Journal of Anesthesia

, Volume 30, Issue 6, pp 977–986 | Cite as

Sevoflurane preconditioning in on-pump coronary artery bypass grafting: a meta-analysis of randomized controlled trials

  • Yan Lu
  • Liwei Wang
  • Na Liu
  • Tianxin Dong
  • Ruhong LiEmail author
Original Article



Sevoflurane preconditioning (SevoPreC) has been proved to prevent organ ischemia/reperfusion (I/R) injury in various animal models and preclinical studies. Clinical trials on cardioprotection by SevoPreC for adult patients undergoing coronary artery bypass graft (CABG) revealed mixed results. The aim of this meta-analysis was to evaluate the cardiac effect of SevoPreC in on-pump CABG.


Randomized controlled trials (RCT) comparing the cardiac effect of SevoPreC (compared with control) in adult patients undergoing CABG were searched from PubMed, Embase, and the Cochrane Library (up to November 2015). The primary endpoints were postoperative troponin levels. Additional endpoints were CK-MB levels, mechanic ventilation (MV) duration, intensive care unit (ICU) stay, and hospital length of stay (LOS).


Six trials with eight comparisons enrolling a total of 384 study patients reporting postoperative troponin levels were identified. Compared with controls, SevoPreC decreased postoperative myocardial troponin levels [standardized mean difference (SMD) = −0.38; 95 % CI, −0.74 to −0.03; P = 0.04; I 2 = 63.9 %]. However, no significant differences were observed in postoperative CK-MB levels [weighted mean difference (WMD) = −1.71; P = 0.37; I 2 = 37.7 %], MV duration (WMD = −0.53; P = 0.47; I 2 = 0.0 %), ICU stay (WMD = −0.91; P = 0.39; I 2 = 0.9 %), and hospital LOS (WMD = 0.08; P = 0.86; I 2 = 8.0 %).


Available evidence from the present systematic review and meta-analysis suggests that sevoflurane preconditioning may reduce troponin levels in on-pump CABG. Future high-quality, large-scale clinical trials should focus on the early and long-term clinical effect of SevoPreC in on-pump CABG.


Sevoflurane preconditioning Cardioprotection Coronary artery bypass graft 



We thank Dr. Yang Liu, and Dr. Li Ma from Beijing Chest Hospital, for their language-editing assistance.

Compliance with ethical standards

Conflict of interest

None declared.


  1. 1.
    Nguyen BA, Suleiman MS, Anderson JR, Evans PC, Fiorentino F, Reeves BC, Angelini GD. Metabolic derangement and cardiac injury early after reperfusion following intermittent cross-clamp fibrillation in patients undergoing coronary artery bypass graft surgery using conventional or miniaturized cardiopulmonary bypass. Mol Cell Biochem. 2014;395:167–75.CrossRefPubMedGoogle Scholar
  2. 2.
    Huang WH, Lee JF, Wang D, Gou WH, Chang CY, Wei J. Postischemia myocardial injury in coronary artery bypass patients (PP6). Transplant Proc. 2010;42:725–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Domanski MJ, Mahaffey K, Hasselblad V, Brener SJ, Smith PK, Hillis G, Engoren M, Alexander JH, Levy JH, Chaitman BR, Broderick S, Mack MJ, Pieper KS, Farkouh ME. Association of myocardial enzyme elevation and survival following coronary artery bypass graft surgery. JAMA. 2011;305:585–91.CrossRefPubMedGoogle Scholar
  4. 4.
    An J, Varadarajan SG, Novalija E, Stowe DF. Ischemic and anesthetic preconditioning reduces cytosolic [Ca2+] and improves Ca(2+) responses in intact hearts. Am J Physiol Heart Circ Physiol. 2001;281:H1508–23.PubMedGoogle Scholar
  5. 5.
    Novalija E, Stowe DF. Prior preconditioning by ischemia or sevoflurane improves cardiac work per oxygen use in isolated guinea pig hearts after global ischemia. Adv Exp Med Biol. 1998;454:533–42.CrossRefPubMedGoogle Scholar
  6. 6.
    Zaugg M, Lucchinetti E, Spahn DR, Pasch T, Schaub MC. Volatile anesthetics mimic cardiac preconditioning by priming the activation of mitochondrial K(ATP) channels via multiple signaling pathways. Anesthesiology. 2002;97:4–14.CrossRefPubMedGoogle Scholar
  7. 7.
    Zhong C, Zhou Y, Liu H. Nuclear factor kappaB and anesthetic preconditioning during myocardial ischemia-reperfusion. Anesthesiology. 2004;100:540–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Lange M, Smul TM, Blomeyer CA, Redel A, Klotz KN, Roewer N, Kehl F. Role of the beta1-adrenergic pathway in anesthetic and ischemic preconditioning against myocardial infarction in the rabbit heart in vivo. Anesthesiology. 2006;105:503–10.CrossRefPubMedGoogle Scholar
  9. 9.
    Zhao J, Wang F, Zhang Y, Jiao L, Lau WB, Wang L, Liu B, Gao E, Koch WJ, Ma XL, Wang Y. Sevoflurane preconditioning attenuates myocardial ischemia/reperfusion injury via caveolin-3-dependent cyclooxygenase-2 inhibition. Circulation. 2013;128:S121–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Lucchinetti E, Ambrosio S, Aguirre J, Herrmann P, Harter L, Keel M, Meier T, Zaugg M. Sevoflurane inhalation at sedative concentrations provides endothelial protection against ischemia-reperfusion injury in humans. Anesthesiology. 2007;106:262–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Lucchinetti E, Aguirre J, Feng J, Zhu M, Suter M, Spahn DR, Harter L, Zaugg M. Molecular evidence of late preconditioning after sevoflurane inhalation in healthy volunteers. Anesth Analg. 2007;105:629–40.CrossRefPubMedGoogle Scholar
  12. 12.
    Wacker J, Lucchinetti E, Jamnicki M, Aguirre J, Harter L, Keel M, Zaugg M. Delayed inhibition of agonist-induced granulocyte-platelet aggregation after low-dose sevoflurane inhalation in humans. Anesth Analg. 2008;106:1749–58.CrossRefPubMedGoogle Scholar
  13. 13.
    Pouzet B, Lecharny JB, Dehoux M, Paquin S, Kitakaze M, Mantz J, Menasche P. Is there a place for preconditioning during cardiac operations in humans? Ann Thorac Surg. 2002;73:843–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Yang L, Wang G, Du Y, Ji B, Zheng Z. Remote ischemic preconditioning reduces cardiac troponin I release in cardiac surgery: a meta-analysis. J Cardiothorac Vasc Anesth. 2014;28:682–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Deng QW, Xia ZQ, Qiu YX, Wu Y, Liu JX, Li C, Liu KX. Clinical benefits of aortic cross-clamping versus limb remote ischemic preconditioning in coronary artery bypass grafting with cardiopulmonary bypass: a meta-analysis of randomized controlled trials. J Surg Res. 2015;193:52–68.CrossRefPubMedGoogle Scholar
  16. 16.
    Yasin NAHM, Herbison P, Saxena P, Praporski S, Konstantinov IE. The role of remote ischemic preconditioning in organ protection after cardiac surgery: a meta-analysis. J Surg Res. 2014;186:207–16.CrossRefGoogle Scholar
  17. 17.
    Thielmann M, Kottenberg E, Kleinbongard P, Wendt D, Gedik N, Pasa S, Price V, Tsagakis K, Neuhauser M, Peters J, Jakob H, Heusch G. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet. 2013;382:597–604.CrossRefPubMedGoogle Scholar
  18. 18.
    Julier K, da Silva R, Garcia C, Bestmann L, Frascarolo P, Zollinger A, Chassot PG, Schmid ER, Turina MI, von Segesser LK, Pasch T, Spahn DR, Zaugg M. Preconditioning by sevoflurane decreases biochemical markers for myocardial and renal dysfunction in coronary artery bypass graft surgery: a double-blinded, placebo-controlled, multicenter study. Anesthesiology. 2003;98:1315–27.CrossRefPubMedGoogle Scholar
  19. 19.
    De Hert SG, Van der Linden PJ, Cromheecke S, Meeus R, Nelis A, Van Reeth V, ten Broecke PW, De Blier IG, Stockman BA, Rodrigus IE. Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration. Anesthesiology. 2004;101:299–310.CrossRefPubMedGoogle Scholar
  20. 20.
    Garcia C, Julier K, Bestmann L, Zollinger A, von Segesser LK, Pasch T, Spahn DR, Zaugg M. Preconditioning with sevoflurane decreases PECAM-1 expression and improves one-year cardiovascular outcome in coronary artery bypass graft surgery. Br J Anaesth. 2005;94:159–65.CrossRefPubMedGoogle Scholar
  21. 21.
    Piriou V, Mantz J, Goldfarb G, Kitakaze M, Chiari P, Paquin S, Cornu C, Lecharny JB, Aussage P, Vicaut E, Pons A, Lehot JJ. Sevoflurane preconditioning at 1 MAC only provides limited protection in patients undergoing coronary artery bypass surgery: a randomized bi-centre trial. Br J Anaesth. 2007;99:624–31.CrossRefPubMedGoogle Scholar
  22. 22.
    Bein B, Renner J, Caliebe D, Hanss R, Bauer M, Fraund S, Scholz J. The effects of interrupted or continuous administration of sevoflurane on preconditioning before cardio-pulmonary bypass in coronary artery surgery: comparison with continuous propofol. Anaesthesia. 2008;63:1046–55.CrossRefPubMedGoogle Scholar
  23. 23.
    Frassdorf J, Borowski A, Ebel D, Feindt P, Hermes M, Meemann T, Weber R, Mullenheim J, Weber NC, Preckel B, Schlack W. Impact of preconditioning protocol on anesthetic-induced cardioprotection in patients having coronary artery bypass surgery. J Thorac Cardiovasc Surg. 2009;137(1436–42):42 (e1–2).Google Scholar
  24. 24.
    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    da Costa BR, Resta NM, Beckett B, Israel-Stahre N, Diaz A, Johnston BC, Egger M, Juni P, Armijo-Olivo S. Effect of standardized training on the reliability of the Cochrane risk of bias assessment tool: a study protocol. Syst Rev. 2014;3:144.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Alkhulaifi AM, Yellon DM, Pugsley WB. Preconditioning the human heart during aorto-coronary bypass surgery. Eur J Cardiothorac Surg. 1994;8:270–5 (discussion 276).CrossRefPubMedGoogle Scholar
  28. 28.
    Amr YM, Yassin IM. Cardiac protection during on-pump coronary artery bypass grafting: ischemic versus isoflurane preconditioning. Semin Cardiothorac Vasc Anesth. 2010;14:205–11.CrossRefPubMedGoogle Scholar
  29. 29.
    Wu ZK, Iivainen T, Pehkonen E, Laurikka J, Tarkka MR. Ischemic preconditioning suppresses ventricular tachyarrhythmias after myocardial revascularization. Circulation. 2002;106:3091–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Czibik G, Wu Z, Berne GP, Tarkka M, Vaage J, Laurikka J, Jarvinen O, Valen G. Human adaptation to ischemia by preconditioning or unstable angina: involvement of nuclear factor kappa B, but not hypoxia-inducible factor 1 alpha in the heart. Eur J Cardiothorac Surg. 2008;34:976–84.CrossRefPubMedGoogle Scholar
  31. 31.
    Walsh SR, Tang TY, Kullar P, Jenkins DP, Dutka DP, Gaunt ME. Ischaemic preconditioning during cardiac surgery: systematic review and meta-analysis of perioperative outcomes in randomised clinical trials. Eur J Cardiothorac Surg. 2008;34:985–94.CrossRefPubMedGoogle Scholar
  32. 32.
    Soraas CL, Friis C, Engebretsen KV, Sandvik L, Kjeldsen SE, Tonnessen T. Troponin T is a better predictor than creatine kinase-MB of long-term mortality after coronary artery bypass graft surgery. Am Heart J. 2012;164:779–85.CrossRefPubMedGoogle Scholar
  33. 33.
    Omland T, de Lemos JA, Sabatine MS, Christophi CA, Rice MM, Jablonski KA, Tjora S, Domanski MJ, Gersh BJ, Rouleau JL, Pfeffer MA, Braunwald E. A sensitive cardiac troponin T assay in stable coronary artery disease. N Engl J Med. 2009;361:2538–47.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Prasad A, Rihal CS, Lennon RJ, Singh M, Jaffe AS, Holmes DR Jr. Significance of periprocedural myonecrosis on outcomes after percutaneous coronary intervention: an analysis of preintervention and postintervention troponin T levels in 5487 patients. Circ Cardiovasc Interv. 2008;1:10–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, Ashley E, Vichare S, Di Salvo C, Kolvekar S, Hayward M, Keogh B, MacAllister RJ, Yellon DM. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet. 2007;370:575–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Hoole SP, Heck PM, Sharples L, Khan SN, Duehmke R, Densem CG, Clarke SC, Shapiro LM, Schofield PM, O’Sullivan M, Dutka DP. Cardiac remote ischemic preconditioning in coronary stenting (CRISP Stent) study: a prospective, randomized control trial. Circulation. 2009;119:820–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Yetgin T, Manintveld OC, Boersma E, Kappetein AP, van Geuns RJ, Zijlstra F, Duncker DJ, van der Giessen WJ. Remote ischemic conditioning in percutaneous coronary intervention and coronary artery bypass grafting. Circ J. 2012;76:2392–404.CrossRefPubMedGoogle Scholar
  38. 38.
    Sloth AD, Schmidt MR, Munk K, Kharbanda RK, Redington AN, Schmidt M, Pedersen L, Sorensen HT, Botker HE. Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention. Eur Heart J. 2014;35:168–75.CrossRefPubMedGoogle Scholar
  39. 39.
    Davies WR, Brown AJ, Watson W, McCormick LM, West NE, Dutka DP, Hoole SP. Remote ischemic preconditioning improves outcome at 6 years after elective percutaneous coronary intervention: the CRISP stent trial long-term follow-up. Circ Cardiovasc Interv. 2013;6:246–51.CrossRefPubMedGoogle Scholar
  40. 40.
    Riess ML, Kevin LG, Camara AK, Heisner JS, Stowe DF. Dual exposure to sevoflurane improves anesthetic preconditioning in intact hearts. Anesthesiology. 2004;100:569–74.CrossRefPubMedGoogle Scholar
  41. 41.
    Fradorf J, Huhn R, Weber NC, Ebel D, Wingert N, Preckel B, Toma O, Schlack W, Hollmann MW. Sevoflurane-induced preconditioning: impact of protocol and aprotinin administration on infarct size and endothelial nitric-oxide synthase phosphorylation in the rat heart in vivo. Anesthesiology. 2010;113:1289–98.CrossRefPubMedGoogle Scholar
  42. 42.
    Lange M, Redel A, Smul TM, Lotz C, Nefzger T, Stumpner J, Blomeyer C, Gao F, Roewer N, Kehl F. Desflurane-induced preconditioning has a threshold that is lowered by repetitive application and is mediated by beta 2-adrenergic receptors. J Cardiothorac Vasc Anesth. 2009;23:607–13.CrossRefPubMedGoogle Scholar
  43. 43.
    Riess ML, Camara AK, Rhodes SS, McCormick J, Jiang MT, Stowe DF. Increasing heart size and age attenuate anesthetic preconditioning in guinea pig isolated hearts. Anesth Analg. 2005;101:1572–6.CrossRefPubMedGoogle Scholar
  44. 44.
    Zhou C. Gender disparity may contribute to the quasi preservation of cardioprotection by remote preconditioning with isoflurane but not propofol in CABG. J Thorac Cardiovasc Surg. 2013;146:732–3.CrossRefPubMedGoogle Scholar
  45. 45.
    Zheng Z, Yang M, Zhang F, Yu J, Wang J, Ma L, Zhong Y, Qian L, Chen G, Yu L, Yan M. Gender-related difference of sevoflurane postconditioning in isolated rat hearts: focus on phosphatidylinositol-3-kinase/Akt signaling. J Surg Res. 2011;170:e3–9.CrossRefPubMedGoogle Scholar
  46. 46.
    Zhou C, Liu Y, Yao Y, Zhou S, Fang N, Wang W, Li L. Beta-blockers and volatile anesthetics may attenuate cardioprotection by remote preconditioning in adult cardiac surgery: a meta-analysis of 15 randomized trials. J Cardiothorac Vasc Anesth. 2013;27:305–11.CrossRefPubMedGoogle Scholar
  47. 47.
    Kleinbongard P, Neuhauser M, Thielmann M, Kottenberg E, Peters J, Jakob H, Heusch G. Confounders of cardioprotection by remote ischemic preconditioning in patients undergoing coronary artery bypass grafting. Cardiology. 2016;133:128–33.CrossRefPubMedGoogle Scholar
  48. 48.
    Ferdinandy P, Hausenloy DJ, Heusch G, Baxter GF, Schulz R. Interaction of risk factors, comorbidities, and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Pharmacol Rev. 2014;66:1142–74.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Anesthesiologists 2016

Authors and Affiliations

  • Yan Lu
    • 1
  • Liwei Wang
    • 1
  • Na Liu
    • 1
  • Tianxin Dong
    • 1
  • Ruhong Li
    • 1
    Email author
  1. 1.Department of AnesthesiologyAffiliated Hospital of Chengde Medical CollegeChengdeChina

Personalised recommendations