Title: Myocardial protection with volatile anaesthetic agents during coronary artery bypass surgery: a meta-analysis
Abstract: Previous studies have investigated the role of volatile anaesthetic agents in myocardial protection during coronary artery bypass graft (CABG) surgery, and some have identified beneficial effects. However, these studies have been too small to identify a significant effect on myocardial infarction (MI) or mortality. We undertook a systematic overview and meta-analysis of all randomized trials comparing volatile with non-volatile anaesthesia in CABG surgery. We identified 27 trials that included 2979 patients. There was no significant difference in myocardial ischaemia, MI, intensive care unit length of stay or hospital mortality between the groups (all P>0.05). Post-bypass, patients randomized to receive volatile anaesthetics had 20% higher cardiac indices (P=0.006), significantly lower troponin I serum concentrations (P=0.002) and lesser requirement for inotropic support (P=0.004) compared with those randomized to receive i.v. anaesthetics. Duration of mechanical ventilation was reduced by 2.7 h (P=0.04), and there was a 1 day decrease in hospital length of stay (P<0.001). Some of these outcomes were based on a smaller number of trials because of incomplete data, largely because the individual trials focused on one or more surrogate endpoints. We found some evidence that volatile anaesthetic agents provide myocardial protection in CABG surgery, but larger adequately powered trials with agreed, defined outcomes need to be done to fully assess a possible beneficial effect of volatile anaesthetic agents on the risk of MI and mortality. Previous studies have investigated the role of volatile anaesthetic agents in myocardial protection during coronary artery bypass graft (CABG) surgery, and some have identified beneficial effects. However, these studies have been too small to identify a significant effect on myocardial infarction (MI) or mortality. We undertook a systematic overview and meta-analysis of all randomized trials comparing volatile with non-volatile anaesthesia in CABG surgery. We identified 27 trials that included 2979 patients. There was no significant difference in myocardial ischaemia, MI, intensive care unit length of stay or hospital mortality between the groups (all P>0.05). Post-bypass, patients randomized to receive volatile anaesthetics had 20% higher cardiac indices (P=0.006), significantly lower troponin I serum concentrations (P=0.002) and lesser requirement for inotropic support (P=0.004) compared with those randomized to receive i.v. anaesthetics. Duration of mechanical ventilation was reduced by 2.7 h (P=0.04), and there was a 1 day decrease in hospital length of stay (P<0.001). Some of these outcomes were based on a smaller number of trials because of incomplete data, largely because the individual trials focused on one or more surrogate endpoints. We found some evidence that volatile anaesthetic agents provide myocardial protection in CABG surgery, but larger adequately powered trials with agreed, defined outcomes need to be done to fully assess a possible beneficial effect of volatile anaesthetic agents on the risk of MI and mortality. Myocardial ischaemia–reperfusion injury, which commonly occurs during and after coronary artery bypass grafting (CABG) surgery, can lead to marked myocardial dysfunction and, possibly, myocardial infarction (MI) and prolonged hospitalization. The concept of pharmacologically protecting the myocardium to prevent this type of injury is an attractive concept. Since 1985, when Freedman and colleagues15Freedman BM Hamm DP Everson CT Wechsler AS Christian II, CM Enflurane enhances postischaemic functional recovery in the isolated rat heart.Anesthesiology. 1985; 62: 29-33Crossref PubMed Scopus (56) Google Scholar reported that enflurane could improve postischaemic myocardial recovery in the isolated rat heart, there has been a body of research into the potential benefits of anaesthetic myocardial protection in both animal and human models. Volatile anaesthetic agents may afford myocardial protection by minimizing ischaemia–reperfusion injury or by having a preconditioning effect on the myocardium (preconditioning is a treatment before an ischaemic event). The mechanisms of volatile anaesthetic protection and preconditioning have been extensively studied in vivo and in vitro. These include: opening mitochondrial KATP channels12de Ruijter W Musters RJP Boer C Stienen GJM Simonides WS de Lange JJ The cardioprotective effect of sevoflurane depends on protein kinase C activation, opening of mitochondrial k+ATP channels, and the production of reactive oxygen species.Anesth Analg. 2003; 97: 1370-1376Crossref PubMed Scopus (32) Google Scholar19Hanouz J-L Yvon A Massetti M et al.Mechanisms of desflurane-induced preconditioning in isolated human right atria in vitro.Anesthesiology. 2002; 97: 33-41Crossref PubMed Scopus (94) Google Scholar20Hara T Tomiyasu S Sungsam C Fukusaki M Sumikawa K Sevoflurane protects stunned myocardium through activation of mitochondrial ATP-sensitive potassium channels.Anesth Analg. 2001; 92: 1139-1145Crossref PubMed Scopus (26) Google Scholar40Nakae Y Kohro S Hogan QH Bosnjak ZJ Intracellular mechanism of mitochondrial adenosine triphosphate-sensitive potassium channel activation with isoflurane.Anesth Analg. 2003; 97: 1025-1032Crossref PubMed Scopus (21) Google Scholar62Zaugg M Lucchinetti E Spahn DR Pasch T Schaub MC Volatile anesthetics mimic cardiac preconditioning by priming the activation of mitochondrial KATP channels via multiple signalling pathways.Anesthesiology. 2002; 97: 4-14Crossref PubMed Scopus (249) Google Scholar63Zaugg M Lucchinetti E Spahn DR Pasch T Garcia C Schaub M Differential effects of anesthetics on mitochondrial KATP channel activity and cardiomyocyte protection.Anesthesiology. 2002; 97: 15-23Crossref PubMed Scopus (108) Google Scholar increasing mitochondrial reactive oxygen species,12de Ruijter W Musters RJP Boer C Stienen GJM Simonides WS de Lange JJ The cardioprotective effect of sevoflurane depends on protein kinase C activation, opening of mitochondrial k+ATP channels, and the production of reactive oxygen species.Anesth Analg. 2003; 97: 1370-1376Crossref PubMed Scopus (32) Google Scholar36Müllenheim J Ebel D Fräβdorf J Preckel B Thämer V Schlack W Isoflurane preconditions myocardium against infarction via release of free radicals.Anesthesiology. 2002; 96: 934-940Crossref PubMed Scopus (149) Google Scholar58Tanaka K Weihrauch D Kehl F et al.Mechanism of preconditioning by isoflurane in rabbits: a direct role for reactive oxygen species.Anesthesiology. 2002; 97: 1485-1490Crossref PubMed Scopus (148) Google Scholar and activation or translocation of protein kinase C, tyrosine kinases and p38 mitogen-activated protein kinase.12de Ruijter W Musters RJP Boer C Stienen GJM Simonides WS de Lange JJ The cardioprotective effect of sevoflurane depends on protein kinase C activation, opening of mitochondrial k+ATP channels, and the production of reactive oxygen species.Anesth Analg. 2003; 97: 1370-1376Crossref PubMed Scopus (32) Google Scholar16Fujimoto K Bosnjak ZJ Kwok W-M Isoflurane-induced facilitation of the cardiac sarcolemmal KATP channel.Anesthesiology. 2002; 97: 57-65Crossref PubMed Scopus (60) Google Scholar42Novalija E Kevin LG Camara AKS Bosnjak ZJ Kampine JP Stowe DF Reactive oxygen species precede the ε-isoform of protein kinase C in the anesthetic preconditioning signaling cascade.Anesthesiology. 2003; 99: 421-428Crossref PubMed Scopus (101) Google Scholar56Stadnicka A Kwok W-M Warltier DC Bosnjak ZJ Protein tyrosine kinase-dependent modulation of isoflurane effects on cardiac sarcolemmal KATP channel.Anesthesiology. 2002; 97: 1198-1208Crossref PubMed Scopus (27) Google Scholar These mechanisms decrease cytosolic and mitochondrial calcium loading.60Varadarajan SG An J Novalija E Stowe DF Sevoflurane before or after ischaemia improves contractile and metabolic function while reducing myoplasmic Ca2+ loading in intact hearts.Anesthesiology. 2002; 96: 125-133Crossref PubMed Scopus (72) Google Scholar Volatile anaesthetic agents may also protect endothelial coronary cells by mediating nitric oxide release.41Novalija E Fujita S Kampine JP Stowe DF Sevoflurane mimics ischaemic preconditioning effects on coronary flow and nitric oxide release in isolated hearts.Anesthesiology. 1999; 91: 701-712Crossref PubMed Scopus (134) Google Scholar Finally, some volatile agents suppress neutrophil activation and the neutrophil–endothelium interactions that cause myocardial dysfunction.24Hu G Vasiliauskas T Salem MR Rhone DP Crystal GJ Neutrophils pretreated with volatile anesthetics lose ability to cause cardiac dysfunction.Anesthesiology. 2003; 98: 712-718Crossref PubMed Scopus (39) Google Scholar32Kowalski C Zahler S Becker BF et al.Halothane, isoflurane, and sevoflurane reduce postischaemic adhesion of neutrophils in the coronary system.Anesthesiology. 1997; 86: 188-195Crossref PubMed Scopus (102) Google Scholar For a more complete review of myocardial protection by anaesthetic agents, the reader is referred to Kato and Foëx U.29Kato R Foëx P Myocardial protection by anaesthetic agents against ischemia-reperfusion injury: an update for anesthesiologists.Can J Anaesth. 2002; 49: 777-791Crossref PubMed Scopus (205) Google Scholar Many studies have explored various endpoints as surrogate markers of myocardial protection by volatile anaesthetic agents during CABG surgery. In all cases, these studies have been underpowered to identify a significant effect on MI or mortality. We, therefore, did a systematic overview and meta-analysis of randomized trials to better define the role of volatile agents in myocardial protection during CABG surgery. We included all randomized control trials of adult cardiac patients undergoing on-pump or off-pump CABG surgery that compared volatile with non-volatile anaesthetic agent(s). Patients having valve surgery, and those who had central neuraxial blockade were excluded. A systematic search for all relevant randomized control trials, in all languages, was conducted. Relevant trials were obtained from the following sources between January 1985 and March 2005: electronic databases (MEDLINE and EMBASE), the Cochrane Controlled Trials Register, abstracts in major journals related to anaesthesia and cardiac surgery, and reference lists of relevant randomized trials and review articles. In addition, the following medical subject headings and text words in various combinations were included in a MEDLINE electronic search: propofol, isoflurane, sevoflurane, desflurane, anaesthetics, volatile agents, inhalational, ischaemic preconditioning, protection, myocardial, cardiac surgery, coronary artery bypass surgery, human, postoperative complications, fast-track, early extubation, tracheal extubation, intensive care, morbidity and mortality. Studies which did not include both a volatile anaesthetic and a non-volatile control group were excluded. In studies which had both CABG and valve surgery in the study groups, the valve surgery data were excluded. We also recorded the temporal relationship of the administration of the volatile anaesthetic agent to the commencement of cardiac bypass, and whether the study was single-blind (patient, but not staff or researchers), double-blind (patient plus staff but not researchers) or triple-blind (patient, staff and researchers). In studies in which there was more than one volatile or non-volatile group, these groups were combined for the pooled analyses. The quality (validity) of individual trials was quantified by the Jadad scale,26Jadad AR Moore RA Carroll D et al.Assessing the quality of reports of randomized clinical trials: is blinding necessary?.Control Clin Trials. 1996; 17: 1-12Abstract Full Text PDF PubMed Scopus (13578) Google Scholar using five criteria (one point each): (i) proper randomization, (ii) double blind, (iii) withdrawals documented, (iv) randomization adequately described, (v) blindness adequately described. Our outcome measures included: myocardial ischaemia in the first 24 h after surgery, MI during hospital admission, hospital mortality, cardiac index post-bypass, troponin I enzyme increase, inotrope requirement in intensive care unit (ICU) (or in the operating theatre, post-bypass, where no ICU data were available), ICU and hospital length of stay, and mechanical ventilation time. Because the definitions of myocardial ischaemia and MI varied between studies, all were accepted. The criteria for tracheal extubation and ICU discharge also varied between studies and all were accepted. For studies where the median and range were reported, the mean and sd were estimated by using the O’Rourke method44O’Rourke K Mixed means and medians: a unified approach to deal with disparate outcome summaries.in: Proceedings of the Symposium on Systematic Reviews: Pushing the Boundaries. Oxford, 2002: 49Google Scholar whereby the median was used as the estimate of the mean, and the sd was a quarter of the range. Troponin T concentrations were converted to troponin I concentrations using a conversion factor of 2/0.65, based on the ratio of the upper limit of their respective reference ranges. Cardiac output was converted to a cardiac index by either dividing the cardiac output by the body surface area (if reported) or otherwise assuming a value of 1.7 m2 (the mean value of pooled studies reporting body surface area). Variables which were not reported numerically in the original papers were estimated from the published figures. All data were abstracted and verified by both authors independently, and differences resolved by consensus. Data were then entered into a Rev Man 3.1 (Cochrane Collaboration) database. Trials with no events in both groups for a particular endpoint were excluded from the relevant meta-analysis. The pooled OR and 95% CI were estimated for dichotomous endpoints: mortality, MI, ischaemia and inotrope use. The weighted mean difference and 95% CI were estimated for numerical variables: ICU and hospital length of stay, mechanical ventilation time, cardiac index and troponin level. We tested each endpoint for heterogeneity23Higgins JPT Thompson SG Deeks JJ Altman DG Measuring inconsistency in meta-analyses.Br Med J. 2003; 327: 557-560Crossref PubMed Scopus (39796) Google Scholar and used random-effects models if significant (P<0.05) heterogeneity was detected; all other comparisons were done with fixed-effects models. Subgroup analyses were done to explore a possible differential effect if the volatile agent was administered throughout the entire CABG surgery or for only a portion of the procedure. In a previous study,11De Hert SG Van der Linden PJ Cromheecke S et al.Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration.Anesthesiology. 2004; 101: 299-310Crossref PubMed Scopus (327) Google Scholar one group (50 patients) received volatile agent throughout the entire procedure, the other two groups (100 patients) received volatile at ‘any time’ and therefore all data for the volatile group from this trial were included in the volatile ‘any time’ group to avoid double-counting of data in the non-volatile group. Our literature search identified 43 studies, 16 of which were excluded because volatile agent was not used at all, the study population was restricted to valve surgery, no relevant outcomes were reported, the study was retrospective, or dealt with long-term outcome (list available from the authors). This left 27 studies,1Bein B Renner J Caliebe D et al.Sevoflurane but not propofol preserves myocardial function during minimally invasive direct coronary artery bypass surgery.Anesth Analg. 2005; 100: 610-616Crossref PubMed Scopus (99) Google Scholar2Belhomme D Peynet J Louzy M Launay J-M Kitakaze M Menasché P Evidence for preconditioning by isoflurane in coronary artery bypass graft surgery.Circulation. 1999; 100: 340-344Google Scholar6Conzen PF Fischer S Detter C Peter K Sevoflurane provides greater protection of the myocardium than propofol in patients undergoing off-pump coronary artery bypass surgery.Anesthesiology. 2003; 99: 826-833Crossref PubMed Scopus (161) Google Scholar8De Hert SG Cromheecke S ten Broecke PW et al.Effects of propofol, desflurane and sevoflurane on recovery of myocardial function after coronary surgery in elderly high-risk patients.Anesthesiology. 2003; 99: 314-323Crossref PubMed Scopus (206) Google Scholar, 9De Hert SG ten Broecke PW Mertens E et al.Sevoflurane but not propofol preserves myocardial function in coronary surgery patients.Anesthesiology. 2002; 97: 42-49Crossref PubMed Scopus (295) Google Scholar, 10De Hert SG Van der Linden PJ Cromheecke S et al.Choice of primary anesthetic regimen can influence intensive care unit length of stay after coronary surgery with cardiopulmonary bypass.Anesthesiology. 2004; 101: 9-20Crossref PubMed Scopus (188) Google Scholar, 11De Hert SG Van der Linden PJ Cromheecke S et al.Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration.Anesthesiology. 2004; 101: 299-310Crossref PubMed Scopus (327) Google Scholar13El-Shobaki A Abd El Aal WAM Tahoun HM Abdel-Rashid A Comparative study between isoflurane and propofol in fast-track cardiac anesthesia for patients undergoing CABG.Egypt J Anesth. 2002; 18: 37-43Google Scholar17Gravel NR Searle NR Taillefer J Carrier M Roy M Gagnon L Comparison of the hemodynamic effects of sevoflurane anesthesia induction and maintenance vs TIVA in CABG surgery.Can J Anaesth. 1999; 46: 240-246Crossref PubMed Scopus (40) Google Scholar18Hall RJ Murphy JT Moffitt EA Landymore R Pollak PT Poole L A comparison of the myocardial metabolic and haemodynamic changes produced by propofol-sufentanil and enflurane-sufentanil anaesthesia for patients having coronary artery bypass graft surgery.Can J Anaesth. 1991; 38: 996-1004Crossref PubMed Scopus (54) Google Scholar21Haroun-Bizri S Khoury SS Chehab IR Kassas CM Baraka A Does isoflurane optimize myocardial protection during cardiopulmonary bypass?.J Cardiothorac Vasc Anesth. 2001; 15: 418-421Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar28Julier K da Silva R Garcia C et al.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: 1315-1327Crossref PubMed Scopus (328) Google Scholar31Kendall JB Russell GN Scawn NDA Akrofi M Cowan CM Fox MA A prospective, randomised, single-blind pilot study to determine the effect of anaesthetic technique on troponin T release after off-pump coronary artery surgery.Anaesthesia. 2004; 59: 545-549Crossref PubMed Scopus (40) Google Scholar33Lu C-C Ho S-T Wang J-J et al.Minimal low-flow isoflurane-based anesthesia benefits patients undergoing coronary revascularization via preventing hyperglycemia and maintaining metabolic homeostasis.Acta Anaesthesiol Sin. 2003; 41: 165-172PubMed Google Scholar35Mora CT Dudek C Torjman MC White PF The effects of anesthetic technique on the hemodynamic response and recovery profile in coronary revascularization patients.Anesth Analg. 1995; 81: 900-910PubMed Google Scholar37Myles PS Buckland MR Weeks AM et al.Haemodynamic effects, myocardial ischaemia, and timing of tracheal extubation with propofol-based anesthesia for cardiac surgery.Anesth Analg. 1997; 84: 12-19Crossref PubMed Google Scholar39Nader ND Li CM Khadra WZ Reedy R Panos AL Anesthetic myocardial protection with sevoflurane.J Cardiothorac Vasc Anesth. 2004; 18: 269-274Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar45Parker FC Story DA Poustie S Liu G McNicol L Time to tracheal extubation after coronary artery surgery with isoflurane, sevoflurane, or target-controlled propofol anesthesia: a prospective, randomized, controlled trial.J Cardiothorac Vasc Anesth. 2004; 18: 613-619Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 46Parsons RS Jones RM Wrigley SR MacLeod KGA Platt MW Comparison of desflurane and fentanyl-based anaesthetic techniques for coronary artery bypass surgery.Br J Anaesth. 1994; 72: 430-438Crossref PubMed Scopus (27) Google Scholar, 47Penta de Peppo A Polisca P Tomai F et al.Recovery of LV contractility in man is enhanced by preischaemic administration of enflurane.Ann Thorac Surg. 1999; 68: 112-118Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar, 48Phillips AS McMurray TJ Mirakhur RK Gibson FM Elliott P Propofol-fentanyl anesthesia: a comparison with isoflurane–fentanyl anesthesia in coronary artery bypass grafting and valve replacement surgery.J Cardiothorac Vasc Anesth. 1994; 8: 289-296Abstract Full Text PDF PubMed Scopus (23) Google Scholar, 49Pouzet B Lecharny J-B Dehoux M et al.Is there a place for preconditioning during cardiac operations in humans?.Ann Thorac Surg. 2002; 73: 843-848Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar, 50Ramsay JG DeLima LGR Wynands JE O’Connor JP Ralley FE Robbins GR Pure opioid versus opioid-volatile anesthesia for coronary artery bypass graft surgery: a prospective, randomized, double-blind study.Anesth Analg. 1994; 78: 867-875Crossref PubMed Google Scholar53Sakaida K Isoflurane anaesthesia with combined use of low dose fentanyl for open heart surgery.Masui. 1998; 47: 576-584PubMed Google Scholar, 54Samuelson PN Reves JG Kirklin JK Bradley E Wilson KD Adams M Comparison of sufentanil and enflurane-nitrous oxide anesthesia for myocardial revascularization.Anesth Analg. 1986; 65: 217-226Crossref PubMed Scopus (32) Google Scholar, 55Slogoff S Keats AS Randomized trial of primary anesthetic agents on outcome of coronary artery bypass operations.Anesthesiology. 1989; 70: 179-188Crossref PubMed Scopus (208) Google Scholar59Tomai F De Paulis R Penta de Peppo A et al.Beneficial impact of isoflurane during coronary bypass surgery on troponin I release.G Ital Cardiol. 1999; 29: 1007-1014PubMed Google Scholar with 2979 patients, included in the analysis. Most of the studies only reported some of the endpoints which were the focus of this review, in which case each meta-analysis included fewer patients. The characteristics of the study populations are summarized in Table 1. There was no evidence of statistical heterogeneity for the endpoints of mortality, MI, or myocardial ischaemia (P>0.1), but there was evidence of heterogeneity for the endpoints of hospital length of stay, ICU length of stay, duration of mechanical ventilation, cardiac index, troponin level and post-bypass inotrope administration.Table 1Characteristics of the trials included in the meta-analysis. Blinding: single-blind (patient, but not staff or researchers); double-blind (patient plus staff but not researchers); triple-blind (patient, staff and researchers). Volatile administration: 1, pre-bypass; 2, during bypass; 3, post-bypassStudyBlindingJadad scale26Jadad AR Moore RA Carroll D et al.Assessing the quality of reports of randomized clinical trials: is blinding necessary?.Control Clin Trials. 1996; 17: 1-12Abstract Full Text PDF PubMed Scopus (13578) Google ScholarMajor i.v. hypnotic drugVolatileVolatile administrationBein and colleagues1Bein B Renner J Caliebe D et al.Sevoflurane but not propofol preserves myocardial function during minimally invasive direct coronary artery bypass surgery.Anesth Analg. 2005; 100: 610-616Crossref PubMed Scopus (99) Google ScholarSingle2Propofol (n=26)Sevoflurane (n=24)1,2,3Parker and colleagues45Parker FC Story DA Poustie S Liu G McNicol L Time to tracheal extubation after coronary artery surgery with isoflurane, sevoflurane, or target-controlled propofol anesthesia: a prospective, randomized, controlled trial.J Cardiothorac Vasc Anesth. 2004; 18: 613-619Abstract Full Text Full Text PDF PubMed Scopus (21) Google ScholarDouble5Propofol (n=118)Isoflurane(n=118)1,2,3Sevoflurane(n=118)1,2,3De Hert and colleagues11De Hert SG Van der Linden PJ Cromheecke S et al.Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration.Anesthesiology. 2004; 101: 299-310Crossref PubMed Scopus (327) Google ScholarDouble5Propofol (n=50)Sevoflurane (n=50)1Sevoflurane (n=50)3Sevoflurane (n=50)1,2,3De Hert and colleagues10De Hert SG Van der Linden PJ Cromheecke S et al.Choice of primary anesthetic regimen can influence intensive care unit length of stay after coronary surgery with cardiopulmonary bypass.Anesthesiology. 2004; 101: 9-20Crossref PubMed Scopus (188) Google ScholarDouble5Propofol (n=80)Sevoflurane (n=80)1,2,3Benzodiazepine (n=80)Desflurane (n=80)1,2,3Nader and colleagues39Nader ND Li CM Khadra WZ Reedy R Panos AL Anesthetic myocardial protection with sevoflurane.J Cardiothorac Vasc Anesth. 2004; 18: 269-274Abstract Full Text Full Text PDF PubMed Scopus (83) Google ScholarTriple5Propofol (n=10)Sevoflurane (n=11)2Kendall and colleagues31Kendall JB Russell GN Scawn NDA Akrofi M Cowan CM Fox MA A prospective, randomised, single-blind pilot study to determine the effect of anaesthetic technique on troponin T release after off-pump coronary artery surgery.Anaesthesia. 2004; 59: 545-549Crossref PubMed Scopus (40) Google ScholarSingle3Propofol (n=10)Isoflurane (n=10)1,2,3Conzen and colleagues6Conzen PF Fischer S Detter C Peter K Sevoflurane provides greater protection of the myocardium than propofol in patients undergoing off-pump coronary artery bypass surgery.Anesthesiology. 2003; 99: 826-833Crossref PubMed Scopus (161) Google ScholarSingle1Propofol (n=10)Sevoflurane (n=10)1,2,3De Hert and colleagues8De Hert SG Cromheecke S ten Broecke PW et al.Effects of propofol, desflurane and sevoflurane on recovery of myocardial function after coronary surgery in elderly high-risk patients.Anesthesiology. 2003; 99: 314-323Crossref PubMed Scopus (206) Google ScholarSingle2Propofol (n=15)Desflurane (n=15)1,2,3Sevoflurane (n=15)1,2,3Julier and colleagues28Julier K da Silva R Garcia C et al.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: 1315-1327Crossref PubMed Scopus (328) Google ScholarTriple2Propofol (n=35)Sevoflurane (n=37)2Lu and colleagues33Lu C-C Ho S-T Wang J-J et al.Minimal low-flow isoflurane-based anesthesia benefits patients undergoing coronary revascularization via preventing hyperglycemia and maintaining metabolic homeostasis.Acta Anaesthesiol Sin. 2003; 41: 165-172PubMed Google ScholarSingle1High-dose opioid (n=53)Isoflurane (n=54)1,2,3De Hert and colleagues9De Hert SG ten Broecke PW Mertens E et al.Sevoflurane but not propofol preserves myocardial function in coronary surgery patients.Anesthesiology. 2002; 97: 42-49Crossref PubMed Scopus (295) Google ScholarSingle2Propofol (n=10)Sevoflurane (n=10)1,2,3El-Shobaki and colleagues13El-Shobaki A Abd El Aal WAM Tahoun HM Abdel-Rashid A Comparative study between isoflurane and propofol in fast-track cardiac anesthesia for patients undergoing CABG.Egypt J Anesth. 2002; 18: 37-43Google ScholarSingle1Propofol (n=25)Isoflurane (n=25)1Pouzet and colleagues49Pouzet B Lecharny J-B Dehoux M et al.Is there a place for preconditioning during cardiac operations in humans?.Ann Thorac Surg. 2002; 73: 843-848Abstract Full Text Full Text PDF PubMed Scopus (56) Google ScholarSingle1High-dose opioid (n=10)Sevoflurane (n=10)2Haroun-Bizri and colleagues21Haroun-Bizri S Khoury SS Chehab IR Kassas CM Baraka A Does isoflurane optimize myocardial protection during cardiopulmonary bypass?.J Cardiothorac Vasc Anesth. 2001; 15: 418-421Abstract Full Text Full Text PDF PubMed Scopus (96) Google ScholarSingle1High-dose opioid, benzo (n=21)Isoflurane (n=28)1Belhomme and colleagues2Belhomme D Peynet J Louzy M Launay J-M Kitakaze M Menasché P Evidence for preconditioning by isoflurane in coronary artery bypass graft surgery.Circulation. 1999; 100: 340-344Google ScholarSingle1High-dose opioid, benzo (n=10)Isoflurane (n=10)2Tomai and colleagues59Tomai F De Paulis R Penta de Peppo A et al.Beneficial impact of isoflurane during coronary bypass surgery on troponin I release.G Ital Cardiol. 1999; 29: 1007-1014PubMed Google ScholarSingle1High-dose opioid (n=20)Isoflurane (n=20)1Gravel and colleagues17Gravel NR Searle NR Taillefer J Carrier M Roy M Gagnon L Comparison of the hemodynamic effects of sevoflurane anesthesia induction and maintenance vs TIVA in CABG surgery.Can J Anaesth. 1999; 46: 240-246Crossref PubMed Scopus (40) Google ScholarSingle4Propofol (n=15)Sevoflurane (n=15)1,2,3Penta de Peppo and colleagues47Penta de Peppo A Polisca P Tomai F et al.Recovery of LV contractility in man is enhanced by preischaemic administration of enflurane.Ann Thorac Surg. 1999; 68: 112-118Abstract Full Text Full Text PDF PubMed Scopus (76) Google ScholarSingle1High-dose opioid (n=8)Enflurane (n=8)1Sakaida53Sakaida K Isoflurane anaesthesia with combined use of low dose fentanyl for open heart surgery.Masui. 1998; 47: 576-584PubMed Google ScholarSingle1High-dose opioid (n=20)Isoflurane (n=20)Not reportedMyles and colleagues37Myles PS Buckland MR Weeks AM et al.Haemodynamic effects, myocardial ischaemia, and timing of tracheal extubation with propofol-based anesthesia for cardiac surgery.Anesth Analg. 1997; 84: 12-19Crossref PubMed Google ScholarDouble4Propofol (n=58)Enflurane (n=66)1Mora and colleagues35Mora CT Dudek C Torjman MC White PF The effects of anesthetic technique on the hemodynamic response and recovery profile in coronary revascularization patients.Anesth Analg. 1995; 81: 900-910PubMed Google ScholarSingle2High-dose opioid (n=22)Enflurane (n=24)1,2,3Propofol (n=23)Thiopentone (n=21)Phillips and colleagues48Phillips A