Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol – a clinical trial E. Kottenberg 1 , M. Thielmann 2 , L. Bergmann 1 , T. Heine 1 , H. Jakob 3 , G. Heusch 4 and J. Peters 5 1 Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen, Universitätsklinikum Essen, Essen, Germany, 2 Klinik für Thorax- und Kardiovaskuläre Chirurgie, Universität Duisburg-Essen, Universitätsklinikum Essen, Essen, Germany, 3 Klinik für Thorax- und Kardiovaskuläre Chirurgie, Universität Duisburg-Essen, Universitätsklinikum Essen, Essen, Germany, 4 Institut für Pathophysiologie, Universität Duisburg-Essen, Universitätsklinikum Essen, Essen, Germany and 5 Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen, Universitätsklinikum Essen, Essen, Germany Background: Remote ischemic preconditioning (RIPC) of the myocardium by limb ischemia/reperfusion may mitigate cardiac damage, but its interaction with the anesthetic regimen is unknown. We tested whether RIPC is associated with differen- tial effects depending on background anesthesia. Specifically, we hypothesized that RIPC during isoflurane anesthesia attenuates myocardial injury in patients undergoing coronary artery bypass graft (CABG) surgery, and that effects may be different during propofol anesthesia. Methods: In a randomized, single-blinded, placebo-controlled prospective study, serum troponin I concentration (cTnI) (base- line, and 1, 6, 12, 24, 48, and 72 h postoperatively) were meas- ured during isoflurane/sufentanil or propofol/sufentanil anesthesia with or without RIPC (three 5-min periods of inter- mittent left upper arm ischemia with 5 min reperfusion each) in non-diabetic patients (n = 72) with three-vessel coronary artery disease (ClinicalTrials.gov NCT01406678). Results: RIPC during isoflurane anesthesia (n = 20) decreased the area under the cTnI time curve (cTnI AUC) (-50%, 190  105 ng/ml ¥ 72 h vs. 383  262 ng/ml ¥ 72 h, P = 0.004), and the peak (7.3  3.6 ng/ml vs. 11.8  5.5, P = 0.004) and serial (P < 0.041) postoperative cTnI when compared to isoflu- rane alone (n = 19). In contrast, RIPC during propofol anesthesia (n = 14) did not alter the cTnI AUC [263  157 ng/ml ¥ 72 h vs. 372  376 ng/ml ¥ 72 h (n = 19), P = 0.318] or peak postopera- tive cTnI (10.1  4.5 ng/ml vs. 12  8.2, P = 0.444). None of the patients experienced harm or side effects from the intermittent left arm ischemia. Conclusion: Thus, RIPC during isoflurane but not during pro- pofol anesthesia decreased myocardial damage in patients undergoing CABG surgery.Accordingly, effects of RIPC evoked by upper limb ischemia/reperfusion depend on background anesthesia, with combined RIPC/isoflurane exerting greater beneficial effects under conditions studied. Accepted for publication 24 September 2011 © 2011 The Authors Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation M itigation of myocardial damage and isch- emia are important challenges of current anesthetic practice because such events are associ- ated with excess mortality. 1 Volatile anesthetics, 2 specifically isoflurane, 3 decrease infarct size when administered before ischemia in animals. 4,5 In patients undergoing coronary artery bypass graft (CABG) surgery, administration of isoflurane 10 min before aortic cross-clamping decreases myo- cardial injury. 6 However, in contrast to rather uniform results obtained in animals, clinical anes- thetic preconditioning studies failed to demonstrate unequivocally a beneficial effect of anesthetic preconditioning. 7–9 Recently, an alternate method, remote ischemic preconditioning (RIPC) has been clinically investi- gated. 10,11 Brief periods of ischemia/reperfusion of remote organs decreased infarct size following prolonged ischemia as effectively as ischemic preconditioning. 12,13 Overall, clinical data encourage the view that RIPC mitigates myocardial damage, 14,15 although two recent studies reported negative results. 16,17 It is unknown, however, whether the anesthetic regime may influence effects of RIPC. 18 Accordingly, we assessed in a randomized, single- blinded, placebo-controlled prospective study the effects of RIPC on serum troponin I concentrations Acta Anaesthesiol Scand 2012; 56: 30–38 Printed in Singapore. All rights reserved © 2011 The Authors Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation ACTA ANAESTHESIOLOGICA SCANDINAVICA doi: 10.1111/j.1399-6576.2011.02585.x 30