- Email: [email protected]
Neuropsychologic alterations after cardiac operation
J
THoRAc CARDIOVASC SURG
1988;96:326-31
Neuropsychologic alterations after cardiac operation To study the incidence and course of neuropsychologic sequelae from cardiac operation, a battery of tests was administered to 46 patients before andafter coronary artery bypass surgery. Their performance was compared with that of 14 peripheral vascular surgery patients and 26 nonsurgical control patients. A subsample of each group was studied again 6 months later. Test results were consistent with previous reports. Neuropsychologic deficits after cardiac operation are not uncommon, though they are often subtle and generally resolve by the sixth month after operation. Postoperative deficit was significant on measures of attention, psychomotor speed, and fine motor dexterity, but considerable interpatient performance variability was noted. Other findings imply that nonspecific aspects or surgery may make a substantial contribution to the immediate postoperative deficit in patients who have cardiac operations.
Thomas A. Hammeke, PhD, and James E. Hastings, PhD, Milwaukee. Wis.
Although incidence of frank neurologic and neuropsychologic complications after cardiac operation have decreased during the last two decades with improvements in surgical technique and equipment, I studies continue to suggest that subtle complications are not uncommon.>" Estimates of incidence of such complications vary considerably depending on patient demographic characteristics (e.g., age,' timing of the postoperative assessment.v' sensitivity of assessment procedures, and whether prospective or retrospective study procedures were used.' Although incidence rates from 0% to 100% have been reported.r" most recent prospective studies concerned with early postoperative complications give estimates of 17% to 79%, with the 35% to 50% range most common. 3.5. 8·10. 20 Higher incidence rates are generally reported in prospective studies of older patient groups with postoperative evaluations performed during the first week after operation incorporating detailed neurologic, neuropsychologic, or electroencephalographic evaluations. When residuals occur, they are transient in most From the Medical College of Wisconsin and Zablocki Veterans Administration and Medical Center. Milwaukee. Wis. Project supported by the American Heart Association (Wisconsin Affiliate), Grant 84-GA-06. Received for publication July 2, 1987. Accepted for publication Dec. 16, 1987. Address for reprints: Dr. Thomas A. Hammeke, Department of Neurology, Medical College of Wisconsin, 1000 N. 92nd St., Milwaukee, WI 53226.
326
Table I. Demographic information on experimental and control groups
Information Age Education (yr) Postoperative testing delay (days) Postoperative testing delay (follow-up, days)
CC
CARG n = 46 mean
n = 14 mean
n = 26 mean
ISD)
ISD)
ISDj
60.3 (7.3) 11.5 (2.8) 9.8 (8.9) 176 (29)
60.8 (8.2) 12.1 (2.8) 10.5 (6.2) 182 (8)
59.0 (5.2) 10.4 (2.7) 15.2 ( 15.9) 169 (21)
PVS
cases. Recent investigations have found clinically significant neurologic residuals to persist beyond a few weeks in only 5% to 9% of patients." Ii. 21 Subtle neuropsychologic deficits also appear to be transient.t'? though the findings of several studies are complicated by test practice effects or lack of adequate comparison groups. Other studies have suggested that select patients who have had cardiac operations may be predisposed to subtle neuropsychologic decline as much as 2 to 8 years after operation. 22.23 Mechanisms of these complications are poorly understood, though factors involved with extracorporeal circulation during operation have been specifically implicated. Several investigations have shown significant correlations between neuropsychologic indexes and measurements of extracorporeal circulation,': II. 14. 15. 22 pre-
Volume 96 Number 2
Neuropsychologic alterations
August 1988
3 27
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0
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CABG n=46
PVS
CC n=25
Fig. I. Mean change score from baseline of 12 summary measures.
sumably inducing microembolization or cerebral ischemia, whereas others have not replicated these findings." Understanding the mechanism is complicated by lack of adequate controls for nonspecific effects of operation or interaction effects in patients who typically have diffuse vascular disease and undergo operation." 26 The current study represents a prospective investigation of the incidence, character, and course of impairment in higher cognitive and affective functions in patients undergoing coronary artery bypass grafting (CABG). Equivalent forms of neuropsychologic measures were used to minimize retest practice effects. A peripheral vascular surgical group was included to control for nonspecific surgical factors.
Methods Subjects. The experimental group consisted of 46 patients who underwent CABG from January through July 1984 at Zablocki Veterans Administration Medical Center, Milwaukee, who met the following criteria: (I) sufficiently fluent in English to give informed consent and comprehend test instructions, (2) heart disease stable enough to permit undertaking 60 to 90 minutes of neuropsychologic testing, and (3) sufficient time to complete testing before scheduled operation. Average time for operation was 370 minutes with a mean of 3.2 grafts performed. Extracorporeal circulation was accomplished with a Sams 7000 heart-lung pump (Sams Inc., Ann Arbor, Mich.) with a pulsatile flow. A Cobe membrane oxygenator (Cobe Laboratories, Inc., Lakewood, Colo.) was employed. Average cardiopulmonary bypass time was 95 minutes (standard deviation [SO] = 34 minutes; range 10 to 153 minutes), and cardiopulmonary bypass flow rate was 3.05 Lyrnin (SO = 0.42 L/min; range 2.0 to 4.1 L/min). The mean lowest diastolic blood pressure during operation was 51.3 mm Hg (SO = 7.9 mm Hg: range 40 to 76 mm Hg), and the lowest body temperature recorded rectally was 29.9° C (SO = 1.9° C; range 26.6° to 34.9° C).
Two control groups were also studied. A surgical control group consisted of 14 patients having operations for peripheral vascular disease (PVS). These procedures generally involved iliofemoral-popliteal bypass or endarterectomy. Patients receiving carotid endarterectomies were excluded from the study. Patients having previous CABG were not excluded from either of the surgery groups providing the procedure did not occur during the year before study entry. A nonsurgical cardiac control (CC) group consisted of 26 patients who had symptomatic coronary artery disease and were admitted for cardiac catheterization; they were not found to be suitable candidates for surgical intervention at the time of the study (i.e., did not need or could not benefit). Selection criteria for these groups were otherwise comparable to the CABG patients. All patients were men and were studied as inpatients. The three groups did not differ in mean age or education. Table I shows the group demographic composition. Measures. Five categories of psychometric measures were used, from which a total of 12 neuropsychologic indexes were derived: Memory (four indexes). An index of learning speed (summed recall across learning trials) and recent memory (recall after 30-minute delay) were used from a verbal (word list) and nonverbal (checkerboard) memory task. The Verbal Selective Reminding Test" was used with equivalent forms developed with data from Hannay and Levin." The 7/24 Spatial Recall Test" was used to assess nonverbal memory. Conceptual reasoning and mental flexibility (two indexes). The Wisconsin Card Sorting Test" (64-card version) requires patients to sort cards into categories on the basis of feedback from the examiner. The number of errors was recorded. Also, the age and education corrected sum of the Controlled Word Association Test)' was used, a task requiring the patient to rapidly generate words beginning with a predesignated letter of the alphabet. Attention, concentration, and psychomotor speed (three indexes). The Digit Symbol subtest of the Wechsler Adult Intelligence Scale-Revised" (raw score) and Trails A and B tests of the Halstead-Reitan Neuropsychological Battery"
328
The Journal of Thoracic and Cardiovascular Surgery
Hammeke and Hastings
5 ~
4
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POSTOP
_CABG: n=25
...J....
~pvs:
FOLLOWUP n=8
_
DCC: n=7
Fig. 2. Mean change score from baseline of subsamples.
were used. These tests involve rapid visual-motor response in the transcription of geometric symbols or sequencing numbers and number-letter combinations. Fine motor dexterity (two indexes). The dominant and nondominant hand performances of Lafayette's grooved pegboard" were recorded. Affect (one index). The total mood deviation quotient of the Profile of Mood States (POMS)35 was used. The patient rates on a 5-point scale the extent to which he experiences each of 65 emotion-bearing adjectives. The adjectives are factored into six categories: anxiety, depression, anger, vigor, fatigue, and confusion. Procedure. Baseline neuropsychologic testing was typically completed within 3 days before operation for each of the surgical patients. Postoperative testing was done approximately 10 days after operation (before hospital discharge). Subsamples of each group (25 CABG patients, eight PVS patients, and seven CC patients) were tested again 6 months later (follow-up). Inclusion of these follow-up cases was made solely on the basis of availability and consent (there was one death among the CABG patients during the interim of follow-up). Nonsurgical CC patients were tested at comparable intervals. There were no significant differences between groups on delay of postoperative and follow-up testing (Table I). Before data analysis, postoperative and follow-up test values were transformed into change scores relative to the subject's baseline performance and then standardized (T-score) with the SD obtained on baseline. Data analysis was then done by analysis of mean change from baseline across the 12 performance indexes at postoperative and follow-up testing, followed by repeated measures multivariate analysis of variance on each of the five test categories. Analysis of individual subject performances was done by tabulating the frequency of postoperative test failure across the 12 performance indexes for each subject in the three groups. Test failure for a subject was defined as a performance decrement that exceeded I SD (SD computed from total sample baseline performance) from the subject's baseline performance.
Results Fig. 1 shows the mean change score (relative to baseline performance) for each group at postoperative testing. Overall group differences were significant (p = 0.(03). CABG patients showed a decline in overall performance, whereas CC patients improved their scores (group comparison significant, p = 0.01). PVS patients had a slight deterioration from baseline performance that was not significantly different from either CABG or CC patients. The postopeorative deficit in CABG subjects did not correlate (correlation coefficient lrD significantly with duration of operation (r = -0.05), duration of extracorporeal circulation (r = 0.04), or cardiopulmonary bypass flow (r = -0.16). Fig. 2 shows the mean change scores for the subsampies of each group studied at 6-month follow-up. Postoperative scores in these subsamples are similar to the larger groups, with CABG patients performing poorer than CC patients (p < 0.02) and PVS patients falling into an intermediate position. Results of follow-up testing at 6 months showed that all groups had improved over baseline performance with no significant difference between groups. On postoperative testing, measures of attention and concentration and fine motor dexterity were significant in group comparisons (e.g., Digit Symbol: CABG < PVS = CC, p < 0.0001; grooved pegboard: CABG = PVS < CC, P < 0.01). No significant effects (group X trial interaction) were found for memory, conceptual reasoning, or affective measures. On 6-month follow-up testing, no group differences were found for any of the five test categories. Analysis of individual subject data indicated that 11
Volume 96 Number 2
Neuropsychologic alterations
August 1988
of the CABG patients (24%) and one PVS patient (7%) failed on three or more performance indexes shortly after operation, whereas none of the CC patients failed (p = 0.02). The incidence of test failure was significantly greater among CABG patients than CC patients (p = 0.02), with incidence of test failure among PVS patients falling into an intermediate position. The most commonly failed test was the measure of nonverbal recent memory (20 CABG patients failed). On followup (subsamples) the test failure rate remained higher for both surgical groups but did not approach statistical significance. Of the II CABG patients who failed three or more tests on postoperative evaluation, five were included in follow-up testing. Four of these five patients improved their test performance (i.e., failed fewer than three tests), whereas one patient continued to show a deficit. To gain a better estimate of proportion of variance in neuropsychological findings attributable to specific and nonspecific aspects of surgery, multiple regression procedures were used. The fact of having surgery was entered into the regression (R) equation first, yielding a multiple R of 0.34 (R 2 = 0.116, P = O.(XH). Next, having CABG was entered, yielding an increment in multiple R to 0.36 (R2 = 0.130, P = 0.003); however, the increment in variance accounted for (1.4%) was not significant (p = 0.25). Thus the majority of variance in neuropsychologic findings was accounted for by surgical factors other than those specifically related to CABG (i.e., extracorporeal circulation).
Discussion Similar to previous reports, our CABG patients showed evidence of postoperative impairment in cognitive functions relative to nonsurgical control patients. The neuropsychologic complications were nonetheless subtle. In no case was hospital discharge delayed because of concerns about mental status. The incidence of such complications, with an arbitrary cutoff of three or more test failures across our 12 performance indexes, was 24%. This figure is lower than findings of other investigators who have used comparable assessment methodology and detailed neuropsychologic testing." The incidence figure, however, is highly dependent on the criterion selected. For example, if we set our cutoff less conservatively at two or more test failures, the resulting incidence rate would be 54% for our CABG patients. This cutoff also yielded a 36% failure rate in the PVS patients and 20% in the CC patients (chi-square still significant, p < 0.02). Although it is possible that the 20% incidence figure in
3 29
CC patients found by the more liberal cutoff represents a meaningful decline in function, it more realistically reflects test error variance that is inherent in psychometric measures. An alternative explanation for the lower incidence rate of neuropsychologic problems in our CABG patients is the use of pulsatile cardiopulmonary bypass. Controlled clinical trials comparing pulsatile with nonpulsatile bypass have found pulsatile flow to prevent intraoperative hypothalamic and pituitary stress responses and enhance intraoperative cerebral blood flow and metabolism.s" Unlike most other studies, the CABG postoperative deficit found in our investigation did not correlate with measurements of extracorporeal circulation. Use of a pulsatile cardiopulmonary bypass may be responsible for the lack of correlation by minimizing the postoperative deficit that is typically associated with extracorporeal circulation. Although CABG patients postoperatively performed poorer on cognitive tests than nonsurgical CC patients, their performance was not significantly different from patients with atherosclerotic disease undergoing noncardiac operations, implying that a substantial portion of the postoperative deficit in our study was related to nonspecific aspects of surgery. Multiple regression analysis failed to show any substantial increment in postoperative deficit accounted for after the nonspecific effects of surgery were considered. The apparent postoperative deficit seen in both our surgery groups may represent complications that are either unique to each surgical procedure or characteristic of the patient groups. It is possible that patients with atherosclerotic disease simply do not tolerate surgery as well as other patient
groups." When group data are considered, measures of attention and concentration, psychomotor speed, and fine motor dexterity proved to be most sensitive to postoperative group differences. There was however, considerable interpatient variability in the type and severity of neuropsychologic problems. Clinically meaningful memory, conceptual reasoning, and affective changes also occurred. For instance, with our cutoff for test failure, a test of recent memory for nonverbal material was most frequently failed (this test, the 7/24 Spatial Recall Test, has proved to be a sensitive measure in other investigations of subtle cerebral dysfunction"). When only PVS and CC patients were compared with regression analysis, a combination of indexes (errors on the Wisconsin Card Sorting Test and dominant hand fine motor dexterity) captured the majority of performance differences between these groups (collectively 38% of variance
3 3 0 Hammeke and Hastings
accounted for). These findings suggest that measures of higher level conceptual flexibility and fine motor dexterity may be the more sensitive indexes of nonspecific surgical effects. Similar to other investigations, our results indicate that neuropsychologic deficits associated with CABG are generally transient, with resolution of deficits occurring before the sixth postoperative month. However, this conclusion is weakened by our inability to collect complete follow-up data. Although there was no obvious sampling bias imposed by our follow-up solication procedures, it is possible that the subsamples studied in a 6-month follow-up period do not adequately represent their respective postoperative groups. The similarity of postoperative findings between the larger samples and subsamples (Figs. 1 and 2), however, argues against the existence of a follow-up selection bias. In addition, postoperative change scores were studied for each group comparing the performance of patients who ultimately completed follow-up testing with those who did not. No significant differences were found between patients who did and did not complete follow-up for any of the three groups. REFERENCES 1. Harrison DC. Coronary bypass: the first 10 years. Hoop Pract 1981;16:49-56. 2. Folks DG, Franceschini J, Sokol RS, Freeman AM, Folks DM. Coronary artery bypass surgery in older patients: psychiatric morbidity. South Med J 1986;79:303-6. 3. Savageau JA, Stanton B, Jenkins CD, Klein MD. Neuropsychological dysfunction following elective cardiac operation. I. Early assessment. J THORAC CARDIOVASC SURG 1982;84:585-94. 4. Savageau JA, Stanton B, Jenkins CD, Frater RW. Neuropsychological dysfunction following elective cardiac operation. II. A six-month reassessment. J THORAC CAR. DlOVASC SURG 1982;84:595-600. 5. Sotaniemi KA. Cerebral outcome after extracorporeal circulation. Arch Neurol 1983;40:75-7. 6. Frank KA, Heller SS, Kornfeld DS, Maim JR. Longterm effects of open-heart surgery on intellectual functioning. J THORAC CARDIOVASC SURG 1972;64:811-5. 7. Sachdev NS, Carter CC, Swank RL, Blachly PH. Relationship between post-cardiotomy delerium, clinical neurological changes and EEG abnormalities. J THORAC CARDIOVASC SURG 1967;54:557-63. 8. Juolasmaa A, Outakoski J, Hirvenoja R, Tienari P, Sotaniemi K, Takkunen J. Effect of open heart surgery on intellectual performance. J Clin Neuropsychol 1981; 3:181-97. 9. Shaw PJ, Bates D, Cartlidge NE, Heaviside D, Julian DG, Shaw DA. Early neurological complications of coronary artery bypass surgery. Br Med J 1985;291: 1384-7.
The Journal of Thoracic and Cardiovascular Surgery
10. Sotaniemi KA, Juolasmaa A, Hokkanen ET. Neuropsychologic outcome after open-heart surgery. Arch Neural 1981;38:2-8. 11. Sotaniemi KA. Five-year neurological EEG outcome after open-heart surgery. J Neurol Neurosurg Psychiatry 1985;48:569-75. 12. Raymond M, Conklin C, Schaeffer J, Newstadt G, Matloff JM, Gray RJ. Coping with transient intellectual dysfunction after coronary bypass surgery. Heart Lung 1984;13:531-9. 13. Henfiksen L. Evidence suggestive of diffuse brain damage following cardiac operations. Lancet 1984;1(8381):81620. 14. Aberg T, Kihlgren M. The use of psychometric testing as a quality criterion in open-heart surgery. In: Speidel H, Rodewald G, eds. Psychic and neurologic dysfunctions after open-heart surgery; 1st international symposium, Hamburg, West Germany. New York: Thieme Medical Publishers, 1980:107-11. 15. Elsass P, Henriksen L. Acute cerebral dysfunction after open-heart surgery. Scand J Thorac Cardiovasc Surg 1984;18:161-5. 16. Heikkinen L. Clinically significant neurological disorders following open heart surgery. Thorac Cardiovasc Surg 1985;33:201-6. 17. Budabin M. Neurologic complications of open heart surgery. Mt Sinai J Med 1982;40:311-3. 18. Brauthwaite MA. Neurological damage related to open heart surgery: a clinical survey. Thorax 1972;27:748-53. 19. Javid H, Tufo HM, Nojafi H, Dye WS, Hunter JA, Julian Oc. Neurological abnormalities following openheart surgery. J THORAC CARDIOVASC SURG 1969;58: 502-9. 20. Shaw PJ, Bates D, Cartlidge NE, et al. Early intellectual dysfunction following coronary bypass surgery. Q J Med 1986;58:59-68. 21. Shaw PJ, Bates D, Cartlidge NE, et al. Neurological complications of coronary artery bypass graft surgery: six-month follow-up study. Br Med J 1986;293:165-7. 22. Sotaniemi KA, Mononen H, Hokkannen TE. Long-term cerebral outcome after open-heart surgery: a five-year neuropsychological follow-up study. Stroke 1986;17: 410-6. 23. Aberg T, Ahlund P, Kihlgren M. Intellectual function late after open-heart operation. Ann Thorac Surg 1983; 36:680-3. 24. Aberg T, Ronquist G, Tyden H, et al. Adverse effects on the brain in cardiac operations as assessed by biochemical, psychometric, and radiologic methods. J THORAC CARDlOVASC SURG 1984:87:99-105. 25. Taylor KM. Pathophysiology of brain damage during open-heart surgery. Tex Heart Inst J 1986;13:91-5. 26. Okies JE, Page US, Bigelow JC, Krause AH, Salomon NW, Laxer KL. The impact of electroencephalography, pressure and p02 monitoring on the risk of stroke during cardiopulmonary bypass. Text Heart Inst J 1986;13:97104.
Volume 96 Number 2 August 1988
27. Buschke H, Fuld PA. Evaluating storage, retention, and retrieval in disordered memory and learning. Neurology 1974;24:1019-25. 28. Hannay HJ, Levin HS. Selective Reminding Test: an examination of equivalence of four forms. J Clin Exp Neuropsychol 1985;7:251-63. 29. Lezak MD. Neuropsychological Assessment. New York: Oxford University Press, 1976. 30. Heaton RK. Wisconsin Card Sorting Test: manual. Odessa, Fla: Psychological Assessment Resources, 1981. 31. Benton AL, Hamsher K. Multilingual aphasia examination (manual revised, 1978. Iowa City: University of Iowa, 1976. 32. Wechsler D. WAIS-R manual. New York: Psychological Corporation, 1981. 33. Reitan RM. Validity of the Trail Making Test as an indication of organic brain damage. Percept Mot Skills 1958;8:271-6.
Neuropsychologic alterations
33 1
34. Lafayette grooved pegboard. Lafayette, Ind.: Lafayette Instrument Co. 35. McNair DM, Lorr M, Droppleman LF. Profile of Mood States. San Diego, California: Educational and Industrial Testing Service. 36. Taylor KM, Wright GS, Reid JS, et al. Comparative studies of pulsatile and non-pulsatile flow during cardiopulmonary bypass. II. The effects on adrenal secretion of cortisol. J THORAC CARDIOVASC SURG 1978;75:574-8. 37. Taylor KM, Wright GS, Bain WH, Caves PK, Beastall GS. Comparative studies of pulsatile and nonpulsatile flow during cardiopulmonary bypass. III. Response of anterior pituitary gland to thyrotropin-releasing hormone. J THORAC CARDIOVASC SURG 1978;75:579-84. 38. Rao SM, Hammeke TA, McQuillen MP, Khatri BO, Lloyd D. Memory disturbance in chronic progressive multiple sclerosis. Arch Neurol 1984;41:625-31.
Bound volumes available to subscribers Bound volumes of THE JOURNAL OFTHORACIC AND CARDIOVASCULAR SURGERY are available to subscribers (only) for the 1988 issues from the Publisher, at a cost of $51.00 ($68.00 international) for Vol. 95 (January-June) and Vol. 96 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copies are shipped within 60 days after publication of the last issue of the volume. The binding is durable buckram with the JOURNAL name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact The C. V. Mosby Company, Circulation Department, 11830 Westline Industrial Drive, St. Louis, Missouri 63146-3318, USA; phone (800) 325-4177, ext. 351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular JOURNAL subscription.
THoRAc CARDIOVASC SURG
1988;96:326-31
Neuropsychologic alterations after cardiac operation To study the incidence and course of neuropsychologic sequelae from cardiac operation, a battery of tests was administered to 46 patients before andafter coronary artery bypass surgery. Their performance was compared with that of 14 peripheral vascular surgery patients and 26 nonsurgical control patients. A subsample of each group was studied again 6 months later. Test results were consistent with previous reports. Neuropsychologic deficits after cardiac operation are not uncommon, though they are often subtle and generally resolve by the sixth month after operation. Postoperative deficit was significant on measures of attention, psychomotor speed, and fine motor dexterity, but considerable interpatient performance variability was noted. Other findings imply that nonspecific aspects or surgery may make a substantial contribution to the immediate postoperative deficit in patients who have cardiac operations.
Thomas A. Hammeke, PhD, and James E. Hastings, PhD, Milwaukee. Wis.
Although incidence of frank neurologic and neuropsychologic complications after cardiac operation have decreased during the last two decades with improvements in surgical technique and equipment, I studies continue to suggest that subtle complications are not uncommon.>" Estimates of incidence of such complications vary considerably depending on patient demographic characteristics (e.g., age,' timing of the postoperative assessment.v' sensitivity of assessment procedures, and whether prospective or retrospective study procedures were used.' Although incidence rates from 0% to 100% have been reported.r" most recent prospective studies concerned with early postoperative complications give estimates of 17% to 79%, with the 35% to 50% range most common. 3.5. 8·10. 20 Higher incidence rates are generally reported in prospective studies of older patient groups with postoperative evaluations performed during the first week after operation incorporating detailed neurologic, neuropsychologic, or electroencephalographic evaluations. When residuals occur, they are transient in most From the Medical College of Wisconsin and Zablocki Veterans Administration and Medical Center. Milwaukee. Wis. Project supported by the American Heart Association (Wisconsin Affiliate), Grant 84-GA-06. Received for publication July 2, 1987. Accepted for publication Dec. 16, 1987. Address for reprints: Dr. Thomas A. Hammeke, Department of Neurology, Medical College of Wisconsin, 1000 N. 92nd St., Milwaukee, WI 53226.
326
Table I. Demographic information on experimental and control groups
Information Age Education (yr) Postoperative testing delay (days) Postoperative testing delay (follow-up, days)
CC
CARG n = 46 mean
n = 14 mean
n = 26 mean
ISD)
ISD)
ISDj
60.3 (7.3) 11.5 (2.8) 9.8 (8.9) 176 (29)
60.8 (8.2) 12.1 (2.8) 10.5 (6.2) 182 (8)
59.0 (5.2) 10.4 (2.7) 15.2 ( 15.9) 169 (21)
PVS
cases. Recent investigations have found clinically significant neurologic residuals to persist beyond a few weeks in only 5% to 9% of patients." Ii. 21 Subtle neuropsychologic deficits also appear to be transient.t'? though the findings of several studies are complicated by test practice effects or lack of adequate comparison groups. Other studies have suggested that select patients who have had cardiac operations may be predisposed to subtle neuropsychologic decline as much as 2 to 8 years after operation. 22.23 Mechanisms of these complications are poorly understood, though factors involved with extracorporeal circulation during operation have been specifically implicated. Several investigations have shown significant correlations between neuropsychologic indexes and measurements of extracorporeal circulation,': II. 14. 15. 22 pre-
Volume 96 Number 2
Neuropsychologic alterations
August 1988
3 27
3
"> Q)
2
0
l-
Q) L-
a. ~
a o
0
VI
I
f-
"~ -1 Q) III
l-
~-2
-3
CABG n=46
PVS
CC n=25
Fig. I. Mean change score from baseline of 12 summary measures.
sumably inducing microembolization or cerebral ischemia, whereas others have not replicated these findings." Understanding the mechanism is complicated by lack of adequate controls for nonspecific effects of operation or interaction effects in patients who typically have diffuse vascular disease and undergo operation." 26 The current study represents a prospective investigation of the incidence, character, and course of impairment in higher cognitive and affective functions in patients undergoing coronary artery bypass grafting (CABG). Equivalent forms of neuropsychologic measures were used to minimize retest practice effects. A peripheral vascular surgical group was included to control for nonspecific surgical factors.
Methods Subjects. The experimental group consisted of 46 patients who underwent CABG from January through July 1984 at Zablocki Veterans Administration Medical Center, Milwaukee, who met the following criteria: (I) sufficiently fluent in English to give informed consent and comprehend test instructions, (2) heart disease stable enough to permit undertaking 60 to 90 minutes of neuropsychologic testing, and (3) sufficient time to complete testing before scheduled operation. Average time for operation was 370 minutes with a mean of 3.2 grafts performed. Extracorporeal circulation was accomplished with a Sams 7000 heart-lung pump (Sams Inc., Ann Arbor, Mich.) with a pulsatile flow. A Cobe membrane oxygenator (Cobe Laboratories, Inc., Lakewood, Colo.) was employed. Average cardiopulmonary bypass time was 95 minutes (standard deviation [SO] = 34 minutes; range 10 to 153 minutes), and cardiopulmonary bypass flow rate was 3.05 Lyrnin (SO = 0.42 L/min; range 2.0 to 4.1 L/min). The mean lowest diastolic blood pressure during operation was 51.3 mm Hg (SO = 7.9 mm Hg: range 40 to 76 mm Hg), and the lowest body temperature recorded rectally was 29.9° C (SO = 1.9° C; range 26.6° to 34.9° C).
Two control groups were also studied. A surgical control group consisted of 14 patients having operations for peripheral vascular disease (PVS). These procedures generally involved iliofemoral-popliteal bypass or endarterectomy. Patients receiving carotid endarterectomies were excluded from the study. Patients having previous CABG were not excluded from either of the surgery groups providing the procedure did not occur during the year before study entry. A nonsurgical cardiac control (CC) group consisted of 26 patients who had symptomatic coronary artery disease and were admitted for cardiac catheterization; they were not found to be suitable candidates for surgical intervention at the time of the study (i.e., did not need or could not benefit). Selection criteria for these groups were otherwise comparable to the CABG patients. All patients were men and were studied as inpatients. The three groups did not differ in mean age or education. Table I shows the group demographic composition. Measures. Five categories of psychometric measures were used, from which a total of 12 neuropsychologic indexes were derived: Memory (four indexes). An index of learning speed (summed recall across learning trials) and recent memory (recall after 30-minute delay) were used from a verbal (word list) and nonverbal (checkerboard) memory task. The Verbal Selective Reminding Test" was used with equivalent forms developed with data from Hannay and Levin." The 7/24 Spatial Recall Test" was used to assess nonverbal memory. Conceptual reasoning and mental flexibility (two indexes). The Wisconsin Card Sorting Test" (64-card version) requires patients to sort cards into categories on the basis of feedback from the examiner. The number of errors was recorded. Also, the age and education corrected sum of the Controlled Word Association Test)' was used, a task requiring the patient to rapidly generate words beginning with a predesignated letter of the alphabet. Attention, concentration, and psychomotor speed (three indexes). The Digit Symbol subtest of the Wechsler Adult Intelligence Scale-Revised" (raw score) and Trails A and B tests of the Halstead-Reitan Neuropsychological Battery"
328
The Journal of Thoracic and Cardiovascular Surgery
Hammeke and Hastings
5 ~
4
~... 3
Q) L-
I
2
~
-1
o(J
o
VI
I
~
1
Ql
~-2
:s -3 til
~
-4
-5..1...---
POSTOP
_CABG: n=25
...J....
~pvs:
FOLLOWUP n=8
_
DCC: n=7
Fig. 2. Mean change score from baseline of subsamples.
were used. These tests involve rapid visual-motor response in the transcription of geometric symbols or sequencing numbers and number-letter combinations. Fine motor dexterity (two indexes). The dominant and nondominant hand performances of Lafayette's grooved pegboard" were recorded. Affect (one index). The total mood deviation quotient of the Profile of Mood States (POMS)35 was used. The patient rates on a 5-point scale the extent to which he experiences each of 65 emotion-bearing adjectives. The adjectives are factored into six categories: anxiety, depression, anger, vigor, fatigue, and confusion. Procedure. Baseline neuropsychologic testing was typically completed within 3 days before operation for each of the surgical patients. Postoperative testing was done approximately 10 days after operation (before hospital discharge). Subsamples of each group (25 CABG patients, eight PVS patients, and seven CC patients) were tested again 6 months later (follow-up). Inclusion of these follow-up cases was made solely on the basis of availability and consent (there was one death among the CABG patients during the interim of follow-up). Nonsurgical CC patients were tested at comparable intervals. There were no significant differences between groups on delay of postoperative and follow-up testing (Table I). Before data analysis, postoperative and follow-up test values were transformed into change scores relative to the subject's baseline performance and then standardized (T-score) with the SD obtained on baseline. Data analysis was then done by analysis of mean change from baseline across the 12 performance indexes at postoperative and follow-up testing, followed by repeated measures multivariate analysis of variance on each of the five test categories. Analysis of individual subject performances was done by tabulating the frequency of postoperative test failure across the 12 performance indexes for each subject in the three groups. Test failure for a subject was defined as a performance decrement that exceeded I SD (SD computed from total sample baseline performance) from the subject's baseline performance.
Results Fig. 1 shows the mean change score (relative to baseline performance) for each group at postoperative testing. Overall group differences were significant (p = 0.(03). CABG patients showed a decline in overall performance, whereas CC patients improved their scores (group comparison significant, p = 0.01). PVS patients had a slight deterioration from baseline performance that was not significantly different from either CABG or CC patients. The postopeorative deficit in CABG subjects did not correlate (correlation coefficient lrD significantly with duration of operation (r = -0.05), duration of extracorporeal circulation (r = 0.04), or cardiopulmonary bypass flow (r = -0.16). Fig. 2 shows the mean change scores for the subsampies of each group studied at 6-month follow-up. Postoperative scores in these subsamples are similar to the larger groups, with CABG patients performing poorer than CC patients (p < 0.02) and PVS patients falling into an intermediate position. Results of follow-up testing at 6 months showed that all groups had improved over baseline performance with no significant difference between groups. On postoperative testing, measures of attention and concentration and fine motor dexterity were significant in group comparisons (e.g., Digit Symbol: CABG < PVS = CC, p < 0.0001; grooved pegboard: CABG = PVS < CC, P < 0.01). No significant effects (group X trial interaction) were found for memory, conceptual reasoning, or affective measures. On 6-month follow-up testing, no group differences were found for any of the five test categories. Analysis of individual subject data indicated that 11
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August 1988
of the CABG patients (24%) and one PVS patient (7%) failed on three or more performance indexes shortly after operation, whereas none of the CC patients failed (p = 0.02). The incidence of test failure was significantly greater among CABG patients than CC patients (p = 0.02), with incidence of test failure among PVS patients falling into an intermediate position. The most commonly failed test was the measure of nonverbal recent memory (20 CABG patients failed). On followup (subsamples) the test failure rate remained higher for both surgical groups but did not approach statistical significance. Of the II CABG patients who failed three or more tests on postoperative evaluation, five were included in follow-up testing. Four of these five patients improved their test performance (i.e., failed fewer than three tests), whereas one patient continued to show a deficit. To gain a better estimate of proportion of variance in neuropsychological findings attributable to specific and nonspecific aspects of surgery, multiple regression procedures were used. The fact of having surgery was entered into the regression (R) equation first, yielding a multiple R of 0.34 (R 2 = 0.116, P = O.(XH). Next, having CABG was entered, yielding an increment in multiple R to 0.36 (R2 = 0.130, P = 0.003); however, the increment in variance accounted for (1.4%) was not significant (p = 0.25). Thus the majority of variance in neuropsychologic findings was accounted for by surgical factors other than those specifically related to CABG (i.e., extracorporeal circulation).
Discussion Similar to previous reports, our CABG patients showed evidence of postoperative impairment in cognitive functions relative to nonsurgical control patients. The neuropsychologic complications were nonetheless subtle. In no case was hospital discharge delayed because of concerns about mental status. The incidence of such complications, with an arbitrary cutoff of three or more test failures across our 12 performance indexes, was 24%. This figure is lower than findings of other investigators who have used comparable assessment methodology and detailed neuropsychologic testing." The incidence figure, however, is highly dependent on the criterion selected. For example, if we set our cutoff less conservatively at two or more test failures, the resulting incidence rate would be 54% for our CABG patients. This cutoff also yielded a 36% failure rate in the PVS patients and 20% in the CC patients (chi-square still significant, p < 0.02). Although it is possible that the 20% incidence figure in
3 29
CC patients found by the more liberal cutoff represents a meaningful decline in function, it more realistically reflects test error variance that is inherent in psychometric measures. An alternative explanation for the lower incidence rate of neuropsychologic problems in our CABG patients is the use of pulsatile cardiopulmonary bypass. Controlled clinical trials comparing pulsatile with nonpulsatile bypass have found pulsatile flow to prevent intraoperative hypothalamic and pituitary stress responses and enhance intraoperative cerebral blood flow and metabolism.s" Unlike most other studies, the CABG postoperative deficit found in our investigation did not correlate with measurements of extracorporeal circulation. Use of a pulsatile cardiopulmonary bypass may be responsible for the lack of correlation by minimizing the postoperative deficit that is typically associated with extracorporeal circulation. Although CABG patients postoperatively performed poorer on cognitive tests than nonsurgical CC patients, their performance was not significantly different from patients with atherosclerotic disease undergoing noncardiac operations, implying that a substantial portion of the postoperative deficit in our study was related to nonspecific aspects of surgery. Multiple regression analysis failed to show any substantial increment in postoperative deficit accounted for after the nonspecific effects of surgery were considered. The apparent postoperative deficit seen in both our surgery groups may represent complications that are either unique to each surgical procedure or characteristic of the patient groups. It is possible that patients with atherosclerotic disease simply do not tolerate surgery as well as other patient
groups." When group data are considered, measures of attention and concentration, psychomotor speed, and fine motor dexterity proved to be most sensitive to postoperative group differences. There was however, considerable interpatient variability in the type and severity of neuropsychologic problems. Clinically meaningful memory, conceptual reasoning, and affective changes also occurred. For instance, with our cutoff for test failure, a test of recent memory for nonverbal material was most frequently failed (this test, the 7/24 Spatial Recall Test, has proved to be a sensitive measure in other investigations of subtle cerebral dysfunction"). When only PVS and CC patients were compared with regression analysis, a combination of indexes (errors on the Wisconsin Card Sorting Test and dominant hand fine motor dexterity) captured the majority of performance differences between these groups (collectively 38% of variance
3 3 0 Hammeke and Hastings
accounted for). These findings suggest that measures of higher level conceptual flexibility and fine motor dexterity may be the more sensitive indexes of nonspecific surgical effects. Similar to other investigations, our results indicate that neuropsychologic deficits associated with CABG are generally transient, with resolution of deficits occurring before the sixth postoperative month. However, this conclusion is weakened by our inability to collect complete follow-up data. Although there was no obvious sampling bias imposed by our follow-up solication procedures, it is possible that the subsamples studied in a 6-month follow-up period do not adequately represent their respective postoperative groups. The similarity of postoperative findings between the larger samples and subsamples (Figs. 1 and 2), however, argues against the existence of a follow-up selection bias. In addition, postoperative change scores were studied for each group comparing the performance of patients who ultimately completed follow-up testing with those who did not. No significant differences were found between patients who did and did not complete follow-up for any of the three groups. REFERENCES 1. Harrison DC. Coronary bypass: the first 10 years. Hoop Pract 1981;16:49-56. 2. Folks DG, Franceschini J, Sokol RS, Freeman AM, Folks DM. Coronary artery bypass surgery in older patients: psychiatric morbidity. South Med J 1986;79:303-6. 3. Savageau JA, Stanton B, Jenkins CD, Klein MD. Neuropsychological dysfunction following elective cardiac operation. I. Early assessment. J THORAC CARDIOVASC SURG 1982;84:585-94. 4. Savageau JA, Stanton B, Jenkins CD, Frater RW. Neuropsychological dysfunction following elective cardiac operation. II. A six-month reassessment. J THORAC CAR. DlOVASC SURG 1982;84:595-600. 5. Sotaniemi KA. Cerebral outcome after extracorporeal circulation. Arch Neurol 1983;40:75-7. 6. Frank KA, Heller SS, Kornfeld DS, Maim JR. Longterm effects of open-heart surgery on intellectual functioning. J THORAC CARDIOVASC SURG 1972;64:811-5. 7. Sachdev NS, Carter CC, Swank RL, Blachly PH. Relationship between post-cardiotomy delerium, clinical neurological changes and EEG abnormalities. J THORAC CARDIOVASC SURG 1967;54:557-63. 8. Juolasmaa A, Outakoski J, Hirvenoja R, Tienari P, Sotaniemi K, Takkunen J. Effect of open heart surgery on intellectual performance. J Clin Neuropsychol 1981; 3:181-97. 9. Shaw PJ, Bates D, Cartlidge NE, Heaviside D, Julian DG, Shaw DA. Early neurological complications of coronary artery bypass surgery. Br Med J 1985;291: 1384-7.
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10. Sotaniemi KA, Juolasmaa A, Hokkanen ET. Neuropsychologic outcome after open-heart surgery. Arch Neural 1981;38:2-8. 11. Sotaniemi KA. Five-year neurological EEG outcome after open-heart surgery. J Neurol Neurosurg Psychiatry 1985;48:569-75. 12. Raymond M, Conklin C, Schaeffer J, Newstadt G, Matloff JM, Gray RJ. Coping with transient intellectual dysfunction after coronary bypass surgery. Heart Lung 1984;13:531-9. 13. Henfiksen L. Evidence suggestive of diffuse brain damage following cardiac operations. Lancet 1984;1(8381):81620. 14. Aberg T, Kihlgren M. The use of psychometric testing as a quality criterion in open-heart surgery. In: Speidel H, Rodewald G, eds. Psychic and neurologic dysfunctions after open-heart surgery; 1st international symposium, Hamburg, West Germany. New York: Thieme Medical Publishers, 1980:107-11. 15. Elsass P, Henriksen L. Acute cerebral dysfunction after open-heart surgery. Scand J Thorac Cardiovasc Surg 1984;18:161-5. 16. Heikkinen L. Clinically significant neurological disorders following open heart surgery. Thorac Cardiovasc Surg 1985;33:201-6. 17. Budabin M. Neurologic complications of open heart surgery. Mt Sinai J Med 1982;40:311-3. 18. Brauthwaite MA. Neurological damage related to open heart surgery: a clinical survey. Thorax 1972;27:748-53. 19. Javid H, Tufo HM, Nojafi H, Dye WS, Hunter JA, Julian Oc. Neurological abnormalities following openheart surgery. J THORAC CARDIOVASC SURG 1969;58: 502-9. 20. Shaw PJ, Bates D, Cartlidge NE, et al. Early intellectual dysfunction following coronary bypass surgery. Q J Med 1986;58:59-68. 21. Shaw PJ, Bates D, Cartlidge NE, et al. Neurological complications of coronary artery bypass graft surgery: six-month follow-up study. Br Med J 1986;293:165-7. 22. Sotaniemi KA, Mononen H, Hokkannen TE. Long-term cerebral outcome after open-heart surgery: a five-year neuropsychological follow-up study. Stroke 1986;17: 410-6. 23. Aberg T, Ahlund P, Kihlgren M. Intellectual function late after open-heart operation. Ann Thorac Surg 1983; 36:680-3. 24. Aberg T, Ronquist G, Tyden H, et al. Adverse effects on the brain in cardiac operations as assessed by biochemical, psychometric, and radiologic methods. J THORAC CARDlOVASC SURG 1984:87:99-105. 25. Taylor KM. Pathophysiology of brain damage during open-heart surgery. Tex Heart Inst J 1986;13:91-5. 26. Okies JE, Page US, Bigelow JC, Krause AH, Salomon NW, Laxer KL. The impact of electroencephalography, pressure and p02 monitoring on the risk of stroke during cardiopulmonary bypass. Text Heart Inst J 1986;13:97104.
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27. Buschke H, Fuld PA. Evaluating storage, retention, and retrieval in disordered memory and learning. Neurology 1974;24:1019-25. 28. Hannay HJ, Levin HS. Selective Reminding Test: an examination of equivalence of four forms. J Clin Exp Neuropsychol 1985;7:251-63. 29. Lezak MD. Neuropsychological Assessment. New York: Oxford University Press, 1976. 30. Heaton RK. Wisconsin Card Sorting Test: manual. Odessa, Fla: Psychological Assessment Resources, 1981. 31. Benton AL, Hamsher K. Multilingual aphasia examination (manual revised, 1978. Iowa City: University of Iowa, 1976. 32. Wechsler D. WAIS-R manual. New York: Psychological Corporation, 1981. 33. Reitan RM. Validity of the Trail Making Test as an indication of organic brain damage. Percept Mot Skills 1958;8:271-6.
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34. Lafayette grooved pegboard. Lafayette, Ind.: Lafayette Instrument Co. 35. McNair DM, Lorr M, Droppleman LF. Profile of Mood States. San Diego, California: Educational and Industrial Testing Service. 36. Taylor KM, Wright GS, Reid JS, et al. Comparative studies of pulsatile and non-pulsatile flow during cardiopulmonary bypass. II. The effects on adrenal secretion of cortisol. J THORAC CARDIOVASC SURG 1978;75:574-8. 37. Taylor KM, Wright GS, Bain WH, Caves PK, Beastall GS. Comparative studies of pulsatile and nonpulsatile flow during cardiopulmonary bypass. III. Response of anterior pituitary gland to thyrotropin-releasing hormone. J THORAC CARDIOVASC SURG 1978;75:579-84. 38. Rao SM, Hammeke TA, McQuillen MP, Khatri BO, Lloyd D. Memory disturbance in chronic progressive multiple sclerosis. Arch Neurol 1984;41:625-31.
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