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Ann Thorac Surg 1995;59:1289-1295
© 1995 The Society of Thoracic Surgeons
Department of Anaesthesia, University Hospital, University of Western Ontario, London, Ontario, Canada; Department of Psychiatry, University College London Medical School, London, United Kingdom; Department of Anesthesia, The Bowman Gray School of Medicine of Wake Forest University, Winston Salem, North Carolina; and Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina
Dr Murkin, Department of Anaesthesia, University Hospital, 339 Windermere Rd, London, Ont, Canada N6A 5A5.
At the recent meeting CNS Dysfunction After Cardiac Surgery: Defining the Problem, held December 10 and 11 in Fort Lauderdale, FL, a draft statement outlining proposed criteria for the assessment of central nervous system (CNS) outcomes after cardiac surgery was circulated beforehand to all registrants and invited speakers. The intent of the draft statement was to act as a focus for discussion by the audience of assembled experts from diverse disciplines including psychology, neuropsychology, neurology, neuroradiology, brain ischemia research, anesthesia, cardiovascular surgery, and epidemiology and biostatistics. After a 12-hour lecture program in which issues relevant to neurobehavioral outcome research were presented by a multidisciplinary group of international experts, the last 4 hours of the conference was devoted to an open discussion and critique of the draft Statement of Consensus. These proceedings were audiotaped and transcribed, and a version of the discussion, edited for syntax, follows.
For clarity, the approved Consensus Statement is presented first, followed by a transcription of the point by point discussion of each of the statements appearing in the original draft. Where possible, speakers have been identified and are listed at the end.
Consensus Statement (Approved)
Recommended Core Neuropsychologic Battery
Edited Transcript of Consensus Discussion
John M. Murkin, MD (London, Ont, Canada): The intent of this conference was to assemble researchers currently involved with investigations in the area of neurobehavioral dysfunction after cardiac surgery as well as those who have an interest in the field. We hope to achieve some consensus as to the principles that should be considered in assessing neurobehavioral dysfunction, and to that end, we have circulated a draft of this proposal to all registrants. What we shall do is go through each of the points in the draft consensus statement individually and seek input from the audience. We also are going to propose a neuropsychologic battery that would form a core of recommended tests. If the investigators present agree, these tests would form a subset recommended for any such future neurobehavioral studies in this group.
1. A spectrum of postoperative CNS dysfunction ranging from brain death and stroke to subtle neurologic signs and neuropsychologic impairment occurs in patients after cardiac operations.
Christopher I. Blauth, FRCS (London, England): The first thing that struck me in reading statement 1 was that it implies that CNS dysfunction occurs in all patients after a cardiac surgical procedure. I think it is absolutely essential that we insert a qualifier.
Graham E. Venn, FRCS (London, England): I agree with that.
Stephen A. Mills, MD (High Point, NC): I think encephalopathy is of the utmost importance, as it is seen in so many of the papers that discuss this issue. If we are to have consistency and credibility, we must take notice of this because of the wide variation in definitions.
Vladimir C. Hachinski, MD (London, Ont, Canada): We need to insert something more generic than encephalopathy. We need an inclusion statement to encompass both neurologic and neuropsychologic dysfunction.
David A. Stump, PhD (Winston-Salem, NC): Can we just say ``a spectrum of postoperative CNS deficits both acute and persistent''?
Dr Hachinski: Dr Stump is correct. In neurology and in Harrison's textbook, we define the term as acute brain syndrome to distinguish it from the old term of chronic brain syndrome.
2. A substantial proportion of patients seen for coronary artery bypass grafting have preexisting CNS abnormalities. Their neuropsychologic performance needs to be assessed at a time prior to operation to provide accurate baseline information.
Mr Blauth: Could someone tell me what the ``substantial proportion'' is?
Stanton P. Newman, Dphil (London, England): If taken from the Hammersmith Hospital data, magnetic resonance imaging indicated an 80% preoperative abnormality. Substantial to me is anything greater than 50%.
Dixon M. Moody, MD (Winston-Salem, NC): If you use a figure like 80%, you have got to be including subtle atrophy.
Dr Newman: Mr Smith asked what evidence there is. There is evidence from our study and indeed from other studies on preexisting CNS abnormalities that people are coming in with cerebral vascular disease.
Peter L. C. Smith, FRCS (London, England): What is the CNS abnormality you are trying to define?
Dr Murkin: I think that what is being said is that if one looks just at postoperative dysfunction, there is the potential to include patients who have a preexisting abnormality. At one extreme, these patients have had a stroke preoperatively and have the same stroke postoperatively, but it is not related to the intraoperative interventions.
3. The individual change in performance from baseline to a time after operation is essential to any evaluation of the impact of the operation or any intervention associated with it.
James A. Blumenthal, PhD (Durham, NC): Part of the rationale for statement 3 is to address the issue that these patients may be abnormal preoperatively. Therefore, it is important to examine change in scores from baseline.
4. Because of time constraints in performing a neuropsychologic assessment in the context of a cardiac operation, care must be taken to select appropriate tests. This evaluation should include the following issues:
Mr Smith: Could you define what you mean by ``the domain of the test.''
Dr Newman: The domain of the test is really referring to the cognitive domain-memory, attention and concentration, perception, motor performance, visual fields, and so on.
Jack Spector, PhD (Washington, DC): The problem with data norms is that they give a false sense of security regarding the validity of the conclusions. There are times when the best norm group is the patient's own prior performance. I think that a portion of instruments that we eventually select should be in common use and should have a variety of norms available.
Torkel Åberg, MD (Lund, Sweden): I would like to include a sentence about the specific situation in the early postoperative period that indicates we cannot have tests that require big movements of the body. They would be an influence because of the pain.
Dr Blumenthal: How about including a statement about having an instrument that has established reliability and validity? I believe that we want to discourage selection of instruments that are idiosyncratic and do not have any documentation of their psychometric properties. We want to ensure that the instruments are worthwhile.
Dr Newman: I think we want a core set of tests, but we need to let people be free to vary. If we constrain the investigators to regular clinical tests that have good norms and so on, I think we really are limiting the possibilities for innovative work. That would concern me.
Dr Blumenthal: I think it behooves the investigator to select procedures that are reliable and to provide validity data that establish the utility of the instrument.
Albert J. Dietz, Jr, MD (Kalamazoo, MI): I suggest that the phrase ``because of time constraints and physical limitations'' become ``there are a number of constraints: the physical condition of the patient, the severity of the illness, time constraints, and physical limitations.''
Dr Newman: So ``time constraints and physical limitations of the patients'' is the suggestion. The idea in doing an assessment is getting a balance. One would not choose ten tests all looking at attention and concentration but would want to select particular domains that are slightly different.
5. Because the expression of a neurobehavioral dysfunction is related to (1) the area or structure of the CNS affected, (2) the volume of tissue affected, (3) the etiology of the insult, and (4) other physiologic variables (eg, temperature and hyperglycemia) at the time of insult as well as variability in the types of neurologic and neuropsychologic testing methods employed, postoperative neurobehavioral impairment may be expressed primarily or exclusively within one domain and detected either as abnormal neurologic signs or conversely, principally as cognitive impairment.
Mr Blauth: I have a fundamental concern with this point, and it also relates to how easily one might communicate what it means to clinical surgeons in practice. The implication from all the neuropsychologic speakers seems to be that a poor performance in a neuropsychologic test inevitably means some kind of brain damage or impairment of cognitive ability. I have a real problem with that. We know that individual performance varies enormously not just in terms of what that person is capable of achieving but also other issues like motivation and attitude to the test. Now it may well be that a lot of these issues are covered in some of the validations, the reliability measures you have, but I think a lot of these issues are not immediately clear or understood by other clinicians such as surgeons. My question here is: Do you think that the neurobehavioral dysfunction you are talking about can occur or can be seen without structural brain injury? The implication is that every decrement in neuropsychologic testing automatically means that some component of the brain, some part of the brain, is damaged. I think this is a very fundamental concept, and it is one that I find very difficult to accept.
Dr Murkin: I think this may be related to an area of the CNS, or it may be related to other physiologic variables, metabolic disturbances, and so on.
Dr Stump: This has to do with the balance in the tests. I do not disagree with you that occasionally we get a false-positive reading if someone did poorly on the neuropsychologic test because he or she dropped the pencil or was looking outside, and that is a real concern. The goal is to be able to tease out what the actual domain is-motor or planning. The proper battery should be able to avoid those false-positives. I understand your dilemma on that.
Dr Åberg: Could this not be resolved by stating the variability in types of neurologic and psychologic testing methods employed? I think that is one of the important things here. If there is a negative or a positive change, one of the very first things to consider is whether this is variability in the method or something that really expresses a more fundamental change.
Mr Blauth: I think we should talk about what we actually measure, which is performance, and get away from the term impairment. Impairment implies pathology. The relationship I am questioning is the relationship between test performance and neurobehavioral impairment.
Dr Newman: I suggest that medication, fatigue, pain, and motivation can all affect neuropsychologic performance.
Dr Murkin: I think there are potentially similar confounders in assessing someone's gait if he or she is medicated. These issues, regardless of modality of neurobehavioral testing, are all potential confounds that can influence performance in both the neuropsychologic and neurologic evaluations.
Dr Newman: This list is getting pretty long. Would it be better to not try to enumerate each and every possible confounder and just provide a few examples? Could we say something like: It is important to recognize that neuropsychologic and neurobehavioral performance is influenced by a range of factors: psychological, pharmacologic, and physiologic.
Donna L. Giles, RN (London, Ont, Canada): We might also add environmental to that list.
6. To ensure objectivity and reliability of the testing, it should be performed by the same individual, and tests should not involve any subjective judgments.
David C. Adams, MD (New York, NY): I think it would be appropriate to include something to the effect of standardized training, perhaps ``qualified individual.''
Mr Blauth: I see a conflict here because if the test has to be performed by the same individual, that, to me, implies it is more subjective rather than less subjective. If the examiner finds an abnormal neurologic sign and can demonstrate it to two or three different neurologists, there is no doubt about it. If only one person has to see a change, then that makes it slightly less transparent than it should be.
Mr Smith: I think that what we are looking at is essentially a change in performance in a test. The way a neuropsychologic test is given is dependent to a large extent on the experience of that examiner, and I think we would minimize the differences in the way each examiner carries out the test by doing it like that. I would have the same person do the assessment because I have looked at other people doing assessments. If you are doing a neuropsychologic test battery and watch different neuropsychologists administer it, one will spend 30 minutes familiarizing the patient with the way to do the test and another, 5 minutes. I think that makes a tremendous difference. Do all the neuropsychologists you train have a standardized method of familiarization with the concepts involved?
Dr Stump: The problem with subjectivity in a neurological examination has largely to do with things like my saying that reflex is a 2 and someone else calling it a 3. If you see the patient before and after operation, you should have some recollection of whether you called it a 2 or a 3. We have had the neurologists argue with each other about whether the reflex is a 2 or a 3. That is why we are saying we can get some degree of consistency if the same person does it.
Dr Åberg: I think that in any scientific endeavor, it is very important to try to reduce background noise, and one of the ways to do this is to have the same tester before and after an operation.
Dr Blumenthal: I think we should use the term encourage because not all situations are necessarily going to be optimal. If there is some interobserver or intertester variability within the study design, it makes sense to encourage having the same examiner perform these assessments.
Dr Spector: Examiners should be trained with standards and competence. It is the obligation of the site neuropsychologist to ensure that examiners or testers, nurses, psychometrists, fellows, or whoever are trained to a standard, that examinations are provided, and that there is less cross-examiner variance than there is with subject variance. Everyone who runs a laboratory has this obligation. There is talk about the potential loss of patients because they are not able to be tested late at night when they come in or right before they go to the operating room or because they get discharged on the weekend. My concern is that if we tie ourselves too closely to one examiner having responsibility for that patient through the entire hospital stay, we might lose patients. I think that would be the worst loss at this point. I am ambivalent about encouraging individuals to ensure that the same examiner is involved. Certainly, the examiners need to be trained in an equivalent manner and held to high standards.
Dr Stump: I am not necessarily disagreeing with you. However, we have a 90+% retention rate with our population, and we encourage the bond the examiners develop with the people they test. If every time an individual comes back for testing there is a different examiner, the return rate drops off.
Mr Venn: I have just a quick addendum to that. Should the examiner not be blinded to any treatment limbs of the associated study? I suggest this because when one submits papers to the journals, the perception is that there is a substantial degree of subjectivity in these tests, which I do not think there is. Also, that subjectivity can be influenced by the tester if there are nonblinded treatment limbs. I think we have to protect against that criticism.
7. As performance of neuropsychologic tests can be influenced by mood state and variations in mood state, it is important that mood state assessments be performed concurrently with the neuropsychologic assessment.
Dr Newman: I would like to pick up Mr Blauth's point because I think it is a very important one. Look at item 6 and 7, which are really designed to indicate the variability and factors that might confound some neuropsychologic scores. That is a part of addressing the issue. In other words, the scores could be due to mood variability and how the testing was done, and so they do not necessarily indicate that there is something going on in the brain. It seems to me that we could roll items 6 and 7 into item 5 to indicate the roots of potential variability in neuropsychologic testing without presuming that they necessarily and solely reflect an organic problem.
Dr Åberg: Logically, I think the best thing to do is to have one paragraph describing the psychometric methods as methods, their variability and influences, even if we know there is no structural change, and go on from there.
8. For quantification of neurologic dysfunction, a comprehensive neurologic examination should include, but not be limited to, assessment of primitive reflexes and visual fields in addition to motor power, gait, cranial nerves, and sensation.
Dr Newman: That takes us to neurologic dysfunction. What does ``comprehensive'' mean? Does a ``suitably trained individual'' mean a neurologist?
Dr Hachinski: No, it does not. My statement is not facetious; actually it is based on the development of the Canadian neurologic scale, which is a very simple and reliable neurologic measure. To validate it, we did videotapes of the examination with a standard description and then showed them to a number of individuals including nurses, residents, fellows interested in cerebral vascular disease, neurologists, and neurologists with an interest in stroke. We found there were no significant differences if training time and adequate instructions were provided. Also, there was a trend toward the nurses performing better than any of the physicians because they tended to describe what they observed as opposed to the physicians who were always interpreting signs. On the basis of that experience, I am quite confident that using a standardized examination, nurses, provided they are qualified and have training, could do a reliable neurologic examination, at the very least, a screening examination. If there are more complex issues, get a neurologist involved.
Dr Newman: I am not sure that is the way to limit the neurologic examination. My concern is to have a consensus statement in the short time we have available. We need to suggest something. I am concerned about the term comprehensive neurologic examination.
Dr Hachinski: Comprehensive and concise would be better, or comprehensive, concise, and preferably validated. Because this is an ongoing process, some things have been validated and some have not.
Dr Adams: I can understand the interest in having a quantitative neurologic examination. At Columbia, we have been a little troubled by a quantitative assessment of neurology and the generating of a score, so we have listed neurologic deficits. The trouble with doing that is that you cannot treat it statistically very easily. I think perhaps implying there might be some efforts toward validating a quantitative scale would be useful for this statement.
Dr Hachinski: It is clear that just as we need to have a core set of neuropsychologic tests, we need to have a core set of neurologic assessments.
9. As the incidence of postoperative neurobehavioral dysfunction is highest in the immediate postoperative period and then declines, care must be taken to perform at least one assessment when performance has stabilized. This would be at least 6 weeks postoperatively.
Mr Venn: I think we accept that the 1-week testing is clouded by noise. We arbitrarily used 6 or 8 weeks somewhat interchangeably as the first stable assessment postoperatively. Now I am not sure we have the data to know when the stabilization has occurred. Is it as soon as 6 to 8 weeks? Should it perhaps be 3 months? I do not know. I would be very keen to take advice, but I think we are still seeing fluctuation at 6 to 8 weeks. Maybe 3 months is better.
Dr Stump: When we talk about transient ischemic attacks preoperatively, we mean something that lasts 24 hours. I think we can look at stroke and head trauma data to suggest, depending on age, that there is not much change from 3 to 6 months. However, let me explain a real problem with this issue. The reason everybody picks 1 month to 6 weeks is that that is when the patient returns to see the surgeon. If you decide to bring your patient back at a time other than the surgical follow-up, you may never see him or her again.
Mr Venn: I entirely agree. That is exactly the problem I have. In earlier studies in which I was involved, my surgical follow-up visit was at 2 months, so we chose a 2-month follow-up for our study to coincide. In the last study with which I was concerned, my own practice was 6 weeks, and we had a slightly higher incidence score. That study design mistake, not making the initial follow-up periods the same, was my own error. It did not allow comparison with our previous work. I suspect the farther out the follow-up visit, the better.
Mr Smith: Surgeons like to see 6-month data. Why not add the statement, ``data should be available at 6 months to 1 year.'' I know there are changes at 6 to 8 weeks, but surgeons are not going to look at 6 to 8 weeks; they want to see 6 months to 1 year.
Mr Blauth: The reason for this is that we normally tell our patients that it will take them 2 to 3 months to achieve a full physical recovery from the operation. It is unreasonable to expect them to achieve mental recovery ahead of that time.
10. Given that new deficits can occur in the postoperative period, ideally a 5 to 6-day postoperative baseline of function would be obtained and then a more extensive evaluation at 4 to 10 weeks to better separate perioperative events from later nonsurgical CNS insults.
Dr Stump: There is another critical issue here, and I think it addresses the point we have about a 10% recruitment. If the patient leaves the hospital with no deficit that can be attributed to anything happening during the operation, when he or she comes back at 6 weeks, there could be a new deficit. These are the deficits that are easy to document because when the patient left, there was nothing wrong. Conversely, there is another group of patients who are discharged with a 20% decline, and when we retest them, they have a 40% decline in function. In other words, they have exacerbation of the existing deficit. One reason to assess them before they leave the hospital is to document these events, even if it is to definitely say what they do not have. If there is something when they come back at 6 weeks, it can be documented. Therefore, I think we document new events that are substantial for a variety of reasons. It is not like 2% to 3% of patients; it may be as many as 25% who return with something that happened to them between discharge and follow-up.
Dr Newman: All the data suggest that 3 months is the best time to look for major insult, and I suspect that it is the best time at this point. The assessment should involve a concise and validated neurologic examination that should include but not be limited to assessment of primitive reflexes and visual fields in addition to motor power, gait, cranial nerves, and sensation.
Mr Smith: I think we should include 6 to 8 weeks, which is when the surgeon sees the patients. The cardiologist usually sees them at 6 to 12 months. We could add: ``ideally the patient should be seen again at 6 to 12 months,'' which is the next follow-up appointment in the cardiology clinic.
Mr Venn: We have conflicting considerations here. There is Dr Stump's recruitment of new episodes occurring after an otherwise uneventful discharge. There is variance as to how to arrange the timing of the first stable assessment, what we believe to be the end result of a surgical insult and not the early noise in the system or a reflection of the recruitment Dr Stump is talking about as a new postoperative, operation-unrelated event. So you do not want an assessment at 6 months, which is operative plus possible recruitment, and you do not want 1 week, which is just noise. Is 6 to 8 weeks operative? There is probably no recruitment, but is the noise gone? I think 3 months is the time frame at which we clinically perceive the patient to have recovered from operation. I think we have seen very variable data at 6 to 8 weeks, and it is too variable.
Dr Murkin: It has become apparent from the discussion that the issue of when to perform the postoperative assessment is of critical importance. I think that what is being implied is that we are searching for an assessment that will have some correlation with functional outcome. As we have already discussed, there are a number of confounders that influence data collected in the immediate postoperative or early convalescent period. I think that the concern being expressed is that we are being driven more and more by the logistics and clinical convenience in our assessment, and that may detract markedly from the validity and the interpretability of the data. My assumption is that there is evidence that focal ischemic lesions, as manifested by stroke, demonstrate a fairly complete recovery by 3 months, but after that, the neurologic signs have essentially stabilized. Therefore, it would appear that a reasonable, biologic rationale is a 3-month interval for the postconvalescent assessment. It is clear that at the 6-week assessment, patients are still being advised against full physical activity with the recognition that they have not fully recovered physically. I think that the intent of the postconvalescent assessment is to measure the functional impact and correlate it with some assessment of functional outcome. If we assess these patients when the lesions are still in a state of flux, the data may be misleading.
Dr Newman: Dr Murkin, if I understand you, the last sentence should indicate at least a 3-month postsurgical assessment. The audience seems to indicate at least 3 months. If someone wants to do an assessment at 6 months or 1 year, he can. We must put this into context because these are recommendations for people interested in doing these studies. They are not binding; they are a set of recommendations, and we need to be careful about being too specific. So we shall end the first sentence as follows: ``... immediate postoperatively and then declines. Care must be taken to perform at least one assessment when performance is more stable. Ideally this should be at least 3 months after operation.''
Mark F. Newman, MD (Durham, NC): I think by writing ``ideally, at least one assessment should be in 3 months'' does not mean it is not appropriate to do a 4- to 6-week or 6- to 8-week assessment. It is just saying ``ideally'' we want at least one of them to be beyond 3 months. I think that that is probably a very good compromise.
Dr S. P. Newman: The 5- to 7-day assessment is very volatile. My recommendation is to drop this assessment even though Dr Stump says exactly the opposite.
Mr Venn: I do not want to be a voice in the wilderness here, but I agree with Dr Stanton Newman. I think this involves very muddy and clouded data, and it gives a very confused message. It may be useful as you say, Dr Stump, to see if there is a consistency in the trends of the specific tests, eg, was the pegboard a reality or was it part of the postoperative noise? However, like Dr Stanton Newton, I think it is something we could well drop.
Maura A. Goldsborough, RN (Baltimore, MD): I appreciate what you are saying about some of the patients who do not have deficits on discharge. However, I definitely agree with Dr Stanton Newman in that in my patient population, 80% to 90% are on a regimen of some type of pain medication at 4 to 6 days postoperatively. So what truly are you testing? You cannot expect a patient to stop pain medications so that you can give him or her a test battery. I think that would be a confounding factor in my group.
Dr Blumenthal: The other practical consideration is that the immediate postoperative period can be particularly frustrating for the patient to be tested. High frustration could discourage patients from coming back for follow-up testing at 3 months.
Dr Åberg: I think that the scientific design has very much to do with this. If one is after a descriptive study, then one does not have to use the early postoperative assessment, whereas if one is after an interventional study, there is a good control group for comparison. Then it does not matter if there is a little bit more noise at that time.
Mr Blauth: I am not going to disagree with this, but I am still trying to understand exactly what Dr Stump means. Do you mean that certain clinical events that can occur, for example, wound complications, or chest infections, which may express themselves as a fever, would impair performance on a neuropsychologic test or suggest a recovery because we do see a deficit and then a slow recovery, or are you implying that the patient can have otherwise occult neurologic or neuropathologic events or both that may be detected and cloud the issue. I am just not quite clear what you are talking about.
Dr Stump: The only data I have are that patients do worse on neurobehavioral tests at 1 month. The presumption was that they might have been developing clots and that they were having CNS dysfunction at 6 weeks that they did not exhibit when they left the hospital.
Dr Åberg: I think that the last sentence ``ideally the use of control groups'' should be enhanced quite a lot. I believe we should not do any studies without proper control groups and that we should take the issue of control groups much higher in the hierarchy.
Dr Murkin: I think the issue might be that when one does just a survey, one wants to look at the incidence of cognitive deficits in patients undergoing coronary artery bypass grafting. If there is nothing with which to compare that directly, such as patients undergoing an operation other than bypass grafting, one needs some sort of comparison, rather than just a blanket statement that ``80% of patients have postoperative deficits.''
11. Cognitive testing can be associated with improvement in performance scores on repeated testing, which is recognized as the ``practice effect.'' This improvement needs to be taken into consideration by avoiding analyses based on group means, as the performance of the group as a whole is likely to be made up of those showing improvement and those showing deterioration. This is likely to result in no change for the group as a whole. A study design incorporating procedures to minimize practice effects (eg, providing sufficient practice trails on each test at each assessment period) and ideally the use of control groups is recommended.
Jeffrey S. Martzke, PhD (Vancouver, BC, Canada): Is the issue of practice effect, learning effect, going to be included as well as a discussion of that anywhere in the document?
Dr S. P. Newman: It is going to remain in item 11. We are going to clear the statement about having sufficient practice trials in each test on each occasion. Then we are going to have a separate statement about the use of control and comparison groups when indicated by the design. We are going to pull out the material on design but leave ``the practice effects within each trial'' in that statement (number 14).
12. Ideally, test instruments should have multiple forms. Some categories of tests are more resistant to practice effects, and these should be used when possible. Tests with an objective measure of performance, such as time to completion or correctly matching to sample, should be used instead of subjective measures, such as scoring nuances of recalled material. Further, such tests should be free from sex, race, and ethnic bias and be age, educationally, and culturally normed to avoid floor and ceiling effects. Study designs incorporating changes in individual performance, incidence scores, a comparison group, or a combination of these will enable the issue of learning to be teased out.
13. Because of the multifocal nature of the potential lesion locations, no single behavioral test will always detect postoperative neurobehavioral dysfunction. Memory, language, psychomotor speed, and attention and concentration skills must always be assessed in these patients to determine if the cortical mantle is functionally intact.
Recommended Core Neuropsychologic Battery
Dr Mills: First, I think it is very important that this group try to delineate a core battery of tests that researchers in other institutions could administer quickly and easily. I think it will generate more interest in the field, more confidence, and more work. I understand that there has been a great proprietary and territorial interest in this field with specific batteries and so forth. I was really impressed to hear that Dr Stanton Newman and Dr Stump had a less than 1% disagreement of testing done several thousand miles apart, and I am not sure that the participants here might not consider adopting a core battery while retaining the scientific freedom to add to it as they see fit.
The second point is that I would like to see tests be somewhat technology independent so that people did not think they had to have sophisticated computer systems to apply them. The final point is that outcome research is going to get more and more attention with managed care and so on in the United States. There are groups, for instance in Minneapolis, that document outcomes and have developed a series of questionnaires for various disease states such as angina or hip replacement. They make these forms available basically free from charge or at a very nominal charge. I wonder if this group should consider doing something like that, in other words, compile a test battery and make it available to interested parties to try to promote its use in the United States and elsewhere. I think that the whole academic field would benefit greatly by having more availability and a very defined battery of tests.
Dr S. P. Newman: I think it is an issue of comparing studies, and one of the points that we can look at is the ability to share data because that will allow anyone to recast the study using any kind of definition of incidence that is needed. I have tried to make a recommendation that in intervention studies, we do not actually have to use them.
We are going to make a proposal about four tests, and I will now give a background for the proposal. We thought it might be useful for people to think about a minimal but not sufficient battery to use. In other words, we are looking for minimal comparability across the studies. We suggest four tests covering three domains to try to pick up a number of areas. We have deliberately chosen paper-and-pencil type, well-standardized, and, indeed, well-normalized tests for these four tests to make a comparison. For verbal memory, we suggest the Rey auditory verbal learning test, test 1.
Dr Åberg: Is that exclusively in English?
Dr S. P. Newman: I think it originated in France in 1964. The test administration takes about 7 minutes. It uses seven trials: trials 1 to 5, the interpolated trial, and then recall of the first five tests.
We are looking just for a minimal comparison across studies. It is not a sufficient battery. The only problem I have with the delay is what you put in it. You cannot control across studies, and that is difficult. That is why it likely interpolates lists when the examiner knows what is being giving as an interference trial.
For motor skills, we recommend the grooved pegboard, test 2, and for attention and concentration, trail-making A and B, tests 3 and 4. That is a minimum necessary for comparability purposes but not a sufficient battery. That gives sufficient time to pick up a test you are particularly interested in for focusing on other issues. It allows some degree of comparability across studies and includes widely used, well-standardized normed paper-and-pencil tests that do not require computers.
Lois M. Borowicz, PhD (Baltimore, MD): It seems to me that four tests you mentioned are going to be pretty easy to accept.
Mr Venn: The grooved pegboard and the Rey seem very appropriate, sensitive, and rigorous tests. I wonder how sensi-tive the trails A is going to be. It is easy to do, but is it useful?
Dr Martzke: I think this is a great selection of tests. The only concern I have is that they may be gauged a little bit high in terms of cognitive levels.
Dr Åberg: I want to make sure they are available in different languages.
Dr S. P. Newman: Certainly the Rey has been widely used in Germany and France. I am not sure about Scandinavia.
Dr Murkin: Thank you all very much for your participation. Thank you to all the speakers. This has been a very enjoyable and most educational conference. I also thank my outstanding research coordinators, Donna Giles and Sandy Adams, and Peter Lok, who has faithfully been recording all of these events.
Participants
Footnotes
Presented at the Conference on CNS Dysfunction After Cardiac Surgery: Defining the Problem, Fort Lauderdale, FL, Dec 10–11, 1994.
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D. van Dijk and C. J. Kalkman Why Are Cerebral Microemboli Not Associated with Cognitive Decline? Anesth. Analg., October 1, 2009; 109(4): 1006 - 1008. [Full Text] [PDF]
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G. Wang, D. Bainbridge, J. Martin, and D. Cheng The Efficacy of an Intraoperative Cell Saver During Cardiac Surgery: A Meta-Analysis of Randomized Trials Anesth. Analg., August 1, 2009; 109(2): 320 - 330. [Abstract] [Full Text] [PDF]
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C. W. Hogue Jr, R. Fucetola, T. Hershey, A. Nassief, S. Birge, V. G. Davila-Roman, B. Barzilai, B. Thomas, K. B. Schechtman, and K. Freedland The Role of Postoperative Neurocognitive Dysfunction on Quality of Life for Postmenopausal Women 6 Months After Cardiac Surgery Anesth. Analg., July 1, 2008; 107(1): 21 - 28. [Abstract] [Full Text] [PDF]
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A. G. Polunina Selection of Neurocognitive Tests and Outcomes of Cardiac Surgery Trials Ann. Thorac. Surg., January 1, 2008; 85(1): 362 - 362. [Full Text] [PDF]
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B. Ramlawi, H. Otu, J. L. Rudolph, S. Mieno, I. S. Kohane, H. Can, T. A. Libermann, E. R. Marcantonio, C. Bianchi, and F. W. Sellke Genomic expression pathways associated with brain injury after cardiopulmonary bypass. J. Thorac. Cardiovasc. Surg., October 1, 2007; 134(4): 996 - 1005.e4. [Abstract] [Full Text] [PDF]
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F. D. Rubens, M. Boodhwani, T. Mesana, D. Wozny, G. Wells, H. J. Nathan, and on behalf of the Cardiotomy Investigators The Cardiotomy Trial: A Randomized, Double-Blind Study to Assess the Effect of Processing of Shed Blood During Cardiopulmonary Bypass on Transfusion and Neurocognitive Function Circulation, September 11, 2007; 116(11_suppl): I-89 - I-97. [Abstract] [Full Text] [PDF]
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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]
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S. Al-Ruzzeh and D. O'Regan Assessment of Neurocognitive Outcome After Cardiac Surgery Ann. Thorac. Surg., July 1, 2007; 84(1): 358 - 358. [Full Text] [PDF]
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F. D. Rubens, M. Boodhwani, and H. Nathan Interpreting studies of cognitive function following cardiac surgery: a guide for surgical teams Perfusion, May 1, 2007; 22(3): 185 - 192. [Abstract] [PDF]
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B. S. Silbert, D. A. Scott, L. A. Evered, M. S. Lewis, and P. T. Maruff Preexisting Cognitive Impairment in Patients Scheduled for Elective Coronary Artery Bypass Graft Surgery Anesth. Analg., May 1, 2007; 104(5): 1023 - 1028. [Abstract] [Full Text] [PDF]
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C. Royse Is Depth of Anesthesia, as Assessed by the Bispectral Index, Related to Postoperative Cognitive Dysfunction and Recovery? Anesth. Analg., May 1, 2007; 104(5): 1297 - 1297. [Full Text] [PDF]
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A. Schubert, E. Farag, and E. J. Mascha Is Depth of Anesthesia, as Assessed by the Bispectral Index, Related to Postoperative Cognitive Dysfunction and Recovery? Anesth. Analg., May 1, 2007; 104(5): 1297 - 1298. [Full Text] [PDF]
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D. Bainbridge, D. Cheng, J. Martin, R. Novick, and The Evidence-based Peri-operative Clinical Outcome Does off-pump or minimally invasive coronary artery bypass reduce mortality, morbidity, and resource utilization when compared with percutaneous coronary intervention? A meta-analysis of randomized trials J. Thorac. Cardiovasc. Surg., March 1, 2007; 133(3): 623 - 631. [Abstract] [Full Text] [PDF]
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S. Koch, A. Forteza, C. Lavernia, J. G. Romano, I. Campo-Bustillo, N. Campo, and S. Gold Cerebral Fat Microembolism and Cognitive Decline After Hip and Knee Replacement Stroke, March 1, 2007; 38(3): 1079 - 1081. [Abstract] [Full Text] [PDF]
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J. R. Keith, D. J. Cohen, and L. B. Lecci Why Serial Assessments of Cardiac Surgery Patients' Neurobehavioral Performances are Misleading Ann. Thorac. Surg., February 1, 2007; 83(2): 370 - 373. [Full Text] [PDF]
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O. A. Selnes and S. L. Zeger Coronary Artery Bypass Grafting Baseline Cognitive Assessment: Essential Not Optional Ann. Thorac. Surg., February 1, 2007; 83(2): 374 - 376. [Full Text] [PDF]
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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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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]
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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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S. Himmelseher and M. E. Durieux Revising a Dogma: Ketamine for Patients with Neurological Injury? Anesth. Analg., August 1, 2005; 101(2): 524 - 534. [Abstract] [Full Text] [PDF]
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Y. Kadoi, S. Saito, N. Fujita, and F. Goto Risk factors for cognitive dysfunction after coronary artery bypass graft surgery in patients with type 2 diabetes J. Thorac. Cardiovasc. Surg., March 1, 2005; 129(3): 576 - 583. [Abstract] [Full Text] [PDF]
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S. Dogan, T. Aybek, P. S. Risteski, F. Detho, A. Rapp, G. Wimmer-Greinecker, and A. Moritz Minimally Invasive Port Access Versus Conventional Mitral Valve Surgery: Prospective Randomized Study Ann. Thorac. Surg., February 1, 2005; 79(2): 492 - 498. [Abstract] [Full Text] [PDF]
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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] [Full Text] [PDF]
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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]
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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]
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G. Iohom, S. Szarvas, V. Larney, J. O'Brien, E. Buckley, M. Butler, and G. Shorten Perioperative Plasma Concentrations of Stable Nitric Oxide Products Are Predictive of Cognitive Dysfunction After Laparoscopic Cholecystectomy Anesth. Analg., October 1, 2004; 99(4): 1245 - 1252. [Abstract] [Full Text] [PDF]
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D.K. Harrington, A.S. Walker, H. Kaukuntla, R.M. Bracewell, T.H. Clutton-Brock, M. Faroqui, D. Pagano, and R.S. Bonser Selective Antegrade Cerebral Perfusion Attenuates Brain Metabolic Deficit in Aortic Arch Surgery: A Prospective Randomized Trial Circulation, September 14, 2004; 110(11_suppl_1): II-231 - II-236. [Abstract] [Full Text] [PDF]
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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]
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S. Martens, M. Dietrich, C. Herzog, M. Doss, G. Schneider, A. Moritz, and G. Wimmer-Greinecker Automatic connector devices for proximal anastomoses do not decrease embolic debris compared with conventional anastomoses in CABG Eur. J. Cardiothorac. Surg., June 1, 2004; 25(6): 993 - 1000. [Abstract] [Full Text] [PDF]
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B. S. Silbert, P. Maruff, L. A. Evered, D. A. Scott, M. Kalpokas, K. J. Martin, M. S. Lewis, and P. S. Myles Detection of cognitive decline after coronary surgery: a comparison of computerized and conventional tests Br. J. Anaesth., June 1, 2004; 92(6): 814 - 820. [Abstract] [Full Text] [PDF]
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W. Nagels, R. Demeyere, J. Van Hemelrijck, E. Vandenbussche, K. Gijbels, and E. Vandermeersch Evaluation of the Neuroprotective Effects of S(+)-Ketamine During Open-Heart Surgery Anesth. Analg., June 1, 2004; 98(6): 1595 - 1603. [Abstract] [Full Text] [PDF]
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J. D. Puskas, W. H. Williams, E. M. Mahoney, P. R. Huber, P. C. Block, P. G. Duke, J. R. Staples, K. E. Glas, J. J. Marshall, M. E. Leimbach, et al. Off-Pump vs Conventional Coronary Artery Bypass Grafting: Early and 1-Year Graft Patency, Cost, and Quality-of-Life Outcomes: A Randomized Trial JAMA, April 21, 2004; 291(15): 1841 - 1849. [Abstract] [Full Text] [PDF]
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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]
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M. Jahangiri and R. Motallebzadeh Neurocognitive deficit following mitral valve surgery Eur. J. Cardiothorac. Surg., October 1, 2003; 24(4): 665 - 665. [Full Text] [PDF]
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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]
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D.K. Harrington, M. Bonser, A. Moss, M.T.E. Heafield, M.J. Riddoch, and R.S. Bonser Neuropsychometric outcome following aortic arch surgery: a prospective randomized trial of retrograde cerebral perfusion J. Thorac. Cardiovasc. Surg., September 1, 2003; 126(3): 638 - 644. [Abstract] [Full Text] [PDF]
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D. J. Culley, G. Crosby, J. Butterworth, and J. W. Hammon Mechanisms of Postoperative Neurobehavioral Deficits and Stroke May Differ * Response Anesth. Analg., August 1, 2003; 97(2): 601 - 601. [Full Text] [PDF]
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J. D. Lee, S. J. Lee, W. T. Tsushima, H. Yamauchi, W. T. Lau, J. Popper, A. Stein, D. Johnson, D. Lee, H. Petrovitch, et al. Benefits of off-pump bypass on neurologic and clinical morbidity: a prospective randomized trial Ann. Thorac. Surg., July 1, 2003; 76(1): 18 - 26. [Abstract] [Full Text] [PDF]
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Y. Kadoi, S. Saito, F. Kunimoto, F. Goto, and N. Fujita Comparative effects of propofol versus fentanyl on cerebral oxygenation state during normothermic cardiopulmonary bypass and postoperative cognitive dysfunction Ann. Thorac. Surg., March 1, 2003; 75(3): 840 - 846. [Abstract] [Full Text] [PDF]
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E. Ahlgren, A. Lundqvist, A. Nordlund, C. Aren, and H. Rutberg Neurocognitive impairment and driving performance after coronary artery bypass surgery Eur. J. Cardiothorac. Surg., March 1, 2003; 23(3): 334 - 340. [Abstract] [Full Text] [PDF]
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V. Zamvar, D. Williams, J. Hall, N. Payne, C. Cann, K. Young, S Karthikeyan, and J. Dunne Assessment of neurocognitive impairment after off-pump and on-pump techniques for coronary artery bypass graft surgery: prospective randomised controlled trial BMJ, November 30, 2002; 325(7375): 1268 - 1268. [Abstract] [Full Text] [PDF]
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S. Dogan, K. Graubitz, T. Aybek, M. F. Khan, P. Kessler, A. Moritz, and G. Wimmer-Greinecker How safe is the port access technique in minimally invasive coronary artery bypass grafting? Ann. Thorac. Surg., November 1, 2002; 74(5): 1537 - 1543. [Abstract] [Full Text] [PDF]
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