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Ann Thorac Surg 2007;84:1174-1179
© 2007 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Coronary Artery Bypass Grafting With Single Cross-Clamp Results in Fewer Persistent Neuropsychological Deficits Than Multiple Clamp or Off-Pump Coronary Artery Bypass Grafting

^a Department of Cardiothoracic Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina
^b Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
^c Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Accepted for publication April 23, 2007.

^_* Address correspondence to Dr Hammon, Department of Cardiothoracic Surgery, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157 (Email: jhammon{at}wfubmc.edu).

Presented at the Fifty-third Annual Meeting of the Southern Thoracic Surgical Association, Tucson, AZ, Nov 8–11, 2006.

Dr Hammon discloses that he has a financial relationship with Bayer Corp.

 

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Discussion Acknowledgments References

 
Background: In coronary artery bypass grafting (CABG) patients, neuropsychological deficits that are present from the time of the operation through 6 months postoperatively are considered permanent and represent organic brain damage related to the operation. We hypothesized that changes in our surgical method would reduce persistent deficits.

Methods: From 1999 to 2004, consenting CABG patients were randomly assigned to multiple aortic cross-clamp or single aortic cross-clamp technique. An additional contemporary group of patients treated with off-pump CABG was studied. All patients underwent an 11-part neuropsychologic examination preoperatively, and at 1 week, 6 weeks, and 6 months postoperatively. One hundred seven patients with no postoperative neurologic deficits had neuropsychologic examinations at all four testing periods.

Results: Off-pump CABG patients were significantly younger (60 ± 11 years) than multiple aortic cross-clamp (66 ± 8 years) and single aortic cross-clamp (64 ± 9 years; p < 0.05) patients. At 6 months, 26% of 27 multiple aortic cross-clamp patients had neuropsychological deficits, 27% of 26 off-pump CABG patients had neuropsychological deficits, and only 9% of 54 single aortic cross-clamp patients had neuropsychological deficits (p = 0.067 versus multiple aortic cross-clamp and off-pump CABG).

Conclusions: These results suggest that surgical technique is very important in determining cognitive outcome after CABG. Cardiopulmonary bypass is not the most important factor in determining outcome and when carefully performed with single cross-clamp and minimal aortic manipulation is equal or may be superior to off-pump operation. We suspect that mild hypothermia in on-pump surgery is additionally neuroprotective, a factor that should be taken into account when planning an operation.

Neuropsychological (NP) testing has become an accepted method to detect subtle brain damage in patients undergoing cardiac surgery [1]. Neuropsychological deficits are more numerous early postoperatively and diminish in number as time passes after the operation. We recently published data from a partially randomized study that suggested that changes in operative technique could markedly influence and improve postoperative cognitive outcomes [2]. In an attempt to further understand the effects of surgical technique on outcomes and to identify those patients who had significant postoperative deficits that then persisted into midterm postoperatively (6 months), we performed a substudy using this data set with the objective of ascertaining which patients had persistent NP deficits extending through all three postoperative testing periods to 6 months postoperatively. We hypothesized that patients with persistent deficits acquired these as a result of injury during surgery. Those with deficits that persisted for 6 months were inferred to be permanent. We further wished to study the number of new deficits that appeared in the period between surgery and 6 months, believing that these represented the natural history of patient disease and not the effects of surgery.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment Discussion Acknowledgments References

 
From January 1999 to July 2004, patients undergoing isolated coronary artery bypass grafting (CABG) were evaluated at our medical center. With approval from our institutional review board, consenting high-risk patients (those with age > 65 years, diabetes, or hypertension) [3] were screened, and those patients with neurodegenerative disease, major depressive disorder within the last 5 years, class IV congestive heart failure, cirrhosis, renal failure with creatinine greater than 1.8 mg/dL, or any other serious life-threatening disease were excluded. Inability to perform NP testing for any reason was also an exclusion factor. The remainder of patients underwent a comprehensive neurologic history and physical examination. A previous history of stroke, known asymptomatic bruits, previous carotid endarterectomy, or other neurologic deficits were recorded and analyzed separately as a risk factor. Patients underwent an 11-part NP examination, which was administered by trained neuropsychologists (Appendix). The elements of the test and results in large numbers of patients in this institution and others have been previously published [4]. An NP deficit was defined as a 20% decrement in two or more tests from preoperative scores.

On the day of operation, patients were premedicated with midazolam (1 to 2 mg intravenously). Anesthesia was administered with a standard technique of a moderate-dose narcotic supplemented as necessary with volatile agents sufficient to maintain stable hemodynamics. Neuromuscular blockade was established using pancuronium 0.1 mg/kg intravenously, and all patients were intubated and ventilated with oxygen-enriched air. After sterile preparation, a median sternotomy was performed, and before cannulation or cardiac manipulation, each patient underwent epiaortic ultrasound scanning and mapping of the ascending aorta. Transesophageal ultrasound scanning was performed on the descending thoracic aorta as well. Using the information collected, an assessment of the ascending aorta was made and graded into separate categories [1]: grade 0, normal; grade 1, extensive intimal thickening with no plaques greater than 2 mm and no plaques protruding into the aortic lumen; grade 2, plaque greater than 2 mm thick with no protrusion into the aortic lumen; grade 3, sessile plaque protruding less than 5 mm into the lumen; grade 4, plaque protruding greater than 5 mm into the aorta with no mobile elements; and grade 5, plaque protruding greater than 5 mm into the lumen with mobile elements or calcification. As we believed that patients with grade 5 aortas were at risk in a randomized study, relating to multiple aortic cross-clamping, patients with these aortas were then excluded from the randomized portion of the study.

The remainder of the patients underwent a randomization procedure in which assignments were accomplished using a random number table. Patients were divided into two groups. The first group underwent traditional CABG with distal anastomoses constructed during a single period of aortic cross-clamping and proximal anastomoses constructed with a single period of partial occlusion of the ascending aorta during rewarming (MAC). A second group of patients (SAC) underwent a procedure in which both proximal and distal anastomoses were constructed during a single period of aortic cross-clamping, and the aorta was usually cross-clamped using a clamp (Bahnson aortic clamp, Pilling Co, Fort Washington, PA) that when tested in our laboratories exerted significantly less force on the aorta than the standard Fogarty aortic cross-clamp, which was used in most patients with multiple aortic clamping (MAC). After randomization, the surgeon had the option to place patients in the other group if the patient was at risk because of the randomization selection. As an example, if a patient was randomized to the SAC group and the surgeon was concerned about the length of the cross-clamp time or if a patient, randomized to the MAC group, had plaques by epiaortic ultrasound that might interfere with placement of a partial occlusion clamp or the placement of holes for proximal anastomoses, the surgeon could switch either of these patients to the other group. The investigators in this study anticipated that surgical techniques would evolve during the course of patient enrollment, and anticipated that some patients would have intraoperative findings that would preclude their inclusion into one or the other of the two groups. Thus, an unequal distribution of patients was not unexpected. In addition, a separate group of patients undergoing off-pump CABG (OPCAB) surgery concurrent with the randomized groups were also subjected to preoperative consent and neurologic and neuropsychologic testing as well as the previously mentioned exclusion criteria. Patients were picked for OPCAB surgery based on cardiologist, surgeon, or patient preference. Patients operated on using cardiopulmonary bypass were managed with a noncoated oxygenator and tubing (Terumo model SX-25, Terumo Corp, Elkton, MD) at standard flow rates (2.2 L · min^–1 · m^–2). Core temperature was allowed to drift to 30° to 32°C, and aortic and left ventricular venting was performed at the surgeon’s discretion. Myocardial protection was provided with antegrade and retrograde blood cardioplegia. Aortic partial occlusion was provided with one of a variety of clamps (Kay-Lambert, Cooley, Shumaker; Codman Co, Piscataway, NJ). Off-pump CABG patients were maintained at normothermia, and coronary exposure was performed with a variety of commercially available stabilizers and retraction devices. Distal coronary arteries undergoing bypass were snared proximally, and visualization was assured using jets of a mixture of carbon dioxide and saline solution. Intracoronary shunts were used in patients suspected of having distal ischemia during the performance of the anastomosis. In OPCAB patients, aortic graft anastomoses were performed using mechanical connectors (St. Jude Medical, St. Paul, MN) or aortic shields (Guidant Corp, Freemont, CA). No partial occlusion clamps were used in the OPCAB group. Postoperative patients underwent repeat NP testing and complete neurologic examination at 3 to 7 days after the operation or just before discharge and at 3 to 6 weeks and 6 months postoperatively.

Definition of Terms
Patient data were collected and analyzed according to the Society of Thoracic Surgeons National Cardiac Database Guidelines and Definitions [5]. Operative mortality was defined as death occurring within 30 days of the operation. Stroke was defined as global or focal neurologic deficit that was evident after emergence from anesthesia (acute stroke) or later in the postoperative period (late stroke). Neurologic events were verified by neurologists and further assessed by computed tomography or magnetic resonance imaging.

Data Analysis
The Sigma Stat 2.03 for Windows (SSPPS, Inc, Chicago, IL) software package was used for all statistical analyses. A probability value of 0.05 or less was considered statistically significant. Nominal variables were compared using ² analysis, with risk ratios calculated using regression analysis. Continuous parametric data were compared using the Student’s t test. Continuous nonparametric distributed variables were compared using the Kruskal-Wallis analysis of variance on ranks. Postoperative comparisons were performed using Dunn’s method for all pairwise multiple comparisons.

	Results

Top Abstract Introduction Patients and Methods Results Comment Discussion Acknowledgments References

 
At the end of data collection, 237 patients were present for analysis. Demographic factors and study results have been previously published [2]. One hundred seven patients (45%) had NP testing at all four periods and are the subject of this analysis. Demographic results are presented in Table 1. There were no statistically significant differences among groups in any of the outcome measures listed, including NP deficits, stroke, transient ischemic attack, or delirium. There were no deaths in any group. The OPCAB patients were significantly younger (60 ± 11 years) than MAC (66 ± 8 years) and SAC (64 ± 9 years; p < 0.05) patients. Six-month neurobehavioral data are presented in Table 2 and Figure 1. The SAC group had the largest number of patients without deficits (74%) and the smallest number with persistent deficits (9.3%; p < 0.067 versus MAC and OPCAB). Of interest, patients in all three groups accumulated deficits from the first postoperative testing to 6 months. Although not significantly different, the OPCAB group had the smallest number (11.5%). Significantly, both MAC and OPCAB patients had at least a 3.5 times greater chance of a persistent deficit at 6 months by regression analysis (Figure 2).

View larger version (21K): [in this window] [in a new window]   Fig 1. Neurobehavioral status at 6 months. p = 0.179 by Fisher’s exact test. Neuropsychological deficits in all three groups out to 6 months. (Multi = multiple aortic cross-clamp; OPCAB = off-pump coronary artery bypass grafting; Single = single aortic cross-clamp.)

View larger version (14K): [in this window] [in a new window]   Fig 2. Odds ratio of a persistent deficit at 6 months. Odds ratios and confidence intervals for multiple aortic cross-clamp (Multi) and off-pump coronary artery bypass grafting (OPCAB) versus single aortic cross-clamp (Single).

	Comment

Top Abstract Introduction Patients and Methods Results Comment Discussion Acknowledgments References

Although it might seem surprising that all three groups developed between 11.5% and 18.5% additional deficits after the operation, these data are supported by a publication from the United Kingdom [6]. A group of patients were imaged before CABG and at 3 months and 1 year after operation. Interestingly, 31% of these patients experienced brain infarcts that were first seen 12 months after operation and were not present at the 3-month study. These findings and ours suggest that new brain infarcts continue to occur beyond the immediate postoperative period. It also suggests that late cognitive decline after CABG may not necessarily be attributable solely to perioperative events.

Although this accumulation of new NP events in the intermediate term after surgery may seem excessive, examination of recent data sheds light on this finding. A recent study performed at the University of California Los Angeles estimated the annual number of Americans who suffered new magnetic resonance imaging–detectable infarcts based on age [7]. Approximately 3% to 5% of the people in their 70s will experience a new infarct each year. In the patients undergoing CABG, if they had no cardiac procedure, the estimated rate of first-time neurologic events would be 10% to 15% [8]. After the first infarct, the probability of a second is much greater; therefore, in the CABG population the event rate would be much higher. In our own study population, the incidence of patients having new brain infarcts after CABG surgery by magnetic resonance imaging and the incidence of new NP deficits is approximately equal so that these numbers then can be correlated [9].

There are significant limitations to the data reported in this manuscript. First, as acknowledged in the first publication on this data set, the inclusion of a nonrandomized OPCAB group is a potential confounder in data analysis for these patients. On the other hand, the OPCAB patients were significantly younger than the other two groups and thus would be expected to have at least similar outcomes to those patients having single aortic clamping. Nevertheless, the number of OPCAB patients carried at least a 3.5 times greater risk for persistent deficits than SAC patients. What might be the reasons for this disparity? Off-pump CABG surgery is performed on patients at normothermia whereas SAC patients were kept mildly hypothermic throughout the entire operative procedure. We have previously shown on experimental animals that mild hypothermia is protective against cerebral ischemic damage after embolism [10]. There is also clinical evidence that supports hypothermic protection [11]. We believe that hypothermia accounts for some of the differences between OPCAB and SAC patients. In addition, we emphasize that by selecting only those patients who had all three postoperative NP testing sessions at the proper time, we reduced the size of the experimental groups for both MAC and OPCAB patients to small numbers. Lack of statistical power is almost certainly why SAC patients did not demonstrate significant difference from the other two groups by ² analysis. Nevertheless, a 9% persistent deficit rate at 6 months in the SAC patients is one of the lowest reported incidences thus far.

In conclusion, we have reanalyzed data from a large group of patients undergoing CABG using three methods of surgical technique. We have found that the number of patients having persistent neurobehavioral deficits is lowest in those undergoing operation using cardiopulmonary bypass and single aortic clamping. At the very least, this would indicate that surgical technique is at least as important in determining NP outcome as the use of cardiopulmonary bypass in patients undergoing surgical myocardial revascularization. Using techniques that avoid aortic manipulation dramatically improve cognitive outcomes in patients having CABG with cardiopulmonary bypass, perhaps producing outcomes that are superior to those from OPCAB. Finally, we emphasize that patients continue to accumulate NP deficits after the operation, which almost certainly are more related to the natural history of their own vascular disease rather than the surgical technique used to treat their myocardial ischemia.

	Appendix

 
Neuropsychological Battery

I Tests of Higher Cortical and Language Functioning

A Vocabulary Test: Split-Half Version (from the Wechsler Adult Intelligence Scale-Revised) (WAIS-R)

II Tests of Memory Functioning

A Rey Auditory Verbal Memory Test

B Nonverbal Memory

III Tests of Attention, Concentration, and Psychomotor Performance

A Trail Making Test A and B (TM)

B Grooved Peg Board

C Finger Tapping Test

D Digit Symbol Task, also called Symbol Digit Task (DS)

E Letter Cancellation Task (LCT)

F Visual Reaction Time Test

	Discussion

Top Abstract Introduction Patients and Methods Results Comment Discussion Acknowledgments References

 
DR WILLIAM A. BAUMGARTNER (Baltimore, MD): I would like to congratulate Dr Hammon and his colleagues on another interesting study analyzing the effects of coronary artery surgery on neurocognition, certainly an area in which they have great expertise. The authors have mined their database of patients involved in a randomized study comparing a single clamp application to a multiple clamp technique in patients undergoing coronary artery bypass grafting. They concluded that the technique of operation, particularly aortic manipulation, was probably more responsible for long-term neurologic deficits than the use of cardiopulmonary bypass. We support the technique of single clamp to reduce neurologic injury. We saw similar results in a retrospective study performed at our institution in regard to reduction of neurologic injury using a single clamp. I think it is also supported by another nonrandomized study by the Brigham group.

The most interesting facets of Dr. Hammon’s study are, one, patients in all three groups had improvements in their neuropsychological testing over time, although the group with single clamp did the best. Second, patients in all three groups developed new deficits over the 6-month follow-up time.

We have been following two cohorts of patients in a nonrandomized prospective study. One group underwent standard coronary artery bypass grafting using the pump, the second group was a control group of patients with documented coronary artery disease but matched in the areas of age and risk factors associated with cerebrovascular disease. At 3 months’ follow-up, we saw a near return to baseline testing in both groups, and at 3 years there was no difference in neurologic testing between the control group or the group that underwent standard coronary artery surgery with the pump, although at that 3-year period both groups had mild decline in their testing scores. These findings support your current results in that long-term neurologic changes are most likely related to aging and the comorbidities linked with cerebrovascular disease and not the use of the pump.

John, I have two questions. Number one, less than half of your available patients underwent complete neurologic testing. What were the reasons for this dropout? The second, you mentioned in your manuscript that appropriate history of stroke, known asymptomatic bruits, previous carotid endarterectomy, and other neurologic deficits were recorded and analyzed separately as risk factors. Were you able to correlate any of these risk factors with the neurologic testing scores?

Once again, I enjoyed your paper and your presentation and want to thank the program committee for inviting me to comment.

DR HAMMON: Thank you very much, Bill. I think everyone here recognizes the amount of work that you and your group have put into your similar studies, and the fact that you followed a control group of patients with vascular disease and they behave similarly to operated patients is very, very important.

You asked two questions. The first is that less than half of our patients underwent complete testing, and that clearly is a marked limitation in the ability to get a statistically significant result. If you noticed on the slide, there was a trend but it didn’t quite achieve statistical significance in the single aortic clamping group. Out of the total group of patients, 45% of patients that we studied had all four examinations and qualified for study of persistent deficits. The 55% that didn’t qualify included a third who could not take the first 1-week test because they were either on a ventilator or they were still in the ICU (intensive carr unit) or were too sick to take the examination, and we usually deferred them to take the 1-month test. Two thirds of the group couldn’t take the 1-month test because they were either at home and they weren’t able to come back for that visit or else they were in a nursing home or a rehab facility. So this is clearly a limitation, and I think it is an opportunity for further study.

In terms of the group that had other risk factors for brain injury, previous stroke, TIA (transient ischemic attack), carotid disease, et cetera. There were a relatively small number of patients in this category, and therefore outcomes did not achieve statistical significance, so I can’t make a comment on that.

I want to thank the Association for the privilege of the floor.

	Acknowledgments

Top Abstract Introduction Patients and Methods Results Comment Discussion Acknowledgments References

 
Supported by a grant from the National Institutes of Neurologic Disease and Stroke (R01NS37242).

	References

Top Abstract Introduction Patients and Methods Results Comment Discussion Acknowledgments References

 

1. Murkin JM, Newman S, Stump DA, Blumenthal JA. Statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery Ann Thorac Surg 1995;59:1289-1295.[Free Full Text]
2. Hammon JW, Stump DA, Butterworth JF, et al. Single crossclamp improves 6-month cognitive outcome in high-risk coronary bypass patients: the effect of reduced aortic manipulation J Thorac Cardiovasc Surg 2006;131:114-121.[Abstract/Free Full Text]
3. Van Dijk D, Keizer AMA, Diephuis JC, et al. Neurocognitive dysfunctions following coronary bypass surgery: a systematic review J Thorac Cardiovasc Surg 2000;120:632-639.[Abstract/Free Full Text]
4. Hammon JW, Stump DA, Butterworth J, Moody DM. Approaches to reduce neurologic complications during cardiac surgery Semin Thorac Cardiovasc Surg 2001;13:184-191.[Medline]
5. Ferguson Jr TB, Hammil BG, Peterson ED, DeLong ER, Grover FL, STS National Database Committee A decade of change-risk profiles and outcomes for isolated coronary artery bypass grafting procedures, 1990–1999A report from the STS National Database Committee and the Duke Clinical Research Institute Society of Thoracic Surgeons. Ann Thorac Surg 2002;73:480-489.[Abstract/Free Full Text]
6. Kohn A. Magnetic resonance imaging registration and quantitation of the brain before and after coronary artery bypass graft surgery Ann Thorac Surg 2002;73(Suppl):S363-S365.[Free Full Text]
7. Leary MC, Saver JL. Annual incidence of first silent stroke in the United States Cerebrovasc Dis 2003;16:280-285.[Medline]
8. Goto T, Baba T, Yoshitake A, et al. Craniocervical and aortic atherosclerosis as neurologic risk factors in coronary surgery Ann Thorac Surg 2000;69:834-840.[Abstract/Free Full Text]
9. Moody DM, Brown WF, Challa VR, et al. Brain microemboli associated with cardiopulmonary bypass: a histologic and magnetic resonance imaging study Ann Thorac Surg 1995;59:1304-1307.[Abstract/Free Full Text]
10. Jones TJ, Stump DA, Deal D, et al. Hypothermia protects the brain from embolization by reducing and redirecting the embolic load Ann Thorac Surg 1999;68:1465(abstract).[Free Full Text]
11. Nathan HJ, Wells GA, Munson JL, Wozny D. Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass: a randomized trial Circulation 2001;104(Suppl 1):85-91.[Abstract/Free Full Text]

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