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Ann Thorac Surg 2000;69:1431-1438
© 2000 The Society of Thoracic Surgeons
a Departments of Department of Cardiothoracic Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia
b Department of Anesthesia, Royal Melbourne Hospital, Melbourne, Victoria, Australia
c Department of Cardiology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
d Department of Neurology and Neuropsychology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
Address reprint requests to Dr Alistair G. Royse, Royal Melbourne Hospital, Suite 3, Private Medical Centre, PO Box 2135, Parkville, Victoria 3052, Australia
e-mail: alistair.royse{at}nwhcn.org.au
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Abstract |
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Methods. Aortic atheroma was detected using epiaortic and transesophageal echocardiography. Atheroma avoidance was facilitated by use of the exclusive Y graft technique, which has no aortic coronary anastomoses. In the control group aortic atheroma was assessed by manual palpation, and we attempted to avoid any atheroma detected. In this group we also used aorta-coronary grafts. Transcranial Doppler imaging of the right middle cerebral artery was used to detect cerebral microemboli. Neuropsychological dysfunction was defined as a 20% or more decline in score for at least 20% of a neuropsychometric battery of ten tests for each patient.
Results. Late dysfunction at 57 ± 2 days postoperatively in the control group was 38.1% and in the echo/Y group was 3.8% (p' = 0.012). Microemboli detected by transcranial Doppler imaging during periods of aortic manipulation was greater for those with late dysfunction (5.2 ± 3.0 compared with 0.5 ± 0.2) (p' = 0.018). No clinical strokes occurred in either group.
Conclusions. The combined techniques of epiaortic screening and exclusive Y graft for coronary artery bypass operations resulted in a low incidence of late neuropsychological dysfunction.
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Introduction |
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We have shown previously that digital palpation to assess the severity of aortic atheroma is unreliable [9]. Conversely, intraoperative epiaortic echocardiography can accurately detect this disease in the region where cannulation and clamping will occur [10, 11]. Epiaortic screening should precede aortic manipulation, thereby allowing movement of the site of aortic manipulation away from the site of detected atheroma. Because the mid-ascending aorta is usually used for constructing proximal coronary graft anastomoses, the site of aortic cannulation and clamping usually occurs in the distal ascending aorta or proximal aortic arch. Unless the technique of coronary artery bypass operation is altered to eliminate anastomoses to the aorta, little scope exists for modifying the site of aortic cannulation and clamping. Therefore, a necessary adjunct to the detection of aortic atheroma using echocardiography is use of the exclusive Y graft operation [12], which will then facilitate alteration of the site of aortic manipulation since there are no aortic anastomoses.
Many approaches have been investigated that may influence cerebral embolism or neurological outcome, including cardiopulmonary arterial line filters [13], aortic resection and replacement [14], intraaortic filters, systemic hypothermia during cardiopulmonary bypass [15] or at the time of aortic clamp removal, avoidance of rapid rewarming during cardiopulmonary bypass, and off pump coronary operations in which cardiopulmonary bypass cannulation and aortic clamping is avoided.
The aim of this study was to determine the neuropsychological outcome for patients in whom aortic atheroma had been detected by echocardiography and successfully avoided in patients undergoing multivessel coronary operations. A control group of patients who had the current best standard practice of digital palpation of the aorta and avoidance of atheroma and had aorta-coronary grafts was used to validate the neuropsychological assessment and to allow comparison with other published studies.
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Patients and methods |
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No randomization was done. The techniques used were the routine operative techniques used by two surgical teams. The surgeons were not informed of the results of the study until completion of recruitment. Twelve preoperative variables were used to compare the two groups, with no significant differences noted (Table 1). The control group received the standard aorta-coronary operation for multivessel coronary revascularization. The purpose of the control group was to validate our neuropsychological assessment. The incidence of neuropsychological decline in the control group should be similar to that in other published series using a similar technique.
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Control group
The control group (n = 21) had aorta-coronary operations in which all patients received the pedicled left internal mammary artery to the left anterior descending artery and at least one proximal aortic anastomosis. Assessment of the aorta was done by digital palpation by the surgeon. Echocardiography (either epiaortic or transesophageal) was not done and CO2 insufflation was not used. Perioperative blood pressure was controlled less rigidly than for the study group, but was similar to that of most other studies.
Atheroma screening
Transesophageal echocardiography was done in all echo/Y patients by using a 5-Mhz or 6.25-Mhz Omniplane transducer and a Hewlett-Packard Sonos 2500 machine (Hewlett-Packard, Andover, MA). Before any aortic manipulation, epiaortic echocardiography allowed direct visualization of the ascending aorta and aortic arch. A hand-held probe (5 Mhz or 7.5 Mhz) placed in a sterile bag was used [10]. A custom-designed spacer was used to improve near field imaging. Standard grading of atheroma was used, with "moderate" referring to intimal thickening of more than 4 mm which was flat or smooth and "severe" referring to intimal thickening of more than 4 mm which was not flat (complex) or if there were mobile segments of atheroma. The classification for the site of atheroma has been described previously [10] and corresponds to site of potential surgical manipulation. The thoracic aorta was divided into six zones. Zones 1 through 3 are the proximal, mid, and distal ascending aorta; zones 4 and 5 are the proximal and distal aortic arch, and zone 6 is the proximal descending aorta. Each zone is further subdivided in cross section into anterior, left lateral, posterior, and right lateral quadrants. The aorta in zones 1 through 4 usually will be at risk from surgical manipulation during coronary artery operations, with zones 5 and 6 rarely manipulated. The epiaortic probe was used to image zones 1 through 4 and transesophageal probe for zones 5 and 6. A single investigator performed the assessment in all patients.
Attempt to avoid dislodging aortic atheroma
In both groups, we attempted to avoid placing cannulas or clamps at or near the site of any detected aortic atheroma. In addition, in both groups the single cross-clamp technique was used, in which a single application of the aortic clamp (Fogarty Hydragrip, V. Mueller, Baxter, Deerfield, IL) was used for all parts of the grafting; in no case was a partial occlusion clamp used.
Definitions
The definition of neuropsychological dysfunction is controversial. We have chosen the consensus view [16, 17] supported by a recent study [5]. Decline or dysfunction was said to occur in an individual patient when a 20% or greater decrease in postoperative neuropsychologic test score compared with the preoperative score was present in at least 20% of a battery of ten tests. Neurological decline was defined as the appearance of any new abnormal cranial or peripheral nerve sign or any decline in mental state examination.
Testing
Neurological and cognitive status was assessed preoperatively, before discharge from hospital, and 2 to 3 months postoperatively. A single medical investigator performed neurological assessment and a single neuropsychologist performed neuropsychometric assessment.
Neurological assessment included a standard mental state examination and combined cranial and peripheral nervous system examination. The neuropsychometric battery included ten tests from established test batteries previously used in studies investigating cognitive function after coronary artery bypass (Table 2). Tests from the Consortium to Establish a Registry for Alzheimer Disease (CEARD) have minimal practice effects and are appropriate for a relatively elderly population. Tests from the Multicenter AIDS Cohert Study (MACS) group are minimally affected by factors of fatigue, depression, or anxiety. This test battery is consistent with the consensus statements [16, 17]. In addition, the National Adult Reading Test (NART) was given on the first assessment only. Anxiety and depression were measured by a visual analogue scale of 0 to 100 [18].
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Anesthesic technique
The anesthetic technique for the control group consisted of fentanyl 15 to 20 µg/kg, supplemented by a propofol infusion of 200 to 400 mg/hour and midazolam 1 to 5 mg/hour. Postoperative pain was treated with intravenous morphine. Anesthesia for the echo/Y group consisted of propofol 100 to 400 mg/hour, supplemented by sevoflurane or isoflurane and with high thoracic epidural anesthesia in 19 of 26 patients. Ropivacaine 0.5% with fentanyl 10 µg/kg (8 to 10 mL) was used as the epidural loading dose and maintained with 5 to 14 mL/hour of ropivacaine 0.2% and fentanyl 2 µg/kg solution, for 2 to 3 days postoperatively [19]. Most patients in the echo/Y group were extubated in the operating room, whereas all control group patients were ventilated postoperatively.
Cardiopulmonary bypass technique
Cardiopulmonary bypass was instituted with flow rates of 2.0 to 2.5 L/min/m2 per minute, using a membrane oxygenator (Medtronic Forte; Medtronic, Anaheim, CA) and 20-µm arterial filter (Medtronic, Anaheim, CA). Carbon dioxide partial pressure was adjusted using the alpha-stat method. Perfusion pressure was maintained between 60 to 80 mm Hg. In the echo/Y group the temperature was maintained at 35°C or higher, whereas in the control group the temperature was allowed to drift without active cooling and the minimum temperature ranged from 32° to 34°C. All patients were actively rewarmed to at least 36°C before removal of the cross-clamp and to 37°C before cessation of bypass.
Blood cardioplegia, at 20°C was administered routinely in both antegrade and retrograde directions. Intermittent retrograde cardioplegia (300 to 500 mL) was administered at the conclusion of each anastomosis. In the echo/Y group, repeat doses were by retrograde administration, and in the control group they were mostly by retrograde, with some antegrade doses given after construction of each aortic anastomosis. Myocardial reperfusion was commenced before aortic clamp removal by releasing the conduit clamps in the echo/Y group and allowing blood to flow via the pedicled graft. In the control group myocardial reperfusion was achieved by retrograde administration of warm blood.
Statistical analysis
Dichotomous variables were analyzed using Fisher exact test and continuous variables by one-way analysis of variance (SPSS V8.0, SPSS Inc, Chicago, IL). Where appropriate, the raw value of p was corrected for multiple hypothesis testing (p') according to the Ryan-Holm step-down Bonferroni procedure [20]. Statistical significance was attained if the two-sided p or p' was less than 0.05. Continuous variables are expressed as mean ± standard error.
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Results |
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Comment |
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The purpose of the control group was to establish a baseline frequency of neuropsychological dysfunction at our institution. Late dysfunction of 38.1% is consistent with the lower to mid range reported in the literature [4, 5]. The echo/Y group had fewer men but a higher rate of diabetes, preoperative stroke, and atrial fibrillation than the control group, which might be expected to adversely affect outcome. However, none of those factors was statistically significantly different from the control group, and thus the groups were well matched (Table 1). Minimum temperature during cardiopulmonary bypass temperature was higher in the echo/Y group, and cerebral metabolic rate would have been slightly higher at the time of embolism and could be expected to result in more adverse outcomes in that group.
Manual palpation of the aorta is a poor technique for detecting atheroma compared with echocardiography [9, 11]. However, the distal ascending aorta and proximal aortic arch, which are the usual sites of aortic cannulation and clamping, cannot reliably be visualized using transesophageal echocardiography because the right main bronchus is situated between the esophagus and the aorta, preventing ultrasound transmission. The solution to this problem is to use a hand-held probe placed directly on the aorta (epiaortic echocardiography) [9, 21]. This technique allows accurate assessment of the ascending aorta and proximal arch (zones 1 through 4), supplemented by transesophageal echocardiography for assessment of the distal arch and descending aorta (zones 5 and 6). In this study, only 35% of the echo/Y group had aortic zones 1 through 4 entirely free of atheroma, and in only 8% were all zones free of disease (Table 6). By contrast, 83% of aortas in the control group was considered to be normal, as assessed using manual palpation. Because the two groups were well matched (Table 1), this difference likely reflects the greater accuracy of echocardiography compared with manual palpation.
The principle of avoidance is to prevent direct penetration or crushing of moderate or severe aortic atheroma by cannulas or clamps. We recommend complete avoidance of atheroma if possible. Movement of the site of aortic manipulation by only 1 or 2 cm can be sufficient to avoid atheroma. It is possible, for example, to cannulate the disease-free anterior wall of the aorta even though the posterior wall might be atheromatous. Previous studies [21, 22] reported atheroma within regions (such as ascending aorta or aortic arch) and recommended complete avoidance of those regions or indeed replacement of them. By using our classification it is possible to place sites of manipulation within these regions but still avoid the atheroma (ie, near to, but not involving the atheroma).
The operative technique is important, because movement of the sites of cannulation or clamping might be difficult or impossible if part of the ascending aorta is required to construct aortic anastomoses. The primary advantage of an exclusive Y graft technique [12] is the increased space available for movement of sites of aortic manipulation. This concept is illustrated in Figure 1, where atheroma in zones 3 and 4 is not avoided by an aorta-coronary technique (Fig 1A) but is easily avoided using a Y graft technique (Fig 1B). The construction of aortic anastomoses also results in aortic manipulation. Although we found atheroma less frequently in the ascending aorta (zones 1 through 3) in this study and in a previous study [10], it can still occur. In this series, we did not use a partial occlusion clamp, which would be expected to dislodge a greater amount of atheroma from the ascending aorta, in addition to use of the straight aortic clamp. If air is trapped in the aorta, gas emboli are possible. Carbon dioxide insufflation was not used in the control group. It is possible that gas emboli, detected by transcranial Doppler imaging, could cause less ischemic brain damage if the gas bubble is CO2, which is rapidly bound to hemoglobin, rather than air, which is 80% nitrogen and does not bind to hemoglobin.
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The definition of neuropsychological decline has been subject to much controversy, leading to the publication of two consensus views [16, 17]. The key points are that assessment should be based on a broad battery of tests (Table 2) and that decline should be determined for each individual rather than for the group [5]. There are also issues relating to the degree to which a decrease in test score constitutes mental decline. We have chosen to fully accept the consensus view. Thus each patient is considered to have decline or no decline (including improvement).
The high incidence of neuropsychological decline before hospital discharge is not surprising and is consistent with the literature (Table 5). Patients are often still receiving numerous medications, such as opiates, that can affect cognition. These data are difficult to analyze because 66% of the control group did not complete all ten tests in the battery, and 33% did not complete any tests in the battery (Table 4). It is debatable whether these patients should be considered missing data and excluded from the analysis or whether they should be considered to have severe neuropsychological dysfunction and included in the analysis. If included, then there was no significant difference between the two groups. Because the late assessment was markedly different, we conclude that the in-hospital assessment was probably of little prognostic significance.
Anxiety and depression can affect some of the tests in the battery. Scores in the control group were greater than the echo/Y group at the preoperative and in-hospital assessments but not at the late assessment (Table 3). Thus it can be expected that scores in the control group preoperatively and in-hospital may be adversely affected, but this was not so (Table 5). Conversely, because there was no difference at the late assessment, one can expect that the improvement in anxiety and depression in the control group would enhance rather than retard neuropsychological function.
Transcranial Doppler imaging has been advocated for detecting particulate or gaseous microemboli that reach the brain, which can lead to ischemic brain damage and neuropsychological dysfunction [24, 25]. We found this technique difficult to apply in several patients because of the inability to image the middle cerebral artery through the temporal bone. Also, although not recorded, we found that the probe position was sensitive to movement during the operation, resulting in abandonment of data collection on several occasions. There is also no definitive way to ensure that the middle cerebral artery is imaged rather than a smaller, adjacent artery. Unilateral right middle cerebral artery imaging might reflect only a small portion of the microembolic load to the brain. In a separate study [10] as for this study, we found that the incidence of atheroma was higher in the proximal arch than in the ascending aorta (Table 6). Forward flow of the blood might carry emboli past the right brachiocephalic artery to the left common carotid artery and so not be detected by a right-sided Doppler probe. We recommend that future studies consider bilateral carotid artery Doppler imaging, because those arteries are simple to image, are not very sensitive to probe movement during the operation, and will capture most of the microembolic load reaching the brain.
In this study, we tried to correlate episodes of embolization with events such as aortic manipulation. The frequency of microemboli counts was low compared with those reported in the literature, which could correspond to the techniques used but might also indicate sampling errors. We found no difference in counts between the echo/Y and control groups (Table 7) or in counts of patients with or without neuropsychological dysfunction at the in-hospital assessment (Table 8). However, there was a greater incidence of emboli during aortic manipulation (such as cannulation, clamping, and declamping) for those with late neuropsychologic dysfunction compared to those without (5.2 ± 3.0 compared with 0.5 ± 0.2) (p' = 0.018) (Table 8). There was no significant difference for microemboli occurring during the remaining operation, including the cardiopulmonary bypass. This finding is consistent with previous reports suggesting that emboli occurring at the time of aortic manipulation result in brain damage, as determined by neuropsychometric tests [8, 24, 25]. These findings suggest that avoidance of dislodging atheroma via the techniques described in this paper is important. Because of the methodologic problems encountered, however, these Doppler data should be interpreted with caution.
Anesthetic techniques differed between the two groups. In the control group we used a moderate-dose opioid technique, whereas in the echo/Y group we used propofol and predominantly high thoracic epidural anesthesia. Although differences in cognition might be affected by anesthesia and analgesic medication in the early postoperative period, it is not expected that these agents would affect cognition at late assessment. It is possible that there were slight differences in postoperative care between the groups, but, in general, treatment followed the same protocol.
The control group was assessed an average of 17 days earlier than the echo/Y group. It is known that the incidence of neuropsychological dysfunction diminishes with time postoperatively [5], but it is unlikely that a 2-week difference accounts for the full magnitude of the observed difference.
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Acknowledgments |
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) = antegrade cardioplegia cannulation site; AV = aortic valve.)