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JANAK MEHTA AWARD  
Year : 2013  |  Volume : 16  |  Issue : 1  |  Page : 4-8
Myocardial protection during off pump coronary artery bypass surgery: A comparison of inhalational anesthesia with sevoflurane or desflurane and total intravenous anesthesia


1 Department of Anesthesiology, Fortis Hospital, Bannerghatta Road, Bangalore, Karnataka, India
2 Cardiac Surgical Intensive Care Unit, Fortis Hospital, Bannerghatta Road, Bangalore, Karnataka, India

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Date of Submission10-Jan-2012
Date of Acceptance06-May-2012
Date of Web Publication2-Jan-2013
 

   Abstract 

Aims and Objectives: The objective of the study was to evaluate the myocardial protective effect of volatile agents-sevoflurane and desflurane versus total intravenous anesthesia (TIVA) with propofol in offpump coronary artery bypass surgery (OPCAB) by measuring cardiac troponin-T (cTnT) as a marker of myocardial cell death. Materials and Methods: The study was conducted on 139 patients scheduled to undergo elective OPCAB surgery. The patients were randomly allocated to receive anesthesia with sevoflurane, desflurane or TIVA with propofol. The cTnT levels were measured preoperatively, at arrival in postoperative intensive care unit, at 8, 24, 48 and 96 hours thereafter. Results: The changes in cTnT levels at all time intervals were comparable in the three groups. Conclusion: The study did not reveal any difference in myocardial protection after OPCAB with either sevoflurane or desflurane or TIVA using propofol as assessed by measuring serial cTnT values.

Keywords: Desflurane, Myocardial protection, OPCAB, Sevoflurane, Total intravenous anesthesia

How to cite this article:
Suryaprakash S, Chakravarthy M, Muniraju G, Pandey S, Mitra S, Shivalingappa B, Chittiappa S, Krishnamoorthy J. Myocardial protection during off pump coronary artery bypass surgery: A comparison of inhalational anesthesia with sevoflurane or desflurane and total intravenous anesthesia. Ann Card Anaesth 2013;16:4-8

How to cite this URL:
Suryaprakash S, Chakravarthy M, Muniraju G, Pandey S, Mitra S, Shivalingappa B, Chittiappa S, Krishnamoorthy J. Myocardial protection during off pump coronary artery bypass surgery: A comparison of inhalational anesthesia with sevoflurane or desflurane and total intravenous anesthesia. Ann Card Anaesth [serial online] 2013 [cited 2014 Sep 23];16:4-8. Available from: http://www.annals.in/text.asp?2013/16/1/4/105361



   Introduction Top


The incidence of coronary artery disease is increasing in India and so is the popularity of off pump coronary artery bypass (OPCAB) surgery. OPCAB is considered a safe alternative to conventional coronary artery bypass grafting with cardiopulmonary bypass (CPB) for myocardial revascularization because it may be associated with decreased postoperative morbidity and reduced total costs. Despite advances in surgical techniques, ischemic injury often complicates coronary revascularization procedures and adversely impacts the short and medium term outcomes. [1] The cardiac troponin T (cTnT) has been found to have excellent sensitivity (99%) and specificity (78%) and is superior to creatine kinase-MB (CK-MB) as an indicator of myocardial injury at 4-8 hours after ischemia. [2] The potential benefits of reducing myocardial damage by pharmacological preconditioning have led to a renewed interest in cardiac protection strategies. Several studies have shown myocardial protective effects of inhalational anesthetics and intravenous anesthetic agents. However, some of the questions such as the possible benefits of these agents in OPCAB remain unanswered. The objective of this study was to evaluate the myocardial protective effects of sevoflurane or desflurane vesus total intravenous anesthesia (TIVA) using propofol in patients undergoing OPCAB surgery by measuring cTnT as a marker of myocardial cell death.


   Materials and Methods Top


In this prospective randomized study, 139 patients scheduled to undergo elective OPCAB surgery were included. The study was approved by the institutional ethical committee and written informed consent was obtained from all the patients. The exclusion criteria were emergency surgery, on-going ischemia or unstable angina, acute myocardial infarction of less than 1 month duration, prior cardiac surgery, left ventricular ejection fraction <0.5, serum creatinine higher than 150 mmol/L, restrictive or obstructive pulmonary disease, resting hypoxia (room air SpO2 < 90%) of any etiology, preoperative mechanical ventilation, intra-aortic balloon pump, chronic liver disease, chronic atrial fibrillation, valvular diseases, and patients receiving sulphonylureas, theophylline or allopurinol. The patients were randomly divided using a computer generated randomization chart into three groups namely sevoflurane (n-48), desflurane (n-52) and TIVA (n-39) group. All preoperative cardiac medications except β- blockers were omitted on the day of surgery. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers were discontinued at least 24 hours before surgery. Aspirin and clopidogrel were withheld at least a week prior to surgery. Oral premedication with pantoprazole 40 mg and alprazolam 0.5 mg, was administered on the night prior to surgery. Electrocardiogram (ECG) was recorded prior to transfer to the operating room. Invasive monitoring lines (femoral arterial catheter and pulmonary artery catheter) were inserted under local anesthesia as per the institutional protocol. Baseline TroponinT (Elecsys® Troponin T assay, Hoffman - Roche) was measured. The anesthesia induction technique was standardized in all patients and included intravenous fentanyl 5-10 μg/ kg, midazolam 0.02 mg/kg, and rocuronium 1 mg/kg to facilitate endotracheal intubation. Additionally, all patients received an intravenous infusion of fentanyl 1μg/kg/h and atracurium 7.5 μg/kg/min during the surgery. Anesthesia was maintained with either 1-2% sevoflurane or 4-6% desflurane in a mixture of air and oxygen in the respective groups. In the TIVA group, anesthesia was maintained with an infusion of propofol at a dose of 2-4 mg/kg/h and the patients were ventilated with a mixture of air and oxygen. Patients received routine monitoring for OPCAB surgery which included five-lead ECG, arterial pressure, pulmonary artery pressure and wedge pressure, pulse oximetry, capnography, and core temperature. In addition, bispectral index (BIS) was monitored and the dose of study drug was adjusted to maintain a BIS value of 40-50.

All the patients were operated by the same surgeon. The surgical steps were standardized. Midline sternotomy was performed and left internal mammary artery harvested in all the patients. Heparin 2 mg/kg was administered intravenously to achieve activated clotting time of more than 300 seconds. Pericardial traction sutures and elevating gauze pads were used to facilitate visibility and access to either the left or the right side of the heart. A mechanical suction stabilizer (Octopus Medtronic; Medtronic Inc, Minneapolis, MN), and a moist air blower (Medtronic Inc, Minneapolis, MN) were used to facilitate the surgery. Coronary shunts were used to maintain coronary flow during the construction of the distal anastomoses. The proximal anastomoses of vein grafts were performed with the aid of a partially occluding aortic side clamp. Fluid administration was tailored to maintain hemodynamics within 20% of baseline values. Dopamine 2.5-5 μg/kg/min and/or noradrenaline 0.02- 0.08 μg/kg/min were used to treat hypotension not responding to alterations in table position and fluids. Post operatively, the patients were managed in the post surgical intensive care unit. Trachea was extubated after ensuring normothermia, absence of significant bleeding and hemodynamic stability. The cTnT was estimated at arrival to intensive care unit (ICU), and at 8, 24, 48 and 96 hours thereafter. ECG was recorded at the same time interval as cTnT to note newly developed ST segment changes, T wave inversions or significant ventricular arrhythmias. The primary end point was post operative cTnT levels among the patients of various groups.

Statistical methods

Statistical tests were performed using SPSS version 16.0 and results are reported as absolute values, mean (SD) or median range where appropriate. The demographic data was analyzed using Pearson's Chi square test. The cTnT data of the three groups were compared using analysis of variance with Bonferroni post-hoc analysis. A P value < 0.05 was considered statistically significant.


   Results Top


The study included a total of 139 patients undergoing elective OPCAB. There were 48 patients in sevoflurane group, 52 in the desflurane group and 39 in the TIVA group. Patients were comparable in terms of age (P- 0.29) and gender distribution (P-0.44). The patients in the sevoflurane group had significantly higher number of patients with hypertension and diabetes mellitus (P-0.00). The groups were comparable with regard to the vessels diseased angiographically (P-0.47), vessels grafted (P-0.15) and inotrope use (P-0.50) [Table 1].
Table 1: Table showing demographic variables


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cTnT Data

The changes in cTnT levels at all time intervals were comparable between all the groups (P-0.73) [Figure 1]. In the sevoflurane group, there was a statistically significant increase of cTnT from baseline mean of 0.18 ng/ml to a maximum of 0.30 ng/ml on arrival at ICU (P-0.02) which decreased to 0.23 ng/ml by 96 hours. In the desflurane group there was a statistically significant increase in levels from baseline mean of 0.12 ng/ml to a maximum of 0.26 ng/ml at 24 hours after arrival in ICU (P-0.04) which declined to 0.16 ng/ml by the end of 96 hours. In the TIVA group, there was a statistically significant increase from baseline mean of 0.10 ng/ml to a maximum of 0.27 ng/ml by 24 hours after ICU arrival (P-0.02) which decreased to 0.18 ng/ml by 96 hours.
Figure 1: Comparison of change in cTnT between groups

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None of the study patients had significant ventricular arrhythmias during or after surgery. Postoperatively, atrial fibrillation developed in 2 patients each in sevoflurane and desflurane group and in 3 patients in the TIVA group. This difference was not significant (P-0.66).

ECG changes of new ST segment depression were observed in 4 patients each in the sevoflurane and desflurane groups and 3 patients in the TIVA group. Only 1 patient in the sevoflurane group had a concomitant increase in cTnT values suggestive of peri-operative myocardial infarction; this patient needed prolonged ventilation and ICU stay.


   Discussion Top


The data from this study indicates that patients receiving sevoflurane, desflurane or propofol for OPCAB, experience similar extent of myocardial protection, which is suggested by insignificant change in the level of cTnT between the groups. The cTnT is an ideal marker of myocardial cell damage in patients undergoing cardiac surgery. Unlike the myocardial fraction of CK-MB, it is not released from skeletal muscle during surgery. The cTnT is normally present in the plasma in very low concentrations, thus providing a wide diagnostic window. [3] During acute myocardial injury, the cTnT exhibits a biphasic pattern of release, the early phase within 3-5 h, peaking at 12 h, and a later phase persisting for at least five days. Although there may be no ECG changes associated with increased cTnT levels, it has been suggested that the patients with a greater release of the enzyme after an otherwise successful coronary intervention have worse long-term outcomes, with an increased incidence of myocardial infarction and death due to undetected sub-endocardial injury. [4]

Several meta-analyses and studies have shown benefit with inhalational agents in surgeries carried out using CPB. However, there is conflicting evidence regarding the benefits of volatile agents in beating heart surgery. The OPCAB avoids the ill effects of CPB, aortic clamping and hyperkalemic cardioplegic solution. Thus performing OPCAB may limit the damage to the myocardium. The OPCAB surgery has been shown to be associated with lower cTnT values than coronary artery bypass surgery using CPB. It has been suggested that this decreased release of cTnT may be due to the intermittent regional ischemic episodes caused by OPCAB surgery rather than the prolonged global ischemic episode due to cross clamping of the aorta during CPB. [5],[6] However, doubts have been expressed about whether local coronary occlusion which is necessary to obtain a bloodless field during OPCAB may itself cause ischemic damage. [7] Therefore, there is emerging interest about myocardial protection during OPCAB.

Volatile agents including isoflurane, sevoflurane and desflurane have been demonstrated to exert a protective effect during coronary artery bypass surgery - whether performed using CPB or OPCAB. This protective action was observed due to both pre and post- conditioning. [8],[9],[10] A detailed discussion of the mechanisms of volatile agent induced cardio protection has been described. [10],[11] In a meta-analysis of 22 studies, it was shown that both desflurane and sevoflurane significantly decreased the rate of myocardial infarction and death in patients undergoing cardiac surgery. [12]

There is controversy regarding the cardio protection offered by propofol. Propofol has been demonstrated to increase the antioxidant capacity of erythrocytes and tissues. Ansley et al., observed that high-dose propofol (2.0-2.5 mg/ kg bolus followed by a continuous infusion of 200 μg/ kg/ min) enhanced red-blood-cell antioxidant capacity during CPB in humans. These authors related this increased antioxidant capacity of high-dose propofol to improved myocardial function. [13],[14] In an animal model propofol infused at clinically relevant concentration during the peri-ischemic period produced delayed myocardial protective effect following regional myocardial ischemia/reperfusion injury up to 48 hours of reperfusion. [15] In yet another study, propofol decreased post-ischemic myocardial mechanical dysfunction, infarct size and histological degeneration. [16] However, in a contradictory study of 20 patients undergoing OPCAB, troponin I concentrations were shown to increase significantly more in propofol-anesthetized patients than in those anesthetized with sevoflurane. [17] In a multicenter randomized controlled study to compare cardiac troponin- I release in patients receiving either volatile anesthetics or TIVA for OPCAB, volatile anesthetics were found to offer better cardio protection. [18] On the contrary, in a small study comparing anesthesia with sevoflurane and remifentanil with propofol and remifentanil in 18 patients undergoing OPCAB, sevoflurane was not found to offer any additional cardio protection. [19] In a prospective, randomized single-blind pilot study Kendall and coworkers studied propofol, isoflurane and isoflurane with high thoracic epidural analgesia. They did not find significant change in cTnT release between the three groups. [20] In a retrospective study of 10,535 cardiac surgeries, it was concluded that sevoflurane and propofol possess some, although different, cardioprotective properties. Sevoflurane appears to be superior to propofol in patients with little or no ischemic heart disease, such as non coronary artery bypass graft surgery and coronary artery bypass surgery without severe preoperative ischemia, whereas propofol seems superior in patients with severe ischemia, cardiovascular instability, or in acute/urgent surgery. [21] Conzen et al, Guarracino et al., and De Hert et al., [17],[18],[22] observed that using TIVA does not seem to provide myocardial protection in patients undergoing cardiac surgery in comparison to volatile agents. Such observations about TIVA might deter anesthesiologists wishing to practice TIVA to provide fast tracking in their practice. The benefit of avoiding operating room pollution is yet another undeniable advantage of TIVA. Contrary to the observation of these authors, the present study shows absence of any difference when either techniques were used. Kendal et al. and Law-Koune et al.,[19],[20] also made similar observations.

The current study has limitations. Fentanyl administered at induction and during anesthesia may have exerted cardioprotective effects. [23] Since fentanyl was used in all the study groups, we presume that all the patients received equal benefit of the agent. Finally, this study is not adequately powered.

In conclusion, this study did not reveal any difference in the myocardial protection after OPCAB with either sevoflurane, or desflurane or propofol anesthesia as assessed by measuring serial cTnT values. This observation can promote the use of TIVA in OPCAB surgeries.


   Acknowledgments Top


The authors thank Dr. Vivek Jawali, Chief cardiothoracic surgeon and Dr. Deepak K.M., Consultant Anesthesiologist for their valuable help in the conduct of the study.

 
   References Top

1.Martin B, Shaw AD, Gal J, Aravindan N, Murphy F, Royston D, et al. The comparison and validity of troponin I assay systems in diagnosing myocardial ischemic injury after surgical coronary revascularization. J Cardiothorac Vasc Anesth 2005;19:288-93.  Back to cited text no. 1
    
2.Maynard SJ, Menown IB, Adgey AA. Troponin T or troponin I as cardiac markers in ischemic heart disease. Heart 2000;83:371-3.  Back to cited text no. 2
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3.Collinson PO. Troponin T or Troponin I or CK-MB (or none?). Eur Heart J 1998;19:N16-24.  Back to cited text no. 3
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4.Saucedo JF, Mehran R, Dangas G, Hong MK, Lansky A, Kent KM, et al. Long term clinical events following creatine kinase-myocardial band elevation after successful coronary stenting. J Am Coll Cardiol 2000;35:1134-41.  Back to cited text no. 4
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5.Krejca M, Skiba J, Szmagala P, Gburek T, Bochenek A. Cardiac troponin T release during surgery using intermittent cross-clamp with fibrillation, on-pump and off-pump beating heart. Eur J Cardiothorac Surg 1999;16:337-41.  Back to cited text no. 5
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6.Koh TW, Carr-White GS, DeSouza AC, Ferdinand FD, Hooper J, Kemp M, et al. Intra operative cardiac troponin T release and lactate metabolism during coronary artery surgery: A comparison of beating heart surgery with conventional coronary artery with cardiopulmonary bypass. Heart 1999;81:495-500.  Back to cited text no. 6
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7.Hartz RS. Minimally invasive heart surgery. Executive Committee of the Council on Cardio-Thoracic and Vascular Surgery. Circulation 1996;94:2669-70.  Back to cited text no. 7
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8.Belhomme D, Peynet J, Louzy M, Launay JM, Kitakaze M, Menasché P. Evidence for preconditioning by isoflurane in coronary artery bypass graft surgery. Circulation 1999;100(19 Suppl):II340-4.  Back to cited text no. 8
    
9.Tanaka K, Ludwig LM, Kersten JR, Pagel PS, Warltier DC. Mechanisms of cardioprotection by volatile anesthetics. Anesthesiology 2004;100:707-21.  Back to cited text no. 9
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10.de Hert SG, Turani F, Mathur S, Stowe DF. Cardioprotection with volatile anesthetics: Mechanisms and clinical implications. Anesth Analg 2005;100:1584-93.  Back to cited text no. 10
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11.Fradorf J, De Hert SG, Schlack W. Anesthesia and myocardial ischaemia/reperfusion injury. Br J Anesth 2009;103:89-98.  Back to cited text no. 11
    
12.Landoni G, Biondi-Zoccai GG, Zangrillo A, Bignami E, D'Avolio S, Marchetti C, et al. Desflurane and Sevoflurane in Cardiac Surgery: A Meta-Analysis of Randomized Clinical Trials. J Cardiothorac Vasc Anesth 2007;21:502-11.  Back to cited text no. 12
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13.Ansley DM, Sun J, Visser WA, Dolman J, Godin DV, Garnett ME, et al. High dose propofol enhances red cell antioxidant capacity during CPB in humans. Can J Anesth 1999;46:641-8.  Back to cited text no. 13
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14.Ansley DM, Xia Z. Propofol preservation of myocardial function in patients undergoing coronary surgery with cardiopulmonary bypass is dose dependent. Anesthesiology 2002;98:1028-9.  Back to cited text no. 14
    
15.Shin IW, Jang IS, Lee SH, Baik JS, Park KE, Sohn JT, et al. Propofol has delayed myocardial protective effects after a regional ischemia/reperfusion injury in an in vivo rat heart model. Korean J Anesthesiol 2010;58:378-82.  Back to cited text no. 15
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16.Kato R, Foëx O. Myocardial protection by anesthetic agents against ischemia-reperfusion injury: An update for anesthesiologists. Can J Anesth 2002;49:777-91.  Back to cited text no. 16
    
17.Conzen 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;99:826-33.  Back to cited text no. 17
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18.Guarracino F, Landoni G, Tritapepe L, Pompei F, Leoni A, Aletti G, et al. Myocardial Damage Prevented by Volatile Anesthetics: A Multicenter Randomized Controlled Study. J Cardiothorac Vasc Anesth 2006;20:477-83.  Back to cited text no. 18
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19.Law-Koune JD, Raynaud C, Liu N, Dubois C, Romano M, Fischler M. Sevoflurane-remifentanil versus propofol-remifentanil anesthesia at a similar bispectral level for off-pump coronary artery surgery: No evidence of reduced myocardial ischemia. J Cardiothorac Vasc Anesth 2006;20:484-92.  Back to cited text no. 19
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20.Kendall JB, Russell GN, Scawn DA, Akrofi M, Cowan CM, Fox MA. A prospective, randomized, single-blind pilot study to determine the effect of anesthetic technique on troponin release after off-pump coronary artery surgery. Anesthesia 2004;59:545-9.  Back to cited text no. 20
    
21.Jakobsen CJ, Berg H, Hindsholm KB, Faddy N, Sloth E. The influence of propofol versus sevoflurane anesthesia on outcome in 10,535 cardiac surgical procedures. J Cardiothorac Vasc Anesth 2007;21:664-71.  Back to cited text no. 21
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22.de Hert SG, ten Broecke PW, Mertens E, van Sommeren EW, de Blier IG, Stockman BA, et al. Sevoflurane but not propofol preserves myocardial function in coronary surgery patients. Anesthesiology 2002;97:42-9.  Back to cited text no. 22
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23.Schultz JE, Gross GJ. Opioids and cardioprotection. Pharmacol Ther 2001;89:123-37.  Back to cited text no. 23
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Correspondence Address:
Sharadaprasad Suryaprakash
Fortis Hospital, Bannerghatta Road, Bangalore, Karnataka - 560 052
India
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DOI: 10.4103/0971-9784.105361

PMID: 23287079

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