HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): John L. Knight Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Andrew, M. J. Articles by Knight, J. L. Search for Related Content PubMed PubMed Citation Articles by Andrew, M. J. Articles by Knight, J. L.

Ann Thorac Surg 1998;66:1611-1617
© 1998 The Society of Thoracic Surgeons

Neuropsychological dysfunction after minimally invasive direct coronary artery bypass grafting

^a Department of Surgery, Flinders Medical Centre and Flinders University of South Australia, Adelaide, South Australia, Australia
^b Department of Health Psychology, Flinders Medical Centre and Flinders University of South Australia, Adelaide, South Australia, Australia

Accepted for publication May 9, 1998.

Address reprint requests to Dr Baker, Cardiac Surgical Research Group, Department of Surgery, Flinders Medical Centre, Bedford Park SA 5042, Australia
e-mail: (Rob.Baker{at}flinders.edu.au)

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. We compared postoperative neuropsychological dysfunction after minimally invasive direct coronary artery bypass grafting (MIDCAB) operation with coronary artery bypass graft operations using cardiopulmonary bypass.

Methods. Neuropsychological assessment was performed preoperatively and before discharge on 7 patients undergoing MIDCAB procedures, 9 patients undergoing single-graft cardiopulmonary bypass operation, and 27 patients undergoing multiple-graft cardiopulmonary bypass operation. From a matched control group of 40 normal subjects reliable change indices were derived for each measure and used to determine the incidence of postoperative decline.

Results. There was little difference between the MIDCAB and single-graft cardiopulmonary bypass groups on the incidence of neuropsychologic decline. However, the multiple-graft cardiopulmonary bypass group had a significantly higher incidence of decline than the MIDCAB and single-graft cardiopulmonary bypass groups on specific neuropsychologic measures, coupled with a significantly greater number of postoperative deteriorations per patient.

Conclusions. The elimination of cardiopulmonary bypass does not prevent neuropsychological dysfunction after cardiac operation as patients undergoing MIDCAB and single-graft cardiopulmonary bypass experience similar deteriorations in performance. However, the deterioration is markedly worsened when the number of surgical grafts is increased.

	Introduction

Top Abstract Introduction Material and methods Results Comment References

 
The use of cardiopulmonary bypass to enable a wide variety of cardiac surgical procedures has increased dramatically since its inception in the 1950s. During this period, progressive technological advancements have resulted in a favorable decline in morbidity and mortality outcomes in a large array of pathologic conditions [1]. However, the risk of neuropsychological injury after cardiopulmonary bypass remains, with a high incidence reported in the immediate postoperative period, which shows significant decline in patients reexamined 6 to 12 months later [2–4].

Although the cause of this cerebral injury is unclear, a number of mechanisms, including intraoperative embolization, cerebral hypoperfusion, and the systemic inflammatory response to cardiopulmonary bypass, are implicated as possible causative factors [5–7]. Although the techniques used to perform cardiopulmonary bypass are continually subjected to modification and improvement, limited advances have been made in terms of improving neuropsychological outcome after bypass operations. Potentially, the best option to reduce the detrimental effects of cardiopulmonary support may be the elimination of the use of extracorporeal circulation altogether.

In this respect, changes to traditional techniques have resulted in promising alternative surgical options to coronary artery bypass grafting (CABG) with cardiopulmonary bypass. In particular, progress in the field of minimally invasive approaches has resulted in the evolution of the minimally invasive direct coronary artery bypass graft (MIDCAB) procedure. This involves the grafting of the left internal mammary artery to the left anterior descending coronary artery under direct vision through a variety of small incisions (eg, small anterior thoracotomy). This approach allows the procedure to be performed without the use of cardiopulmonary bypass and obviates the need for a full median sternotomy. As well as increasing patient comfort and reducing general morbidity resulting from adverse consequences of the cardiopulmonary bypass circuit, an additional potential advantage of the MIDCAB procedure is the possible reduction in adverse cerebral consequences resulting from cardiopulmonary bypass. Although the consensus from the First International Live Teleconference on Less Invasive Coronary Bypass Surgery was that "the damaging effects of cardiopulmonary bypass (particularly on the brain) justify the search for new methods" [8, p 930], no data have yet been provided concerning the neuropsychological sequelae associated with the MIDCAB procedure.

The aim of this study is to compare the incidence of postoperative acquired neuropsychological dysfunction after the MIDCAB procedure with the incidence of decline obtained from patients undergoing traditional single-graft cardiopulmonary bypass (SGC) operation and multiple-graft cardiopulmonary bypass (MGC) operation.

	Material and methods

Top Abstract Introduction Material and methods Results Comment References

 
Patients
The MIDCAB patient sample consisted of 7 patients who underwent operation between December 3, 1996, and July 24, 1997. The CABG patient sample consisted of 9 patients who underwent SGC operation (3 internal mammary artery grafts, 6 vein grafts) between March 12, 1996, and July 17, 1997, and 27 patients who underwent MGC operation (three grafts or more; 15 involving internal mammary grafts) between January 30, 1996, and July 17, 1997. All procedures were performed by a single surgeon. None of the patients had previously undergone cardiac operation or had documented neurologic pathology. All spoke English as their first language.

Control subjects for neuropsychological testing
Forty unpaid volunteers were recruited from bowling clubs, senior citizens groups, and the Flinders Medical Centre Volunteers Service. Volunteers were ineligible for inclusion in the study if they had a past history of cardiac operation, neurologic injury or disease, or did not speak English as their first language. The demographic characteristics and baseline neuropsychologic data for the four groups (MIDCAB, SGC, MGC, and controls) are presented in Table 1.

Neuropsychologic test selection was substantially based on the Statement of Consensus on Assessment of Neurobehavioral Outcomes After Cardiac Surgery [9], which includes measures of learning and memory, attention, and psychomotor speed. The test battery in order of administration was as follows: California Verbal Learning Test (CVLT), Purdue Pegboard (Peg R, Peg L, Peg RL), Controlled Oral Word Association Test (COWAT; initial letter verbal fluency), Trail Making Test (TMT A and TMT B), Wechsler Adult Intelligence Scale-Revised (WAIS-R): Digit Symbol subtest (Dig Symb), Boston Naming Test (BNT), and National Adult Reading Test-Revised (NART-R; administered only at baseline) [10]. Mood state was assessed with the self-report Depression, Anxiety, Stress Scale (DASS) [11]. Subjective pain was estimated with a visual analog scale [12]. All tests were administered and scored in a standardized manner.

The CVLT is able to generate various measures of different aspects of learning and memory. In the present study we elected to analyze four measures composed of learning (Total: sum of the number of words recalled on trials 1 through 5), free recall (Long Free: number of words recalled after a 20-minute delay), cued recall (Long Cued: number of words recalled after a 20-minute delay with category cues provided), and recognition discriminability (Disc: 1-[(false-positives + misses)/44] x 100). To minimize practice effects on the CVLT alternate test forms [13] were administered at preoperative and postoperative examinations. Every second patient or control subject was administered the alternate form first.

On all measures except TMT A, TMT B, DASS, and the pain scale, higher scores equal better performance. On TMT A and TMT B higher scores equal slower performance, and high scores on the DASS and the pain scale equal increasing levels of depression, anxiety, stress, and pain.

Method of defining postoperative neuropsychologic change
The incidence of neuropsychological decline was established using reliable change (RC) indices. This statistical method of defining postoperative neuropsychological change overcomes many of the limitations inherent in other commonly used methods by incorporating measurement error and practice effects in the analysis of change data.

Using the methodology outlined by Jacobson and Truax [14] an RC index was calculated for each neuropsychological measure and the mood measures using the baseline and follow-up data of the control subjects. The following four steps allow calculation of RC intervals:

1. Test–retest reliability coefficient (r_xx).
   
2. Standard error of measurement
   

   (where SD₁ is the standard deviation of the baseline score).
   

3. Standard error of the difference
   

   .
   

4. RC interval (90%) = (SE_diff) x (±1.64) + practice effect.
   

For a detailed methodology, see Kneebone and colleagues [10].

For each test measure, difference scores (postoperative minus preoperative) were calculated for each patient. If this difference score fell outside the corrected RC interval a statistically significant change was considered to have occurred on that measure. The procedure for calculating the RC interval for the mood measures was identical, with the exception of no correction for practice effects.

Data analysis
Statistical analyses were performed using the SPSS statistical software package (SPSS Inc, Chicago, IL), with an value of 0.05 considered statistically significant. Quantitative data were compared with one-way analysis of variance (ANOVA) or Mann-Whitney U tests (depending on normality of variable distribution). Categorical data were analyzed with the ² statistic, with Fisher’s two-tailed exact test used if the expected cell sizes were small.

Group differences were examined on two primary end points; incidence of decline on each neuropsychological measure and number of measures per patient showing a statistically significant decline. These end points were analyzed first with Mann-Whitney U tests to test for overall significance, followed by Kruskall-Wallis tests for differences between individual surgical groups.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
As shown in Table 1, analysis of population demographics and baseline neuropsychological data revealed the four groups (MIDCAB, SGC, MGC, and controls) were well matched on all demographic variables and the majority of neuropsychological measures. At baseline assessment the control subjects performed significantly better than the MIDCAB patients on the Peg L measure, and also better than the SGC group on Peg RL and Dig. Symb, and better than both bypass patient groups on the TMT B measure.

The one significant difference on the mood measures was between both bypass patient groups and the control group on the anxiety subscale of the DASS. However, preoperative levels of depression, anxiety, and stress did not correlate with any of the preoperative neuropsychological scores. Furthermore, the MIDCAB and bypass groups did not differ significantly on the amount of change on depression, anxiety, and stress.

No patient was complaining of any pain at preoperative assessment, nor did the postoperative pain scores differ between the three surgical groups. Postoperatively, no patient had an overt neurologic deficit, confusion, or frank psychosis.

Reliable change indices
The data obtained from control subjects used to calculate the RC indices are summarized in Table 3. All of the measures showed acceptable test–retest reliability with coefficients ranging from 0.51 (Disc) to 0.91 (Dig Symb).

Incidence of neuropsychological impairment
The percentage of MIDCAB, SGC, and MGC patients experiencing a postoperative decline on each of the neuropsychological measures is shown in Table 4. The MIDCAB group had a significantly lower incidence of decline than the SGC group on the Peg R measure. Similarly, the MIDCAB group experienced significantly less decline than the MGC group on the Peg R and Peg RL measures.

The percentage of patients in each group in whom there was a deterioration in from one to five measures is displayed in Fig 1. There was a significant difference in the distributions of patients across the number of measures showing a deterioration. Only 1 MIDCAB patient (14.3%) and 1 SGC patient (11.1%) experienced a decline on 4 or more measures, whereas 12 patients (44.4%) in the MGC group showed a decline on 4 or more measures.

View larger version (66K): [in this window] [in a new window]   Fig 1. Percentage of patients in each surgical group who declined on from 1 to 5 neuropsychological measures. (MCG = multiple-graft cardiopulmonary bypass; MIDCAB = minimally invasive direct coronary artery bypass; SGC = single-graft cardiopulmonary bypass.)

	Comment

Top Abstract Introduction Material and methods Results Comment References

Differences between the MIDCAB and SGC groups were limited to one significant difference in incidence of neuropsychological decline on the Peg R measure. With respect to the remaining neuropsychological measures, the patterns of decline were comparable between the MIDCAB and SGC groups, with a number of measures (Peg L, Peg RL, COWAT, and TMT A) not affected in the immediate postoperative period. There were no differences between the MIDCAB and SGC group in terms of number of measures per patient in which there was a significant decline.

We found that the MGC group displayed a larger degree of neuropsychological impairment than both the MIDCAB and SGC groups on the majority of neuropsychological measures. Furthermore, the patterns of decline experienced by the MGC patients were distinct from the MIDCAB and SGC groups. Whereas a subset of neuropsychological measures were not affected postoperatively in the MIDCAB and SGC groups, at least 2 patients in the MGC group experienced significant deterioration on every neuropsychological measure. Moreover, the MGC group showed a significantly higher number of significant declines per patient than both the MIDCAB and SGC groups.

A number of studies have compared the neuropsychological sequelae of CABG operation with nonbypass surgical procedures, such as vascular or thoracic procedures, in an attempt to isolate the debilitating effects of cardiopulmonary bypass. Newman and colleagues [4] compared postoperative neuropsychological decline in a group of 67 CABG and 24 thoracic surgical patients 8 days and 8 weeks after operation. They reported that 73% of the CABG and 50% of the thoracic surgical group were either moderately or severely impaired at 8 days. However, at 8 weeks’ follow-up, 37% and 48% of the CABG and thoracic surgical patients, respectively, showed either moderate or severe impairment, suggesting that the nonbypass procedures were also associated with sustained neuropsychological impairment. Two studies that used both nonbypass controls and nonsurgical controls [15, 16] reported the performance of the nonbypass surgical group to fall consistently between that of the CABG group and the nonsurgical controls. Neither study reported significant group differences between the bypass and nonbypass surgical groups. Similarly, Malheiros and coworkers [17] compared the neurologic and neuropsychological complications of patients undergoing CABG with and without cardiopulmonary bypass. They reported no significant differences between the groups on neurologic abnormalities or incidence of neuropsychological decline.

In a recent review, Benedict [18] concluded that the majority of the work comparing CABG operations with nonbypass operations has shown that CABG patients typically perform worse at immediate postoperative assessment than nonbypass controls. However, although the research indicates that cardiopulmonary bypass operation may be associated with a higher incidence of postoperative neuropsychological dysfunction, nonbypass patients were not immune to these deficits. This suggests that some of the variance in immediate postoperative acquired neuropsychological dysfunction may be caused by nonspecific aspects of the operation, such as hospitalization, sleep deprivation, and potential adverse effects of anesthesia [19].

In the present study, no advantage in terms of neuropsychologic impairment was demonstrated by the MIDCAB group when compared with the SGC group, supporting the assertion that postsurgical neuropsychologic deficits may not be so intimately related to the cardiopulmonary bypass circuit as suspected. This finding is particularly pertinent for patients who require only a single-graft procedure as they may have the option of choice between the MIDCAB procedure and conventional bypass operation. If the MIDCAB procedure does not result in a lower incidence of neuropsychological decline than traditional bypass operation for single grafts, then other advantages of the procedure will have to be provided before this technique can be regarded as an acceptable alternative.

In contrast to other published literature in this field, we used RC indices to define the degree of neuropsychologic impairment after cardiac operation. We believe the RC method is a superior method for assessing postoperative change in that corrections for test–retest reliability and practice effects are incorporated into the analysis of change data [10]. The majority of the neuropsychologic measures used in this study displayed a susceptibility to practice effects as demonstrated by a mean improvement in control subjects’ scores on retesting. Of particular interest was the negative practice effect displayed by control subjects on the CVLT. However, this negative practice effect was not entirely unexpected as the alternate form of the CVLT was designed specifically to limit practice effects in a normal population [13].

The potential for patient misclassification when not correcting for practice effects and test reliability has been demonstrated previously. Kneebone and associates [10] compared the results obtained with the RC method with the commonly used SD method and reported differences in the incidence rates of neuropsychologic decline produced by the two methods. They concluded that the calculated incidence of neuropsychologic impairment can vary widely if measurement error and practice effects are not taken into account. The RC method provides a technique for defining the incidence of postoperative acquired neuropsychologic dysfunction that is theoretically and statistically sound. Although RC indices have been applied in the analysis of neuropsychologic change after epilepsy surgical procedures [20], experience with this technique in cardiac surgical patients is limited [10].

Because of the developmental status of the MIDCAB procedure the sample size of this study is small. Although the resulting lack of statistical power limits the general conclusions that can be drawn from this study, the findings indicate that MIDCAB patients do show some degree of neuropsychologic impairment after operation. Consideration of neuropsychologic sequelae has formed a vital component of discussion concerning the relative risks and benefits of this new surgical option; however, further data are required to validate the proposal that MIDCAB operation is beneficial in terms of central nervous system outcomes.

	References

Top Abstract Introduction Material and methods Results Comment References

 

1. Pryor D.B., Harrell F.E., Rankin J.S., et al. The changing survival benefits of coronary revascularization over time. Circulation 1987;76(Suppl 5):V-13-V-21.
2. Nevin M., Colchester A.C.F., Adams S., Pepper J.R. Evidence for involvement of hypocapnia and hypoperfusion in aetiology of neurological deficit after cardiopulmonary bypass. Lancet 1987;2:1493-1495.[Medline]
3. Jenkins C.D., Stanton B.-A., Savageau J.A., Denlinger P., Klein M.D. Coronary artery bypass surgery: physical, psychological, social, and economic outcomes six months later. JAMA 1983;250:782-788.[Abstract]
4. Newman S., Smith P., Treasure T., Joseph P., Ell P., Harrison M. Acute neuropsychological consequences of coronary artery bypass surgery. Curr Psychol Res Rev 1987;6:115-124.
5. Gill R., Murkin J.M. Neuropsychologic dysfunction after cardiac surgery: what is the problem?. J Cardiothorac Vasc Anesth 1996;10:91-98.[Medline]
6. Stump D.A., Rogers A.T., Hammon J.W., Newman S.P. Cerebral emboli and cognitive outcome after cardiac surgery. J Cardiothorac Vasc Anesth 1996;10:113-119.[Medline]
7. Smith P.L.C. The systemic inflammatory response to cardiopulmonary bypass and the brain. Perfusion 1996;11:196-199.[Free Full Text]
8. Westaby S., Benetti F.J. Less invasive coronary surgery: consensus from the Oxford meeting. Ann Thorac Surg 1996;62:924-931.[Free Full Text]
9. Murkin J.M., Newman S.P., Stump D.A., Blumenthal J.A. Statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery. Ann Thorac Surg 1995;59:1289-1295.[Free Full Text]
10. Kneebone A.C., Andrew M.J., Baker R.A., Knight J.L. Neuropsychological change following coronary artery surgery: use of reliable change indices. Ann Thorac Surg 1998;65:1320-1325.[Abstract/Free Full Text]
11. Lovibond S.H., Lovibond P.F. Manual for the depression anxiety stress scales. Sydney: Psychology Foundation Monograph, 1995.
12. Price D.D., McGrath P.A., Rafii A., Buckingham B. The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain 1983;17:45-56.[Medline]
13. Delis D.C., McKee R., Massman P.J., Kramer J.H., Kaplan E., Gettman D. Alternate form of the California Verbal Learning Test: development and reliability. Clin Neuropsychol 1991;5:154-162.
14. Jacobson N.S., Truax P. Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. J Consult Clin Psychol 1991;59:12-19.[Medline]
15. Gilberstadt H., Sako Y. Intellectual and personality changes following open-heart surgery. Arch Gen Psychiatry 1967;16:210-214.[Medline]
16. Hammeke T.A., Hastings J.E. Neuropsychologic alterations after cardiac operation. J Thorac Cardiovasc Surg 1988;96:326-331.[Abstract]
17. Malheiros S.M.F., Brucki S.M.D., Gabbai A.A., et al. Neurological outcome in coronary artery surgery with and without cardiopulmonary bypass. Acta Neurol Scand 1995;92:256-260.[Medline]
18. Benedict RHB Cognitive function after open-heart surgery: are postoperative neuropsychological deficits caused by cardiopulmonary bypass?. Neuropsychol Rev 1994;4:223-255.[Medline]
19. Klafta J.M., Zacny J.P., Young C.J. Neurological and psychiatric adverse effects of anaesthetics. Drug Safety 1995;13:281-295.[Medline]
20. Chelune G.J., Naugle R.I., Luders H., Sedlak J., Awad I.A. Individual change after epilepsy surgery: practice effects and base-rate information. Neuropsychology 1993;7:41-52.

This article has been cited by other articles:

				C. S. Ernest, M. U.C. Worcester, J. Tatoulis, P. C. Elliott, B. M. Murphy, R. O. Higgins, M. R. Le Grande, and A. J. Goble Neurocognitive Outcomes in Off-Pump Versus On-Pump Bypass Surgery: A Randomized Controlled Trial Ann. Thorac. Surg., June 1, 2006; 81(6): 2105 - 2114. [Abstract] [Full Text] [PDF]

				R. A. Baker, L. J. Hallsworth, and J. L. Knight Stroke After Coronary Artery Bypass Grafting Ann. Thorac. Surg., November 1, 2005; 80(5): 1746 - 1750. [Abstract] [Full Text] [PDF]

				M. A. Ozatik, S. A. Kucuker, H. Tuluce, A. Sartias, E. sener, S. Karakas, and O. Tasdemir Neurocognitive functions after aortic arch repair with right brachial artery perfusion Ann. Thorac. Surg., August 1, 2004; 78(2): 591 - 595. [Abstract] [Full Text] [PDF]

				D. R. Holmes Jr, B. G. Firth, and D. L. Wood Paradigm shifts in cardiovascular medicine J. Am. Coll. Cardiol., February 18, 2004; 43(4): 507 - 512. [Abstract] [Full Text] [PDF]

				P. M. Ho, D. B. Arciniegas, J. Grigsby, M. McCarthy Jr, G. O. McDonald, T. E. Moritz, A. L. Shroyer, G. K. Sethi, W. G. Henderson, M. J. London, et al. Predictors of cognitive decline following coronary artery bypass graft surgery Ann. Thorac. Surg., February 1, 2004; 77(2): 597 - 603. [Abstract] [Full Text] [PDF]

				P. Demers and R. Cartier Multivessel off-pump coronary artery bypass surgery in the elderly Eur. J. Cardiothorac. Surg., November 1, 2001; 20(5): 908 - 912. [Abstract] [Full Text] [PDF]

				G. Asimakopoulos Systemic inflammation and cardiac surgery: an update Perfusion, September 1, 2001; 16(5): 353 - 360. [Abstract] [PDF]

				S. C. Stamou and P. J. Corso Coronary revascularization without cardiopulmonary bypass in high-risk patients: a route to the future Ann. Thorac. Surg., March 1, 2001; 71(3): 1056 - 1061. [Abstract] [Full Text] [PDF]

				S. Westaby, K. Saatvedt, S. White, T. Katsumata, W. van Oeveren, and P. W. Halligan Is there a relationship between cognitive dysfunction and systemic inflammatory response after cardiopulmonary bypass? Ann. Thorac. Surg., February 1, 2001; 71(2): 667 - 672. [Abstract] [Full Text] [PDF]

				M. J. Mack Pro: beating-heart surgery for coronary revascularization: is it the most important development since the introduction of the heart-lung machine? Ann. Thorac. Surg., November 1, 2000; 70(5): 1774 - 1778. [Full Text] [PDF]

				D. A. Cooley Con: beating-heart surgery for coronary revascularization: is it the most important development since the introduction of the heart-lung machine? Ann. Thorac. Surg., November 1, 2000; 70(5): 1779 - 1781. [Abstract] [Full Text] [PDF]

				P. A. Tunick and I. Kronzon Atheromas of the thoracic aorta: clinical and therapeutic update J. Am. Coll. Cardiol., March 1, 2000; 35(3): 545 - 554. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): John L. Knight Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Andrew, M. J. Articles by Knight, J. L. Search for Related Content PubMed PubMed Citation Articles by Andrew, M. J. Articles by Knight, J. L.