Neuropsychological
Dysfunction After Cardiopulmonary A Comparison of Two institutions
Nancy
A. Nussmeier,
MD, and Kevin
Bypass:
J. Fish, MB, ChB
The authors compared perioperative neuropsychologic dysfunction in patients participating in two studies conducted in institutions using different strategies to manage cardiopulmonary bypass. These differences included hypothermia versus normothermia, presence versus absence of arterial microfilters, and the presence versus absence of glucose-containing solution in the pump prime. Other differences between the two institutions included the type of surgery (intracardiac v extracardiac), the mean duration of cardiopulmonary bypass, and degree of low perfusion pressure during bypass. Despite these major differences, perioperative neuropsychologic dysfunction measured by the two-part Trail-Making psychomet-
ric test was similar in the two institutions. Several factors were analyzed for their possible contribution to development of dysfunction, including institution, anesthetic management, age, sex, degree of low perfusion pressure during bypass, and duration of bypass; only age was significant. These results suggest that differences in surgical procedure and management of cardiopulmonary bypass previously thought to contribute to the development of subtle cognitive deficits after cardiac surgery may have been overemphasized. Copyright a(:,1991 by W.B. Saunders Company
C
and the management of CPB were very different. However. anesthetic management of the control groups was similar in that the primary anesthetic agent was moderateto highdose fentanyl. More importantly, the same two-part TrailMaking Test was administered to patients at both institutions. Accordingly, the results of psychometric testing at these two institutions were compared, addressing two major questions: (1) did the severity of perioperative dysfunction differ between institutions; and (2) what factors contributed to development of such dysfunction?
EREBRAL INJURY, evident as either overt neurological deficit or subtle cognitive dysfunction, has long been recognized as a complication of cardiac surgery and cardiopulmonary bypass (CPB). Overt neurological scquelae are usually caused by large emboli from the surgical field.‘.’ Fortunately, devastating complications such as major strokes are infrequent, occurring in < 10% of patients having intracardiac surgery’~” and in 400 seconds. At THI, a glucose-containing solution was used to prime the CPB circuit (20 mL/kg of 5% dextrose in lactated Ringer’s solution, 200 U/L of heparin), whereas the prime at VAMC contained no glucose (2,000 mL of lactated Ringer’s solution, 50 mL of 8.4% sodium bicarbonate, 5,000 U of heparin) (Table 1). No arterial line filters were used at THI; Bentley AF-10 arterial filters (Bentley Laboratories, Irvine, CA) were used in all patients at VAMC. At THI, nasopharyngeal temperature was ~34°C throughout CPB; whereas at VAMC, moderate systemic hypothermia (30°C) was present during the period of aortic cross-clamping. Mean arterial perfusion pressure was maintained between 40 and 90 mm Hg at THI and between 30 and 70 mm Hg at VAMC. Nonpulsatile pump flow varied between 40 and 60 mL/kg/ min at THI and between 35 and 55 mL/kg/min at VAMC.
StatisticalAnalysis The perioperative change in performance of the Trail-Making Tests was calculated as the percent change between a patient’s preoperative and postoperative score. A positive percent change indicated an increased time to perform the task, ie, a deterioration in performance. This was felt to be the best representation of the change in an individual’s score from preoperative to postoperative testing. Paired t tests were used to determine whether the postoperative mean scores of each group were significantly different from the preoperative scores. Results for the four groups were analyzed
THI
Intracardiac
Surgery
Yes
No
Arterial line filter
No
Yes
Temperature
I”C)
Perfusion pressure (mm Hg)
234
530
40-90
30-70
by the Kruskal-Wallis one-way analysis of variance for nonparamet-
ric means. To identify the contribution of different factors to the development of neuropsychological dysfunction, stepwise multiple linear regression analysis was performed. Factors included in this analysis were institution, group, age, sex, duration of CPB, and TM-“‘. Subsequent statistical analyses were based on the results of the multiple linear regression analysis, which indicated age as the only significant factor. Each group was stratified according to age into two subgroups (5 60 v > 60 years). The Kruskal-Wallis test (with Bonferroni correction) was used to evaluate the effects of subdividing groups by age and compare results based on institution, treatment, and age. Differences were considered significant when P < 0.05. RESULTS
Patients were excluded from analysis of neuropsychologic results if they developed immediate (n = 13) or late (n = 4) postoperative onset of overt neurological or psychiatric dysfunction or other nonneurological complications (n = 6) that prevented postoperative psychometric testing. The mean age of patients was similar in the two institutions (Table 2). The duration of CPB was significantly longer and cumulative TM-‘” values were significantly higher in the VAMC control group than in the THI control group. TMd5” values were also significantly higher in the VAMC prostacyclin study group than in the VAMC control group. Comparison of All Groups A deterioration in perioperative performance on the Trail-Making Tests was noted in many patients in both institutions, although there was considerable interpatient variability (Table 3). Comparison of all groups, including the THI control, VAMC control, THI thiopental study, and VAMC prostacyclin study groups, showed no significant differences among these four groups in performance decrements on either part of the Trail-Making Test. Stepwise multilinear regression analysis identified age as the only Table 2. Patient and Perioperative Characteristics
No. of Patients Age (v) CPB time* (min)
TM-‘” value is a quantitative measure of low perfusion during CPB. It is calculated by multiplying the magnitude less than 50 mm Hg by the number of minutes that MAP less than 50 mm Hg. It is expressed in mm Hg min.
Extracardiac
Glucose prime
TM-“*(mmHg.min)
*The pressure of MAP remains
VAMC
THI
VAMC
THI
VAMC
Control
Control
Thiopental
Prostacyclin
47
82
542
81 15
58 + 6
56 + 14
58 k 6
492
18
98 r 27
49 2 17
99 2 25
151 2 136 286+
177 19Ok
49
159 663+450t
NOTE. Values are expressed as mean k SD. *Significant difference between the two control groups. tsignificant trol groups.
difference between VAMC prostacyclin and VAMC con-
NUSSMEIER AND Fist-
586
Table
3.
Neuropsychological
VAMC
THI
VAMC
CO~~tWY
Control
Thiopentai
Prostacyclln ____-
All patients
10 2 37*
11 135
23 _+48*
1 i 30
>60yr
13 i 36
11 440
40 i 53t
8 I 34
THI Tf?Si
Age Group
Trails A
Trials B
260yr
8 2 34
10 t 32
10240
All patients
27 2 44*
10 I37
29 i- 47”
24 ? 56*
>60yr
37 k 58
12 + 48
45 i 56
35 2 71
60 years (Table 3). Comparisons between THI and VAMC control groups showed no differences in patients aged 160 years or in patients aged > 60 years on either part A or B of the Trail-Making Test. There was no correlation between duration of CPB and perioperative neuropsychological dysfunction at either institution. THI control and thiopental study groups. The performance of patients aged > 60 years in the thiopental study group was significantly worse than patients aged r: 60 years in the same group on part A. but not on part B of the Trail-Making Test. Comparison of perioperative dysfunction between the THI thiopental study and the THI control group did not reach statistical significance on either part A or part B in patients 5 60 or > 60 years old. VAMC control andprostacyclin study groups. There were no significant differences between patients aged 560 and aged >60 years within the prostacyclin study group, and there were no differences between this group and the VAMC control group in patients aged I 60 or > 60 years. DISCUSSION
There were major differences between institutions in the type of surgery, management of perfusion, duration of CPB, and degree of low perfusion pressure during CPB (Table 1). These differences encompass many of the factors that are thought to be of importance in the development of postoperative cerebral dysfunction. In addition, patients at THI were retested 2 days earlier in the postoperative period than were VAMC patients. The effect of so many differences in management cannot be predicted. It could be argued that many of these variables may have created potentially offsetting effects, eg, intracardiac surgery, shorter bypass times, higher temperatures, no in-line filters, and earlier postoperative neurological assessment in the THI group, as compared with extracardiac surgery, longer by-
pass times, lower temperatures, and the use of arterial line filters in the VAMC groups. Despite these differences, the severity of postoperative dysfunction was similar in the two institutions. This suggests that such changes in cognitive function are attributable to factors intrinsic to the process of CPB, regardless of differences in perfusion techniques. These conclusions are drawn from the results of a single two-part psychometric test, but it should be emphasized that this test is one of the most widely used and wellstandardized psychometric tests for the assessment of cerebral function. Although it would have been ideal for a number of the same psychometric tests to have been administered to both groups of patients on the same postoperative day, these studies had very different foci and were conceived in isolation. Only after the two studies were completed were the two authors aware of the opportunity to compare the results of the two studies. It would also have been ideal if there had been no missing data points, but in studies of this nature, it would be unrealistic not to expect some loss of patients. In fact, the “dropouts” were relatively few in relation to the numbers involved, and were not always due to neurological complications.‘.” The purpose of this comparison was to examine neuropsychological dysfunction in patients who did not have overt neurological dysfunction. Clearly, inclusion ot the patients who suffered a stroke or other debilitating postoperative complication, even had they been capable of completing the neuropsychological assessments, would have distorted the results. Deterioration was more marked in patients aged >60 years compared with those aged 160 years who received thiopental at THI. Because patients at THI were retested relatively early (on postoperative day 5), these results may reflect drug effects in the elderly (slower metabolism of large thiopental doses in combination with significant doses of diazepam) rather than an actual difference in neuropsychological dysfunction. This hypothesis is supported by the finding that postoperative performance of younger THI thiopental study group patients (aged I 60 years) did not differ from the THI control group. Perioperative deterioration in performance on psychometric tests is more marked in patients undergoing surgery requiring CPB than in patients having noncardiac surgery. “~I4Several theories have been advanced to account for
NEUROPSYCHOLOGICAL DYSFUNCTION AFTER CPB
587
development of neuropsychological dysfunction after CPB. These include inadequate cerebral perfusion due to hypotension during CPB,‘3,‘8,‘9diffuse gaseous microemboli from bubble oxygenators,‘@= particulate microemboli such as platelet aggregates, fibrin, and foreign particles taken up by the cardiotomy suction,*“~22and prolonged CPB time.8.‘3.20 Advanced patient age also has been associated with development of neuropsychological dysfunction,‘.’ a finding partially corroborated by these data. No significant relationship was found between the duration of CPB and postoperative neuropsychological dysfunction. Similarly, a low perfusion pressure during CPB, quantified by the TMe5’ index, was not found to be a significant predisposing factor. Values for TM-“’ were highest in patients who received prostacyclin, yet the psychometric test results of this group were similar to those of the other groups. Data from other centers, including psychometric tests, also fail to support the utility of the TMe5’ index as a measure of inadequate cerebral perfusion during CPB.‘6,24 Other factors hypothesized to protect the brain from injury during CPB, eg, the use of microfilters in the arterial line, hypothermia during CPB, and a nonglucose-containing prime,” were present at VAMC and absent at THI. The data do not support the supposition that these practices provide cerebral protection. Recent data from another center specifically document the lack of correlation between the use of arterial microfilters and overt neurological or subclinical neuropsychological dysfunction.26 No controlled studies currently exist to support or refute using hypothermia or nonglucose-containing prime to provide cerebral protection during CPB. Subclinical neuropsychological dysfunction was not mitigated by either thiopental or prostacyclin. This was true despite the previously reported efficacy of thiopental in mitigating overt neurological sequelae, presumed to result from air or particulate macroemboli during intracardiac surgery.’ This neuroprotective effect of thiopental may not extend to patients having extracardiac surgery. In a recent
study, neurological outcome following coronary artery surgery was not affected by the administration of high-dose thiopental.” Similarly, reduction in platelet microemboli by prostacyclin administered during CPB was not associated with significant reduction in neuropsychological dysfunction.15 Consequently, minor cognitive impairment, as measured by psychometric tests, may be caused by mechanisms other than emboli. This hypothesis is supported by the similarity of the neuropsychological results at THI, where patients undergoing intracardiac procedures with high risk for air or particulate embolization were studied (and arterial line microfilters were not used) and those at VAMC, where patients undergoing extracardiac procedures having lower risk for embolization were studied (and microfilters were used). This dual-institutional comparison of post-CPB neuropsychologic dysfunction demonstrated that the severity of postoperative neuropsychological dysfunction was similar in these studies from THI and VAMC, despite differences in the surgical procedures and management of CPB. The data suggest that factors previously thought to contribute to the development of subtle cognitive deficits after CPB may have been overemphasized. The etiology of perioperative neuropsychological dysfunction remains undetermined. Fortunately, these changes are temporary in many patients. “J~J~J~Prospective studies examining the contribution of individual factors are necessary to determine their role in the etiology of neuropsychological dysfunction after CPB. ACKNOWLEDGMENT The authors gratefully acknowledge the participation of Kenneth N. Helms, BA, Frank H. Sarnquist, MD, Carol van Steenis, RN, Otto I. Linet, MD, Mark Hilberman, MD, R. Scott Mitchell, MD, Stuart W. Jamieson, MD, D. Craig Miller, MD, Jared S. Tinklenberg, MD, Carolee Arlund, RN, and Stephen Slogoff, MD in these studies. The assistance of Dr Dennis M. Fisher with the statistical analysis and the counsel of Dr Stephen Slogoff in the preparation of this manuscript are particularly appreciated.
REFERENCES 1. Slogoff S, Girgis KZ, Keats AS: Etiologic factors in neuropsychiatric complications associated with cardiopulmonary bypass. Anesth Analg 61:903-911, 1982
brain in cardiac operations as assessed ric, and radiologic methods. J Thorac 1984
2. Nussmeier NA, Arlund C, Slogoff S: Neuropsychiatric complications after cardiopulmonary bypass: Cerebral protection by a barbiturate. Anesthesiology 64:165-170,1986
8. Sotaniemi KA: Cerebral outcome after extracorporeal lation: Comparison between prospective and retrospective tions. Arch Neurol40:75-77,1983
3. Sotaniemi KA: Brain damage and neurological outcome after open-heart surgery. J Neurol Neurosurg Psychiatry 43:127-135, 1980
9. Shaw PJ, Bates dysfunction following 1986
4. Oka Y, Moriwaki KM, Hong Y, et al: Detection of air emboli in the left heart by M-mode transesophageal echocardiography following cardiopulmonary bypass. Anesthesiology 63:109-113,1985
10. Hammeke TA, Hastings JE: Neuropsychologic alterations after cardiac operation. J Thorac Cardiovasc Surg 96:326-331,1988
5. Martin WRW, Hashimoto SA: Stroke surgery. Can J Neurol Sci 9:21-26,1982
in coronary
bypass
6. Breuer AC, Furlan AJ, Hanson MR, et al: Central nervous system complications of coronary artery bypass graft surgery: Prospective analysis of 421 patients. Stroke 14:682-687, 1983 7. Aberg T, Ronquist
G, Tyden H, et al: Adverse
effects on the
by biochemical, psychometCardiovasc Surg 87:99-105, circuevalua-
D, Cartlidge NEF, et al: Early intellectual coronary bypass surgery. Q J Med 58:59-68,
11. Shaw PJ, Bates D, Cartlidge NEF, et al: Neurologic and neuropsychologicai morbidity following major surgery: Comparison of coronary artery bypass and peripheral vascular surgery. Stroke 18:700-707,1987 12. Townes BD, Bashein G, Hornbein TF, et al: Neurobehavioral outcomes in cardiac aperations: A prospective controlled study. J Thorac Cardiovasc Surg 98:774-782,1989
588
13. Smith PL, Treasure T, Newman SP, et al: Cerebral consequences of cardiopulmonary bypass. Lancet 1:823-X25. 1986 14. Raymond M, Conklin C, Schaeffer J, et al: Coping with transient intellectual dysfunction after coronary bypass surgery. Heart Lung 13:531-530. lY84 IS. Fish KJ, Helms KN, Sarnquist FH, et al: A prospective, randomized study of the effects of prostacyclin on neuropsychologic dysfunction after coronary artery operation. J Thorac Cardiovast Surg 93:609-6 15. 19X7 16. Aren C, Blomstrand C, Wikkelso C, Radegran K: Hypotension induced by prostacyclin treatment during cardiopulmonary bypass does not increase the risk of cerebral complications. .I Thorac Cardiovasc Surg X8:748-753, 19X4 17. Reitan RM: Validity of the trail making test as an indicator of organic brain damage. Percept Mot Skill 8:271-276, 195X IX. Stockard JJ, Bickford RG, Schauble JF: Pressure-dependent cerebral ischemia during cardiopulmonary bypass. J Neural 23:521529, 1973 19. Aberg T, Kihlgren M: Effect of open heart surgery on intellectual dysfunction. Stand J Thorac Cardiovasc Surg 8:1-63, 1974 (suppl IS) 20. Aberg T, Kihlgren M: Cerebral protection during openheart surgery. Thorax 32525.533,1977 21. Taylor KM: Brain damage during open-heart surgery. Thorax 37:873-876. 1982
YUSSMEIEH
AND
FlSk-
22. Blauth (‘I. Arnold JL. Schulcnberg Wk. et al: (‘crchla~ microembolism during cardiopulmonary bypass. J Thorac I‘ardio vast Surg YS:h68-676. 198X 23. Padayachee TS. Parsons S. I‘hrobold R. et al: The etfect ot arterial tiltration on reduction of gaseous microemboli in the middle cerebral artery during cardiopulmonary bypass. Ann Thorat Surg 45:h47-649. IYXX 24. Govier AV. Revra JG. McKay RD. et al: Factors and thetr influence on regional cerebral blood flow during nonpulsatilc cardiopulmonary bypass. ,Ann Thorac Surg 3X:5Y1-599. 1984 25. Scheller MS. Drummond JC. Todd MM, et al: Are recommendations regarding harhituratc protection during bypass just]fied? Anesthesiology h5:730-231. I986 26. /iris A. Solanes Il. C’smara ML. et al: Arterial line filtration during cardiopulmonary hypa\s: Neurologic, neuropsychologic. and hematologic studies. J Thorac Cardiovasc Surg 91:525-533. 1986 27. Zaidan JR, Klochany A. Martin WM, et al: Effect 01 thiopental on neurologic outcome following coronary artery bypass grafting. Anesthesiology 74:406-41 I. IYY1 28. Savageau Neuropsychologic II. A six-month 600. lYX2
JA. Stanton dysfunction reassessment.
BA, Jenkins CD, Fratcr RWM: following elective cardiac operation. J Thorac Cardiovasc Surg X4:595-
Dysfunction After Cardiopulmonary A Comparison of Two institutions
Nancy
A. Nussmeier,
MD, and Kevin
Bypass:
J. Fish, MB, ChB
The authors compared perioperative neuropsychologic dysfunction in patients participating in two studies conducted in institutions using different strategies to manage cardiopulmonary bypass. These differences included hypothermia versus normothermia, presence versus absence of arterial microfilters, and the presence versus absence of glucose-containing solution in the pump prime. Other differences between the two institutions included the type of surgery (intracardiac v extracardiac), the mean duration of cardiopulmonary bypass, and degree of low perfusion pressure during bypass. Despite these major differences, perioperative neuropsychologic dysfunction measured by the two-part Trail-Making psychomet-
ric test was similar in the two institutions. Several factors were analyzed for their possible contribution to development of dysfunction, including institution, anesthetic management, age, sex, degree of low perfusion pressure during bypass, and duration of bypass; only age was significant. These results suggest that differences in surgical procedure and management of cardiopulmonary bypass previously thought to contribute to the development of subtle cognitive deficits after cardiac surgery may have been overemphasized. Copyright a(:,1991 by W.B. Saunders Company
C
and the management of CPB were very different. However. anesthetic management of the control groups was similar in that the primary anesthetic agent was moderateto highdose fentanyl. More importantly, the same two-part TrailMaking Test was administered to patients at both institutions. Accordingly, the results of psychometric testing at these two institutions were compared, addressing two major questions: (1) did the severity of perioperative dysfunction differ between institutions; and (2) what factors contributed to development of such dysfunction?
EREBRAL INJURY, evident as either overt neurological deficit or subtle cognitive dysfunction, has long been recognized as a complication of cardiac surgery and cardiopulmonary bypass (CPB). Overt neurological scquelae are usually caused by large emboli from the surgical field.‘.’ Fortunately, devastating complications such as major strokes are infrequent, occurring in < 10% of patients having intracardiac surgery’~” and in 400 seconds. At THI, a glucose-containing solution was used to prime the CPB circuit (20 mL/kg of 5% dextrose in lactated Ringer’s solution, 200 U/L of heparin), whereas the prime at VAMC contained no glucose (2,000 mL of lactated Ringer’s solution, 50 mL of 8.4% sodium bicarbonate, 5,000 U of heparin) (Table 1). No arterial line filters were used at THI; Bentley AF-10 arterial filters (Bentley Laboratories, Irvine, CA) were used in all patients at VAMC. At THI, nasopharyngeal temperature was ~34°C throughout CPB; whereas at VAMC, moderate systemic hypothermia (30°C) was present during the period of aortic cross-clamping. Mean arterial perfusion pressure was maintained between 40 and 90 mm Hg at THI and between 30 and 70 mm Hg at VAMC. Nonpulsatile pump flow varied between 40 and 60 mL/kg/ min at THI and between 35 and 55 mL/kg/min at VAMC.
StatisticalAnalysis The perioperative change in performance of the Trail-Making Tests was calculated as the percent change between a patient’s preoperative and postoperative score. A positive percent change indicated an increased time to perform the task, ie, a deterioration in performance. This was felt to be the best representation of the change in an individual’s score from preoperative to postoperative testing. Paired t tests were used to determine whether the postoperative mean scores of each group were significantly different from the preoperative scores. Results for the four groups were analyzed
THI
Intracardiac
Surgery
Yes
No
Arterial line filter
No
Yes
Temperature
I”C)
Perfusion pressure (mm Hg)
234
530
40-90
30-70
by the Kruskal-Wallis one-way analysis of variance for nonparamet-
ric means. To identify the contribution of different factors to the development of neuropsychological dysfunction, stepwise multiple linear regression analysis was performed. Factors included in this analysis were institution, group, age, sex, duration of CPB, and TM-“‘. Subsequent statistical analyses were based on the results of the multiple linear regression analysis, which indicated age as the only significant factor. Each group was stratified according to age into two subgroups (5 60 v > 60 years). The Kruskal-Wallis test (with Bonferroni correction) was used to evaluate the effects of subdividing groups by age and compare results based on institution, treatment, and age. Differences were considered significant when P < 0.05. RESULTS
Patients were excluded from analysis of neuropsychologic results if they developed immediate (n = 13) or late (n = 4) postoperative onset of overt neurological or psychiatric dysfunction or other nonneurological complications (n = 6) that prevented postoperative psychometric testing. The mean age of patients was similar in the two institutions (Table 2). The duration of CPB was significantly longer and cumulative TM-‘” values were significantly higher in the VAMC control group than in the THI control group. TMd5” values were also significantly higher in the VAMC prostacyclin study group than in the VAMC control group. Comparison of All Groups A deterioration in perioperative performance on the Trail-Making Tests was noted in many patients in both institutions, although there was considerable interpatient variability (Table 3). Comparison of all groups, including the THI control, VAMC control, THI thiopental study, and VAMC prostacyclin study groups, showed no significant differences among these four groups in performance decrements on either part of the Trail-Making Test. Stepwise multilinear regression analysis identified age as the only Table 2. Patient and Perioperative Characteristics
No. of Patients Age (v) CPB time* (min)
TM-‘” value is a quantitative measure of low perfusion during CPB. It is calculated by multiplying the magnitude less than 50 mm Hg by the number of minutes that MAP less than 50 mm Hg. It is expressed in mm Hg min.
Extracardiac
Glucose prime
TM-“*(mmHg.min)
*The pressure of MAP remains
VAMC
THI
VAMC
THI
VAMC
Control
Control
Thiopental
Prostacyclin
47
82
542
81 15
58 + 6
56 + 14
58 k 6
492
18
98 r 27
49 2 17
99 2 25
151 2 136 286+
177 19Ok
49
159 663+450t
NOTE. Values are expressed as mean k SD. *Significant difference between the two control groups. tsignificant trol groups.
difference between VAMC prostacyclin and VAMC con-
NUSSMEIER AND Fist-
586
Table
3.
Neuropsychological
VAMC
THI
VAMC
CO~~tWY
Control
Thiopentai
Prostacyclln ____-
All patients
10 2 37*
11 135
23 _+48*
1 i 30
>60yr
13 i 36
11 440
40 i 53t
8 I 34
THI Tf?Si
Age Group
Trails A
Trials B
260yr
8 2 34
10 t 32
10240
All patients
27 2 44*
10 I37
29 i- 47”
24 ? 56*
>60yr
37 k 58
12 + 48
45 i 56
35 2 71
60 years (Table 3). Comparisons between THI and VAMC control groups showed no differences in patients aged 160 years or in patients aged > 60 years on either part A or B of the Trail-Making Test. There was no correlation between duration of CPB and perioperative neuropsychological dysfunction at either institution. THI control and thiopental study groups. The performance of patients aged > 60 years in the thiopental study group was significantly worse than patients aged r: 60 years in the same group on part A. but not on part B of the Trail-Making Test. Comparison of perioperative dysfunction between the THI thiopental study and the THI control group did not reach statistical significance on either part A or part B in patients 5 60 or > 60 years old. VAMC control andprostacyclin study groups. There were no significant differences between patients aged 560 and aged >60 years within the prostacyclin study group, and there were no differences between this group and the VAMC control group in patients aged I 60 or > 60 years. DISCUSSION
There were major differences between institutions in the type of surgery, management of perfusion, duration of CPB, and degree of low perfusion pressure during CPB (Table 1). These differences encompass many of the factors that are thought to be of importance in the development of postoperative cerebral dysfunction. In addition, patients at THI were retested 2 days earlier in the postoperative period than were VAMC patients. The effect of so many differences in management cannot be predicted. It could be argued that many of these variables may have created potentially offsetting effects, eg, intracardiac surgery, shorter bypass times, higher temperatures, no in-line filters, and earlier postoperative neurological assessment in the THI group, as compared with extracardiac surgery, longer by-
pass times, lower temperatures, and the use of arterial line filters in the VAMC groups. Despite these differences, the severity of postoperative dysfunction was similar in the two institutions. This suggests that such changes in cognitive function are attributable to factors intrinsic to the process of CPB, regardless of differences in perfusion techniques. These conclusions are drawn from the results of a single two-part psychometric test, but it should be emphasized that this test is one of the most widely used and wellstandardized psychometric tests for the assessment of cerebral function. Although it would have been ideal for a number of the same psychometric tests to have been administered to both groups of patients on the same postoperative day, these studies had very different foci and were conceived in isolation. Only after the two studies were completed were the two authors aware of the opportunity to compare the results of the two studies. It would also have been ideal if there had been no missing data points, but in studies of this nature, it would be unrealistic not to expect some loss of patients. In fact, the “dropouts” were relatively few in relation to the numbers involved, and were not always due to neurological complications.‘.” The purpose of this comparison was to examine neuropsychological dysfunction in patients who did not have overt neurological dysfunction. Clearly, inclusion ot the patients who suffered a stroke or other debilitating postoperative complication, even had they been capable of completing the neuropsychological assessments, would have distorted the results. Deterioration was more marked in patients aged >60 years compared with those aged 160 years who received thiopental at THI. Because patients at THI were retested relatively early (on postoperative day 5), these results may reflect drug effects in the elderly (slower metabolism of large thiopental doses in combination with significant doses of diazepam) rather than an actual difference in neuropsychological dysfunction. This hypothesis is supported by the finding that postoperative performance of younger THI thiopental study group patients (aged I 60 years) did not differ from the THI control group. Perioperative deterioration in performance on psychometric tests is more marked in patients undergoing surgery requiring CPB than in patients having noncardiac surgery. “~I4Several theories have been advanced to account for
NEUROPSYCHOLOGICAL DYSFUNCTION AFTER CPB
587
development of neuropsychological dysfunction after CPB. These include inadequate cerebral perfusion due to hypotension during CPB,‘3,‘8,‘9diffuse gaseous microemboli from bubble oxygenators,‘@= particulate microemboli such as platelet aggregates, fibrin, and foreign particles taken up by the cardiotomy suction,*“~22and prolonged CPB time.8.‘3.20 Advanced patient age also has been associated with development of neuropsychological dysfunction,‘.’ a finding partially corroborated by these data. No significant relationship was found between the duration of CPB and postoperative neuropsychological dysfunction. Similarly, a low perfusion pressure during CPB, quantified by the TMe5’ index, was not found to be a significant predisposing factor. Values for TM-“’ were highest in patients who received prostacyclin, yet the psychometric test results of this group were similar to those of the other groups. Data from other centers, including psychometric tests, also fail to support the utility of the TMe5’ index as a measure of inadequate cerebral perfusion during CPB.‘6,24 Other factors hypothesized to protect the brain from injury during CPB, eg, the use of microfilters in the arterial line, hypothermia during CPB, and a nonglucose-containing prime,” were present at VAMC and absent at THI. The data do not support the supposition that these practices provide cerebral protection. Recent data from another center specifically document the lack of correlation between the use of arterial microfilters and overt neurological or subclinical neuropsychological dysfunction.26 No controlled studies currently exist to support or refute using hypothermia or nonglucose-containing prime to provide cerebral protection during CPB. Subclinical neuropsychological dysfunction was not mitigated by either thiopental or prostacyclin. This was true despite the previously reported efficacy of thiopental in mitigating overt neurological sequelae, presumed to result from air or particulate macroemboli during intracardiac surgery.’ This neuroprotective effect of thiopental may not extend to patients having extracardiac surgery. In a recent
study, neurological outcome following coronary artery surgery was not affected by the administration of high-dose thiopental.” Similarly, reduction in platelet microemboli by prostacyclin administered during CPB was not associated with significant reduction in neuropsychological dysfunction.15 Consequently, minor cognitive impairment, as measured by psychometric tests, may be caused by mechanisms other than emboli. This hypothesis is supported by the similarity of the neuropsychological results at THI, where patients undergoing intracardiac procedures with high risk for air or particulate embolization were studied (and arterial line microfilters were not used) and those at VAMC, where patients undergoing extracardiac procedures having lower risk for embolization were studied (and microfilters were used). This dual-institutional comparison of post-CPB neuropsychologic dysfunction demonstrated that the severity of postoperative neuropsychological dysfunction was similar in these studies from THI and VAMC, despite differences in the surgical procedures and management of CPB. The data suggest that factors previously thought to contribute to the development of subtle cognitive deficits after CPB may have been overemphasized. The etiology of perioperative neuropsychological dysfunction remains undetermined. Fortunately, these changes are temporary in many patients. “J~J~J~Prospective studies examining the contribution of individual factors are necessary to determine their role in the etiology of neuropsychological dysfunction after CPB. ACKNOWLEDGMENT The authors gratefully acknowledge the participation of Kenneth N. Helms, BA, Frank H. Sarnquist, MD, Carol van Steenis, RN, Otto I. Linet, MD, Mark Hilberman, MD, R. Scott Mitchell, MD, Stuart W. Jamieson, MD, D. Craig Miller, MD, Jared S. Tinklenberg, MD, Carolee Arlund, RN, and Stephen Slogoff, MD in these studies. The assistance of Dr Dennis M. Fisher with the statistical analysis and the counsel of Dr Stephen Slogoff in the preparation of this manuscript are particularly appreciated.
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