| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 1995;59:84-89
© 1995 The Society of Thoracic Surgeons
Divisions of Cardiothoracic Surgery and Anesthesiology, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island
Accepted for publication June 30, 1994.
 |
Abstract |
|---|
 TopFootnotes Abstract IntroductionMaterial and MethodsResultsCommentReferences |
|---|
|
Introduction |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentReferences |
|---|
The present study, based on our experience with more than 2,500 patients undergoing CABG with normothermic perfusion during CPB, seeks to identify the incidence of stroke with normothermia and compare it with a historical hypothermic perfusion group operated on at our institution. In addition, we sought predictive risk factors for stroke in both groups.
|
Material and Methods |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentReferences |
|---|
Surgical Technique
All operations were performed by two of us (A.K.S. and W.C.F.) using similar operative techniques with the exception of the temperature of systemic perfusion during CPB. During the 13-year study period, other apparent surgical differences between the groups did occur, including a greater use of internal mammary artery conduits in the normothermic group. Not only did the surgeons gain experience over this time span, but surgical techniques to avoid dislodgment of atheromatous debris from the aortic root matured as well.
After median sternotomy and pericardiotomy, the aorta was palpated, and areas of aortic calcification were identified and graded from none to severe by the surgeon. In addition, the presence and severity of aortic root calcification were noted on chest roentgenogram or on cineangiogram when visualized. Intraoperative ultrasonography of the ascending aorta and transesophageal echocardiography were not performed during the study period. Cardiopulmonary bypass was routinely instituted in both groups by aortic cannulation and bicaval cannula with an in-line arterial filter. The left ventricle was vented through the right superior pulmonary vein. A membrane oxygenator with a nonpulsatile pump was used. In patients with moderate to severe atherosclerosis of the ascending aorta, a long-tip aortic cannula was used to cannulate the arch. The tip of the aortic cannula was placed distal to the carotid vessels to prevent blast injury. Femoral artery cannulation was carried out in cases of extensive calcification of the arch.
Myocardial preservation was accomplished with cold antegrade blood cardioplegia and topical cooling with saline slush in the pericardial sac. The technique and composition of cardioplegia did not change over the study period. No retrograde cardioplegia was used. There was a single period of aortic cross-clamping for construction of proximal and distal anastomoses. The extracorporeal circuit was primed with a crystalloid solution, thus resulting in a hemodilution hematocrit ranging between 20% and 30%. The flow rate was maintained at 2.5 L • min-1 • m-2 for the normothermic group and between 1.8 to 2.5 L • min-1 • m-2, reduced in proportion to the level of hypothermia, in the hypothermic group. The normothermic perfusion technique included active warming throughout CPB to at least a 37°C bladder temperature. During normothermic perfusion, the systemic vascular resistance is low, and 65% of these patients required a moderate dose of a vasopressor (Neo-Synephrine [phenylephrine hydrochloride]) to maintain mean arterial pressure between 50 and 70 mm Hg. Only 5% of patients in the hypothermic group required a vasopressor during CPB.
Data Collection
Demographic and operative data were collected prospectively in both groups. Neurologic outcome was collected prospectively in the normothermic group but obtained by retrospective chart review in the hypothermic group. Postoperative outcomes were defined as follows: Perioperative myocardial infarction was defined as the presence of new Q waves or new and persistent ST-segment changes or a poor R-wave progression associated with an elevation of creatine kinase MB isoenzyme levels greater than 6% of total creatine kinase or more than 75 IU/L. Renal insufficiency was defined as elevation of serum creatinine levels greater than 1 mg/dL over the preoperative baseline or urine output falling to less than 30 mL • m-2 • h-1. Low cardiac output syndrome was defined as a cardiac index of 2 L • min-1 • m-2 or less or the need of positive inotropic agents or use of an intraaortic balloon pump to maintain a cardiac index of 2 L • min-1 • m-2 or higher or a systolic blood pressure of 90 mm Hg or higher. Stroke was defined as a new focal central nervous system (CNS) deficit postoperatively that persisted for more than 24 hours. Operative death was defined as death within 30 days of operation or at any time during the same hospitalization.
Any apparent changes in neurologic status were evaluated by an attending staff neurologist. Computed tomographic scans were obtained in all patients evaluated for stroke. In most instances, the scan confirmed the clinical impression of a focal CNS injury. Patients diagnosed as having postoperative disorders such as psychosis, dementia, or confusion without an associated focal neurologic deficit were excluded from the series in both groups. To define the risk factors for stroke during CABG, multiple variables were collected and evaluated: age, sex, history of hypertension, diabetes, prior stroke or history of transient ischemic attacks, presence of carotid artery disease as defined by a stenosis of greater than 70% on carotid angiogram, severity of aortic calcification by surgeon's estimate or by presence of aortic calcification on chest roentgenogram or visualization on aortic angiogram, cardiopulmonary bypass time, cross-clamp time, lowest hematocrit on CPB, and occurrence of perioperative hypotension (defined as systolic blood pressure 
90 mm Hg for at least 30 minutes).
Data Analysis
Patient demographics, intraoperative variables, and neurologic outcome were compared between groups by 
2 test if categoric data and unpaired t test if continuous data. Risk factors for stroke were correlated with neurologic outcome by univariate 2 analysis with Yates' correction. A p value of less than 0.05 was considered significant. Categoric data are reported as absolute and percentage frequencies are continuous variables, as the mean +/- the standard error.
|
Results |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentReferences |
|---|
. There were significant differences in a number of clinical and operative variables. The normothermic group included a significantly greater number of patients older than 70 years (p < 0.0001). Measures of severity of illness including unstable angina, previous myocardial infarction, and left ventricular ejection fraction of 0.40 or less (as measured on cineangiogram, echocardiogram, or multiple-gated acquisition scan) were present in significantly greater numbers of patients in the normothermic group. A marked difference in the use of the left internal mammary artery conduit is apparent between the groups (p < 0.0001) with the more recent surgical patients (normothermic group) receiving this conduit more than twice as frequently as the historical hypothermic group. Other surgical variables analyzed (number of bypass grafts, cross-clamp time, and CPB time) were similar between groups.
|
. Patients undergoing normothermic perfusion during CPB sustained fewer perioperative myocardial infarctions, had fewer low cardiac output syndromes, and had lower operative mortality. In addition, no intraoperative placement of an intraaortic balloon pump occurred in the normothermic group. The incidence of stroke did not differ significantly between the groups.
|
summarizes the neurologic complications in both groups. Twenty-five patients (1%) in the normothermic group experienced overt CSN deficits after operation versus 21 patients (1.3%) in the hypothermic group. Neurologic complications were divided into three groups. Patients in group 1 sustained severe neurologic injuries, never regained consciousness after operation, and died after support system withdrawal. Patients in group 2 emerged from operation with clinical evidence of focal cerebral infarction such as hemiplegia, visual disturbance, or alteration in memory and cognitive function that persisted at the time of discharge. Patients in group 3 had minor neurologic deficits that cleared by the time of discharge. The mortality rate for patients in whom neurologic injuries developed was high at nearly 25% (11/46 patients). The incidence of neurologic complications after CABG correlated significantly with increasing age (p = 0.001) in both groups as shown in Figure 1. The incidence of stroke in patients less than 70 years of age was 0.6% in both groups combined (17/2,990 patients) compared with 2.4% (29/1,200 patients) in patients aged 70 years or older. Patients with a neurologic complication had significantly longer hospital stays as well.
|
|
. Risk of stroke was higher in patients with moderate or severe atherosclerosis of the ascending aorta in both groups than in patients with no or mild atherosclerosis. One patient sustained diffuse neurologic injury after intraoperative dissection of the aorta, which necessitated partial graft replacement of the aorta. In patients diagnosed as having had embolic neurologic deficits, computed tomographic scans showed multiple areas of infarction in both cerebral hemispheres compatible with embolization.
|
Multiple logistic regression analysis was performed on these same variables. Age of 70 years and older and severity of aortic atherosclerosis remained strong predictors of stroke. Perfusion technique, perioperative hypotension, and preexisting cerebrovascular disease were not predictive.
|
Comment |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentReferences |
|---|
The use of hypothermia as a technique of organ protection, including cerebral protection, during cardiac surgical procedures dates back to the first successful intracardiac repair under direct vision [9]. Bigelow and colleagues [10] had previously demonstrated longer tolerance to inflow occlusion in hypothermic animals than in their normothermic counterparts. The protective effect is presumably the result of a decrease of neuronal metabolic activity. The consequent reduction in oxygen consumption permits neurons to tolerate longer periods of ischemia before permanent infarction occurs. The most dramatic clinical application of the cerebral protective effects of hypothermia occurs during deep hypothermia and circulatory arrest used extensively for repairs of complex congenital cardiac lesions and aortic arch aneurysms. In this setting, the brain is the organ at most risk for injury and limits the duration of ``safe'' arrest time. Profound hypothermia prolongs the time the brain can tolerate global cerebral ischemia from nonperfusion. However, CPB for myocardial revascularization does not routinely include circulatory arrest or deliberate periods of global cerebral ischemia. Thus the utility of hypothermia in reducing CNS injuries associated with routine cardiac surgical procedures is currently unproved.
Macroembolization from the surgical field is thought to be the most common cause of stroke associated with CPB [3, 11, 12]. Using examinations by a consulting neurologist and computed tomographic scans, our study identified atheromatous emboli of the ascending aorta as the suspected cause of stroke in the majority of our patients who sustained this complication. Dislodgment of atherosclerotic debris is most likely to occur at the time of aortic cannulation or aortic cross-clamping or during the construction of proximal vein graft anastomoses. Normothermia exists at the time of aortic cannulation and is restored at the end of CPB. Thus the application and the release of the aortic clamp, the times of greatest risk of embolization of large particulate material to the cerebral circulation, will occur when the patient is normothermic, irrespective of the temperature at which systemic perfusion was conducted during CPB. Embolization to the CNS is unlikely during the hypothermic period, as the surgical field and heart are excluded from the circulation by the aortic cross-clamp. Therefore, we did not expect hypothermic perfusion to offer substantial cerebral protection during routine CPB.
The results of this study argue that the incidence of stroke is not related to the systemic perfusion temperature during CPB in patients undergoing CABG. The incidence of stroke was no greater in patients who had warm-body perfusion than those with moderate hypothermic perfusion. This contrasts with a recent report by Martin and co-workers [8] in which, during a large trial of warm blood cardioplegia with systemic normothermic perfusion versus cold crystalloid cardioplegia and hypothermic perfusion, a significantly greater stroke rate was found in the normothermic group (3.1% versus 1.0%). Although these authors abandoned the use of normothermic perfusion on this basis, they noted no significant differences in a subset of nearly 150 patients between the treatment groups in a battery of neuropsychologic tests. Wong and associates [13], in a prospective, randomized study of neuropsychologic function after normothermic or hypothermic CPB, found no evidence of cerebral protection or improved neurologic function in the hypothermic group. Similar to us, Kavanagh and colleagues [14] reported the clinical outcomes for their institutional practice of warm heart surgery and normothermic CPB versus cold heart surgery and hypothermic perfusion in a retrospective control group. They did not find an increased incidence of stroke in the normothermic group. The increased incidence of stroke in the normothermic group of Martin and co-authors [8] may well be explained by a number of confounding variables, such as differences between the groups in preexisting cerebrovascular disease or some alteration in the surgical technique because of the different cardioplegia regimens. They cite a significantly greater incidence of hyperglycemia in the normothermic group as a possible confounding variable potentiating cerebral vulnerability to ischemia. Hyperglycemia may enhance the effects of ischemia in the brain [15].
The use of a historical control group for comparison to a prospectively followed group in our study presents some analytic limitations. Sotaniemi [16] and others [17] have demonstrated that the incidence of detected neurologic deficits is greater when the data are collected prospectively rather than by a retrospective review. In our study, the neurologic outcomes were sought prospectively in the normothermic perfusion group, and this should introduce a bias toward an increased incidence of detected CNS injuries in that group. However, the normothermic group did not have a higher stroke rate than that found in the retrospectively reviewed hypothermic patients. Historical control groups introduce unstudied or not readily apparent differences between groups as potential sources of error. For example, the greater use of arterial conduits in the later normothermic group does indicate that the surgical technique used in both groups, although similar, was not identical. Patients who receive a left internal mammary artery graft require one fewer puncture site in the aortic root, the most common site of atheroemboli, and therefore should be less likely to sustain a stroke.
We believe that cerebral emboli resulting from manipulation of a diseased ascending aorta are the major cause of overt neurologic deficits after CABG. Surgical techniques that minimize the dislodgment of atheromatous debris should be efficacious in reducing the incidence of stroke. In our study, we attempted to control for the variable of surgical skill and technique by including only those patients cared for by a single surgical team. However, our awareness of the high risk of a severely diseased ascending aorta has resulted in alterations in the surgical approach when we are faced with that situation. Such alterations included more frequent use of the internal mammary artery conduit, femoral artery cannulation, long-tip aortic cannulas to avoid blast injury, and use of the ``no-touch'' technique as described by Mills and Everson [18]. These techniques have matured with our experience over the years and are clearly in more widespread use now than at the time our historical hypothermic group underwent operation. Whatever role they have had in minimizing cerebral emboli introduces a bias toward a reduced incidence of stroke in the normothermic group.
Our study supports the work of others [3, 19, 20] who found the perioperative risk of stroke during CABG increases significantly with advancing age. In both groups, the stroke rate was approximately four times greater in patients 70 years of age or older versus their younger counterparts (2.4% versus 0.6%). It is presumed that this increased risk of stroke is due to a greater incidence and severity of aortic atherosclerosis in the elderly. Worsening severity of aortic arch atherosclerosis, as rated by the surgeon at the time of operation, correlated with an increased risk of stroke. As our normothermic group included significantly more patients aged 70 years or older, these differences should have biased the normothermic group toward a higher incidence of stroke, a result we did not find. Other demographic differences between our study groups, including more patients with ventricular dysfunction and a greater incidence of unstable angina and more women in the normothermic group, should have biased our results toward greater cardiac morbidity and mortality in the normothermic patients, a prediction opposite to the actual findings and suggestive that normothermic perfusion is clearly at least as safe for both cerebral and myocardial protection as hypothermic perfusion [21].
In summary, this study reports a low incidence of stroke in a large clinical series of patients undergoing myocardial revascularization with normothermic bypass. The incidence was no greater than that in a retrospectively studied control group operated on by the same surgical team at the same institution but with hypothermic perfusion during CPB.
|
Footnotes |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentReferences |
|---|
|
References |
|---|
|
TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  K. G. Shann, D. S. Likosky, J. M. Murkin, R. A. Baker, Y. R. Baribeau, G. R. DeFoe, T. A. Dickinson, T. J. Gardner, H. P. Grocott, G. T. O'Connor, et al. An evidence-based review of the practice of cardiopulmonary bypass in adults: A focus on neurologic injury, glycemic control, hemodilution, and the inflammatory response. J. Thorac. Cardiovasc. Surg., August 1, 2006; 132(2): 283 - 290.e3. [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Hogue Jr, C. A. Palin, and J. E. Arrowsmith Cardiopulmonary bypass management and neurologic outcomes: an evidence-based appraisal of current practices. Anesth. Analg., July 1, 2006; 103(1): 21 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Calafiore, M. Di Mauro, G. Teodori, G. Di Giammarco, S. Cirmeni, M. Contini, A. L. Iaco, and M. Pano Impact of aortic manipulation on incidence of cerebrovascular accidents after surgical myocardial revascularization Ann. Thorac. Surg., May 1, 2002; 73(5): 1387 - 1393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D C Whitaker, J Stygall, and S P Newman Neuroprotection during cardiac surgery: strategies to reduce cognitive decline Perfusion, March 1, 2002; 17(2_suppl): 69 - 75. [Abstract] [PDF]
|
|
|
|
|
|
M. Swaminathan, C. East, B. Phillips-Bute, M. F. Newman, J. G. Reves, P. K. Smith, and M. Stafford-Smith Report of a substudy on warm versus cold cardiopulmonary bypass: changes in creatinine clearance Ann. Thorac. Surg., November 1, 2001; 72(5): 1603 - 1609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gaudino, L. Martinelli, G. Di Lella, F. Glieca, P. Marano, R. Schiavello, and G. Possati SUPERIOR EXTENSION OF INTRAOPERATIVE BRAIN DAMAGE IN CASE OF NORMOTHERMIC SYSTEMIC PERFUSION DURING CORONARY ARTERY BYPASS OPERATIONS J. Thorac. Cardiovasc. Surg., September 1, 1999; 118(3): 432 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bao, J. Y. Geng, and B. Guo Management of Cardiopulmonary Bypass During Minimally Invasive Cardiac Surgery Asian Cardiovasc Thorac Ann, June 1, 1999; 7(2): 93 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Engelman, A. B. Pleet, J. A. Rousou, J. E. Flack III, D. W. Deaton, P. S. Pekow, and C. A. Gregory Influence of cardiopulmonary bypass perfusion temperature on neurologic and hematologic function after coronary artery bypass grafting Ann. Thorac. Surg., June 1, 1999; 67(6): 1547 - 1555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Cook Changing Temperature Management for Cardiopulmonary Bypass Anesth. Analg., June 1, 1999; 88(6): 1254 - 1254. [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Wolman, N. A. Nussmeier, A. Aggarwal, M. S. Kanchuger, G. W. Roach, M. F. Newman, C. M. Mangano, K. E. Marschall, C. Ley, D. M. Boisvert, et al. Cerebral Injury After Cardiac Surgery : Identification of a Group at Extraordinary Risk Stroke, March 1, 1999; 30(3): 514 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Birdi, I. Regragui, M. B. Izzat, A. J. Bryan, and G. D. Angelini INFLUENCE OF NORMOTHERMIC SYSTEMIC PERFUSION DURING CORONARY ARTERY BYPASS OPERATIONS: A RANDOMIZED PROSPECTIVE STUDY J. Thorac. Cardiovasc. Surg., September 1, 1997; 114(3): 475 - 481. [Abstract] [Full Text]
|
|
|
|
|
|
M Ranucci, G Soro, A Frigiola, L Menicanti, A Ditta, G Candido, and S Tambalo Normothermic perfusion and lung function after cardiopulmonary bypass: effects in pulmonary risk patients Perfusion, September 1, 1997; 12(5): 309 - 315. [Abstract] [PDF]
|
|
|
|
|
|
C. O'Dwyer, L. C. Woodson, B. P. Conroy, C. Y. Lin, D. J. Deyo, T. Uchida, and W. E. Johnston Regional Perfusion Abnormalities With Phenylephrine During Normothermic Bypass Ann. Thorac. Surg., March 1, 1997; 63(3): 728 - 735. [Abstract] [Full Text]
|
|
|
|
|
|
I. Regragui, I. Birdi, M. Bashar Izzat, A. M. S. Black, A. Lopatatzidis, C. J. E. Day, F. Gardner, A. J. Bryan, and G. D. Angelini THE EFFECTS OF CARDIOPULMONARY BYPASS TEMPERATURE ON NEUROPSYCHOLOGIC OUTCOME AFTER CORONARY ARTERY OPERATIONS: A PROSPECTIVE RANDOMIZED TRIAL J. Thorac. Cardiovasc. Surg., October 1, 1996; 112(4): 1036 - 1045. [Abstract] [Full Text]
|
|
|
|
|
|
M. I. Buss, R. F. McLean, B. I. Wong, S. E. Fremes, C. D. Naylor, E. M. Harrington, W. G. Snow, and M. Gawel Cardiopulmonary Bypass, Rewarming, and Central Nervous System Dysfunction Ann. Thorac. Surg., May 1, 1996; 61(5): 1423 - 1427. [Abstract] [Full Text]
|
|
|
|
|
|
I. Birdi, M. B. Izzat, A. J. Bryan, and G. D. Angelini Normothermic Techniques During Open Heart Operations Ann. Thorac. Surg., May 1, 1996; 61(5): 1573 - 1580. [Abstract] [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
