The importance of intraoperative selenium blood levels on organ dysfunction in patients undergoing off-pump cardiac surgery: a randomised controlled trial

Abstract

Introduction: Cardiac surgery is accompanied by an increase of oxidative stress, a significantly reduced antioxidant (AOX) capacity, postoperative inflammation, all of which may promote the development of organ dysfunction and an increase in mortality. Selenium is an essential co-factor of various antioxidant enzymes. We hypothesized a less pronounced decrease of circulating selenium levels in patients undergoing off-pump coronary artery bypass (OPCAB) surgery due to less intraoperative oxidative stress.

Methods: In this prospective randomised, interventional trial, 40 patients scheduled for elective coronary artery bypass grafting were randomly assigned to undergo either on-pump or OPCAB-surgery, if both techniques were feasible for the single patient. Clinical data, myocardial damage assessed by myocard specific creatine kinase isoenzyme (CK-MB), circulating whole blood levels of selenium, oxidative stress assessed by asymmetric dimethylarginine (ADMA) levels, antioxidant capacity determined by glutathionperoxidase (GPx) levels and perioperative inflammation represented by interleukin-6 (IL-6) levels were measured at predefined perioperative time points.

Results: At end of surgery, both groups showed a comparable decrease of circulating selenium concentrations. Likewise, levels of oxidative stress and IL-6 were comparable in both groups. Selenium levels correlated with antioxidant capacity (GPx: r = 0.720; p<0.001) and showed a negative correlation to myocardial damage (CK-MB: r = -0.571, p<0.001). Low postoperative selenium levels had a high predictive value for the occurrence of any postoperative complication.

Conclusions: OPCAB surgery is not associated with less oxidative stress and a better preservation of the circulating selenium pool than on-pump surgery. Low postoperative selenium levels are predictive for the development of complications.

Trial registration: ClinicalTrials.gov NCT01409057.

Conflict of interest statement

Competing Interests: D.H. has received less than $5000 for travel support honorarium for lectures. W.W. has received 1050€ for special lab work from biosyn Arzneimittel GmbH, http://www.biosyn.de/. S.R. and C.S have received in each case 10000€, to perform clinical studies and special lab work, from biosyn Arzneimittel GmbH, http://www.biosyn.de/. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Flowchart.

According to the CONSORT-statement for randomised clinical trials. From the initially screened 60 patients, 46 patients received the allocated intervention. 6 patients had to be excluded from further analysis.

Figure 2. Perioperative selenium-levels.

A) Comparison of whole blood selenium levels between the on-pump group (open circles) and the OPCAB-group (closed circles) at baseline (preoperative) and at ICU admission (postoperative). Data are presented as mean ± standard deviation. *p<0.05, **p<0.01 versus baseline, analyzed with 2-way ANOVA. B) Comparison of the intraoperative percentual decrease of whole blood selenium between the on-pump group (white bar) and the OPCAB-group (black bar). *p<0.05, **p<0.01 between the two groups, analyzed with the Mann–Whitney U test.

Figure 3. Perioperative time course of markers of oxidative stress and antioxidant capacity.

A) Comparison of the intraoperative decrease of ADMA levels in serum between the on-pump group (open circles) and the OPCAB-group (closed circles) at baseline (preoperative) and at ICU admission (postoperative). Data are presented as mean ± standard deviation. §p<0.05, §§p<0.01 versus OPCAB group, analyzed with 2-way ANOVA. B) Correlation of whole blood selenium levels and ADMA in serum between the two groups. Data are depicted as linear regression (black line) with 95% confidence intervals (long dashed line). C) Comparison of GPx levels between the on-pump group (open circles) and the OPCAB-group (closed circles) at baseline (preoperative) and at ICU admission (postoperative). Data are presented as mean ± standard deviation. *p<0.05, **p<0.01 versus baseline, analyzed with 2-way ANOVA. D) Correlation of whole blood selenium and GPx content in serum between the two groups. Data are depicted as linear regression (black line) with 95% confidence intervals (long dashed line).

Figure 4. Perioperative inflammatory response and myocardial damage.

A) Comparison of serum IL-6 levels between the on-pump group (open circles) and the OPCAB-group (closed circles) at baseline (preoperative) and at ICU admission (postoperative). Data are presented as mean ± standard deviation. *p<0.05, **p<0.01 versus baseline, analyzed with 2-way ANOVA. B) Correlation of whole blood selenium levels and IL-6 levels in serum, between the two groups. Data are depicted as linear regression (black line) with 95% confidence intervals (long dashed line). C) Comparison of serum CK-MB levels between the on-pump group (open circles) and the OPCAB-group (closed circles) at baseline (preoperative) and at ICU admission (postoperative). Data are presented as mean ± standard deviation. *p<0.05, **p<0.01 versus baseline, analyzed with 2-way ANOVA. D) Correlation of whole blood selenium levels and CK-MB in serum between the two groups. Data are depicted as linear regression (black line) with 95% confidence intervals (long dashed line).

Figure 5. Receiver operating characteristic curve (all patients).

Receiver operating characteristic curve for the significance of postoperative (admission to ICU) selenium, GPx, ADMA and CK-MB concentrations in all patients to predict the development of organ dysfunction in the postoperative period. AUC, area under the receiver operating curve.

Figure 6. Receiver operating characteristic curve (OPCAB group).

Receiver operating characteristic curve for the significance of postoperative (admission to ICU) selenium, GPx, ADMA and CK-MB concentrations in the OPCAB group to predict the development of organ dysfunction in the postoperative period. AUC, area under the receiver operating curve.