Most of the inflammatory mediators showed a high initial extracorporeal clearance of 70-100 ml/min after CS installation, which dropped quickly to 10-30 ml/min after 6 h of treatment. No difference in clearance was observed between pro- and anti-inflammatory cytokines. Despite extracorporeal adsorption, a significant (p < 0.05) decrease in the blood concentration after 6 h was only observed for the pro-inflammatory cytokines tumor necrosis factorα (TNF-α) (median 284 vs. 230 pg/ml), vascular endothelial growth factor (VEGF) (median 294 vs. 252 pg/ml), macrophage inflammatory protein 1a (MIP-1a) (median 11.1 vs. 9.0 pg/ml), and regulated upon activation, normal T cell expressed and secreted (RANTES) (median 811 vs. 487 pg/ml) as well as the anti-inflammatory cytokines interleukin 4 (median 9.3 vs. 6.4 pg/ml), interleukin 10 (median 88 vs. 56 pg/ml), and platelet-derived growth factor (PDGF) (median 177 vs. 104 pg/ml). A significant (p < 0.05) decrease in patients' blood after 12 h was only detected for interleukin 10.ConclusionsCS can adsorb pro- as well as anti-inflammatory mediators with no relevant difference regarding the adsorption rate. A fast saturation of the adsorber resulted in a rapid decrease of the clearance. The potential clinical benefit or harm of this unspecific cytokine adsorption needs to be evaluated in the future.Trial registrationClinicalTrials.gov NCT04913298, registration date June 4, 2021.

Project description:BackgroundThe evidence for systemic treatments for severe childhood eczema is limited and largely based on extrapolation of data from adult studies. Current therapies are often immunosuppressant and may be associated with both short- and long-term side effects. There is increasing in vitro and murine-model evidence for the role of IgE in the immunopathogenesis of atopic eczema. The aim of the study is to assess whether anti-IgE treatment (omalizumab) improves eczema, compared to placebo.Methods/designThe Atopic Dermatitis Anti-IgE Paediatric Trial (ADAPT) is a randomised, double-blind, placebo-controlled study assessing the role of anti-IgE in the management of severe paediatric eczema. Children with severe atopic eczema, with an objective SCORing Atopic Dermatitis (SCORAD) score of over 40 will be recruited. These children are candidates for systemic therapy, have failed systemic therapy or have experienced side effects from systemic therapy. Sixty-two patients aged between 4 and 19 years will receive anti-IgE for 6 months. The primary outcome measure will be the validated eczema score, the objective SCORAD at 24 weeks. This study has 90% power to detect a 33% relative reduction in SCORAD between active and placebo groups, with 5% significance.DiscussionIgE may have a role to play in eczema, particularly in childhood. This forms the basis for the hypothesis that anti-IgE may be an effective treatment in this patient population. This will be the largest study to evaluate the efficacy of anti-IgE (omalizumab) versus placebo in children with severe eczema. The findings will help to clarify the role of anti-IgE as a potential treatment option in patients with severe childhood eczema.Trial registrationEuropean Clinical Trials Database (EudraCT) Number: 2010-020841-29 . Assigned on 14 May 2010. ISRCTN Registry, Identifier: ISRCTN15090567 . Retrospectively assigned on 3 December 2014. ClinicalTrials.gov, Identifier: NCT02300701 . First received 21 November 2014.

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Effect of ketamine on pro- and anti-inflammatory cytokine response in paediatric cardiac surgery: A prospective randomised controlled study.

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