Asian Cardiovasc Thorac Ann 2006;14:134-138
© 2006 Asia Publishing EXchange Ltd
Terminal Warm Blood Cardioplegia in Mitral Valve Replacement: Prospective Study
Chareonkiat Rergkliang, MD,
Apirak Chetpaophan, MD,
Voravit Chittithavorn, MD,
Prasert Vasinanukorn, MD,
Vorapong Chowchuvech, MD
Division of Cardiovascular and Thoracic Surgery, Songkhlanagarind Hospital, Department of Surgery, Prince of Songkla University, Songkhla, Thailand
For reprint information contact: Chareonkiat Rergkliang, MD Tel: 66 74 451 401 Fax: 66 74 429 384 Email: chareonkiat{at}yahoo.com, Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Prince of Songkla University, Had Yai, Songkhla, Thailand 90110.
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ABSTRACT
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Terminal warm blood cardioplegia has had a profound impact on cardiac surgery, especially in coronary artery bypass surgery, but there have been few studies on its use in mitral valve replacement. The purpose of this study was to determine whether terminal warm blood cardioplegia offers any advantages in mitral valve replacement. Forty patients with mitral valve disease were prospectively randomized to one of two groups of 20 with different techniques of myocardial protection: group A had cold blood cardioplegia, and group B had cold blood cardioplegia with terminal warm blood cardioplegia. Intraoperative and postoperative variables were used to assess primary outcomes. Postoperative troponin T release was measured as a secondary outcome. Improved spontaneous recovery of sinus rhythm was observed in group B, but the difference was not significant. The maximum doses of inotropics, duration of inotropic support, intensive care unit stay, and postoperative left ventricular ejection fraction were similar in both groups. Troponin T release at 0 and 6 h postoperatively was not different between the two groups. This study did not find any benefit of terminal warm blood cardioplegia in either clinical outcome or troponin T release after mitral valve replacement.
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INTRODUCTION
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There are numerous strategies available for intraoperative myocardial protection, which have made cardiac operations much safer.1,2 Among the advances, the introduction of terminal warm blood cardioplegia (TWBC) has had a profound impact, especially in coronary artery bypass surgery.3,4 Terminal warm blood cardioplegia is used to modify reperfusion injury, resulting in improved postoperative contractile function and decreased mortality.3,4 However, there has been no study documenting the effect of TWBC in mitral valve replacement (MVR). This study was intended to address this lack of knowledge, and examine the benefits, if any, of using TWBC in MVR. We designed a study to compare 2 techniques of myocardial protection: intermittent cold blood cardioplegia, and intermittent cold blood cardioplegia with TWBC. The results were primarily assessed on the basis of clinical outcome, and postoperative troponin T release was measured as a secondary outcome.
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PATIENTS AND METHODS
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Between August 2003 and July 2004, 58 consecutive patients who were scheduled for MVR with or without tricuspid valve repair in Songkhlanagarind Hospital, Prince of Songkla University, were enrolled in this study. Eighteen patients were excluded; exclusion criteria were: re-operation, concomitant coronary artery bypass surgery, emergency surgery, and more than a mild grade of aortic regurgitation. The other 40 patients were prospectively randomized to one of 2 groups of 20 each using different techniques of myocardial protection. In group A, intermittent antegrade cold blood cardioplegia was used. In group B, the same cold blood cardioplegia was used in combination with TWBC before aortic declamping. Randomization was performed in blocks of 20, with a plan for interim analysis after 40 patients. Initial power calculations were hampered by the lack of preliminary data defining the effect of TWBC on MVR. Randomization assignments were placed in sealed envelopes and revealed to the surgical team shortly before they began the operation. The study was approved by our Institutional Ethics Committee, and informed consent of the patients was obtained.
All operations were performed using cardiopulmonary bypass (CPB) with ascending aortic and bicaval cannulation. Systemic hypothermia was between 32°C and 34°C. Antegrade cold blood cardioplegia was injected immediately after aortic crossclamping at 20 mL·kg–1, and then at 20 min intervals. In group B, TWBC was infused during closure of the left atrial incision and before aortic declamping. If tricuspid valve repair was required, it was undertaken after aortic declamping. Blood cardioplegic solution was made by mixing oxygenated blood with a hyperkalemic crystalloid solution in a 4:1 dilution, which was cooled to 9°C. Terminal warm blood cardioplegia was infused over 5 min at a rate of 15 mL·kg–1. The TWBC temperature was gradually increased from 32°C to 36°C by the end of the infusion. The approximate final potassium concentration was 20 mEq·L–1 in induction cardioplegia, and 10 mEq·L–1 in maintenance cardioplegia and TWBC. Electrical defibrillation was applied if ventricular fibrillation persisted beyond 2 min after aortic declamping, and a temporary pacemaker was used if there was no spontaneous rhythm or if the patient’s heart rate was less than 50 beats·min–1. After the operation, if systolic blood pressure was lower than 90 mm Hg and urine output less than 1 mL·kg–1·h–1 with central venous pressure between 10 and 12 mm Hg, inotropic support was started. Our first choice of inotropic agent was dopamine.
Intraoperative and postoperative variables were used to assess primary clinical outcomes including spontaneous rhythm recovery after aortic declamping (no requirement for electrical defibrillation or temporary pacemaker), maximum doses of inotrope, duration of inotropic support, length of intensive care unit stay, postoperative hospital stay, and postoperative left ventricular ejection fraction before discharge (5 to 7 days after the operation). Cardiac troponin T was measured at 0 and 6 h postoperatively in the intensive care unit as a marker of myocardial injury. The troponin T level was measured by an electrochemiluminescence immunoassay.
Statistical analysis was performed with the STATA version 7.0 statistical package (STATA Corporation, College Station, TX, USA). Commutative data are expressed as the mean ± standard deviation of the mean. Analysis of the difference in clinical outcome and troponin T release between the two groups was performed using Student’s t test. The significance level for differences in all tests was p < 0.05. Univariate linear regression analysis was used to perform correlation analysis.
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RESULTS
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There were no preoperative or operative differences between the groups with regard to age, sex, diagnosis, rhythm, New York Heart Association functional class, left ventricular ejection fraction, estimated pulmonary artery systolic pressure, operation, or duration of the operation, CPB, or aortic crossclamping (Table 1
). There was no death in our series. Clinical outcomes are shown in Table 2. There appeared to be a trend towards better spontaneous recovery of sinus rhythm after removal of the aortic crossclamp in group B compared with group A, although the difference did not reach statistical significance. According to our protocol for postoperative care, 14 patients (8 in group A and 6 in group B) did not require inotropic support postoperatively. There were no differences between the 2 groups in the maximum doses or duration of inotropic support. Postoperative echocardiography showed good left ventricular ejection fractions in both groups. Slightly higher troponin T concentrations at 0 and 6 h after the operation were observed in group B compared with group A, but the difference was not significant. Univariate linear regression analysis demonstrated a correlation between CPB time and the troponin T concentration at 6 h postoperatively; p < 0.001 and 95% confidence interval = 0.0078–0.0199. However, CPB time did not correlate with spontaneous rhythm recovery or the requirement for inotropics ( p > 0.05).
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DISCUSSION
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The basic concept of TWBC is reduction of myocardial energy demand by maintaining cardiac arrest with hyperkalemic warm blood perfusate during initial reperfusion, to restore high-energy phosphates and enhance cellular repair after ischemic cardiac arrest.3–5 The beneficial effects of TWBC have been studied both experimentally and clinically. They include better preservation of high-energy phosphates and endogenous amino acids, less anerobic metabolic activity on reperfusion, reduced release of cardiac troponin T, and improved post-ischemic functional recovery.3,4,6–8 These effects facilitate coronary vasodilatation and accelerate early myocardial tissue oxygen saturation during warm reperfusion.4,6 Tenpaku and colleagues7 demonstrated complete microtubule repolymerization after 10 min of reperfusion with warm blood. This mechanism may be responsible for the early and improved recovery of cardiac function associated with TWBC.
Most clinical studies of TWBC have been undertaken on coronary artery bypass surgery, with more recent investigations on TWBC in congenital heart surgery.3,4,9,10 Most results have indicated definite advantages in the use of TWBC, although there have been some that showed no beneficial effect of TWBC.11–13 This study did not find any difference in clinical outcomes and postoperative release of troponin T between the 2 techniques of myocardial protection. Our findings were similar to other reports.11–13 Some possible explanations for our results are the short duration of TWBC infusion, short crossclamp time, not using substrate-enriched TWBC, and the efficacy of cold blood cardioplegia.11 Modi and colleagues10 demonstrated a superior biochemical outcome from TWBC in patients with longer crossclamp times, a finding also supported by Hayashi and colleagues.14 In this study, the mean crossclamp time was less than 50 min, which may not have been long enough to demonstrate the advantage of TWBC. The duration of TWBC infusion may be an important factor.6,15 In this study, the average infusion time of TWBC was 5 min, which may not have been long enough to reperfuse the myocardium thoroughly, especially in cases where cardiomegaly was associated with the mitral valve disease.
There is some evidence that a glutamate-aspartate supplement to the TWBC (substrate-enriched cardioplegia) may reduce reperfusion injury and improve both metabolic and myocardial function recovery.8,13 Glutamate and aspartate are not available at our institute, so our TWBC was not a substrate-enriched solution, and it is possible that the TWBC benefits would be more obvious if this technique were employed. Improved spontaneous rhythm recovery has also been observed with the use of TWBC.6,9 There appeared to be a trend towards a better cardiac rhythm recovery in the TWBC group (less requirement of electrical defibrillation and temporary pacemakers), but the difference did not reach statistical significance when compared with patients in the non-TWBC group. Troponin T and troponin I are unique biochemical markers of myocardial damage because of their high level of sensitivity and specificity. These characteristics make troponin T and troponin I ideal markers for myocardial cell damage in patients undergoing cardiac surgery, and useful for comparison of different myocardial protective techniques during routine cardiac operations.16,17 We found a slightly higher troponin T concentration at 0 and 6 h postoperatively in patients given TWBC, although the difference was not significant when compared with the non-TWBC group. Our finding was similar to that reported by Edwards and colleagues.12
It should be noted that due to the necessarily small sample size in this study, nothing conclusive was determined to avoid type II statistical errors. The only beneficial trend of TWBC in this study was better spontaneous rhythm recovery after aortic declamping (50% vs. 75%). Sample sizes were calculated for a two-sided significance level alpha = 0.05 and power = 0.8 to a difference of spontaneous rhythm recovery after aortic declamping between groups; the number of patients required in each group was 66.
In this study, adding TWBC to cold blood cardioplegia offered no advantage in either clinical outcomes or troponin release in MVR. A further prospective randomized study with a larger sample size may be needed, and also some long-term comparative studies of these two methods of myocardial protection in mitral valve surgery.
Presented at the 13th Annual Meeting of the Asian Society for Cardiovascular Surgery. February 5–7, 2005, Chiang Mai, Thailand.
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REFERENCES
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ABSTRACT
INTRODUCTION
