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Ann Thorac Surg 1996;61:1342-1347
© 1996 The Society of Thoracic Surgeons


Original Articles: Cardiovascular

Defining Neuropsychological Dysfunction After Coronary Artery Bypass Grafting

Elizabeth P. Mahanna, BA, James A. Blumenthal, PhD, William D. White, MPH, Narda D. Croughwell, Crna, Carolina P. Clancy, BA, L. Richard Smith, PhD, Mark F. Newman, MD

Departments of Psychiatry and Behavioral Sciences, Community and Family Medicine, and Anesthesiology, and Duke Heart Center, Duke University Medical Center, Durham, North Carolina

Accepted for publication October 27, 1995.


    Abstract
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Background. Despite the large body of literature documenting the presence of cognitive decline after coronary artery bypass grafting, there is little consensus as to the frequency and extent of cognitive impairment. One potential reason for this lack of agreement is the absence of uniform criteria for assessing cognitive decline.

Methods. Two hundred thirty-two patients underwent cognitive testing the day before operation and were examined before discharge, and at 6 weeks and 6 months after grafting. For comparative purposes, five different sets of criteria were used to define cognitive decline.

Results. There was little agreement between the criteria as to which patients declined at each test period. The incidence of decline ranged from 66% to 15.3% before discharge, 34% to 1.1% at 6 weeks, and 19.4% to 3.4% at 6 months.

Conclusions. A large variation in reported incidence of cognitive decline after coronary artery bypass grafting can be attributed to the different criteria used to define cognitive impairment.


    Introduction
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Improvements in the surgical, anesthetic, and postoperative management of patients undergoing cardiac operation have reduced morbidity and mortality, even in patient populations that are older and sicker than those treated a decade ago [1, 2]. Despite improved myocardial protection and better surgical outcomes, rates of cognitive dysfunction after cardiac operation have not improved. Indeed, the percentage of deaths from neurologic complications has increased, and accounts for up to 20% of deaths [35]. More subtle signs of impaired cognitive performance secondary to operation may be especially prevalent, and in some reports may exceed 70% [6, 7]. However, there is no consensus as to the magnitude of the problem.

For editorial comment, see page 1295

Table 1Go summarizes studies that have examined the incidence of cognitive decline after cardiac operation. Considerable variability exists between studies in reported rates of decline. This variability may result from a variety of factors, including differences in surgical technique and type of anesthesia, instruments used to measure cognitive function, timing of cognitive testing, and patient characteristics such as age, education, and severity of illness. In addition, differences in how cognitive deficits are defined affect the reported incidence of surgically related decline. The purpose of this investigation was (1) to examine the incidence of cognitive decline after cardiac operation by comparing those criteria typically used to define decline, (2) to consider the relative strengths and limitations of each method, and (3) to discuss recommendations for future research.


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Table 1. . Studies With Prevalence Rates of Cognitive Decline After Coronary Artery Bypass Grafting
 

    Material and Methods
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Subjects
After institutional review board approval and written informed consent, 232 consecutive patients undergoing elective coronary artery bypass grafting (CABG) participated in the study. The demographic and clinical characteristics of the sample are presented in Table 2Go. Patients who could not read, had a major psychiatric illness, had suffered a stroke, or were involved in a competing research protocol (eg, protocols comparing different anesthetic agents) were excluded.


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Table 2. . Baseline Characteristics Associated With Coronary Artery Bypass Grafting (n = 232)
 
Procedures
All patients received standardized anesthetic and bypass management, which has been described elsewhere [29]. Briefly, patients were premedicated orally with diazepam (0.1 mg/kg) and methadone (0.1 mg/kg) 90 minutes before induction of anesthesia. Anesthesia was induced with midazolam hydrochloride, 50 to 100 µg/kg, and fentanyl citrate, 5 to 10 µg • kg-1 • min-1, followed by continuous infusions of midazolam, 0.5 to 1.0 µg • kg-1 • min-1, and fentanyl, 0.05 to 0.1 µg • kg-1 • min-1. Vercuronium bromide was given as needed to maintain complete neuromuscular blockade.

Patients underwent neuropsychological testing the day before operation (baseline), the day before discharge from the hospital (mean, 6.2 ± 2.3 days; range, 3 to 21 days), 6 weeks after operation, and 6 months after operation. The neuropsychological test battery was administered by trained psychometricians. Cognitive functioning was assessed by the following instruments:

  1. The short story section of the Randt memory test [30] requires subjects to remember the details of a short story immediately after it has been read to them (immediate recall) as well as 30 minutes later (delayed recall). Scoring consists of either gist or verbatim recall for both recall intervals. For the purposes of this report, both scoring systems were considered separately.
  2. Digit symbol subtest from the Wechsler adult intelligence scale-revised (WAIS-R [31]) requires subjects to reproduce in 90 seconds as many coded symbols as possible according to a coding scheme for pairing digits with symbols.
  3. Digit span subtest from the WAIS-R [31] requires subjects to repeat a series of digits that have been presented orally to them both forward and in reverse order. Independent measures of forward and backward recall are obtained.
  4. Trail making test, part B [32], from the Halstead-Reitan neuropsychological test battery requires subjects to connect, as quickly as possible, a series of numbers and letters in alternating sequence (ie, 1-A-2-B, etc).
  5. Benton revised visual retention test [33] requires subjects to draw from memory a series of geometric shapes after a 10-second exposure.

Definitions of Decline
To determine the presence and extent of cognitive change, we compared five different sets of criteria:

  1. Percent change. To calculate percent change in cognitive performance after operation, difference scores were calculated at each testing period and then converted to percent-of-baseline (pre-CABG) scores for each measure. Percent changes on individual measures were averaged to obtain an overall ``percent change'' score. Unlike the subsequent criteria, overall percent change is a continuous, rather than a categorical, measure and represents the mean change score of the nine measures.
  2. Standard deviation (SD). Decline of more than 1 SD from baseline test score on at least 20% of the measures (ie, decline of 1 SD or more on two of nine measures).
  3. 20% change. Decline in test scores by at least 20% from baseline on at least 20% of measures.
  4. Impairment index. Decline of at least one impairment index rating (IR), not adjusted for age. The unadjusted IR is a rating from 0 (none) to 5 (severe) based on T scores of all nine measures. T scores were calculated from the baseline sample mean and SD, then converted to IRs ranging from 0 to 5 (see Table 3Go). At each test period, a mean IR was calculated from the nine IR scores, and then compared to the mean baseline IR.
  5. Impairment index, adjusted for age. The adjusted IR is a rating from 0 (none) to 5 (severe) based on age-adjusted scaled scores where age-adjusted normative data were available.


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Table 3. . Impairment Index Ratings
 

    Results
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Percent change neuropsychologic test scores before discharge, at 6 weeks, and at 6 months are presented in Figure 1Go. The analysis of mean percent change revealed that, before discharge, there was no change in overall mean performance compared to baseline. Scores improved significantly at 6-week (p < 0.0001) and 6-month follow-up (p < 0.0001).



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Fig 1. . Mean percent change (± standard error) in cognitive test scores for the sample at discharge (n = 206), 6-week (n = 94), and 6-month (n = 91) testing.

 
A comparison of cognitive change measured by the different categorical criteria is presented in Figure 2Go. The 20% drop criteria consistently identified the largest proportion of patients with cognitive deficits. At predischarge testing, 66% of patients exhibited cognitive deficit using this criterion; at 6-week follow-up, 34% of patients continued to show impairment; and at 6-month follow-up, the percentage of impaired patients was 19.4%.



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Fig 2. . Comparison of criteria for determining cognitive decline in the sample for each testing period. The four criteria include 20% decline on at least 20% of measures, 1 standard deviation (S.D.) decline on 20% or more of the measures, 1 impairment index rating (IR) (not adjusted for age) decline or greater, and 1 impairment index rating (age-adjusted) decline or greater. The 20% decline on 20% of measures consistently yielded the greatest percent decline at discharge, 6-week, and 6-month follow-up periods.

 
The 1 SD criteria identified a smaller number of patients with significant decline than the 20% drop criteria. Thirty-five percent of patients at predischarge testing had significant cognitive decline according to the 1 SD criteria, 13.8% showed a deficit at 6-week follow-up, and 4.4% of patients evidenced significant cognitive decline at 6-month testing.

The two IR criteria consistently yielded the most conservative estimates of cognitive deficit after operation. At predischarge testing, only 15.3% of patients evidenced deficits according to the IR-unadjusted method; the age-adjusted IR method yielded a decline of 16.3%. At 6-week testing, the percentage of impaired patients dropped to 7.9% for the unadjusted IR and dropped to only 1.1% for the adjusted IR. At 6-month testing, the unadjusted IR identified 7.9% of patients as showing cognitive deficit; the adjusted IR identified 3.4% of patients with significant cognitive decline, a slight increase from the 6-week follow-up.

There was little agreement among the four categoric measures of cognitive impairment at each testing interval. Only 2.8% of the sample was rated as impaired by all four criteria at predischarge testing; there was 31.5% agreement by all four criteria as to which patients did not decline. At 6 weeks, there was no (0%) agreement by all four criteria as to which patients declined, whereas the agreement between criteria as to which patients did not decline was 60%. At 6-month testing, there continued to be no (0%) agreement between the criteria as to which patients declined; the agreement as to which patients did not decline was 79.3%.

Because a number of studies of cognitive functioning after cardiac operation have used the 1 SD criterion as a standard to measure cognitive decline, we performed an additional analysis to address one potential limitation of this method-whether any patients scored too low at baseline to be able to decline 1 SD at subsequent test times. This analysis revealed that 34.6% of the sample obtained baseline scores that were so low that they could not score at least 1 SD lower on at least one test at discharge, and 18.5% could not fall 1 SD on at least two tests. Furthermore, 14.6% (n = 30) of the sample could not fall 1 SD on two or more tests and had been rated as ``nondeclined'' according to the 1 SD criteria; however, more than half (n = 17) of those patients were rated as ``declined'' by the 20% criteria.


    Comment
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Recently there has been a great interest in the effects of CABG on cognitive function. Numerous studies have documented cognitive decline after CABG (Table 1Go). Two general approaches are typically used: (1) using continuous data to analyze mean change scores for the entire group by comparing mean differences over relatively fixed follow-up intervals (eg, comparing scores at baseline, discharge, 6 weeks, and 6 months); and (2) using categorized data to examine patterns of individual decline using a specific definition of cognitive decline over these same follow-up intervals. A mean change analysis has the advantage of taking into account improvement as well as decline in a sample, as well as allowing consideration of the amount of improvement or decline over time. Because a mean change analysis does not use specific cutoffs to define impairment, it may be considered less arbitrary than methods using preestablished criteria (eg, 20% decline). However, simply considering mean change scores for a sample can obscure individual declines when they are offset by the improvements of others in the sample.

In the present study, the mean change method actually revealed a slight overall effect of improvement at discharge and a steady improvement at 6 weeks and 6 months. This improvement can be attributed to practice and selective attrition. Patients undergo serial assessments and benefit from repeated practice as versions of the same tests are administered at each test period. Patients become more familiar with the tests and their performance is enhanced. Also, group scores at follow-up intervals tend to be elevated because patients who are less impaired are more likely to return for subsequent testing.

Categoric criteria (eg, 20% decline; 1 SD decline; 1 IR) defined cognitive deficits in a significant subset of patients at each testing interval. This pattern is even more striking given the beneficial effects of practice for the majority of the sample.

The use of impairment criteria for decline permits greater sensitivity in identifying individuals who exhibit a decline in their cognitive abilities, as a subset of patients exhibiting deficits will not be obscured by a subset of patients exhibiting improvement. However, different criteria identify different individuals, and there is no single ``gold standard'' for defining cognitive decline. Thus, any single criterion may be considered arbitrary. One advantage of impairment criteria is that categoric ratings of individual cognitive decline can show changes in cognitive functioning that are clinically significant. Researchers have used impairment ratings to predict job performance, employment status, and everyday functioning after chronic illnesses [3438]. Impairment ratings also have the advantage of permitting comparisons to normal populations. However, one disadvantage of impairment ratings is that ratings may be far removed computationally from the actual raw scores; also, the 0 to 5 scale may be arbitrary. In the present sample, the unadjusted and age-adjusted impairment ratings proved to be the most conservative measures of cognitive decline at all test periods, with estimates of decline ranging from 15.3% at discharge to only 1.1% at 6 weeks.

Other categoric ratings are more sensitive to subtle changes in patient performance. In our sample, the 20% drop in scores on 20% of tests method consistently identified the greatest proportion of patients with cognitive decline. This sensitivity may be attributable to its ability to show decline in patients who scored too low at baseline to evidence further impairment in other rating systems at subsequent test times. However, this sensitivity also may be problematic. For example, a minor change in a low score may appear to constitute significant decline for some patients (eg, a single point decline would constitute impairment of 20% for a patient with a baseline score of 5).

The criterion of 1 SD decline to define cognitive impairment is the most frequently used index to define cognitive decline [7,8,10,11,1416,21,23-28]. This method yields a fixed, standard amount of decline for all patients and is referenced to the unique sample by the calculation of sample mean and SD. In the present study, the 1 SD decline criterion provided an estimate of cognitive decline that was a middle ground between the higher (20% drop) and lower (IRs) estimates of cognitive decline. However, the 1 SD decline definition of cognitive decline has major disadvantages. Because it is limited to the sample, cross-study comparisons are difficult. Moreover, the 1 SD drop method cannot show cognitive decline if a patient's baseline score is too low. In our sample, more than one-third (34.6%) of patients scored below the sample SD at baseline on at least one test, and close to one-fifth (18.5%) of the sample scored below the sample SD on two tests or more. Therefore, it is possible that when cognitive decline was defined as 1 SD decline on two tests, up to one-third of the sample may have been misclassified.

It also is important to note that there was significant attrition of our sample at 6-week and 6-month follow-up testing sessions. At 6 weeks, 94 patients (40.5%) returned for follow-up testing; at 6 months, 91 patients (39.2%) returned. Therefore, the present data are not necessarily an accurate estimate of cognitive decline after CABG; rather, the data are presented for illustrative purposes to compare different methodologies. Previously, we reported that patients who drop out of the study after the baseline and predischarge assessments had significantly greater cognitive impairment at baseline than patients who completed 6-week and 6-month follow-ups [39]. Completers also were more likely to be younger, better educated, male, white, and married. Thus, the reported incidence of cognitive decline at 6 weeks and 6 months after CABG may underestimate the true level of impairment because the more impaired patients were not available for follow-up.

Selection of impairment criteria partly depends on the purpose of the study. Studies that aim to determine the presence and extent of cognitive decline after cardiac operation, particularly if a surgical or anesthetic intervention is involved, could benefit from criteria sensitive to subtle declines, especially as subtle declines may be a marker for later, more serious cognitive impairment [40]. The 20% drop criteria appears to be the most sensitive method to identify impaired patients; unlike the 1 SD drop criteria, it can identify impaired patients with low baseline scores. Also, because the 20% drop criteria is not referenced to a unique sample mean and SD, it has the advantage of being generalizable to other studies and populations.

Further research on cognitive outcome after CABG would benefit from developing standard criteria to assess cognitive change. Because there was little agreement between the four criteria as to which patients evidenced cognitive decline after operation, the generalizability between studies that use different criteria is low. At a recent consensus conference [41], researchers suggested that a core neuropsychological battery and more standardized methodologic approaches would facilitate comparisons between investigative teams. Future research also should focus on relating cognitive decline after cardiac operation to activities of daily living at work and at home. For this purpose, criteria such as IRs that identify clinically meaningful deficits may be better able to relate impairment to everyday behaviors. Clinical ratings of deficits by psychologists or psychiatrists also can identify those patients whose cognitive decline may affect their everyday behaviors.


    Acknowledgments
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
This work was supported by National Institutes of Health grants HL49572, AG12058, AG11268, and AG09663.


    Footnotes
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
Address reprint requests to Dr Blumenthal, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 3119, Durham, NC 27710.


    References
 Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 

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Ann. Thorac. Surg.Home page
R. Motallebzadeh, J. M. Bland, H. S. Markus, J. C. Kaski, and M. Jahangiri
Neurocognitive Function and Cerebral Emboli: Randomized Study of On-Pump Versus Off-Pump Coronary Artery Bypass Surgery
Ann. Thorac. Surg., February 1, 2007; 83(2): 475 - 482.
[Abstract] [Full Text] [PDF]


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PerfusionHome page
P. D Raymond, M. Radel, M. J Ray, A. D Hinton-Bayre, and N. A Marsh
Investigation of factors relating to neuropsychological change following cardiac surgery
Perfusion, January 1, 2007; 22(1): 27 - 33.
[Abstract] [PDF]


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ICVTSHome page
A. Royse and C. Royse
A standardised intraoperative ultrasound examination of the aorta and proximal coronary arteries
Interactive CardioVascular and Thoracic Surgery, December 1, 2006; 5(6): 701 - 704.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
C. S. Ernest, B. M. Murphy, M. U.C. Worcester, R. O. Higgins, P. C. Elliott, A. J. Goble, M. R. Le Grande, N. Genardini, and J. Tatoulis
Cognitive function in candidates for coronary artery bypass graft surgery.
Ann. Thorac. Surg., September 1, 2006; 82(3): 812 - 818.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
O. A. Selnes, L. Pham, S. Zeger, and G. M. McKhann
Defining Cognitive Change After CABG: Decline Versus Normal Variability
Ann. Thorac. Surg., August 1, 2006; 82(2): 388 - 390.
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Anesth. Analg.Home page
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]


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Ann. Thorac. Surg.Home page
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]


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Eur. J. Cardiothorac. Surg.Home page
P. D. Raymond, A. D. Hinton-Bayre, M. Radel, M. J. Ray, and N. A. Marsh
Assessment of statistical change criteria used to define significant change in neuropsychological test performance following cardiac surgery
Eur. J. Cardiothorac. Surg., January 1, 2006; 29(1): 82 - 88.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
C. Lund, K. Sundet, B. Tennoe, P. K. Hol, K. A. Rein, E. Fosse, and D. Russell
Cerebral Ischemic Injury and Cognitive Impairment After Off-Pump and On-Pump Coronary Artery Bypass Grafting Surgery
Ann. Thorac. Surg., December 1, 2005; 80(6): 2126 - 2131.
[Abstract] [Full Text] [PDF]


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NeurologyHome page
G. M. McKhann, M. A. Grega, L. M. Borowicz Jr, M. M. Bailey, S.J.E. Barry, S. L. Zeger, W. A. Baumgartner, and O. A. Selnes
Is there cognitive decline 1 year after CABG?: Comparison with surgical and nonsurgical controls
Neurology, October 11, 2005; 65(7): 991 - 999.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
M. S. Lewis, P. T. Maruff, and B. S. Silbert
Examination of the Use of Cognitive Domains in Postoperative Cognitive Dysfunction After Coronary Artery Bypass Graft Surgery
Ann. Thorac. Surg., September 1, 2005; 80(3): 910 - 916.
[Abstract] [Full Text] [PDF]


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PerfusionHome page
A. Khosravi, C. A Skrabal, B. Westphal, G. Kundt, B. Greim, E. Kunesch, A. Liebold, and G. Steinhoff
Evaluation of coated oxygenators in cardiopulmonary bypass systems and their impact on neurocognitive function
Perfusion, September 1, 2005; 20(5): 249 - 254.
[Abstract] [PDF]


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J. Neurol. Neurosurg. PsychiatryHome page
A C Kneebone, M A Luszcz, R A Baker, and J L Knight
A syndromal analysis of neuropsychological outcome following coronary artery bypass graft surgery
J. Neurol. Neurosurg. Psychiatry, August 1, 2005; 76(8): 1121 - 1127.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
C. Lund, R. B. Nes, T. P. Ugelstad, P. Due-Tonnessen, R. Andersen, P. K. Hol, R. Brucher, and D. Russell
Cerebral emboli during left heart catheterization may cause acute brain injury
Eur. Heart J., July 1, 2005; 26(13): 1269 - 1275.
[Abstract] [Full Text] [PDF]


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ChestHome page
N. Stroobant, G. Van Nooten, Y. Van Belleghem, and G. Vingerhoets
Relation Between Neurocognitive Impairment, Embolic Load, and Cerebrovascular Reactivity Following On- and Off-Pump Coronary Artery Bypass Grafting
Chest, June 1, 2005; 127(6): 1967 - 1976.
[Abstract] [Full Text] [PDF]


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ICVTSHome page
Y. Carrascal, E. Casquero, J. Gualis, S. Di Stefano, S. Florez, E. Fulquet, J. R. Echevarria, and L. Fiz
Cognitive decline after cardiac surgery: proposal for easy measurement with a new test
Interactive CardioVascular and Thoracic Surgery, June 1, 2005; 4(3): 216 - 221.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
S. J.E. Barry, S. L. Zeger, O. A. Selnes, M. A. Grega, L. M. Borowicz Jr, and G. M. McKhann
Quantitative Methods for Tracking Cognitive Change 3 Years After Coronary Artery Bypass Surgery
Ann. Thorac. Surg., April 1, 2005; 79(4): 1104 - 1109.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
E. Iriz, F. Kolbakir, H. Akar, B. Adam, and H. T. Keceligil
Comparison of Hydroxyethyl Starch and Ringer Lactate as a Prime Solution Regarding S-100{beta} Protein Levels and Informative Cognitive Tests in Cerebral Injury
Ann. Thorac. Surg., February 1, 2005; 79(2): 666 - 671.
[Abstract]