Dataset Information

Identifying a target group for selenium supplementation in high-risk cardiac surgery: a secondary analysis of the SUSTAIN CSX trial.

ABSTRACT:

Background

Recent data from the randomized SUSTAIN CSX trial could not confirm clinical benefits from perioperative selenium treatment in high-risk cardiac surgery patients. Underlying reasons may involve inadequate biosynthesis of glutathione peroxidase (GPx3), which is a key mediator of selenium's antioxidant effects. This secondary analysis aimed to identify patients with an increase in GPx3 activity following selenium treatment. We hypothesize that these responders might benefit from perioperative selenium treatment.

Methods

Patients were selected based on the availability of selenium biomarker information. Four subgroups were defined according to the patient's baseline status, including those with normal kidney function, reduced kidney function, selenium deficiency, and submaximal GPx3 activity.

Results

Two hundred and forty-four patients were included in this analysis. Overall, higher serum concentrations of selenium, selenoprotein P (SELENOP) and GPx3 were correlated with less organ injury. GPx3 activity at baseline was predictive of 6-month survival (AUC 0.73; p = 0.03). While selenium treatment elevated serum selenium and SELENOP concentrations but not GPx3 activity in the full patient cohort, subgroup analyses revealed that GPx3 activity increased in patients with reduced kidney function, selenium deficiency and low to moderate GPx3 activity. Clinical outcomes did not vary between selenium treatment and placebo in any of these subgroups, though the study was not powered to conclusively detect differences in outcomes.

Conclusions

The identification of GPx3 responders encourages further refined investigations into the treatment effects of selenium in high-risk cardiac surgery patients.

SUBMITTER: Notz Q

PROVIDER: S-EPMC10709283 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Identifying a target group for selenium supplementation in high-risk cardiac surgery: a secondary analysis of the SUSTAIN CSX trial.

Notz Quirin Q Heyland Daren K DK Lee Zheng-Yii ZY Menger Johannes J Herrmann Johannes J Chillon Thilo S TS Fremes Stephen S Mohammadi Siamak S Elke Gunnar G Mazer C David CD Hill Aileen A Velten Markus M Ott Sascha S Kleine-Brueggeney Maren M Meybohm Patrick P Schomburg Lutz L Stoppe Christian C

Intensive care medicine experimental 20231208 1

<h4>Background</h4>Recent data from the randomized SUSTAIN CSX trial could not confirm clinical benefits from perioperative selenium treatment in high-risk cardiac surgery patients. Underlying reasons may involve inadequate biosynthesis of glutathione peroxidase (GPx3), which is a key mediator of selenium's antioxidant effects. This secondary analysis aimed to identify patients with an increase in GPx3 activity following selenium treatment. We hypothesize that these responders might benefit from ...[more]

PMID: 38063975

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Project description:ImportanceSelenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery.ObjectiveTo assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients.Design, setting, and participantsThis multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score-predicted mortality of 5% or more or planned combined surgical procedures were randomized.InterventionsPatients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 μg/L of sodium selenite prior to cardiopulmonary bypass, 2000 μg/L immediately postoperatively, and 1000 μg/L each day in intensive care for a maximum of 10 days or placebo.Main outcomes and measuresThe primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery.ResultsA total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction-free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups.Conclusions and relevanceIn high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery.Trial registrationClinicalTrials.gov Identifier: NCT02002247.

Project description:BackgroundSelenium is needed by all living cells in order to ensure the optimal function of several enzyme systems. However, the selenium content in the soil in Europe is generally low. Previous reports indicate that a dietary supplement of selenium could reduce cardiovascular disease but mainly in populations in low selenium areas. The objective of this secondary analysis of a previous randomised double-blind placebo-controlled trial from our group was to determine whether the effects on cardiovascular mortality of supplementation with a fixed dose of selenium and coenzyme Q10 combined during a four-year intervention were dependent on the basal level of selenium.MethodsIn 668 healthy elderly individuals from a municipality in Sweden, serum selenium concentration was measured. Of these, 219 individuals received daily supplementation with selenium (200 μg Se as selenized yeast) and coenzyme Q10 (200 mg) combined for four years. The remaining participants (n = 449) received either placebo (n = 222) or no treatment (n = 227). All cardiovascular mortality was registered. No participant was lost during a median follow-up of 5.2 years. Based on death certificates and autopsy results, all mortality was registered.FindingsThe mean serum selenium concentration among participants at baseline was low, 67.1 μg/L. Based on the distribution of selenium concentration at baseline, the supplemented group was divided into three groups; <65 μg/L, 65-85 μg/L, and >85 μg/L (45 and 90 percentiles) and the remaining participants were distributed accordingly. Among the non-treated participants, lower cardiovascular mortality was found in the high selenium group as compared with the low selenium group (13.0% vs. 24.1%; P = 0.04). In the group with the lowest selenium basal concentration, those receiving placebo or no supplementation had a mortality of 24.1%, while mortality was 12.1% in the group receiving the active substance, which was an absolute risk reduction of 12%. In the middle selenium concentration group a mortality of 14.0% in the non-treated group, and 6.0% in the actively treated group could be demonstrated; thus, there was an absolute risk reduction of 8.0%. In the group with a serum concentration of >85 μg/L, a cardiovascular mortality of 17.5% in the non-treated group, and 13.0% in the actively treated group was observed. No significant risk reduction by supplementation could thus be found in this group.ConclusionsIn this evaluation of healthy elderly Swedish municipality members, two important results could be reported. Firstly, a low mean serum selenium concentration, 67 μg/L, was found among the participants, and the cardiovascular mortality was higher in the subgroup with the lower selenium concentrations <65 μg/L in comparison with those having a selenium concentration >85 μg/L. Secondly, supplementation was cardio-protective in those with a low selenium concentration, ≤85 at inclusion. In those with serum selenium>85 μg/L and no apparent deficiency, there was no effect of supplementation. This is a small study, but it presents interesting data, and more research on the impact of lower selenium intake than recommended is therefore warranted.Trial registrationClinicaltrials.gov NCT01443780.

Project description:ObjectivesTo understand the effect of tight glycemic control on cardiac surgery-associated acute kidney injury.DesignSecondary analysis of data from the Safe Pediatric Euglycemia after Cardiac Surgery trial of tight glycemic control versus standard care.SettingPediatric cardiac ICUs at University of Michigan, C.S. Mott Children's Hospital, and Boston Children's Hospital.PatientsChildren 0-36 months old undergoing congenital cardiac surgery.InterventionsNone.Measurements and main resultsCardiac surgery-associated acute kidney injury was assigned using the Acute Kidney Injury Network criteria with the modification that a greater than 0.1 mg/dL increase in serum creatinine was required to assign cardiac surgery-associated acute kidney injury. We explored associations between cardiac surgery-associated acute kidney injury and tight glycemic control and clinical outcomes. Of 799 patients studied, cardiac surgery-associated acute kidney injury occurred in 289 patients (36%), most of whom had stage II or III disease (72%). Cardiac surgery-associated acute kidney injury rates were similar between treatment groups (36% vs 36%; p = 0.99). Multivariable modeling showed that patients with cardiac surgery-associated acute kidney injury were younger (p = 0.002), underwent more complex surgery (p = 0.005), and had longer cardiopulmonary bypass times (p = 0.002). Cardiac surgery-associated acute kidney injury was associated with longer mechanical ventilation and ICU and hospital stays and increased mortality. Patients at University of Michigan had higher rates of cardiac surgery-associated acute kidney injury compared with Boston Children's Hospital patients (66% vs 15%; p < 0.001), but University of Michigan patients with cardiac surgery-associated acute kidney injury had shorter time to extubation and ICU and hospital stays compared with Boston Children's Hospital patients.ConclusionsTight glycemic control did not reduce the cardiac surgery-associated acute kidney injury rate in this trial cohort. We observed significant differences in cardiac surgery-associated acute kidney injury rates between the two study sites, and there was a differential effect of cardiac surgery-associated acute kidney injury on clinical outcomes by site. These findings warrant further investigation to identify causal variation in perioperative practices that affect cardiac surgery-associated acute kidney injury epidemiology.

Project description:BackgroundImplementation of point-of-care tests is recommended to provide tailored substitution during cardiac surgery. The measurement and substitution of fibrinogen have gained particular interest since it is the first coagulation factor to become depleted during cardiac surgery. However, the prognostic ability of thromboelastography (TEG) 6s has not been evaluated in pediatric patients. The aim of the present study was to describe patient characteristics of infants receiving fibrinogen substitution during cardiac surgery and evaluate the prognostic ability of TEG6s after weaning off cardiopulmonary bypass (CPB).MethodsInfants undergoing congenital cardiac surgery with CPB were retrospectively included (n = 279) between January 2017 to July 2019. Patient and perioperative data were collected on the day of surgery until 6:00 AM the next morning. Hemostatic capacity was assessed with TEG6s. The efficacy of TEG-functional fibrinogen-maximal amplitude (TEG-FF-MA) measurements for the prediction of intraoperative bleeding, and thereby cryoprecipitate need, was evaluated by a sensitivity and specificity analysis.ResultsAmong 174 children with TEG-FF-MA data, 147 (84%) received cryoprecipitate intraoperatively. Cryoprecipitate administration was associated with younger age 66 (10-132) versus 98 (45-204) days (p = .044), higher RACHS-1 classification, and intraoperative bleeding 21 (11-47) versus 5 (3-13) ml/kg (p < .001, mean difference 29 ml/kg [CI: 8-50]). Median TEG-FF-MA values were lower in transfused children 7.6 (5.3-11.0) versus 10.5 (7.3-13.4) mm (p = .004, mean difference - 2.4 mm [CI: -4.1 to - 0.73]). The volume of cryoprecipitate was associated with bypass time, TEG-FF-MA values, and in particular intraoperative bleeding volumes. A TEG-FF-MA threshold of 10.0 mm, resulted in sensitivity: 74%, specificity: 56%, positive predictive value: 80%, and a negative predictive value of 47% for the prediction of intraoperative bleeding (>10 ml/kg) and consequently a need of cryoprecipitate transfusion.ConclusionFibrinogen substitution in infants was associated with younger age and higher RACHS-1 category. The prognostic value of TEG6s was evaluated, and cryoprecipitate transfusion was related to TEG-FF-MA values, but also CPB-time, surgical complexity, and in particular excessive intraoperative bleeding. A clear-cut threshold for TEG-FF-MA is difficult to establish in infants undertaken congenital heart surgery.

Dataset Information

Identifying a target group for selenium supplementation in high-risk cardiac surgery: a secondary analysis of the SUSTAIN CSX trial.

Background

Methods

Results

Conclusions

Publications

Identifying a target group for selenium supplementation in high-risk cardiac surgery: a secondary analysis of the SUSTAIN CSX trial.

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