Dataset Information

Novel inflammatory mediator profile observed during pediatric heart surgery with cardiopulmonary bypass and continuous ultrafiltration.

ABSTRACT:

Background

Cardiopulmonary bypass (CPB) is associated with systemic inflammation, featuring increased levels of circulating pro-inflammatory cytokines. Intra-operative ultrafiltration extracts fluid and inflammatory factors potentially dampening inflammation-related organ dysfunction and enhancing post-operative recovery. This study aimed to define the impact of continuous subzero-balance ultrafiltration (SBUF) on circulating levels of major inflammatory mediators.

Methods

Twenty pediatric patients undergoing cardiac surgery, CPB and SBUF were prospectively enrolled. Blood samples were collected prior to CPB initiation (Pre-CPB Plasma) and immediately before weaning off CPB (End-CPB Plasma). Ultrafiltrate effluent samples were also collected at the End-CPB time-point (End-CPB Effluent). The concentrations of thirty-nine inflammatory factors were assessed and sieving coefficients were calculated.

Results

A profound increase in inflammatory cytokines and activated complement products were noted in plasma following CBP. Twenty-two inflammatory mediators were detected in the ultrafiltrate effluent. Novel mediators removed by ultrafiltration included cytokines IL1-Ra, IL-2, IL-12, IL-17A, IL-33, TRAIL, GM-CSF, ET-1, and the chemokines CCL2, CCL3, CCL4, CXCL1, CXCL2 and CXCL10. Mediator extraction by SBUF was significantly associated with molecular mass < 66 kDa (Chi² statistic = 18.8, Chi² with Yates' correction = 16.0, p < 0.0001). There was a moderate negative linear correlation between molecular mass and sieving coefficient (Spearman R = - 0.45 and p = 0.02). Notably, the anti-inflammatory cytokine IL-10 was not efficiently extracted by SBUF.

Conclusions

CPB is associated with a burden of circulating inflammatory mediators, and SBUF selectively extracts twenty of these pro-inflammatory factors while preserving the key anti-inflammatory regulator IL-10. Ultrafiltration could potentially function as an immunomodulatory therapy during pediatric cardiac surgery. Trial registration ClinicalTrials.gov, NCT05154864. Registered retrospectively on December 13, 2021. https://clinicaltrials.gov/ct2/show/record/NCT05154864 .

SUBMITTER: Bierer J

PROVIDER: S-EPMC10320928 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Novel inflammatory mediator profile observed during pediatric heart surgery with cardiopulmonary bypass and continuous ultrafiltration.

Bierer Joel J Stanzel Roger R Henderson Mark M Sett Suvro S Sapp John J Andreou Pantelis P Marshall Jean S JS Horne David D

Journal of translational medicine 20230705 1

<h4>Background</h4>Cardiopulmonary bypass (CPB) is associated with systemic inflammation, featuring increased levels of circulating pro-inflammatory cytokines. Intra-operative ultrafiltration extracts fluid and inflammatory factors potentially dampening inflammation-related organ dysfunction and enhancing post-operative recovery. This study aimed to define the impact of continuous subzero-balance ultrafiltration (SBUF) on circulating levels of major inflammatory mediators.<h4>Methods</h4>Twenty ...[more]

PMID: 37408044

Similar Datasets

Project description:ObjectiveThe impact of nitric oxide (NO) administered via cardiopulmonary bypass (CPB) on pediatric heart surgery remains controversial. The objective of this study is to conduct a comprehensive systematic review and meta-analysis to examine the impact of NO administered via CPB on pediatric heart surgery.MethodsThis study searched 7 electronic databases to identify Randomized Controlled Trials (RCTs) on the impact of NO administration during CPB on postoperative outcomes in pediatric heart surgery. The searched databases included Embase, Medline (though PubMed), Cochrane Library, Web of Science, Wan Fang database, China National Knowledge Infrastructure (CNKI), and ClinicalTrials.gov from their inception to November 2, 2022. The included RCTs compared NO administration during CPB with standard CPB procedures or placebo gas treatment in pediatric heart surgery. fixed-effects models and/or random-effects models were used to estimate the effect size with 95% confidence interval (CI). Heterogeneity among studies was indicated by p-values and I2. All analyses were performed using Review Manager software (version 5.4) in this study.ResultsA total of 6 RCTs including 1,739 children were identified in this study. The primary outcome was duration of postoperative mechanical ventilation, with the length of hospital and intensive care unit (ICU) stay as the second outcomes. Through a pooled analysis, we found that exogenous NO administered via CPB for pediatric heart surgery could not shorten the duration of postoperative mechanical ventilation when compared with the control group (standardized mean difference (SMD) -0.07, CI [-0.16, 0.02], I2 = 45%, P = 0.15). Additionally, there were also no difference between the two groups in terms of length of hospital stay (mean difference (MD) -0.29, CI [-1.03, 0.46], I2 = 32%, P = 0.45) and length of ICU stay (MD -0.22, CI [-0.49 to 0.05], I2 = 72%, P = 0.10).ConclusionsThis meta-analysis showed that exogenous NO administration via CBP had no benefits on the duration of mechanical ventilation, the length of postoperative hospital, and ICU stay after pediatric heart surgery.

Project description:Introduction: To our knowledge, methylprednisolone pharmacokinetics and plasma concentrations have not been comprehensively investigated in children with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass. It is unknown whether there is a significant influence of cardiopulmonary bypass on the plasma concentrations of methylprednisolone and whether this may be an explanation for the limited reported efficacy of steroid administration in cardiac surgery with cardiopulmonary bypass. Methods: The study was registered in the Dutch Trial Register (NTR3579; https://www.trialregister.nl/trial/3428). Methylprednisolone 30 mg/kg was administered as an intravenous bolus after induction of anesthesia. Methylprednisolone concentration was measured with liquid chromatography tandem mass spectrometry and analyzed using linear mixed-effects modeling. Results: Thirty-nine patients were included in the study, of which three were excluded. There was an acute decrease in observed methylprednisolone plasma concentration on initiation of cardiopulmonary bypass (median = 26.8%, range = 13.9-48.14%, p < 0.001). We found a lower intercept (p = 0.02), as well as a less steep slope of the model predicted methylprednisolone concentration vs. time curve for neonates (p = 0.048). A lower intercept (p = 0.01) and a less steep slope (p = 0.0024) if the volume of cell saver blood processed was larger than 91 ml/kg were also found. Discussion: We report similar methylprednisolone plasma concentrations as earlier studies performed in children undergoing cardiopulmonary bypass, and we confirmed the large interindividual variability in achieved methylprednisolone plasma concentrations with weight-based methylprednisolone administration. A larger volume of distribution and a lower clearance of methylprednisolone for neonates were suggested. The half-life of methylprednisolone in our study was calculated to be longer than 6 h for neonates, 4.7 h for infants, 3.6 h for preschool children and 4.7 h for school children. The possible influence of treatment of pulmonary hypertension with sildenafil and temperature needs to be investigated further.

Project description:BackgroundCardiac surgery with cardiopulmonary bypass (CPB) is associated with a systemic inflammatory syndrome that adversely impacts cardiopulmonary function and can contribute to prolonged postoperative recovery. Intra-operative ultrafiltration during CPB is a strategy developed by pediatric cardiac specialists, aiming to dampen the inflammatory syndrome by removing circulating cytokines and improving coagulation profiles during the cardiac operation. Although ultrafiltration is commonly used in the pediatric population, it is not routinely used in the adult population. This study aims to evaluate if randomized evidence supports the use of continuous intra-operative ultrafiltration to enhance recovery for adults undergoing cardiac surgery with CPB.MethodsThis systematic review and meta-analysis will include randomized controlled trials (RCT) that feature continuous forms of ultrafiltration during adult cardiac surgery with CPB, specifically assessing for benefit in mortality rates, invasive ventilation time and intensive care unit length of stay (ICU LOS). Relevant RCTs will be retrieved from databases, including MEDLINE, Embase, CENTRAL and Scopus, by a pre-defined search strategy. Search results will be screened for inclusion and exclusion criteria by two independent persons with consensus. Selected RCTs will have study demographics and outcome data extracted by two independent persons and transferred into RevMan. Risk of bias will be independently assessed by the Revised Cochrane Risk-of-Bias (RoB2) tool and studies rated as low-, some-, or high- risk of bias. Meta-analyses will compare the intervention of continuous ultrafiltration against comparators in terms of mortality, ventilation time, ICU LOS, and renal failure. Heterogeneity will be measured by the χ2 test and described by the I2 statistic. A sensitivity analysis will be completed by excluding included studies judged to have a high risk of bias. Summary of findings and certainty of the evidence, determined by the GRADE approach, will display the analysis findings.DiscussionThe findings of this systematic review and meta-analysis will summarize the evidence to date of continuous forms of ultrafiltration in adult cardiac surgery with CPB, to both inform adult cardiac specialists about this technique and identify critical questions for future research in this subject area.Systematic review registrationThis systematic review and meta-analysis is registered in PROSPERO CRD42020219309 ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020219309 ).

Project description:ObjectivesTo determine the production of 9-hydroxyoctadecadienoic acid and 13-hydroxyoctadecadienoic acid during cardiopulmonary bypass in infants and children undergoing cardiac surgery, evaluate their relationship with increase in cell-free plasma hemoglobin, provide evidence of bioactivity through markers of inflammation and vasoactivity (WBC count, milrinone use, vasoactive-inotropic score), and examine their association with overall clinical burden (ICU/hospital length of stay and mechanical ventilation duration).DesignProspective observational study.SettingTwelve-bed cardiac ICU in a university-affiliated children's hospital.PatientsChildren were prospectively enrolled during their preoperative clinic appointments with the following criteria: greater than 1 month to less than 18 years old, procedures requiring cardiopulmonary bypass INTERVENTIONS:: None.Measurements and main resultsPlasma was collected at the start and end of cardiopulmonary bypass in 34 patients. 9-hydroxyoctadecadienoic acid, 13-hydroxyoctadecadienoic acid, plasma hemoglobin, and WBC increased. 9:13-hydroxyoctadecadienoic acid at the start of cardiopulmonary bypass was associated with vasoactive-inotropic score at 2-24 hours postcardiopulmonary bypass (R = 0.25; p < 0.01), milrinone use (R = 0.17; p < 0.05), and WBC (R = 0.12; p < 0.05). 9:13-hydroxyoctadecadienoic acid at the end of cardiopulmonary bypass was associated with vasoactive-inotropic score at 2-24 hours (R = 0.17; p < 0.05), 24-48 hours postcardiopulmonary bypass (R = 0.12; p < 0.05), and milrinone use (R = 0.19; p < 0.05). 9:13-hydroxyoctadecadienoic acid at the start and end of cardiopulmonary bypass were associated with the changes in plasma hemoglobin (R = 0.21 and R = 0.23; p < 0.01). The changes in plasma hemoglobin was associated with milrinone use (R = 0.36; p < 0.001) and vasoactive-inotropic score less than 2 hours (R = 0.22; p < 0.01), 2-24 hours (R = 0.24; p < 0.01), and 24-48 hours (R = 0.48; p < 0.001) postcardiopulmonary bypass. Cardiopulmonary bypass duration, 9:13-hydroxyoctadecadienoic acid at start of cardiopulmonary bypass, and plasma hemoglobin may be risk factors for high vasoactive-inotropic score. Cardiopulmonary bypass duration, changes in plasma hemoglobin, 9:13-hydroxyoctadecadienoic acid, and vasoactive-inotropic score correlate with ICU and hospital length of stay and/mechanical ventilation days.ConclusionsIn low-risk pediatric patients undergoing cardiopulmonary bypass, 9:13-hydroxyoctadecadienoic acid was associated with changes in plasma hemoglobin, vasoactive-inotropic score, and WBC count, and may be a risk factor for high vasoactive-inotropic score, indicating possible inflammatory and vasoactive effects. Further studies are warranted to delineate the role of hydroxyoctadecadienoic acids and plasma hemoglobin in cardiopulmonary bypass-related dysfunction and to explore hydroxyoctadecadienoic acid production as a potential therapeutic target.

Dataset Information

Novel inflammatory mediator profile observed during pediatric heart surgery with cardiopulmonary bypass and continuous ultrafiltration.

Background

Methods

Results

Conclusions

Publications

Novel inflammatory mediator profile observed during pediatric heart surgery with cardiopulmonary bypass and continuous ultrafiltration.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets