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 Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Dijk, D. Articles by Hijman, R. Search for Related Content PubMed PubMed Citation Articles by van Dijk, D. Articles by Hijman, R.

J Thorac Cardiovasc Surg 2000;120:632-639
© 2000 The American Association for Thoracic Surgery

Surgery for Acquired Cardiovascular Disease

Neurocognitive dysfunction after coronary artery bypass surgery: A systematic review

From the Departments of Anesthesiology^a and Psychiatry,^b Utrecht University Hospital, Utrecht, The Netherlands.

Address for reprints: Diederik van Dijk, MD, Utrecht University Hospital, Department of Anesthesiology, HpN E03-511, PO Box 85500, 3508 GA Utrecht, The Netherlands (E-mail: d.vandijk{at}anest.azu.nl).

	Abstract

Top Abstract Introduction Methods Results Discussion Conclusions References

 
Objective: Substantial, albeit scattered, evidence suggests that coronary artery bypass grafting may impair cognitive function. As methods and definitions differ greatly across studies, the reported incidence of cognitive decline after coronary bypass surgery varies widely as well. The aim of the present study was to systematically review those studies on cognitive decline that are relatively comparable and meet with certain quality criteria.
Methods: Four electronic databases and the references of several abstract books and earlier reviews were used to identify relevant literature. Stringent criteria, based in part on the 1994 consensus meeting on assessment of neurobehavioral outcomes after cardiac surgery, were used to assess the studies that were found. In total, 256 different titles were found, of which 23 met with the formulated selection criteria.
Results: Twelve cohort studies and eleven intervention studies were evaluated. A pooled analysis of six highly comparable studies yielded a proportion of 22.5% (95% confidence interval, 18.7%-26.4%) of patients with a cognitive deficit (a decrease of at least 1 standard deviation in at least two of nine or ten tests) 2 months after the operation.
Conclusions: Neurocognitive dysfunction is a frequently occurring complication of coronary artery bypass grafting. The etiologic contribution of cardiopulmonary bypass to this complication will remain unclear until a randomized trial that directly compares off-pump and on-pump bypass surgery is carried out.

	Introduction

Top Abstract Introduction Methods Results Discussion Conclusions References

 
Coronary artery bypass grafting (CABG) with the use of cardiopulmonary bypass (CPB) is associated with significant cerebral morbidity. ¹ The two main clinical manifestations of brain injury after CABG are stroke and cognitive decline. ¹ The incidence of postoperative stroke is consistently reported to be around 3% ^1,2 and as high as 9% in patients older than 75 years. ^3,4 However, the reported incidence of cognitive decline varies widely. ⁵ This variability is partly caused by methodologic problems: a multitude of definitions of cognitive decline are used, and a large number of neuropsychologic tests exist to assess the various cognitive domains. ⁶ Moreover, the interval between operation and administration of the neuropsychologic tests may range from a few days to several years. Some literature reviews on cognitive deficits after CPB have been published, ^7-10 but the methodologic variability of the studies hampers comparison of the results.

At a consensus meeting in 1994, several guidelines for the assessment of neuropsychologic deficits after CPB were established. ¹¹ It was recommended that the neurologic and neuropsychologic state be assessed before the operation to provide accurate baseline information. A second important recommendation was that the analysis should be based on the individual change in performance from baseline to a particular time after the operation. In general, practice effects cause the overall group performance to improve after the operation. Accordingly, when the overall postoperative mean is compared with the preoperative mean, the decline of some individuals is overshadowed by the improvement of others. Also, it was agreed that a late assessment (ideally after 3 months) should be included in the study design, because the patients' performances are unstable in the immediate postoperative period.

Although these consensus guidelines were developed for the design of new research protocols, we found some of them also suitable to interpret studies carried out in the past. This systematic review is restricted to studies on cognitive decline 1 to 12 months after CABG, which were considered methodologically homogeneous according to well-defined and strict criteria. Both the primary selection of studies and the assessment and comparison of the studies that were included were largely based on recommendations of the 1994 consensus. ¹¹ As a result of the technical improvements of CPB and the alterations in anesthetic management, studies published before 1980 were considered less relevant and therefore were excluded.

	Methods

Top Abstract Introduction Methods Results Discussion Conclusions References

 
Literature search
For the literature search, four electronic databases (MEDLINE, PsychLit, PubMed, and Current Contents) and references of four earlier published (abstract) books and three reviews were used. The precise search strategy is described inTable I. To assess the quality of the search strategy, we sampled ten studies that we already had on file and considered relevant. The search strategy was able to identify these articles. The total number of different titles found was 256(Table I).

• Inclusion criteria:
  
• Primary research on cognitive decline after CABG, including a preoperative neuropsychologic assessment to provide baseline information
  
• Postoperative neuropsychologic assessment between 1 and 12 months after the operation
  
• Data analysis based on the individual change in performance from baseline to a time after the operation
  

• Exclusion criteria:
  
• Studies published before 1980
  
• Studies including open chamber or valvular procedures
  
• Studies with unclear timing of test administration
  
• Articles describing the same or an overlapping patient sample as other articles already included in the review
  

These selection criteria were applied on the 256 titles found. Thirty-four articles could be excluded on the basis of the title only and 111 articles were excluded on the basis of the abstract. For the remaining 111 titles, the complete article was studied. The majority of these publications were written in English. Many articles were excluded because data of patients undergoing CABG were mixed with data of patients having valve replacement, because data analysis was based on comparison of mean group performance before and after the operation, or because only an early postoperative neuropsychologic assessment (ie, less than 1 month) was performed. Seven studies were excluded ^14-20 because the same patient series had (partly) been used in other studies already included in the review and their inclusion would have overemphasized the results of these series. Finally, one article published in Japanese was rejected because a translation could not be obtained. Only 23 articles matched all the selection criteria. ^5,21-42

Literature processing
The 23 articles meeting the selection criteria were processed independently by a psychologist and a clinician using a three-page standard form. This form was filled out to systematically assess the research question, study design, neuropsychologic tests used, statistics, main conclusions, and other items. The forms were the basis forTables II andIII in the "Results" section.

Analysis
Studies were classified as (1) cohort studies, aiming to determine the incidence of cognitive decline at a certain moment after the operation and/or to identify determinants of cognitive decline, or (2) intervention (controlled) studies, investigating the cerebral protective effect of intraoperative interventions.

To determine whether a pooled analysis could be carried out, we assessed the comparability of the studies entered into the review in terms of precise timing of neuropsychologic testing, comparability of tests, and definition of decline.

	Results

Top Abstract Introduction Methods Results Discussion Conclusions References

 
Cohort studies
The twelve cohort studies meeting the selection criteria are presented inTable II. Some of these studies exclusively aimed to determine the incidence of neuropsychologic decline, whereas others were designed to identify determinants of cognitive decline. The studies inTable II are ordered by year of publication. The mean age of the patients studied increased over time, but no clear time trend could be observed in the incidences of cognitive deficits, which varied from 4% to 47%.

None of the studies designed as a correlation study ^{21,25,26,28,31} was able to identify determinants of cognitive decline in the primary analysis. However, in a multivariate analysis, Tardiff and associates ²⁶ found a significant association between short-term memory dysfunction after CABG and a variant form of the apolipoprotein E gene, especially in patients with lower educational levels. This gene encodes the APOE protein, which is responsible for repair of neuronal injury and probably involved in the development of Alzheimer disease.

Intervention studies
The eleven intervention studies included are shown inTable III. Ten of them were randomized trials. In two studies, the initial data analysis demonstrated that the intervention studied led to a statistically significantly (P < .05) decreased risk of cognitive decline. Hammon and colleagues ⁴² compared the results in patients operated on in 1991 and 1992 with results in patients operated on in the next 2 years. In the second time period, the surgical team had adopted the use of epiaortic scanning and had increased the use of the single crossclamp technique and left ventricular venting. This combined strategy reduced the incidence of cognitive decline by 11% (P = .01). The other study with a significant result in the initial analysis showed a beneficial effect of the use of an arterial line filter. ³⁵

Many intervention studies had insufficient statistical power to detect clinically meaningful differences. In some of these studies, post hoc use of another definition of cognitive decline led to significant results. One example is the remacemide trial by Arrowsmith and coworkers. ³³ Individual cognitive decline was less frequent in the treated group, but the study lacked power to reach statistical significance. Redefining cognitive decline as "overall postoperative change" made the favorable effect of remacemide statistically significant.

Pulsatile blood flow during CPB did not improve neurocognitive outcome in 316 patients, ³⁶ but in the same series, alpha-stat blood gas management reduced the incidence of cognitive deficits. This reduction was significant in patients with a bypass time of more than 90 minutes. The protective effect of alpha-stat blood gas management was also found by Patel and associates. ³⁷ The observed difference became statistically significant when a more stringent definition of neuropsychologic deficit (decline on three tests instead of two tests) was used.

The three studies on the influence of perfusion temperature ^39-41 failed to demonstrate a clear advantage of hypothermia compared with normothermia, but the sample sizes of the studies were relatively small, and in the study of Heyer and colleagues ⁴¹ only 26% of the study patients were available for follow-up.

Neuropsychology
The selected studies included neuropsychologic tests as the measure of cognitive decline. Of the 23 selected studies, six included the core battery as recommended by the Statement of Consensus. ¹¹ In addition, four studies used tests similar to the recommended core battery (seeTables II andIII). Accordingly, ten studies were at least partially comparable and met with widely accepted quality criteria.

Four study groups ^5,22,30,37 used several definitions of cognitive decline in their samples. The definition used most frequently (in nine studies) was a postoperative deterioration of at least 1 standard deviation (of the population's performance at baseline) compared with preoperative testing in at least two tests. In one study the same definition was used with a minimum of three tests showing deterioration, whereas one other study took deterioration in one test as criterion. Comparability in terms of definition of cognitive decline was thus limited to nine studies.

Pooled analysis
Four cohort studies ^23-25,28 and two intervention studies ^33,35 were comparable not only in definition of decline and use of the core battery or comparable tests, but also in timing of test administration. These six studies in total included 505 patients, of whom 448 completed 2 months of follow-up(Table IV). We combined the results of these studies in a weighted average (the sum of the proportions of patients with cognitive decline per study times number of patients per study, divided by the total number of patients). For the two intervention studies, the weighted mean of the two treatment groups was used. On average, 22.5% of the CABG patients had a decline of at least 1 standard deviation in at least two of a total of nine or ten tests 2 months after their operation (P < .0001; 95% confidence interval, 18.7%-26.4%).

	Discussion

Top Abstract Introduction Methods Results Discussion Conclusions References

The reported incidences of cognitive deficits varied widely. At least in part, this can be explained by the differences in timing of test administration and definitions of cognitive deficit. A high loss to follow-up in 3 studies ^5,24,41 may also have influenced the incidences found, as loss to follow-up is seldom random. ⁶ Most of the included studies were comparable in terms of neuropsychologic tests used, which is probably encouraged by the Statement of Consensus that was held in 1994. ¹¹

Within the six studies used for the pooled analysis, there was still a considerable variation in the reported incidence of cognitive decline (10%-38% 2 months after the operation). It is not possible to conclude from these studies that the incidence of cognitive deficits has decreased in the past 10 years. Improved outcome as a result of better anesthesiologic and perfusion management may be offset by the increasing age of the patients, which in itself is associated with an increased risk for cerebral complications. ^36,42 With the six selected studies, we calculated an average incidence of cognitive deficits of 22.5% 2 months after CABG. This figure must be interpreted with caution because, even within these six studies, methodologic differences were present. For example, the cutoff value of 1 standard deviation, used to define a deficit, varied per study, because the baseline performances of the six patient series are inevitably not the same. A formal meta-analysis, which is typically performed with a series of methodologically comparable randomized trials, includes the use of more advanced weighing factors, testing of homogeneity of the effect estimates of the different studies, and a sensitivity analysis. However, the methodology of meta-analysis of uncontrolled observational studies is subject to debate, ⁴³ and its use in this review would have unjustly suggested a high level of objectiveness and precision.

The clinical meaning of a decline of 1 standard deviation in two tests is relative, because the figure calculated, 22.5%, does not indicate the percentage of patients who are significantly disabled after CABG. Several authors emphasize that, in most patients, the deficit does not matter to the patient in functional terms. Apparently, many activities of daily life do not require the level of performance called for during neuropsychologic testing. However, a small proportion of patients with intellectual dysfunction or memory deficits become sufficiently disabled to prevent return to employment. ^1,22

The discrepancy between decline in test performance and functional decline is also expressed by the methodologic difficulties of defining a cognitive deficit. Mahanna and colleagues ⁵ demonstrated the enormous influence of the definition of cognitive deficit that is chosen by applying five different definitions on the same patient sample. Depending on the definition used, the incidence of cognitive deficit ranged from 1.1% to 34% at 6 weeks and from 3.4% to 19.4% at 6 months postoperatively.

Most authors defined deficit as a certain deterioration in one or more tests, which may seem accurate. However, some tests comprise more than one test variable, and from most studies it was not clear whether test deficit meant deterioration in one or all of the variables of one test. This obviously creates a multitude of possible outcomes and is therefore a factor complicating the interpretation of the incidence data. A deterioration of 1 standard deviation in postoperative functioning compared with preoperative functioning was the most frequently used cutoff value. This is arbitrary and does not necessarily reveal real cognitive change, since it does not take into account the reliability of the change scores. Practice effects were almost always mentioned but not included in analyses, which may have resulted in an underestimation of incidence figures. There is emerging recognition of the importance of defining real change in test-retest scores as opposed to artifactual change resulting from low test reliability and susceptibility to practice effects. Recent research is increasingly focused on the use of reliable change indices. These indices define the range in which an individual score is likely to fluctuate because of the imprecision of the measure, providing statistically based cutoff scores for cognitive change on each measure. ^44,45 For example, a 90% reliable change interval is calculated on the basis of the correlation and the standard error of the difference between baseline and follow-up scores of control subjects. When the difference between an individual patient's postoperative and preoperative scores falls outside this interval, he or she is considered to have a statistically significant change in performance on this particular neuropsychologic measure. ⁴⁴

The single-case analysis technique, recommended in the consensus statements, ^11,46 uses the patient as his or her own control and defines a cognitive deficit as a 20% decrease in at least 20% of the tests. This method also has some drawbacks. In the first place, reducing the continuous test scores to a dichotomous outcome measure (presence of a 20% decrease or not) is a "costly" way of data handling that reduces statistical power and may have made several randomized studies fail to reach statistically significant results. The 20% decrease rule is as arbitrary as the 1 standard deviation decrease rule. The problem may be overcome by refraining from "dichotomizing" data and just calculating how much the patient's performance deviates from the expected (baseline or control group) performance. Second, due to floor effects it may be difficult to demonstrate a deficit in patients with a low preoperative test performance. In the third place, as demonstrated by Browne and colleagues, ³⁰ "regression toward the mean" may strongly influence single-case definitions of cognitive deterioration. High baseline performers may be wrongly classified as impaired and low baseline performers may not show a deficit although deterioration had actually occurred. This problem can be overcome by using group mean analysis, which is free from the influence of regression to the mean (in contrast to analysis by single-case definitions). As discussed before, comparison of mean group performance before and after surgery does have disadvantages, especially if large practice effects are present. However, if a suitable control group is available (randomized trial), comparison of group means allows for the control of both practice effects and regression to the mean.

	Conclusions

Top Abstract Introduction Methods Results Discussion Conclusions References

 
A pooled analysis of six highly comparable studies yielded a proportion of 22.5% of patients with a cognitive deficit 2 months after CABG. Although this percentage is partly determined by the definition of cognitive deficit that was used, it demonstrates that cognitive dysfunction is a frequently occurring complication of CABG. The etiologic contribution of CPB to this complication will remain unclear until a randomized trial that directly compares off-pump CABG with on-pump CABG is carried out. To improve comparability of future studies, we advocate that researchers use the guidelines of the 1994 consensus meeting. However, the recommended single-case analysis technique has some drawbacks and may be replaced by other analysis techniques, especially when a control group is included in the study design.

	Acknowledgments

 
We thank Professor D. E. Grobbee, Professor C. J. Kalkman, Professor R. S. Kahn, and Doctor E. Buskens for revising the manuscript.

	References

Top Abstract Introduction Methods Results Discussion Conclusions References

 

1. Roach GW, Kanchuger M, Mangano CM, Newman M, Nussmeier N, Wolman R, et al. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med 1996;335:1857-63.[Abstract/Free Full Text]
   
2. Newman MF, Wolman R, Kanchuger M, Marschall K, Mora-Mangano C, Roach G, et al. Multicenter preoperative stroke risk index for patients undergoing coronary artery bypass graft surgery. Circulation 1996;94(Suppl):II-74-80.
   
3. Mills SA. Risk factors for cerebral injury and cardiac surgery. Ann Thorac Surg 1995;59:1296-9.[Abstract/Free Full Text]
   
4. Tuman KJ, McCarthy RJ, Najafi H, Ivankovich AD. Differential effects of advanced age on neurologic and cardiac risks of coronary artery operations. J Thorac Cardiovasc Surg 1992;104:1510-7.[Abstract]
   
5. Mahanna EP, Blumenthal JA, White WD, Croughwell ND, Clancy CP, Smith LR, et al. Defining neuropsychological dysfunction after coronary artery bypass grafting. Ann Thorac Surg 1996;61:1342-7.[Abstract/Free Full Text]
   
6. Blumenthal JA, Mahanna EP, Madden DJ, White WD, Croughwell ND, Newman MF. Methodological issues in the assessment of neuropsychologic function after cardiac surgery. Ann Thorac Surg 1995;59:1345-50.[Abstract/Free Full Text]
   
7. Benedict RH. Cognitive function after open-heart surgery: Are postoperative neuropsychological deficits caused by cardiopulmonary bypass? Neuropsychol Rev 1994;4:223-55.[Medline]
   
8. Robin ED, McCauley RF, Notkin H. Long-term cognitive abnormalities associated with cardiopulmonary bypass (CPB) and the Babel effect. Chest 1994;106:278-81.[Abstract/Free Full Text]
   
9. Gill R, Murkin JM. Neuropsychologic dysfunction after cardiac surgery: What is the problem? J Cardiothorac Vasc Anesth 1996;10:91-8.[Medline]
   
10. Borowicz LM, Goldsborough MA, Selnes OA, McKhann GM. Neuropsychologic change after cardiac surgery: a critical review. J Cardiothorac Vasc Anesth 1996;10:105-11.[Medline]
    
11. Murkin JM, Newman SP, Stump DA, Blumenthal JA. Statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery. Ann Thorac Surg 1995;59:1289-95.[Free Full Text]
    
12. Smith PL, Taylor KM, editors. Cardiac surgery and the brain. Sevenoaks, Great Britain: Hodder and Stoughton Publishers; 1993.
    
13. Taylor KM. Brain damage during cardiopulmonary bypass. Ann Thorac Surg 1998;65:S20-6.
    
14. Venn GE, Patel RL, Chambers DJ. Cardiopulmonary bypass: perioperative cerebral blood flow and postoperative cognitive deficit. Ann Thorac Surg 1995;59:1331-5.[Abstract/Free Full Text]
    
15. Patel RL, Turtle MR, Chambers DJ, Newman S, Venn GE. Hyperperfusion and cerebral dysfunction: effect of differing acid-base management during cardiopulmonary bypass. Eur J Cardiothorac Surg 1993;7:457-63.[Abstract]
    
16. Toner I, Taylor KM, Lockwood G, Newman S, Smith PL. EEG changes during cardiopulmonary bypass surgery and postoperative neuropsychological deficit: the effect of bubble and membrane oxygenators. Eur J Cardiothorac Surg 1997;11:312-9.[Abstract]
    
17. McKhann GM, Borowicz LM, Goldsborough MA, Enger C, Selnes OA. Depression and cognitive decline after coronary artery bypass grafting. Lancet 1997;349:1282-4.[Medline]
    
18. Smith PL, Treasure T, Newman SP, Joseph P, Ell PJ, Schneidau A, et al. Cerebral consequences of cardiopulmonary bypass. Lancet 1986;1:823-5.[Medline]
    
19. Selnes OA, Goldsborough MA, Borowicz LM, Enger C, Quaskey SA, McKhann, GM. Determinants of cognitive change after coronary artery bypass surgery: a multifactorial problem. Ann Thorac Surg 1999;67:1669-76.[Abstract/Free Full Text]
    
20. Toner I, Taylor KM, Newman S, Smith PL. Cerebral functional changes following cardiac surgery: neuropsychological and EEG assessment. Eur J Cardiothorac Surg 1998;13:13-20.[Abstract/Free Full Text]
    
21. Ellis RJ, Wisniewski A, Potts R, Calhoun C, Loucks P, Wells MR Reduction of flow rate and arterial pressure at moderate hypothermia does not result in cerebral dysfunction. J Thorac Cardiovasc Surg 1980;79:173-80.[Medline]
    
22. Shaw PJ, Bates D, Cartlidge NE, French JM, Heaviside D, Julian DG, et al. Long-term intellectual dysfunction following coronary artery bypass graft surgery: a six month follow-up study. Q J Med 1987;62:259-68.[Abstract/Free Full Text]
    
23. Treasure T, Smith PL, Newman S, Schneidau A, Joseph P, Ell P, et al. Impairment of cerebral function following cardiac and other major surgery. Eur J Cardiothorac Surg 1989;3:216-21.[Abstract]
    
24. Harrison MJ, Schneidau A, Ho R, Smith PL, Newman S, Treasure T. Cerebrovascular disease and functional outcome after coronary artery bypass surgery. Stroke 1989;20:235-7.[Abstract/Free Full Text]
    
25. Toner I, Taylor KM, Newman S, Smith PL. Cerebral functional deficit in cardiac surgical patients investigated with p300 and neuropsychological tests. Electroencephalogr Clin Neurophysiol Suppl 1996;46:243-51.[Medline]
    
26. Tardiff BE, Newman MF, Saunders AM, Strittmatter WJ, Blumenthal JA, White WD, et al. Preliminary report of a genetic basis for cognitive decline after cardiac operations. The Neurologic Outcome Research Group of the Duke Heart Center. Ann Thorac Surg 1997;64:715-20.[Abstract/Free Full Text]
    
27. McKhann GM, Goldsborough MA, Borowicz LM Jr, Selnes OA, Mellits ED, Enger C, et al. Cognitive outcome after coronary artery bypass: a one-year prospective study. Ann Thorac Surg 1997;63:510-5.[Abstract/Free Full Text]
    
28. Braekken SK, Reinvang I, Russell D, Brucher R, Svennevig JL. Association between intraoperative cerebral microembolic signals and postoperative neuropsychological deficit: comparison between patients with cardiac valve replacement and patients with coronary artery bypass grafting. J Neurol Neurosurg Psychiatry 1998;65:573-6.[Abstract/Free Full Text]
    
29. Vanninen R, Aikia M, Kononen M, Partanen K, Tulla H, Hartikainen P, et al. Subclinical cerebral complications after coronary artery bypass grafting: prospective analysis with magnetic resonance imaging, quantitative electroencephalography, and neuropsychological assessment. Arch Neurol 1998;55:618-27.[Abstract/Free Full Text]
    
30. Browne SM, Halligan PW, Wade DT, Taggart DP. Cognitive performance after cardiac operation: implications of regression toward the mean. J Thorac Cardiovasc Surg 1999;117:481-5.[Abstract/Free Full Text]
    
31. Rasmussen LS, Christiansen M, Hansen PB, Moller JT. Do blood levels of neuron-specific enolase and S-100 protein reflect cognitive dysfunction after coronary artery bypass? Acta Anesthesiol Scand 1999;43:495-500.
    
32. Fish KJ, Helms KN, Sarnquist FH, van Steennis C, Linet OI, Hilberman M, et al. A prospective, randomized study of the effects of prostacyclin on neuropsychologic dysfunction after coronary artery operation. J Thorac Cardiovasc Surg 1987;93:609-15.[Abstract]
    
33. Arrowsmith JE, Harrison MJ, Newman SP, Stygall J, Timberlake N, Pugsley WB. Neuroprotection of the brain during cardiopulmonary bypass: a randomized trial of remacemide during coronary artery bypass in 171 patients. Stroke 1998;29:2357-62.[Abstract/Free Full Text]
    
34. Sellman M, Holm L, Ivert T, Semb BK. A randomized study of neuropsychological function in patients undergoing coronary bypass surgery. Thorac Cardiovasc Surg 1993;41:349-54.[Medline]
    
35. Pugsley W, Klinger L, Paschalis C, Treasure T, Harrison M, Newman S. The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning. Stroke 1994;25:1393-9.[Abstract]
    
36. Murkin JM, Martzke JS, Buchan AM, Bentley C, Wong CJ. A randomized study of the influence of perfusion technique and pH management strategy in 316 patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg 1995;110:349-62.[Abstract/Free Full Text]
    
37. Patel RL, Turtle MR, Chambers DJ, James DN, Newman S, Venn GE. Alpha-stat acid-base regulation during cardiopulmonary bypass improves neuropsychologic outcome in patients undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 1996;111:1267-79.[Abstract/Free Full Text]
    
38. Gold JP, Charlson ME, Williams RP, Szatrowski TP, Peterson JC, Pirraglia PA, et al. Improvement of outcomes after coronary artery bypass: a randomized trial comparing intraoperative high versus low mean arterial pressure. J Thorac Cardiovasc Surg 1995;110:1302-11.[Abstract/Free Full Text]
    
39. Mora CT, Henson MB, Weintraub WS, Murkin JM, Martin TD, Craver JM, et al. The effect of temperature management during cardiopulmonary bypass on neurologic and neuropsychologic outcomes in patients undergoing coronary revascularization. J Thorac Cardiovasc Surg 1996;112:514-22.[Abstract/Free Full Text]
    
40. Regragui I, Birdi I, Izzat MB, Black AM, Lopatatzidis A, Day C, et al. The effects of cardiopulmonary bypass temperature on neuropsychologic outcome after coronary artery operations: a prospective randomized trial. J Thorac Cardiovasc Surg 1996;112:1036-45.[Abstract/Free Full Text]
    
41. Heyer EJ, Adams DC, Delphin E, McMahon DJ, Steneck SD, Oz MC, et al. Cerebral dysfunction after coronary artery bypass grafting done with mild or moderate hypothermia. J Thorac Cardiovasc Surg 1997;114:270-7.[Abstract/Free Full Text]
    
42. Hammon JW Jr, Stump DA, Kon ND, Cordell AR, Hudspeth AS, Oaks TE, et al. Risk factors and solutions for the development of neurobehavioral changes after coronary artery bypass grafting. Ann Thorac Surg 1997;63:1613-8.[Abstract/Free Full Text]
    
43. Egger M, Schneider M, Davey Smith G. Spurious precision? Meta-analysis of observational studies. BMJ 1998;316:140-4.[Free Full Text]
    
44. Kneebone AC, Andrew MJ, Baker RA, Knight JL. Neuropsychologic changes after coronary artery bypass grafting: use of reliable change indices. Ann Thorac Surg 1998;65:1320-5.[Abstract/Free Full Text]
    
45. Bruggemans EF, Van de Vijver FJ, Huysmans HA. Assessment of cognitive deterioration in individual patients following cardiac surgery: correcting for measurement error and practice effects. J Clin Exp Neuropsychol 1997;19:543-59.[Medline]
    
46. Murkin JM, Stump DA, Blumenthal JA, McKhann G. Defining dysfunction: group means versus incidence analysis—a statement of consensus. Ann Thorac Surg 1997;64:904-5.
    

This article has been cited by other articles:

				P. S. Teirstein Percutaneous Revascularization Is the Preferred Strategy for Patients With Significant Left Main Coronary Stenosis Circulation, February 24, 2009; 119(7): 1021 - 1033. [Full Text] [PDF]

				J. van den Goor, B. Saxby, J. Tijssen, K. Wesnes, B. de Mol, and R Nieuwland Improvement of cognitive test performance in patients undergoing primary CABG and other CPB-assisted cardiac procedures Perfusion, September 1, 2008; 23(5): 267 - 273. [Abstract] [PDF]

				K. E. Glas, M. Swaminathan, S. T. Reeves, J. S. Shanewise, D. Rubenson, P. K. Smith, J. P. Mathew, S. K. Shernan, and Council for Intraoperative Echocardiography of the Guidelines for the Performance of a Comprehensive Intraoperative Epiaortic Ultrasonographic Examination: Recommendations of the American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists; Endorsed by the Society of Thoracic Surgeons Anesth. Analg., May 1, 2008; 106(5): 1376 - 1384. [Full Text] [PDF]

				S. C. Knipp, N. Matatko, H. Wilhelm, M. Schlamann, M. Thielmann, C. Losch, H. C. Diener, and H. Jakob Cognitive Outcomes Three Years After Coronary Artery Bypass Surgery: Relation to Diffusion-Weighted Magnetic Resonance Imaging Ann. Thorac. Surg., March 1, 2008; 85(3): 872 - 879. [Abstract] [Full Text] [PDF]

				D. van Dijk, K. G.M. Moons, H. M. Nathoe, E. H.L. van Aarnhem, C. Borst, A. M.A. Keizer, C. J. Kalkman, R. Hijman, and Octopus Study Group Cognitive Outcomes Five Years After Not Undergoing Coronary Artery Bypass Graft Surgery Ann. Thorac. Surg., January 1, 2008; 85(1): 60 - 64. [Abstract] [Full Text] [PDF]

				Z. I. Khalpey, R. B. Ganim, and J. D. Rawn Postoperative Care of Cardiac Surgery Patients Card. Surg. Adult, January 1, 2008; 3(2008): 465 - 486. [Full Text]

				S. J. Durham and J. P. Gold Late Complications of Cardiac Surgery Card. Surg. Adult, January 1, 2008; 3(2008): 535 - 548. [Full Text]

				F. Hernandez Jr, J. R. Brown, D. S. Likosky, R. A. Clough, A. L. Hess, R. M. Roth, C. S. Ross, C. M. Whited, G. T. O'Connor, and J. D. Klemperer Neurocognitive Outcomes of Off-Pump Versus On-Pump Coronary Artery Bypass: A Prospective Randomized Controlled Trial Ann. Thorac. Surg., December 1, 2007; 84(6): 1897 - 1903. [Abstract] [Full Text] [PDF]

				J. W. Hammon, D. A. Stump, J. F. Butterworth, D. M. Moody, K. Rorie, D. D. Deal, E. H. Kincaid, T. E. Oaks, and N. D. Kon Coronary Artery Bypass Grafting With Single Cross-Clamp Results in Fewer Persistent Neuropsychological Deficits Than Multiple Clamp or Off-Pump Coronary Artery Bypass Grafting Ann. Thorac. Surg., October 1, 2007; 84(4): 1174 - 1179. [Abstract] [Full Text] [PDF]

				T. Kunihara, D. Tscholl, F. Langer, G. Heinz, F. Sata, and H.-J. Schafers Cognitive brain function after hypothermic circulatory arrest assessed by cognitive P300 evoked potentials Eur. J. Cardiothorac. Surg., September 1, 2007; 32(3): 507 - 513. [Abstract] [Full Text] [PDF]

				M. Appelblad and K. G. Engstrom Fat content in pericardial suction blood and the efficacy of spontaneous density separation and surface adsorption in a prototype system for fat reduction J. Thorac. Cardiovasc. Surg., August 1, 2007; 134(2): 366 - 372. [Abstract] [Full Text] [PDF]

				R. L.C. Vogels, P. Scheltens, J. M. Schroeder-Tanka, and H. C. Weinstein Cognitive impairment in heart failure: A systematic review of the literature Eur J Heart Fail, May 1, 2007; 9(5): 440 - 449. [Abstract] [Full Text] [PDF]

				Y. Kadoi Pharmacological Neuroprotection During Cardiac Surgery Asian Cardiovasc Thorac Ann, April 1, 2007; 15(2): 167 - 177. [Abstract] [Full Text] [PDF]

				D. van Dijk, M. Spoor, R. Hijman, H. M. Nathoe, C. Borst, E. W. L. Jansen, D. E. Grobbee, P. P. T. de Jaegere, C. J. Kalkman, and for the Octopus Study Group Cognitive and Cardiac Outcomes 5 Years After Off-Pump vs On-Pump Coronary Artery Bypass Graft Surgery JAMA, February 21, 2007; 297(7): 701 - 708. [Abstract] [Full Text] [PDF]

				L. G. Wolf, Y. Abu-Omar, B. P. Choudhary, D. Pigott, and D. P. Taggart Gaseous and solid cerebral microembolization during proximal aortic anastomoses in off-pump coronary surgery: The effect of an aortic side-biting clamp and two clampless devices J. Thorac. Cardiovasc. Surg., February 1, 2007; 133(2): 485 - 493. [Abstract] [Full Text] [PDF]

				Y. Abu-Omar, S. Cader, L. G. Wolf, D. Pigott, P. M. Matthews, and D. P. Taggart Short-term changes in cerebral activity in on-pump and off-pump cardiac surgery defined by functional magnetic resonance imaging and their relationship to microembolization. J. Thorac. Cardiovasc. Surg., November 1, 2006; 132(5): 1119 - 1125. [Abstract] [Full Text] [PDF]

				A. Sedrakyan, A. W. Wu, A. Parashar, E. B. Bass, and T. Treasure Off-Pump Surgery Is Associated With Reduced Occurrence of Stroke and Other Morbidity as Compared With Traditional Coronary Artery Bypass Grafting: A Meta-Analysis of Systematically Reviewed Trials * Supplemental Appendix I Stroke, November 1, 2006; 37(11): 2759 - 2769. [Full Text] [PDF]

				G. Dupuis, E. Kennedy, R. Lindquist, F. B. Barton, M. L. Terrin, B. J. Hoogwerf, S. M. Czajkowski, J. A. Herd, and for the Post CABG Biobehavioral Study Investigator Coronary artery bypass graft surgery and cognitive performance. Am. J. Crit. Care., September 1, 2006; 15(5): 471 - 478. [Abstract] [Full Text] [PDF]

				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]

				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. [Full Text] [PDF]

				J. Vedin, H. Nyman, A. Ericsson, S. Hylander, and J. Vaage Cognitive function after on or off pump coronary artery bypass grafting. Eur. J. Cardiothorac. Surg., August 1, 2006; 30(2): 305 - 310. [Abstract] [Full Text] [PDF]

				M. Boodhwani, F. D. Rubens, D. Wozny, R. Rodriguez, A. Alsefaou, P. J. Hendry, and H. J. Nathan Predictors of Early Neurocognitive Deficits in Low-Risk Patients Undergoing On-Pump Coronary Artery Bypass Surgery Circulation, July 4, 2006; 114(1_suppl): I-461 - I-466. [Abstract] [Full Text] [PDF]

				C. W. Hogue Jr, C. A. Palin, and J. E. Arrowsmith Cardiopulmonary bypass management and neurologic outcomes: an evidence-based appraisal of current practices. Anesth. Analg., July 1, 2006; 103(1): 21 - 37. [Abstract] [Full Text] [PDF]

				B. O. Jensen, P. Hughes, L. S. Rasmussen, P. U. Pedersen, and D. A. Steinbruchel Cognitive Outcomes in Elderly High-Risk Patients After Off-Pump Versus Conventional Coronary Artery Bypass Grafting: A Randomized Trial Circulation, June 20, 2006; 113(24): 2790 - 2795. [Abstract] [Full Text] [PDF]

				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]

				B. Phillips-Bute, J. P. Mathew, J. A. Blumenthal, H. P. Grocott, D. T. Laskowitz, R. H. Jones, D. B. Mark, and M. F. Newman Association of Neurocognitive Function and Quality of Life 1 Year After Coronary Artery Bypass Graft (CABG) Surgery Psychosom Med, May 1, 2006; 68(3): 369 - 375. [Abstract] [Full Text] [PDF]

				H. K. Fong, L. P. Sands, and J. M. Leung The role of postoperative analgesia in delirium and cognitive decline in elderly patients: a systematic review. Anesth. Analg., April 1, 2006; 102(4): 1255 - 1266. [Abstract] [Full Text] [PDF]

				J. A. Hayden, P. Cote, and C. Bombardier Evaluation of the quality of prognosis studies in systematic reviews. Ann Intern Med, March 21, 2006; 144(6): 427 - 437. [Abstract] [Full Text] [PDF]

				D. C Whitaker, J. Stygall, C. Hope-Wynne, R. K Walesby, M. J. Harrison, and S. P Newman A prospective clinical study of cerebral microemboli and neuropsychological outcome comparing vent-line and auto-venting arterial line filters: both filters are equally safe Perfusion, March 1, 2006; 21(2): 83 - 86. [Abstract] [PDF]

				G. M. McKhann, M. A. Grega, L. M. Borowicz Jr, W. A. Baumgartner, and O. A. Selnes Stroke and Encephalopathy After Cardiac Surgery: An Update Stroke, February 1, 2006; 37(2): 562 - 571. [Abstract] [Full Text] [PDF]

				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]

				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]

				R. P. Alston Pumphead--or not! Does avoiding cardiopulmonary bypass for coronary artery bypass surgery result in less brain damage? Br. J. Anaesth., June 1, 2005; 94(6): 699 - 701. [Full Text] [PDF]

				J. C. Diephuis, K. G. M. Moons, A. N. Nierich, M. Bruens, D. van Dijk, and C. J. Kalkman Jugular bulb desaturation during coronary artery surgery: a comparison of off-pump and on-pump procedures Br. J. Anaesth., June 1, 2005; 94(6): 715 - 720. [Abstract] [Full Text] [PDF]

				M. W Hall, R. O Hopkins, J. W Long, S F. Mohammad, and K. A Solen Hypothermia-induced platelet aggregation and cognitive decline in coronary artery bypass surgery: a pilot study Perfusion, May 1, 2005; 20(3): 157 - 167. [Abstract] [PDF]

				P. Wahrborg, J. E. Booth, T. Clayton, F. Nugara, J. Pepper, W. S. Weintraub, U. Sigwart, R. H. Stables, and for the SoS Neuropsychology Substudy Investigators Neuropsychological Outcome After Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting: Results From the Stent or Surgery (SoS) Trial Circulation, November 30, 2004; 110(22): 3411 - 3417. [Abstract] [Full Text] [PDF]

				S. Bar-Yosef, M. Anders, G. B. Mackensen, L. K. Ti, J. P. Mathew, B. Phillips-Bute, R. H. Messier, H. P. Grocott, and the Neurological Outcome Research Group and CARE I Aortic Atheroma Burden and Cognitive Dysfunction After Coronary Artery Bypass Graft Surgery Ann. Thorac. Surg., November 1, 2004; 78(5): 1556 - 1562. [Abstract] [Full Text] [PDF]

				H. Kaukuntla, A. Walker, D. Harrington, T. Jones, and R. S. Bonser Differential brain and body temperature during cardiopulmonary bypass--a randomised clinical study Eur. J. Cardiothorac. Surg., September 1, 2004; 26(3): 571 - 579. [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]

				G. J.M.G. van der Heijden, H. M. Nathoe, E. W.L. Jansen, and D. E. Grobbee Meta-analysis on the effect of off-pump coronary bypass surgery Eur. J. Cardiothorac. Surg., July 1, 2004; 26(1): 81 - 84. [Abstract] [Full Text] [PDF]

				Y. Abu-Omar, L. Balacumaraswami, D. W. Pigott, P. M. Matthews, and D. P. Taggart Solid and gaseous cerebral microembolization during off-pump, on-pump, and open cardiac surgery procedures J. Thorac. Cardiovasc. Surg., June 1, 2004; 127(6): 1759 - 1765. [Abstract] [Full Text] [PDF]

				D van Dijk, K G M Moons, A M A Keizer, E W L Jansen, R Hijman, J C Diephuis, C Borst, P P T de Jaegere, D E Grobbee, and C J Kalkman Association between early and three month cognitive outcome after off-pump and on-pump coronary bypass surgery Heart, April 1, 2004; 90(4): 431 - 434. [Abstract] [Full Text] [PDF]

				C Casey and D. P Faxon Multi-vessel coronary disease and percutaneous coronary intervention Heart, March 1, 2004; 90(3): 341 - 346. [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]

				M. Schoenburg, B. Kraus, A. Muehling, U. Taborski, H. Hofmann, G. Erhardt, S. Hein, M. Roth, P. R. Vogt, G. F. Karliczek, et al. The dynamic air bubble trap reduces cerebral microembolism during cardiopulmonary bypass J. Thorac. Cardiovasc. Surg., November 1, 2003; 126(5): 1455 - 1460. [Abstract] [Full Text] [PDF]

				J. E. Scarborough, W. White, F. E. Derilus, J. P. Mathew, M. F. Newman, and K. P. Landolfo Combined use of off-pump techniques and a sutureless proximal aortic anastomotic device reduces cerebral microemboli generation during coronary artery bypass grafting J. Thorac. Cardiovasc. Surg., November 1, 2003; 126(5): 1561 - 1567. [Abstract] [Full Text] [PDF]

				R. J. Petrucci Finding our way from the heart to the head J. Thorac. Cardiovasc. Surg., October 1, 2003; 126(4): 944 - 946. [Full Text] [PDF]

				C. W. Hogue Jr, R. Lillie, T. Hershey, S. Birge, A. M. Nassief, B. Thomas, and K. E. Freedland Gender influence on cognitive function after cardiac operation Ann. Thorac. Surg., October 1, 2003; 76(4): 1119 - 1125. [Abstract] [Full Text] [PDF]

				D P Taggart, S M Browne, D T Wade, and P W Halligan Neuroprotection during cardiac surgery: a randomised trial of a platelet activating factor antagonist Heart, August 1, 2003; 89(8): 897 - 900. [Abstract] [Full Text] [PDF]

				P. L. Stavinoha, D. E. Fixler, and L. Mahony Cardiopulmonary Bypass to Repair an Atrial Septal Defect Does Not Affect Cognitive Function in Children Circulation, June 3, 2003; 107(21): 2722 - 2725. [Abstract] [Full Text] [PDF]

				A. M.A. Keizer, R. Hijman, D. van Dijk, C. J. Kalkman, and R. S. Kahn Cognitive self-assessment one year after on-pump and off-pump coronary artery bypass grafting Ann. Thorac. Surg., March 1, 2003; 75(3): 835 - 838. [Abstract] [Full Text] [PDF]

				E. H. Blackstone Neurologic injury from cardiac surgery--an important but enormously complex phenomenon J. Thorac. Cardiovasc. Surg., March 1, 2003; 125(90030): S28 - 30. [Full Text] [PDF]

				D. J. Cook, T. A. Orszulak, K. J. Zehr, N. A. Nussmeier, J. J. Livesay, J. W. Hammon, and X. Chen Effectiveness of the Cobra aortic catheter for dual-temperature management during adult cardiac surgery J. Thorac. Cardiovasc. Surg., February 1, 2003; 125(2): 378 - 384. [Abstract] [Full Text] [PDF]

				D. Taggart About impaired minds and closed hearts BMJ, November 30, 2002; 325(7375): 1255 - 1256. [Full Text] [PDF]

				D. Van Dijk, E. W. L. Jansen, R. Hijman, A. P. Nierich, J. C. Diephuis, K. G. M. Moons, J. R. Lahpor, C. Borst, A. M. A. Keizer, H. M. Nathoe, et al. Cognitive Outcome After Off-Pump and On-Pump Coronary Artery Bypass Graft Surgery: A Randomized Trial JAMA, March 20, 2002; 287(11): 1405 - 1412. [Abstract] [Full Text] [PDF]

				D C Whitaker, J Stygall, and S P Newman Neuroprotection during cardiac surgery: strategies to reduce cognitive decline Perfusion, March 1, 2002; 17(2_suppl): 69 - 75. [Abstract] [PDF]

				P. Menasche The systemic factor: the comparative roles of cardiopulmonary bypass and off-pump surgery in the genesis of patient injury during and following cardiac surgery Ann. Thorac. Surg., December 1, 2001; 72(6): S2260 - 2265. [Abstract] [Full Text] [PDF]

				C. Schmitz and E. H. Blackstone International Council of Emboli Management (ICEM) Study Group results: risk adjusted outcomes in intraaortic filtration Eur. J. Cardiothorac. Surg., November 1, 2001; 20(5): 986 - 991. [Abstract] [Full Text] [PDF]

				E. H. Blackstone Editorial: Neurologic injury from cardiac surgery--An important but enormously complex phenomenon J. Thorac. Cardiovasc. Surg., October 1, 2000; 120(4): 629 - 631. [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 Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Dijk, D. Articles by Hijman, R. Search for Related Content PubMed PubMed Citation Articles by van Dijk, D. Articles by Hijman, R.