Asian Cardiovasc Thorac Ann 2003;11:116-121
© 2003 Asia Publishing EXchange Ltd
Intermittent Tepid Blood Cardioplegia Improves Clinical Outcome
Teing Ee Tan, FRCS,
Sulman Ahmed, MBBS,
Hugh S Paterson, FRACS
Department of Cardiothoracic Surgery, Westmead Hospital, Department of Surgery, University of Sydney, Sydney, Australia
For reprint information contact: Hugh S Paterson, FRACS Tel: 61 2 98457994 Fax: 61 2 98458314 email: patersonH{at}aol.com Dept of Cardiothoracic Surgery, Westmead Hospital, Westmead, NSW 2151, Australia.
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ABSTRACT
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Intermittent antegrade cold blood cardioplegia is the predominant method of myocardial protection, but recent studies suggest that warm or tepid blood cardioplegia may improve the return of myocardial metabolic and contractile function. Data were collected prospectively on 1,533 patients undergoing cardiopulmonary bypass in a single surgeon’s practice. The use of intermittent antegrade cold (4°C) blood cardioplegia in 951 consecutive patients from September 1994 to November 1997 was compared with intermittent antegrade tepid (28°C) blood cardioplegia in 582 consecutive patients from July 1998 to July 2000. The two groups were similar, but the symptom class was more severe and there were more redo and combined procedures and more operations within 7 days of myocardial infarction in the tepid group. Significant clinical benefits identified in the tepid group included reduced usage of intraaortic balloon pumping postoperatively (4.4% versus 2.2%) and reduced incidence of postoperative atrial fibrillation (25.7% versus 20.6%). There was no significant difference in mortality, perioperative myocardial infarction, cerebrovascular events, or use of inotropics between the groups. Intermittent tepid blood cardioplegia is clinically appropriate and safe to use in patients undergoing cardiac surgery.
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INTRODUCTION
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The introduction of cardioplegia and cardiopulmonary bypass (CPB) has made even complex heart surgery safe with low morbidity and mortality. Techniques of myocardial protection have undergone many modifications in the composition of the solution, addition of blood, route of delivery, mode of delivery, and temperature. The optimal temperature of cardioplegia has been controversial. Several randomized controlled trials showed that tepid cardioplegia resulted in better early postoperative left ventricular function on echocardiographic assessment, less creatine kinase-MB release, and reduced need for defibrillation immediately after aortic declamping, compared with cold cardioplegia.1–11 However, these were all small trials (72 to 134 patients) and no benefits in terms of morbidity or mortality were demonstrated. The aim of this study was to investigate the clinical results of using tepid instead of cold antegrade blood cardioplegia in a larger population with no other change in operative technique or perioperative care.
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PATIENTS AND METHODS
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All 1,533 patients undergoing CPB procedures in a single surgeon’s practice from September 1994 to July 2000 were included in the study. Early in the study, only intermittent cold blood cardioplegia (4°C) was used; these 951 consecutive patients comprised the cold group. From July 1998 to July 2000, only tepid blood cardioplegia (28°C) was used for all patients; these 582 patients comprised the tepid group. Patients who underwent surgery in the intervening period were excluded from the analysis due to variations in the cardioplegia temperature.
Cardioplegia in both groups was delivered via a roller pump that mixed oxygenated blood with modified St Thomas’ cardioplegic solution in a 4:1 ratio. It was passed through a cardioplegia coil and tubing into the aortic root via a 14F cardioplegia/vent cannula. Initial cardioplegia was achieved using a high-potassium solution (16 mEq•L-1) over 31/2 min, followed by maintenance doses containing 8 mEq•L-1 of potassium over 11/2 min. All doses were given at a cardioplegia line pressure of 180 to 200 mm Hg to achieve an infusion rate of 0.30 to 0.45 L•min-1. Cardioplegia was delivered using the same protocol in each group (every 20 min or earlier if there was cardiac activity). Neither warm induction nor terminal hot shots were given. Retrograde delivery was used in selected cases only. The only difference between the groups was the placement of the cardioplegia coil into ice water (cold group) or room air (tepid group). The CPB was instituted with a single two-stage right atrial cannula or bicaval cannulae, an ascending aortic perfusion cannula, and an ascending aortic cardioplegia and vent cannula. Standard CPB management included a membrane oxygenator, arterial line filter, non-pulsatile flow of 2.4 L•min-1•m-2, mean arterial pressure > 50 mm Hg, moderate hemodilution (hematocrit 20%–25%), and alpha-stat acid-base balance. Systemic temperatures were kept at 30°C–33°C in the majority of cases in both groups. The surgical technique was the same in both groups. The left internal mammary artery (IMA) was used in 1,237 patients, usually as a pedicled graft. When both IMA were used, the right IMA was usually employed as a free graft from either the left IMA or the aorta. When the long saphenous vein was used, it was most often deployed to graft several sites sequentially with only one proximal anastomosis to the aorta; the proximal end was usually anastomosed to the aorta using a partial occlusion clamp.
Demographic, clinical, and outcome data were collected prospectively and entered into a database. Data on 27 patient variables and 18 outcome variables were amassed. Data analysis was performed with SPSS software version 10.0.1 (SPPS, Inc., Chicago, IL, USA) using the chi-squared test and Student’s t test. In addition to comparing the two groups for differences in preoperative and outcome variables, high-risk subgroups were also analyzed. These were patients with poor left ventricular function, acute myocardial infarction (MI), severe symptom classes, urgent or emergency procedures, aortic valve surgery, and ischemic mitral regurgitation. Low-risk elective CABG cases were also analyzed separately. Multivariate analyses of the patient-related variables were performed to confirm the significance of cardioplegia temperature on the clinical outcome of IABP and the occurrence of atrial fibrillation.
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RESULTS
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Demographic characteristics and risk factors are summarized in Table 1
. The two groups were similar in demographic profile, with a few exceptions: symptom class in the tepid group was significantly more severe; although the incidence of prior MI was not significantly different, more patients had surgery within 7 days of MI in the tepid group. The tepid group had also more patients undergoing redo operations. The types of operations performed are summarized in Table 2. In the tepid group, there were more combined operations. The total number of CABG operations was similar, but the percentage of isolated CABG cases was significantly less in the tepid group, reflecting the trend towards more combined procedures. There were also more mitral valve procedures and left ventricular aneurysmectomies in the tepid group.
Table 3 shows the techniques and conduits used for CABG. The use of radial artery grafts was higher in the tepid group. There was no significant difference in the percentages of patients who had total arterial grafting. Relatively fewer grafts had aortic inflow in the cold group. The left IMA was used in 88.4% of all 1,400 CABG operations performed, and its usage was similar in both groups. The number of distal anastomoses was similar in both groups. Similar doses of cardioplegia were given in each group (Table 4), but the mean crossclamp time in the tepid group was longer. This was because of the greater number of consultant-as-assistant procedures in the tepid group. The non-crossclamp bypass times were significantly reduced (by 7 min) in the tepid group, regardless of whether they were carried out by the registrar or consultant, (p < 0.01) reflecting a significantly faster and more consistent recovery to normal sinus rhythm after release of the crossclamp.
Operative outcomes are summarized in Table 5. The rates of MI, stroke, dialysis, pulmonary complications (pneumonia, atelectasis), pleural effusions or pneumothorax requiring drainage, ventricular arrhythmias, operative mortality, and disability at discharge were not significantly different. Statistically significant outcomes included the rates of atrial fibrillation, reexploration in the intensive care unit, need for IABP postoperatively, and delayed sternal closure. On multivariate analysis, age (odds ratio, 1.039; confidence interval, 1.026–1.052) and cardioplegia temperature (odds ratio, 0.729; confidence interval, 0.567–0.937) were the only independent predictors of postoperative atrial fibrillation. Multivariate analyses also confirmed that cardioplegia temperature was an independent predictor of the need for IABP postoperatively or delayed sternal closure.
In subgroup analysis of 25 patients who had ischemic mitral regurgitation, all outcome variables were compared between those who had tepid and cold cardioplegia. There was a strongly significant reduction in the use of IABP in the tepid group (62.5% versus 5.9%, p = 0.001). When this subgroup was excluded from the study population and the chi-squared test applied, the difference in IABP usage between the cold and tepid group was reduced (3.9% versus 2.1%, p = 0.058). The benefit of tepid cardioplegia was most apparent in this high-risk subgroup. Further analysis of the 98 patients with ejection fractions < 30% showed no significant difference between those in the cold (60 patients) versus tepid (38 patients) groups with regard to mortality (8 versus 7, p = 0.496), MI (0 versus 1, p = 0.21), use of IABP (8 versus 2, p = 0.198) or inotropics (38 versus 25, p = 0.445). The need for delayed sternal closure in this subgroup was significantly higher in those who had cold cardioplegia (7 versus 0, p = 0.02). The number of consultantas-assistant procedures in the tepid group was greater (28.9% versus 11.7%, p = 0.031).
The subgroup of elective isolated CABG operations performed by the consultant surgeon comprised 401 in the cold group and 201 in the tepid group. In the tepid group, there were slightly lower rates of atrial fibrillation (24.4% versus 20.4%), MI (1.5% versus 0.5%), postoperative IABP (2.2% versus 1.0%), postoperative delayed sternal closure (1.2% versus 0%), reexploration in ICU (0.7% versus 0%), and mortality (1.5% versus 1.0%). Stroke was the only complication with a higher rate in the tepid group (0.7% versus 1.0%). However, none of these differences reached statistical significance, probably because of the small sample size. Cross tabulations within other high-risk subgroups between cardioplegia temperature and clinical outcomes did not reveal any differences. This is also most likely related to the small sample sizes.
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DISCUSSION
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Since cardioplegia was first developed approximately 20 years ago, it has undergone several modifications. The standard method of delivery is currently intermittent infusion of hypothermic (4°C–10°C) blood or crystalloid cardioplegia solution via the aortic root. Buckburg13 demonstrated that electromechanical arrest is associated with a 90% decrease in myocardial oxygen consumption at 37°C, whereas hypothermia of 10°C–20°C produces only a further 7% to 8.6% reduction. Several clinical studies have demonstrated that hypothermia delays the recovery of myocardial metabolism and ventricular function.4–6 Cold blood cardioplegia has also been documented in in-vitro studies to have deleterious effects on mitochondrial metabolism, substrate utilization, and membrane stability.14–16 Cold cardioplegia has been shown to induce a defect in mitochondrial state-3 respiration and a decrease in citrate synthetase activity, which persists up to 1 hour after reperfusion.16
Teoh and colleagues17 found that a "hot shot" immediately prior to release of the crossclamp resulted in prolongation of electromechanical arrest, improved aerobic metabolism, and increased diastolic compliance. This effect was thought to be due to early recovery of temperature-dependent mitochondrial respiration and adenosine triphosphate generation. Warm induction has also been shown to benefit energy-depleted hearts. Extrapolating these results, Lichtenstein and colleagues 1 suggested that continuous warm cardioplegia might be of benefit. Randomized clinical trials have all shown improved ventricular function, fewer anaerobic byproducts, and better metabolic function with warm cardioplegia.2,3,18 Some studies showed improvements in clinical outcome and mortality but this was not seen consistently. Martin and colleagues3 found an increased incidence of neurological events. This might be related to the normothermic body temperature used in the warm group. The incidence of postoperative strokes in this study was slightly higher in the tepid group but it did not reach statistical significance (Table 5
).
It has been suggested that tepid blood cardioplegia may have the benefits of better metabolic and contractile recovery associated with warm blood cardioplegia and the hypothermic protection against ischemic insult associated with cold blood cardioplegia. Several randomized trials have evaluated tepid blood cardioplegia in elective myocardial revascularization.8–12 Although the clinical endpoints of operative complications and mortality were not significantly improved in these studies, echocardiographic and biochemical tests for the efficacy of myocardial protection tended to indicate that tepid blood cardioplegia was better than cold or warm blood cardioplegia.
In our study, there was a significant decrease in the incidence of atrial fibrillation, use of postoperative IABP, and time required for return of normal sinus rhythm after crossclamp release. We believe that these were due to better myocardial protection from tepid cardioplegic temperatures. Our subgroup analyses indicated that the benefits of tepid cardioplegia are small and not statistically significant in routine low-risk CABG, but more apparent in the higher-risk subgroups, especially ischemic mitral regurgitation. The limitations of this study include the fact that it was not randomized. The two groups were separated by time but there were no changes in the operative management protocols during the study period. The postoperative intensive care unit was relocated closer to the operating theatre suite during the study period, and this may explain the reduction in the number of cases of sternal reopening in the intensive care unit in the later period. It was concluded from this study that the use of intermittent antegrade tepid blood cardioplegia for myocardial protection is safe and clinically appropriate during cardiac surgery. Clinical benefit was most apparent in high-risk subgroups. The advantages are probably small in low-risk patients, and larger trials would be required to settle this issue.
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Footnotes
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Presented at the Annual Inter-ASC meeting of the Cardiothoracic Section of the Royal Australasian College of Surgeons, Melbourne, Australia, October 26–29, 2000.
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ABSTRACT
INTRODUCTION
