Desflurane Versus Propofol in Patients Undergoing Mitral Valve Surgery

Desflurane Versus Propofol in Patients Undergoing Mitral Valve Surgery Giovanni Landoni, MD,* Maria Grazia Calabrò, MD,* Chiara Marchetti, MD,* Elena Bignami, MD,* Anna Mara Scandroglio, MD,* Elisa Dedola, MD,* Monica De Luca, MD,* Luigi Tritapepe, MD,† Giuseppe Crescenzi, MD,* and Alberto Zangrillo, MD* Objective: Myocardial ischemic damage is reduced by volatile anesthetics in patients undergoing coronary artery bypass graft surgery, but it is unknown whether this benefit exists in patients undergoing valvular surgery with ischemia-reperfusion injury related to cardioplegic arrest and cardiopulmonary bypass. This study compared cardiac troponin release in patients receiving either volatile anesthetics or total intravenous anesthesia for mitral valve surgery. Design: Randomized controlled study. Setting: University hospital. Participants: One hundred twenty patients undergoing mitral valve surgery. Interventions: Fifty-nine patients received the volatile anesthetic desflurane for 30 minutes before cardiopulmonary bypass, whereas 61 patients received a total intravenous anesthetic with propofol. All patients had an opioid-based anesthetic for the mitral valve surgery. Measurements and Main Results: Peak postoperative troponin I release was measured as a marker of myocardial

necrosis after mitral valve surgery. Patient mean age was 60 years, and 54% were men. There was no significant (p ⴝ 0.7) reduction in median (25th-75th percentiles) postoperative peak troponin, 11.0 (7.5-17.4) ng/dL in the desflurane group versus 11.5 (6.9-18.0) ng/dL in the propofol group. A subgroup of patients with concomitant coronary artery disease had the expected reduction (p ⴝ 0.02) of peak troponin I in those receiving desflurane, 14.0 (9.7-17.3) ng/dL, when compared with patients receiving total intravenous anesthesia, 31.6 (15.7-52.0) ng/dL. Conclusions: Myocardial damage measured by cardiac troponin release was not reduced by volatile anesthetics in patients undergoing mitral valve surgery, whereas it was reduced in patients with concomitant coronary artery disease. © 2007 Elsevier Inc. All rights reserved.

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myocardial injury after cardiac surgery. One approach to evaluate postischemic injury of the heart is to assess cardiac biomarker release. At present, the most popular biomarker for myocardial damage is cardiac troponin I (cTnI), with nearly total myocardial tissue specificity and extreme sensitivity, reflecting a very small amount of myocardial necrosis.5 cTnI predicts short- and long-term outcomes after cardiac6-8 and noncardiac surgery.9 In the context of surgical revascularization, patients showing troponin increases show evidence of new irreversible myocardial injury on delayed-enhancement magnetic resonance imaging.10 The magnitude of this injury correlates directly with the extent of troponin I elevation. Studies evaluating the effects of volatile anesthetics have been performed on human patients undergoing coronary artery bypass graft (CABG) surgery, either with cardiopulmonary bypass (CPB)11-16 or on the beating heart.17-19 Lower postoperative values of cTnI are consistent with a cardioprotective effect of these anesthetics. Although in recent years valvular surgery has steadily grown in importance, previous studies of anesthetic preconditioning during cardiac surgery have been performed on CABG patients. No studies have been performed on the effects of volatile anesthetics in patients undergoing surgery for chronic mitral regurgitation. It was hypothesized that the use of a volatile anesthetic would be associated with a lower postoperative cTnI release in MV surgery, as has been shown in CABG surgery. Therefore, a prospective randomized trial comparing a volatile anesthetic to a total intravenous anesthetic in MV surgery for MR was performed in order to evaluate the effects of volatile anesthetics versus intravenous anesthetics on cTnI release and subsequent patient outcomes.

ATIENTS UNDERGOING mitral valve (MV) surgery for mitral regurgitation (MR) may exhibit postoperative depression of myocardial performance leading to postoperative morbidity and mortality. The choice of an anesthetic that preserves myocardial function may help prevent such postoperative cardiac dysfunction. Controversies exist as to the precise etiology of the postoperative reduction in left ventricular performance; plausible explanations include acute afterload mismatch, unmasking of preoperative contractile impairment, disruption of the subvalvular apparatus, and postoperative stunning secondary to ischemia-reperfusion injury. Surgical strategies for improving survival in patients with chronic MR are evolving, and recent changes include mitral reconstructive procedures and preservation of the subvalvular apparatus. However, no clinical trials have been conducted to determine whether myocardial injury and subsequent patient outcomes could be modified by different anesthetic strategies. Volatile anesthetics, commonly used to induce and maintain hypnosis, analgesia, amnesia, and muscle relaxation, improve postischemic recovery at the cellular level in isolated hearts and in animals,1-4 mainly through pharmacologic preconditioning. In the clinical setting, several indices besides postischemic ventricular dysfunction can be examined to assess the degree of

From the *Department of Cardiovascular Anesthesia, Università Vita-Salute San Raffaele, Milano, Italia e Istituto Scientifico San Raffaele, Milan, Italy; and †Dipartimento di Scienze Anestesiologiche, Medicina Critica e Terapia del Dolore, Università degli Studi “La Sapienza” di Roma, Rome, Italy. Address reprint requests to Giovanni Landoni, MD, Department of Cardiovascular Anesthesia and Intensive Care, Istituto Scientifico San Raffaele, Milano, Italia via Olgettina 60, Milan 20132, Italy. E-mail: [email protected] © 2007 Elsevier Inc. All rights reserved. 1053-0770/07/2105-0009$32.00/0 doi:10.1053/j.jvca.2006.11.017 672

KEY WORDS: desflurane, preconditioning, coronary artery bypass grafting, troponin, mitral valve surgery

METHODS The study was peformed according to the Declaration of Helsinki principles. The ethical committee approved the study, and written informed consent was obtained from each patient. Patients scheduled

Journal of Cardiothoracic and Vascular Anesthesia, Vol 21, No 5 (October), 2007: pp 672-677

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for MV surgery at this university hospital were randomly assigned to receive 30 minutes of a volatile anesthetic (desflurane) before CPB or to continue with their total intravenous anesthesia (TIVA). This article was written following the www.consort-statement.org check list. Subjects undergoing MV surgery for MR were eligible if they were over 18 years of age and signed the written informed consent. Patients were excluded for preoperative cardiac troponin I values ⬎0.04 ng/mL; previous unusual response to an anesthetic; or use of sulfonylurea, theophylline, or allopurinol. Patients in the volatile anesthetic group received desflurane (Suprane; Baxter, Lessines, Belgium), 0.5 to 2.0 end-tidal minimum alveolar concentrations (MAC) (3%-12%), for 30 minutes before CPB starting immediately after intubation; this anesthetic has known beneficial effects on postischemic mechanical function.20 Patients in the TIVA group received 2-3 mg/kg/h of propofol (Diprivan; Astra Zeneca, Brussels, Belgium) throughout the procedure; this drug is the standard hypnotic drug in most cardiac anesthesia units but has no known pharmacologic preconditioning effect.2 During the 30 minutes, all patients received desflurane or propofol on top of an opioid (fentanyl)based anesthetic. After the 30 minutes, all patients had a propofolbased TIVA until the end of the operation. In the study, the hypothesis was tested that volatile anesthetics would decrease perioperative myocardial damage as measured by cTnI release when compared with TIVA. Reference demographics and clinical characteristics were collected as described in Table 1. All preoperative medications were routinely omitted on the day of surgery. Preoperative ␤-blockers were continued postoperatively if permitted by heart rate, blood pressure, and cardiac index evaluations. No other drugs were continued routinely or given for cardiac protection. All patients older than 40 years underwent coronary angiography, whereas this examination was limited to high-risk patients if younger than 40 years. All patients were premedicated with morphine, 0.1 mg/kg, and scopolamine, 0.25 mg intramuscularly, and received standard monitoring. During anesthesia induction, each patient received an intravenous bolus of propofol (1-2 mg/kg), fentanyl (5-10 ␮g/kg), and pancuronium (0.1 mg/kg). Patient monitoring included invasive radial artery blood pressure measurement, continuous electrocardiographic leads II and V5 with ST-segment monitoring, pulse oximetry, central venous pressure (CVP), capnometry, and urine output. Transesophageal echocardiography was used in all patients at CPB weaning for clinical purposes, but the data were not recorded. Pulmonary artery catheters were not used in the study. Anesthesia was maintained with repeated doses of fentanyl, pancuronium, and either desflurane or propofol for the first 30 minutes as described previously and with propofol later on in both groups. All patients received an intraoperative infusion of tranexamic acid, 1g in 20 minutes, followed by a 400-mg/h infusion. No aprotinin was administered. All patients underwent MV surgery using a median sternotomy approach. CPB was conducted at moderate hypothermia (32°-34°C). Myocardial protection during aortic cross-clamping was obtained by antegrade and/or retrograde cold blood cardioplegia. Activated coagulation time was maintained greater than 480 seconds for CPB, and the effect of heparin (starting dose 300 U/kg) was reversed with protamine sulphate in a 1:1 ratio. If the target mean arterial pressure of 65 mmHg was not achieved with volume loading to a CVP of 10 cmH2O after weaning from CPB, an infusion of dopamine (initial dose of 5 ␮g/kg/ min) was started. After surgery, patients were transferred to the intensive care unit (ICU), sedated with propofol for 4 hours, and weaned from the ventilator as soon as they were hemodynamically stable with no major bleeding, normothermic, and adequate levels of consciousness and pain control had been achieved. Weaning from the catecholamine infusion

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Table 1. Baseline Demographic and Clinical Characteristics

Variables

Age (y) Female sex, n (%) Height Weight (kg) NYHA I, n (%) II, n (%) III, n (%) IV, n (%) Euroscore Euroscore predicted mortality (%) Chronic obstructive pulmonary disease, n (%) Hypertension, n (%) Severe vasculopathy, n (%) Stroke, n (%) Previous cardiac surgery, n (%) Concomitant CAD Medications ACE inhibitors, n (%) ␤-blockers, n (%) Calcium antagonists, n (%) Diuretics, n (%) Transesophageal echocardiography data Ejection fraction (%) Functional mitral regurgitation, n (%) Rheumatic-degenerative mitral regurgitation, n (%) End-diastolic diameter (mm) End-diastolic volume (mL) End-systolic diameter (mm) End-systolic volume (mL) Pulmonary artery pressure (mmHg) Intraventricular septum (mm) Cardiopulmonary bypass time (min) Aortic cross-clamp time (min) Mitral replacement, n (%) Mitral repair, n (%)

Volatile Anesthetics (n ⫽ 59)

TIVA (n ⫽ 61)

62 ⫾ 12.8 24 (40.7) 168 ⫾ 8.2 69 ⫾ 13.4

59 ⫾ 14.2 31 (50.1) 168 ⫾ 9.0 70 ⫾ 13.8

14 (23.7) 29 (49.2) 14 (23.7) 2 (3.4) 5 ⫾ 2.7

10 (16.4) 29 (47.5) 21 (34.4) 1 (1.6) 5 ⫾ 2.8

3.5 (2.1-5.7)

3.3 (1.7-6.0)

3 (5.1) 17 (28.8) 4 (6.8%) 1 (1.7) 6 (10.2) 8 (13.6)

5 (8.2) 19 (31.1) 4 (6.6%) 3 (4.9) 12 (19.7) 11 (18.0)

30 (50.8) 8 (13.6) 4 (6.8) 33 (55.9)

31 (50.8) 15 (24.6) 7 (11.5) 38 (62.3)

57 ⫾ 9.6

55 ⫾ 10.5

5 (8.5)

9 (14.7)

54 (91.5) 56 ⫾ 6.8 129 ⫾ 48.7 34 ⫾ 6.1 52 ⫾ 28.7

52 (85.3) 58 ⫾ 16.2 135 ⫾ 75.1 37 ⫾ 10.1 52 ⫾ 45.4

47 ⫾ 17.9 12 ⫾ 2.1

46 ⫾ 14.2 12 ⫾ 2.2

83 ⫾ 24.0 64 ⫾ 21.8 23 (39.0) 36 (61.0)

84 ⫾ 25.7 65 ⫾ 22.3 27 (44.3) 34 (55.7)

Abbreviations: ACE, angiotensin-converting enzyme; NYHA, New York Heart Association; CAD, coronary artery disease.

was guided by standard hemodynamic criteria. Postoperative pain relief was provided to all patients by boluses of intravenous morphine. Blood pressure (systolic, mean, and diastolic), heart rate, and CVP were recorded at 7 time points: before induction of anesthesia, before and after CPB, at ICU arrival, and 4, 8, and 12 hours later. Neurologic events were classified into type 1 (focal injury, stupor, or coma at discharge) and type 2 (deterioration in intellectual function, memory deficit, or seizures). New Q waves were defined as the appearance of a Q wave ⱖ40 milliseconds in at least 2 adjacent leads or as the loss of R-wave amplitude in the precordial leads. Criteria for hospital discharge were hemodynamic and cardiac rhythm stability, presence of clean and dry incisions, afebrile, normal bowel movement, and independent ambulation and feeding.

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Table 2. Intra- and Postoperative Data

Variables

Volatile Anesthetics (n ⫽ 59)

TIVA (n ⫽ 61)

Fentanyl (␮g) 1,360 ⫾ 336 1,410 ⫾ 388 Electrical cardioversion, n (%) 1 (0-2) 1 (0-3) Intraoperative inotropes, n (%) 38 (64.4) 37 (60.7) Postoperative inotropes, n (%) 25 (42.4) 33 (54.1) Low cardiac output syndrome, n (%) 6 (10.2) 12 (19.7) Organ failure secondary to low cardiac output, n (%) 3 (5.1) 3 (4.9) Q-wave myocardial infarction, n (%) 1 (1.7) 1 (1.6) Hematocrit (ICU arrival) (%) 35 ⫾ 9.9 35 ⫾ 9.4 Bleeding first 12 hours (mL), median (25th and 75th percentiles) 220 (160-300) 240 (170-300) Transfusion of blood products, no. of patients (%) 10 (16.9) 15 (24.6) Serum creatinine (mg/dL) Preoperative 0.9 ⫾ 0.24 0.9 ⫾ 0.25 ICU arrival 0.8 ⫾ 0.21 0.8 ⫾ 0.26 Day 1 1.0 ⫾ 0.3 1.0 ⫾ 0.4 Day 2 1.0 ⫾ 0.39 1.1 ⫾ 0.65 Peak value 1.1 ⫾ 0.37 1.1 ⫾ 0.61 Acute renal failure, n (%) 10 (16.9) 13 (21.3) Pneumonia or sepsis, n (%) 1 (1.8) 2 (3.3) Postoperative atrial fibrillation 22 (37.3) 19 (31.1) Neurologic event type I or II 2 (3.4) 1 (1.6) Prolonged mechanical ventilation (⬎24 hours), n (%) 4 (6.8) 15 (24.6) Prolonged ICU stay (⬎72 hours), n (%) 12 (20.3) 18 (29.5) ICU stay (days), median (25th and 75th percentiles) 2 (1-3) 2 (1-4) Prolonged hospitalization (⬎7 days), n (%) 17 (28.8) 23 (37.7) Length of hospitalization (days), median (25th and 75th percentiles) 6 (4.5-8.5) 6 (5-10) Tracheostomy, n (%) 1 (1.7) 2 (33) Death at 30 days, n (%) 0 2 (3.3)

p Value

0.5 0.6 0.8 0.3 0.2 0.7 0.7 0.8

0.9

0.4

0.2 0.9 0.5 0.9 0.7 0.9 0.6 0.9

0.01 0.3 0.5

The cTnI method is a 1-step enzyme immunoassay based on the sandwich principle. Sensitivity of the assay is 0.04 ng/mL. Sample-size calculation was based on a 2-sided alpha error of 0.05 and 80% power. On the basis of previous reports21,22 investigating postoperative cTnI release after MV surgery, it was anticipated that there would be a mean peak postoperative release of 10 ⫾ 7 ng/mL in the TIVA group, with an assumed 4-ng/mL reduction in peak cTnI concentration after treatment with a volatile anesthetic. It was calculated that a sample size of 50 patients per group was needed. Therefore, the authors randomly selected 120 patients in order to take into account possible protocol deviations. All 120 patients were analyzed according to the intention-to-treat principle, beginning immediately after randomization. The sample-size calculation followed the suggestions of the consensus conference5 that the analysis of the actual distribution of myocardial damage observed (peak values of a biomarker) is more appropriate than that of the simple presence or absence of events. The details of the randomization, created by a computer-generated list, were contained in a set of sealed, opaque envelopes that were opened at the beginning of the anesthetic. All study personnel, including those involved in cTnI measurement, were blinded to treatment assignment for the duration of the study, except for the cardiac anesthesiologists who were not involved in data collection, entry, or analysis. No interim analyses were performed during the course of this study. Data were stored electronically and analyzed by use of the Epi Info 2002 (CDC, Atlanta, GA) and SAS software, version 8 (SAS Institute, Cary, NC). All data analysis was performed according to a pre-established analysis plan. Dichotomous data were compared by using a 2-tailed chi-square test with the Yates correction or a Fisher exact test when appropriate. Continuous measurements, including the primary outcome (cTnI release), were compared by using the Mann-Whitney U test. Two-sided significance tests were used throughout. Data are presented as medians (25th and 75th percentiles) or as means (⫾ standard deviation) unless otherwise indicated. To analyze data on plasma troponin I levels, the area under the concentration-time curve was calculated with the trapezoidal method for each patient, and treatment-related differences in the area under the curve were then compared by using a Student t test.

0.4

RESULTS 0.6 0.9 0.5

The primary endpoint of the study was peak postoperative cTnI release reduction. Data were collected by trained observers who did not participate in patient care and who were blinded to the anesthetic regimen used. Medical treatment and decision making in the ICU and in the ward were performed by physicians who were also blinded to the anesthetic regimen used. Caregivers were interviewed daily for the occurrence of postoperative adverse events as described in Table 2. cTnI concentration was determined preoperatively, on ICU admission, 4 hours later, and on the first and second postoperative days. cTnI, which has nearly absolute myocardial tissue specificity as well as high sensitivity, thereby reflecting even microscopic zones of myocardial necrosis, was used as the biomarker. Blood was collected in plastic tubes with clot activator (Becton Dickinson Vacutainer Systems, Plymouth, UK) and was centrifuged (2,500 g for 15 minutes) before analysis. cTnI was assayed with Dimension XPand (Dade-Behring Diagnostic, Paris, France) according to the manufacturer’s instructions.

Between May 2005 and September 2005, 120 consenting patients were randomly assigned to receive either the volatile anesthetic (59 patients) or TIVA (61 patients) (Fig 1). The baseline demographic and clinical characteristics of the 2 groups are summarized in Table 1 (no value showed a statistical difference). Heart rate, CVP, blood pressure (systolic, mean, and diastolic), temperature, and arterial blood results were similar in the 2 groups at all 7 time points. Fentanyl administration did not differ between patients receiving volatile anesthetics (1,360 ⫾ 336 ␮g) or TIVA (1,410 ⫾ 388 ␮g; p ⫽ 0.5). All patients had detectable cTnI after MV surgery, and patients in the volatile anesthetic group had no significant reduction of myocardial damage. This was documented by a postoperative median (interquartile) peak cTnI release of 11.0 (7.5-17.4) ng/dL compared with that of patients receiving TIVA (11.5 [6.9-18.0] ng/dL; p ⫽ 0.7). Figure 2 shows cTnI levels at different points in time. Troponin release at ICU arrival, 4 hours later, and on the first and second postoperative days showed no statistically significant differences at any time point (Fig 2). The median (interquartile) area under the curve

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repair (p ⫽ 0.005). The study also confirmed that in each of these 2 subgroups there was no difference in peak cTnI release between patients receiving volatile anesthetic or TIVA: MV replacement 15 (9-23 ng/mL) versus 15 (8-22 ng/mL, p ⫽ 0.6) and MV repair 9 (7-13 ng/mL) versus 11 (6-16 ng/mL, p ⫽ 0.4). DISCUSSION

Fig 1.

Flow diagram.

analysis confirmed these results: 324 (237-553) versus 351 (232-575) h ⫻ ng/mL (p ⫽ 0.5). Clinical outcomes are reported in Table 2 and show a difference with prolonged mechanical ventilation (⬎24 h): 4 patients (6.8%) in the volatile anesthetic group and 15 patients (24.6%) in the TIVA group (p ⫽ 0.01). Notably, no patient died in the volatile anesthetic group, whereas 2 patients died in the TIVA group (p ⫽ 0.5). Because previous studies suggested that pharmacologic preconditioning with volatile anesthetics is effective in patients with coronary artery disease,11-19 a subgroup analysis of 20 patients with concomitant coronary artery disease was done and observed the expected reduction (p ⫽ 0.02) of median (25th75th percentiles) peak of troponin I in patients receiving volatile anesthetics: 14.0 (9.7-17.3) ng/dL compared with patients receiving TIVA 31.6 (15.7-52.0) ng/dL. Of these 20 patients, 7 of 8 receiving desflurane underwent CABG surgery, whereas 9 of 12 receiving propofol underwent CABG surgery. Notably, no patient died among the 8 patients who received volatile anesthetics, whereas 2 of 11 (18%) deaths (p ⫽ 0.3) were observed among the patients who received TIVA for MV surgery with concomitant CABG surgery. Since one previous study23 suggested a higher troponin release in patients undergoing MV replacement when compared with MV repair, the following subgroups were studied: 15 (8-22 ng/mL) in MV replacement versus 9 (7-15 ng/mL) in MV

The present study is the first evaluation of the role of pharmacologic preconditioning in MV surgery. No cardioprotective effect of the volatile anesthetic was found in this population. An increasing number of investigations have shown the cardioprotective effects of volatile anesthetics in patients undergoing CABG surgery.11-19 The mechanisms underlying such benefits are not completely clear, however. Possibly, the anesthetic preconditions the myocardium by mechanisms that are similar to ischemic preconditioning, with the clear advantage of not requiring ischemia to produce this effect. In a manner similar to ischemic preconditioning, volatile anesthetics can trigger an acute cardioprotective memory effect that lasts beyond their elimination3 called anesthetic or pharmacologic preconditioning. Clinical studies involving patients undergoing CABG surgery with CPB11-16 showed a lower cTn release and an improvement of systolic function in patients preconditioned with volatile anesthetics. Clinical confirmation of these volatile anesthetic properties occurred with recent studies by DeHert et al11,12 in a large single-center population of CABG patients with CPB, in which they showed reductions in hospital and ICU lengths of stay. Three existing studies focused on the effects of volatile anesthetics in off-pump coronary artery bypass graft surgery. Conzen et al17 and Guarracino et al19 in small studies (20 patients) showed that cTnI concentration increased more after TIVA than after volatile anesthetics. Bein et al18 had echocardiographic evidence of preserved myocardial function in their volatile anesthetic group when compared with TIVA in patients undergoing brief periods of ischemia during off-pump coronary artery bypass graft surgery. In the present study, a reduction in mechanical ventilation time was observed in the desflurane group even if there was no difference in postoperative complication rate and the same amount of intraoperative opioid was used in the two groups. This result has no clear explanation and it is difficult to attribute it to an improved global tissue perfusion with better recovery from surgery in the absence of differences in cardiac troponin release. The authors conclude, therefore, that in MV surgery there must be prominent mechanisms of troponin release other than ischemiareperfusion injury at work. These include cutting to remove valvular leaflets, to open the atrial wall, and “acute afterload mismatch” because of partial or total destruction of the subvalvular apparatus. These would all result in significant increase in endsystolic circumferential wall stress and geometric distortion of the left ventricle.24 The current study focused on cardiac biomarker release after MV surgery and was not aimed at relating the choice of the anesthetic agent to mortality because it was not sufficiently powerful to address such an issue. Nonetheless, it would be important to perform an adequate study in high-risk patients with coronary artery disease undergoing cardiac surgery (with or without mitral disease) to demonstrate a reduction in mortality. Even if other authors25,26 have used inhalation agent exposure for only 10 min-

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Fig 2. Median (25th-75th percentiles) of troponin I after off-pump coronary artery bypass graft surgery in patients receiving either volatile anesthetics (59) or a total intravenous anesthesia (61).

utes to successfully achieve preconditioning, the present authors recognize that larger doses and longer duration likely could have yielded different results. A recently published paper demonstrated a cardiac protective effect of a volatile anesthetic regimen administered throughout aortic valve surgery.27 The present authors also acknowledge that important postoperative transesophageal echocardiography data were not measured. Furthermore, it is noted that numerous positive (alpha-agonists, delta opioid agonists, betaadrenergic agonists, cardiopulmonary bypass, nitrates) and negative (hypothermia, hyperglicemia, aspirin) factors can influence pharmacologic preconditioning. In this randomized controlled study, it was shown that a volatile

agent in the pre-CPB period does not protect against myocardial damage as documented by cTnI release in patients undergoing MV surgery. No benefit was shown by desflurane in reducing cardiac damage after MV surgery when compared with a propofol-based TIVA. The cardioprotective properties of volatile anesthetics in patients with coronary artery disease were not confirmed in patients with patent coronary vessels. ACKNOWLEDGMENT The authors thank Mariano Fichera, RN, Giardina Giuseppe, RN, Marco Costantini, RN, Marina Tolja, RN, Arianna Poli, RN, and Lara Castelnuovo, RN, for their help in data collection and data entry.

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Mechanism of desflurane-induced cardioprotection. Anesthesiology 92:1731-1739, 2000 21. Crescenzi G, Cedrati V, Landoni G, et al: Cardiac biomarker release after CABG with different surgical techniques. J Cardiothorac Vasc Anesth 18:34-37, 2004 22. Landoni G, Pappalardo F, Calabrò MG, et al: Myocardial necrosis biomarkers after different cardiac surgical operations. Minerva Anestesiol 2006 Dec 12 [Epub ahead of print] 23. Zangrillo A, Crescenzi G, Landoni G, et al: The effect of concomitant radiofrequency ablation and surgical technique (repair versus replacement) on release of cardiac biomarkers during mitral valve surgery. Anesth Analg 101:24-29, 2005 24. Goldfine H, Aurigemma GP, Zile MR, et al: Left ventricular length-force-shortening relations before and after surgical correction of chronic mitral regurgitation. J Am Coll Cardiol 31:180-185, 1998 25. Julier 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 98:13151327, 2003 26. Garcia C, Julier K, Bestmann L, et al: Preconditioning with sevoflurane decreases PECAM-1 expression and improves one-year cardiovascular outcome in coronary artery bypass graft surgery. Br J Anaesth 94:159-165, 2005 27. Cromheecke S, Pepermans V, Hendrickx E, et al: Cardioprotective properties of sevoflurane in patients undergoing aortic valve replacement with cardiopulmonary bypass. Anesth Analg 103:289-296, 2006