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  1. Notz Q, Heyland DK, Lee ZY, Menger J, Herrmann J, Chillon TS, et al.
    Intensive Care Med Exp, 2023 Dec 08;11(1):89.
    PMID: 38063975 DOI: 10.1186/s40635-023-00574-8
    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.

  2. Ott S, Lee ZY, Müller-Wirtz LM, Cangut B, Roessler J, Patterson W, et al.
    Life Sci, 2024 Aug 15;351:122841.
    PMID: 38897349 DOI: 10.1016/j.lfs.2024.122841
    AIM: The cardiac surgery-related ischemia-reperfusion-related oxidative stress triggers the release of cytotoxic reactive oxygen and nitrogen species, contributing to organ failure and ultimately influencing patients' short- and long-term outcomes. Selenium is an essential co-factor for various antioxidant enzymes, thereby contributing to the patients' endogenous antioxidant and anti-inflammatory defense mechanisms. Given these selenium's pleiotropic functions, we investigated the effect of a high-dose selenium-based anti-inflammatory perioperative strategy on functional recovery after cardiac surgery.

    MATERIALS AND METHODS: This prospective study constituted a nested sub-study of the SUSTAIN CSX trial, a double-blinded, randomized, placebo-controlled multicenter trial to investigate the impact of high-dose selenium supplementation on high-risk cardiac surgery patients' postoperative recovery. Functional recovery was assessed by 6-min walk distance, Short Form-36 (SF-36) and Barthel Index questionnaires.

    KEY FINDINGS: 174 patients were included in this sub-study. The mean age (SD) was 67.3 (8.9) years, and 78.7 % of the patients were male. The mean (SD) predicted 30-day mortality by the European System for Cardiac Operative Risk Evaluation II score was 12.6 % (9.4 %). There was no difference at hospital discharge and after three months in the 6-min walk distance between the selenium and placebo groups (131 m [IQR: not performed - 269] vs. 160 m [IQR: not performed - 252], p = 0.80 and 400 m [IQR: 299-461] vs. 375 m [IQR: 65-441], p = 0.48). The SF-36 and Barthel Index assessments also revealed no clinically meaningful differences between the selenium and placebo groups.

    SIGNIFICANCE: A perioperative anti-inflammatory strategy with high-dose selenium supplementation did not improve functional recovery in high-risk cardiac surgery patients.

  3. Ott S, Dresen E, Lee ZY, Müller-Wirtz LM, Procopiuc L, Ekrami E, et al.
    J Crit Care, 2024 Oct;83:154853.
    PMID: 38955117 DOI: 10.1016/j.jcrc.2024.154853
    PURPOSE: Cardiac surgery, post-cardiotomy cardiogenic shock (PCCS), and temporary mechanical circulatory support (tMCS) provoke substantial inflammation. We therefore investigated whether a selenium-based, anti-inflammatory strategy would benefit PCCS patients treated with tMCS in a post-hoc analysis of the sustain CSX trial.

    METHODS: Post-hoc analysis of patients receiving tMCS for PCCS in the Sustain CSX trial, which investigated the effects of high-dose selenium on postoperative organ dysfunction in cardiac surgery patients.

    PRIMARY OUTCOME: duration of tMCS therapy.

    SECONDARY OUTCOMES: postoperative organ dysfunction and 30-day mortality.

    RESULTS: Thirty-nine patients were treated with tMCS for PCCS. There was no difference in the median duration of tMCS between the selenium and the placebo group (3 days [IQR: 1-6] vs. 2 days [IQR: 1-7], p = 0.52). Median dialysis duration was longer in the selenium group (1.5 days [0-21.8] vs. 0 days [0-1.8], p = 0.048). There was no difference in 30-day mortality (53% vs. 41%, OR 1.44, 95% CI 0.32-6.47, p = 0.62).

    CONCLUSION: In this explorative study, a perioperative high-dose selenium-supplementation did not show beneficial effects on organ dysfunctions and mortality rates in patients with PCCS receiving tMCS.

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