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Electroencephalographic changes and cerebral complications in open-heart surgery
Electroencephalographic changes and cerebral complications in open-heart surgery Marian M. Witoszka, M.D. (by invitation), Hisashi Tamura, M.D. (by invitation), Robert lndeglia, M.D., Ph.D. (by invitation), Robert W. Hopkins, M.D. (by invitation), and F. A. Simeone, M.D., Providence, R. I.
Cerebral dysfunction and behavioral disorders are commonly recognized complications of open-heart surgery. However, hemodynamic alterations occurring during operation do not always correlate with postoperative neurological abnormalities, which may result from decreased cerebral perfusion, embolism of air or particulate matter, or acid-base disturbances during surgery. Continuous electroencephalographic (EEG) monitoring during cardiopulmonary bypass has been suggested as an important technique for the early recognition of hypoxia and alterations of cerebral metabolism. 1 However, few reports have considered correlation between the occurrence of abnormalities of the EEG during surgery and postoperative neurological complications.": 3 The study reported herein was undertaken to evaluate the importance of EEG changes during cardiopulmonary bypass and to correlate them with clinical and pathological cerebral sequelae. From the Division of Biological and Medical Sciences. Brown University, and the Departments of Surgery and Pathology, The Miriam Hospital, Providence, R. I. Read at the Fifty-third Annual Meeting of The American Association for Thoracic Surgery, Dallas, Texas, April 16,17, and 18, 1973. Address for reprints: Dr. Marian M. Witoszka, the Department of Surgery, The Miriam Hospital, Providence, R. I. 02906.
Materials and methods
All patients undergoing open-heart surgery between 1968 and 1972 were continuously monitored with the EEG during the procedure. Detailed analysis of 100 patients comprises the basis of this report. The patients were grouped as follows: Group I, 50 patients who survived; Group II, 5 patients who died during the operation; Group III, 45 patients who died in the postoperative period. The selection of patients for the group of survivors was made as follows: From 130 surviving patients, 100 were selected on the basis of their being comparable to those in Groups II and III in regard to sex, age, and the operation done, They were grouped chronologically, and alternate patients were chosen to form Group I (50 cases) . Groups II and III comprised all of the patients who died during the period of study. Twenty of these had a postmortem examination of the brain. Operative and postoperative care of each patient was under the direct supervision of one of the several cardiac surgeons participating in the open-heart surgical program at this institution. Perfusion techniques were altered during the period of study. The Travenol 3RF oxygenator was employed in 55 cases (27 in Group I) and the Bentley oxygenator in 45 cases (23 in Group I).
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Table I. Hypotension and clinical neurological changes in relation to electroencephalograie Hypotension during operation
Patients
Abnormalities in the EEG*
No.
Present Absent Total No. of patients
7 43 50
I
Per cent
14
86 100
No.
3 4 7
I
Hypotension ajter operation
I
Per
Per cent
No.
43 9 14
I
14
10
23 22
II
celli
"Electroencephalogram.
Table II. Hypotension and clinical neurological changes in relation to electroencephalographic A bnormalities in the EEG
Present Absent Total No. of patients
No. of patients No.
I
Per cent
25
20
55 44
45
100
Partial hemodilution (whole blood and 5 per cent dextrose in water) was used in 79 patients, and total hemodilution (PlasmaLyte 148 electrolyte solution entirely) was used in the other 21 patients. There was no obvious difference in the postoperative course of these two groups. Arterial and central venous pressures were continually monitored during and after surgery on an oscillographic monitor. Continuous EEG recordings were obtained during operation with an 8-channel Grass EEG (Model 6) under standard conditions. Ten standard external electrodes were applied in bipolar patterns, two pairs in the frontal area, one in the occipital area, and two in the temporal areas. Recording was begun prior to the induction of anesthesia and was continued through closure of the skin. Postmortem examinations of the brains were made by standard gross and microscopic techniques. In every case, sections were taken from the frontal, parietal, and occipital cortices, basal ganglia, hippocampi, cerebellar hemispheres, medulla oblongata, and calcarine cortices. All grossly apparent lesions were liberally sampled. Statistical calculations were made with the use of the chi-square test for independence of two variables. A level of 0.05 for the p value was chosen for acceptable significance.'
Hypotension during operation No.
16
10 25
I
Hypotension after operation
Per cent
No.
64 50 57
18 14 32
I
Per
celli
72 70 71
Definitions of criteria
1. EEG abnormality was defined as an isoelectric record or a slowing of the basic rhythm to an activity of less than 3 cycles per second for at least 60 seconds. 2. Encephalopathy included confusion, delirium, disorientation, and coma." 3. Motor dysfunction was defined as clinically demonstrable physical signs of focal central nervous system malfunction varying from overt hemiplegia to subtle asymmetry in muscle strength. 4. The combination of encephalopathy and motor changes was labeled multiple neurological changes. 5. Operative hypotension was considered present if a mean arterial pressure of less than 45 mm. Hg lasted more than 5 minutes as measured through a catheter in the radial artery. 6. Postoperative hypotension was defined as a systolic pressure less than 70 mm. Hg and diastolic pressure less than 45 mm. Hg which occurred in the first 12 hours after surgery and lasted more than 2 hours, as measured through a catheter in the radial artery. Results Group I (survivors). Correlation of the EEG during operation with operative hypotension and postoperative neurological ab-
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abnormalities after cardiac surgery in Group I (50 patients who survived) Encephalopathy without motor changes No.
I
Motor changes without encephalopathy
Per cent
No.
3 II
42 25
14
28
o o
I
Per cent
o
o
o
o
Both encephalopathy and motor changes No.
I
3 8
11
All with any neurological changes
Per cent
No.
42 18 22
6 19 25
I
Per cent 85 44 50
abnormalities after cardiac surgery in Group III (45 patients who died) Encephalopathy without motor changes No. 10 4 14
I Per cent 40
20 31
Motor changes without encephalopathy No. 3 5 8
I
Both encephalopathy and motor changes
Per cent
No.
12 25 17
10 4
20
14
31
normalities is shown in Table I. Twentyfive (50 per cent) of the patients in this group of survivors developed at least one neurological complication. Seven patients (14 per cent) had EEG changes during operation, and 6 of them (85 per cent) developed postoperative neurological changes. In the absence of EEG changes, 19 (44 per cent) of the patients developed postoperative neurological changes; the difference was statistically significant (p < 0.05). Although deterioration shown by the EEG during operation does correlate with the development of neurological defects, some patients with EEG changes during operation may manifest no neurological deficit postoperatively, while others may exhibit neurological changes postoperatively despite a normal EEG during operation. Among the survivors there was no significant correlation of EEG changes with neurological complications or with postoperative hypotension. All 7 (14 per cent) surviving patients who developed significant hypotension, however, did develop encephalopathy (p < 0.01). Group II (intraoperative death). All 5 patients who died during operation had isoelectric EEG recordings which lasted more than 5 minutes during the course of the operation. They all had prolonged perfusions with EEG evidence of deterioration
I
All with neurological changes
Per cent
No.
40
23 13 36
I
Per cent
92 65 80
as the procedure progressed beyond 2 hours. One patient developed EEG abnormalities associated with a retrograde dissection of the aorta early in the procedure. Despite rapid conversion to prograde arch perfusion, a return to normal EEG tracings was never achieved. Another patient developed EEG changes secondary to severe anoxia of the brain because of technical problems at the onset of bypass. The abnormal EEG continued to the conclusion of the procedure. Two of the 5 patients died of acute massive myocardial infarction and 1 from uncontrollable bleeding from the right atrium. In these patients EEG activity slowed to 3 cycles per second with low voltage just after completion of cardiopulmonary bypass: Group III (postoperative deaths). Table II shows the relationship between EEG changes, operative hypotension, and postoperative clinical disorders. Twenty-five of the 45 patients (55 per cent) in this group had alterations of the EEG during operation. Twenty-three (92 per cent) developed neurological changes. Twenty of the 45 patients in this group (44 per cent) did not develop EEG abnormalities during operation. Among this group only 13 (65 per cent) developed postoperative neurological defects. The difference between the two groups is statistically significant (p < 0.05). Thus patients with abnormalities in
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Table III. Operative and postoperative findings among patients who survived and patients who died Findings during and after operation
EEG changes Hypotension during operation Hypotension after operation Encephalopathy without motor changes Motor changes without encephalopathy Both encephalopathy and motor changes All neurological changes
Patients who Died (45 patients)
Patients who survived (50 patients) Per cent
No.
7 7 11
14 14 22
25 26 32
55 57 71
< <
<
0.02 0.01 0.01
14
28
14
31
>
0.05
0
0
8
17
< 0.01
11 25
22 50
14 36
31 80
>
No.
I
p value
Per cent
I
0.05
< 0.01
Table IV. Hypotension, clinical neurological changes, and postmortem findings in relation to electroencephalographic abnormalities after cardiac surgery (20 patients who died and had postmortem examination) Findings during and after operation and at postmortem examination
Hypotension during operation Hypotension after operation Encephalopathy without motor changes Motor changes without encephalopathy Both encephalopathy and motor changes All neurological changes Patients with anatomic brain damage
Table V. Pathological findings in 16 patients with brain damage No.
Severe diffuse cortical necrosis Anoxic neuronal degeneration Infarction of the brain Embolization due to particles of calcium Herniation of cerebral tonsils
6
13 8 3 2
the EEG during operation had a significantly higher incidence of encephalopathy with or without focal motor defects. Among the patients who did not survive, there was no correlation between the development of EEG changes during surgery and operative or postoperative hypotension as defined. There was no relationship of the EEG to localizing neurological defects, as such defects generally appeared to be more directly re-
EEG changes (/8 patients)
9 9 1 6 9
16 15
No EEG changes (2 patients)
o
o o o 1
1 1
A II (20 patients)
9 9 1 6
10 17 16
lated to embolic phenomena which were not detected by the EEG. Correlations between operative and postoperative disorders in the survival and nonsurvival groups (Groups I and II) are shown in Table III. It is clear that patients who died in the postoperative period, when compared with those who survived, were four times more likely to have developed intraoperative EEG abnormalities, four times more likely to have developed hypotension during operation, more likely to have developed hypotension postoperatively, and more likely to have developed neurological disorders of some kind. Pathological findings. A postmortem examination of the brain was performed in 20 patients. Clinical and EEG observations in these patients are summarized in Table IV. At least one histologic abnormality was noted in each of
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Fig. 1. Photomicrograph from the cerebellum of a 22-year-old woman who died 2 days after replacement of an old mitral prosthesis. Extensive necrosis of Purkinje cells can be seen. (Hematoxylin and eosin; original magnification x200.)
Fig. 2. Photomicrograph of the hippocampus from a 55-year-old woman who died 5 days after mitral valve replacement with a prosthesis. Severe ischemic degeneration of neuronal cells is apparent. (Hematoxylin and eosin; original magnification x200.)
16 cases. The changes are recorded in Table V. The most common histologic manifestation was the kind of neuronal degeneration commonly attributed to anoxia (13 patients) . Ten of the 13 had both encephalopathy and localizing motor changes. The lesions appeared as focal areas of tissue vacuolization, neuronal death, and loss of neuronal cells. They occurred most fre-
quently in the hippocampus, cerebral cortex, and cerebellar cortex (Figs. 1 and 2). Eight of the 16 had postoperative localizing motor defects; all of them showed evidence of cerebral infarction (Fig. 3). Calcium emboli were found in 3 of the 6 patients. In 1 case, basilar artery thrombosis with severe parenchymal damage was demonstrated (Fig. 4). In 6 patients, each
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Fig. 3. Photomicrograph from the same patient as in Fig . 2, showing the margin of an infarct in the cerebral cortex with cellular reaction. (Hematoxylin and eosin ; original magnification x200.)
Fig 4. Photomicrograph of the cerebellum in a 47-year-old woman who died 11/2 months after replacement of the mitral valve with a prosthesis. A calcified fragment can be seen in the lumen of a small artery (Hem atoxylin and eo sin: original magnification x200.)
of whom had hypotension at some time during the operation, the cerebral cortex was diffusely necrotic. Death in these 20 patients was ascribed to the following causes: Nine patients died as a direct result of brain damage. F ive died from cardiac complications, including 4 with acute massive myocardial infarction and I with acute mitral regurgitation following separation of a Magovern prosthesis
from the mitral annulus. Five died because of persistent hemorrhage and shock. One death resulted from embolism to the hepatic artery and necrosis of the liver. Discussion
Neurological disorders which follow open-heart procedures may manifest themselves by a variety of signs and symptoms. Behavioral and gnostic disorders are the
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most common, reported by Javid and colleagues' to occur in 43 per cent of patients who survive cardiac surgery. In their series, such disorders of intellectual function or disturbances of recognition or memory were usually transient and disappeared by the time the patient was discharged from the hospital. However, 15 per cent of their patients had signs of cerebral dysfunction at the time of discharge. Of patients not surviving surgery, up to 85 per cent have been noted to have gross or microscopic pathologic changes in the brains at autopsy.';' L' Diffuse cerebral injury and necrosis were often demonstrated among them. but localized or focal abnormalities appear to be the most common and are believed to be due to embolization by air or particular matter. Tufo" has postulated that cerebral damage is related to arterial hypotension during or after surgery and that its incidence is significantly increased with advanging age, particularly over 70 years. Aguilar reported that among 166 patients who did not survive extracorporeal circulation, the most significant changes were embolic (78 per cent) within the small cerebral vessels, resulting in acute ischemic neuronal damage, foci of infarction, and perivascular and focal subarachnoid hemorrhage. Earlier studies by Wright and associates' indicated that EEG monitoring was an essential adjunct to cardiopulmonary bypass since it provided early warning of unacceptable perfusion characteristics. In a study of 100 patients undergoing open-heart surgery, they concluded that careful EEG monitoring during the procedure could significantly decrease neurological abnormalities resulting from inadequate perfusion. On the other hand Coons and associates" concluded that a level of cerebral perfusion can exist during which irreversible hypoxic tissue damage does not result despite the fact that EEG activity may cease at some time during the course of the operation. In the present studies, patients were examined neurologically for major clinical changes after operation, and attempts were
made to relate them to the EEG alterations recorded during the operative procedure. The presence of EEG abnormalities during operation was found to correlate significantly with the development of postoperative neurological disorders. On the other hand, it became apparent that patients may develop neurological deficits despite normal EEG tracings, whereas postoperative neurological abnormalities may fail to develop in patients who demonstrated EEG changes. A relationship was also identified between operative hypotension, which was defined as a fall in the mean arterial pressure to less than 45 mm. Hg for at least 5 minutes, and the occurrence of postoperative neurological abnormalities. In the group of patients who died in the postoperative period and had a postmortem examination, 80 per cent had neuronal degeneration, which was clearly related to hypotension during operation and encephalopathy after the operation. Neuronal degeneration was observed in 13 patients who had tolerated the operative procedure poorly and whose postoperative course was complicated by a low cardiac output syndrome. Although cerebral cortical necrosis was often demonstrable, lesions were most commonly confined to the cerebellar cortex, the cornu Ammonis of the hippocampus, and to other areas known to be vulnerable to hypoxia. Focal infarction was observed in 8 of the 16 cases. Most of these may have been secondary to air embolism, since intravascular particulate matter could not be identified in relation to the lesions. Embolization by calcific particles was identified in only 3 of the cases. In the patients who died, the incidence of EEG abnormalities was high. Although the abnormalities generally occurred shortly after the institution of bypass, they often suddenly occurred later in the procedure without obvious relationship to alterations in the blood pressure. The flow-rate was maintained at about 2,100 ml. per square meter of body surface area, regardless of variations in the blood pressure. Abnor-
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malities in the EEG appeared to correlate with the duration of perfusion in the patients who died. Indeed, of the 5 patients who died during operation, all had gross abnormalities in the EEG prior to the conclusion of the procedure. The duration of cardiopulmonary bypass averaged 125 minutes in patients who died and 85 minutes in patients who lived. Despite numerous reports describing the neurological disorders which occur following open-heart surgery.:":':' no single etiologic factor has been identified. Certainly the level of tissue perfusion is critical because of the extreme sensitivity of neurons in the brain and cord to hypoxia levels of perfusion. Techniques for monitoring the level of tissue perfusion have not been developed to the point of general availability for the central nervous system. In both animals and man the EEG has been found to be a very sensitive indicator of carbon dioxide accumulation or oxygen depletion.':' Indeed, among the patients who died postoperatively and who had developed abnormalities of the EEG, 16 (64 per cent) had had hypotension during the course of the operation. An isoelectric ("flat") EEG was found in 28 per cent of patients who died (Group III) and in only 2 per cent of the patients who survived (Group I). This suggests that the severity of EEG changes correlates with postoperative prognosis and could provide early warning of organic cerebral alteration. Some of the EEG changes that occur during the operation could reflect alterations in metabolism resulting from the development of new and different flow relationships which, at the present time, are poorly understood. When cardiopulmonary bypass is discontinued, however, abrupt EEG changes may indicate the development of an inadequate cardiac output. Therefore, such EEG changes in the postperfusion period may indicate that continued mechanical circulatory support is necessary. The EEG can provide early warning of unacceptable perfusion characteristics which may give rise to neurological abnormalities.
Summary and conclusions
1. The EEG was recorded continuously in patients undergoing cardiopulmonary bypass for open-heart surgery. Observations of the EEG were correlated with survival, postoperative neurological abnormalities, and operative or postoperative hypotension in 50 surviving and 50 nonsurviving patients. 2. Abnormalities in the EEG during operation correlated with the development of neurological abnormalities in the surviving and nonsurviving groups of patients (Tables I and II). 3. Abnormalities of the EEG and neurological complications were more common among patients who died than among those who lived (Table III). 4. A significant correlation was observed between operative hypotension and the occurrence of postoperative neurological disorders. 5. Histopathological changes in the brain were demonstrated in 80 per cent of autopsied cases. Diffuse neuronal degeneration was the most common pathological manifestation of the encephalopathic syndrome after operation, while focal cerebral necrosis (8 patients) was most often associated with postoperative motor changes. 6. In nearly half the patients, brain injury was an important cause of death after openheart surgery. REFERENCES
2
3
4
5
Lorenz, R., and Hehrlein, F.: Electroencephalographic Findings in Heart Surgery, Minn. Med. 53: 1069, 1970. Davenport, H. T., Arfel, G., and Sanchez, E. R.: The Electroencephalogram in Patients Undergoing Open Heart Surgery With HeartLung By-pass, Anesthesiology 20: 674, 1959. Fisher-Williams, M., and Cooper, R. A.: Some Aspects of Electroencephalographic Changes During Open Heart Surgery, Neurology 14: 472, 1964. Snedecor, G. W.: Statistical Methods, Ames, Iowa, 1971, Iowa University Press, pp. 215219. Javid, H., Tufo, H., Najafi, H., Dye, W. S., Hunter, T. A., and Julian, O. c.: Neurological Abnormalities Following Open-Heart Surgery, J. THoRAc. CARDIOVASC. SURG. 58: 502, 1969.
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6 Tufo, H. M., Ostefeld, A. M., and Shekelle, R.: Central Nervous System Dysfunction Following Open-Heart Surgery, 1. A. M. A. 212: 1933, 1970. 7 Aguilar, M. 1., Gerbode, F., and Hill, D.: Neuropathological Complications of Cardiac Surgery, 1. THoRAc. CARDIOVASC. SURG. 61: 676, 1971. 8 Wright, 1. S., Lethlean, A. K., Hicks, R. G., Torda, T. A., and Stacey, R.: Electroencephalographic Studies During Open-Heart Surgery, 1. THORAC. CARDIOVASC. SURG. 63: 631, 1972. 9 Coons, R. E., Skeats, A. S., and Cooley, D. A.: Significance of Electroencephalographic Changes Occurring During Cardio-pulmonary Bypass, Anesthesiology 20: 674, 1959. 10 Gilman, S.: Cerebral Disorders After OpenHeart Operations, N. Engl. 1. Med. 272: 489, 1965. 11 Blachly, P. H., and Starr, A.: Post-cardiotomy Delirium, Am. 1. Psychiatry 121: 371, 1964. 12 Sachdev, N. S., Carter, C. C., Swank, R. L., and Blachly, P. H.: Relationship Between Post-cardiotomy Delirium, Clinical Neurological Changes, and EEG Abnormalities, 1. THoRAc. CARDIOVASC. SURG. 54: 557, 1967. I3 Brierley, 1. B.: Brain Damage Complicating Open-Heart Surgery (A Neuropathological Study), Proc. R. Soc. Med. 60: 858, 1967. 14 Juneja, 1., Flynn, R. E., and Berger, R. L.: The Arterial-Venous Pressure and the Electroencephalogram During Open-Heart Surgery, Acta Neurol. Scand. 48: 163, 1972. 15 Clowes, G. H., lr., Kretchmer, H. E., McBurney, R. W., and Simeone, F. A.: The Electroencephalogram in the Evaluation of the Effects of Anesthetic Agents and Carbon Dioxide Accumulation During Surgery, Ann. Surg. 138: 558, 1953. 16 Faulconer, A., lr.: Correlation of Concentration of Ether in Arterial Blood With Electroencephalographic Patterns Occurring During Ether-Oxygen and During Nitrous Oxide, Oxygen and Ether Anesthesia of Human Surgical Patients, Anesthesiology 13: 361, 1952.
Discussion DR. lAMES R. MALM New York. N. Y.
Dr. Kornfeld and Dr. Heller of our Department of Psychiatry at the Columbia Presbyterian Medical Center carried out a prospective study on a group of 96 patients undergoing heart surgery. Their investigations included preoperative electroencephalograms, personal interviews, and psychological testing. They found several interesting things. First, there was a high incidence of abnormal preopera-
tive electroencephalograms in the adult patients with acquired heart disease. Second, in the immediate postoperative period there was a 4 per cent incidence of organic neurological defects. An additional 20 per cent of the patients developed postperfusion delirium, a behavioral pattern which develops in the intensive care unit about the fourth or fifth day and clears promptly when the patient is removed from the intensive care environment and has periods of continued sleep. All the patients were restudied at 6 months and, almost without exception, their scores on the psychological testing showed improvement over the original scores. This was a rather uniform finding. The improvement was over and above that which one would expect from training or retaking the examination. Their conclusion was that there was no evidence of intellectual impairment or what is known as the coping index, i.e., a person's ability to deal with problems. Instead, there was a general improvement. DR. FRANK GERBODE San Francisco. Calif.
1 congratulate Dr. Simeone's group for being willing to analyze their results so straightforwardly. We should do this more often. We have not analyzed our own results so completely in this respect. However, fortunately, we haven't had quite the high incidence he has described, possibly because we haven't analyzed it so carefully as he has. We have found that microembolic picked up during perfusion are extremely important. Since we began using blood filters in the line-the Swank filter has been used exclusively in our unit-the incidence of neurological complications has decreased enormously. We have found it interesting to analyze the brains of patients who have died, determining what kind of microemboli have gone into the brain during operation. The Swank filter has reduced the number of fat emboli found in the cerebral microcirculation but hasn't eliminated them. Other types of microemboli have almost entirely been eliminated We are careful to wash the wound very thoroughly before initiating bypass. Before the start of bypass, after all the cannulation has been done, there is much free fat floating over the blood that is in the pericardium. Of course, as soon as one starts returning pericardial blood to the circulation, the fat, unless it has been removed, goes with it. These fat emboli go into the microcirculation. The incidence of postoperative delirium in older patients has almost been eliminated in the past 2 years. I believe this has been due to two things:
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(I) perhaps more careful psychological observations during and immediately after bypass; (2) the removal of microemboli during perfusion. DR. WITOSZKA (Closing) I would like to thank Drs. Gerbode and Maim for their comments. In our studies we were interested only in the severe EEG changes and
severe encephalopathies. Our study did not concern subtle psychological disorders. No extra filter was used until I \/2 years ago, when a second filter was placed in the venous return line. The use of the second filter may have influenced the prevalence of postoperative cerebral complications, but we have no data to indicate this.
Cerebral dysfunction and behavioral disorders are commonly recognized complications of open-heart surgery. However, hemodynamic alterations occurring during operation do not always correlate with postoperative neurological abnormalities, which may result from decreased cerebral perfusion, embolism of air or particulate matter, or acid-base disturbances during surgery. Continuous electroencephalographic (EEG) monitoring during cardiopulmonary bypass has been suggested as an important technique for the early recognition of hypoxia and alterations of cerebral metabolism. 1 However, few reports have considered correlation between the occurrence of abnormalities of the EEG during surgery and postoperative neurological complications.": 3 The study reported herein was undertaken to evaluate the importance of EEG changes during cardiopulmonary bypass and to correlate them with clinical and pathological cerebral sequelae. From the Division of Biological and Medical Sciences. Brown University, and the Departments of Surgery and Pathology, The Miriam Hospital, Providence, R. I. Read at the Fifty-third Annual Meeting of The American Association for Thoracic Surgery, Dallas, Texas, April 16,17, and 18, 1973. Address for reprints: Dr. Marian M. Witoszka, the Department of Surgery, The Miriam Hospital, Providence, R. I. 02906.
Materials and methods
All patients undergoing open-heart surgery between 1968 and 1972 were continuously monitored with the EEG during the procedure. Detailed analysis of 100 patients comprises the basis of this report. The patients were grouped as follows: Group I, 50 patients who survived; Group II, 5 patients who died during the operation; Group III, 45 patients who died in the postoperative period. The selection of patients for the group of survivors was made as follows: From 130 surviving patients, 100 were selected on the basis of their being comparable to those in Groups II and III in regard to sex, age, and the operation done, They were grouped chronologically, and alternate patients were chosen to form Group I (50 cases) . Groups II and III comprised all of the patients who died during the period of study. Twenty of these had a postmortem examination of the brain. Operative and postoperative care of each patient was under the direct supervision of one of the several cardiac surgeons participating in the open-heart surgical program at this institution. Perfusion techniques were altered during the period of study. The Travenol 3RF oxygenator was employed in 55 cases (27 in Group I) and the Bentley oxygenator in 45 cases (23 in Group I).
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Table I. Hypotension and clinical neurological changes in relation to electroencephalograie Hypotension during operation
Patients
Abnormalities in the EEG*
No.
Present Absent Total No. of patients
7 43 50
I
Per cent
14
86 100
No.
3 4 7
I
Hypotension ajter operation
I
Per
Per cent
No.
43 9 14
I
14
10
23 22
II
celli
"Electroencephalogram.
Table II. Hypotension and clinical neurological changes in relation to electroencephalographic A bnormalities in the EEG
Present Absent Total No. of patients
No. of patients No.
I
Per cent
25
20
55 44
45
100
Partial hemodilution (whole blood and 5 per cent dextrose in water) was used in 79 patients, and total hemodilution (PlasmaLyte 148 electrolyte solution entirely) was used in the other 21 patients. There was no obvious difference in the postoperative course of these two groups. Arterial and central venous pressures were continually monitored during and after surgery on an oscillographic monitor. Continuous EEG recordings were obtained during operation with an 8-channel Grass EEG (Model 6) under standard conditions. Ten standard external electrodes were applied in bipolar patterns, two pairs in the frontal area, one in the occipital area, and two in the temporal areas. Recording was begun prior to the induction of anesthesia and was continued through closure of the skin. Postmortem examinations of the brains were made by standard gross and microscopic techniques. In every case, sections were taken from the frontal, parietal, and occipital cortices, basal ganglia, hippocampi, cerebellar hemispheres, medulla oblongata, and calcarine cortices. All grossly apparent lesions were liberally sampled. Statistical calculations were made with the use of the chi-square test for independence of two variables. A level of 0.05 for the p value was chosen for acceptable significance.'
Hypotension during operation No.
16
10 25
I
Hypotension after operation
Per cent
No.
64 50 57
18 14 32
I
Per
celli
72 70 71
Definitions of criteria
1. EEG abnormality was defined as an isoelectric record or a slowing of the basic rhythm to an activity of less than 3 cycles per second for at least 60 seconds. 2. Encephalopathy included confusion, delirium, disorientation, and coma." 3. Motor dysfunction was defined as clinically demonstrable physical signs of focal central nervous system malfunction varying from overt hemiplegia to subtle asymmetry in muscle strength. 4. The combination of encephalopathy and motor changes was labeled multiple neurological changes. 5. Operative hypotension was considered present if a mean arterial pressure of less than 45 mm. Hg lasted more than 5 minutes as measured through a catheter in the radial artery. 6. Postoperative hypotension was defined as a systolic pressure less than 70 mm. Hg and diastolic pressure less than 45 mm. Hg which occurred in the first 12 hours after surgery and lasted more than 2 hours, as measured through a catheter in the radial artery. Results Group I (survivors). Correlation of the EEG during operation with operative hypotension and postoperative neurological ab-
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Cerebral dysfunction after open-heart surgery
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abnormalities after cardiac surgery in Group I (50 patients who survived) Encephalopathy without motor changes No.
I
Motor changes without encephalopathy
Per cent
No.
3 II
42 25
14
28
o o
I
Per cent
o
o
o
o
Both encephalopathy and motor changes No.
I
3 8
11
All with any neurological changes
Per cent
No.
42 18 22
6 19 25
I
Per cent 85 44 50
abnormalities after cardiac surgery in Group III (45 patients who died) Encephalopathy without motor changes No. 10 4 14
I Per cent 40
20 31
Motor changes without encephalopathy No. 3 5 8
I
Both encephalopathy and motor changes
Per cent
No.
12 25 17
10 4
20
14
31
normalities is shown in Table I. Twentyfive (50 per cent) of the patients in this group of survivors developed at least one neurological complication. Seven patients (14 per cent) had EEG changes during operation, and 6 of them (85 per cent) developed postoperative neurological changes. In the absence of EEG changes, 19 (44 per cent) of the patients developed postoperative neurological changes; the difference was statistically significant (p < 0.05). Although deterioration shown by the EEG during operation does correlate with the development of neurological defects, some patients with EEG changes during operation may manifest no neurological deficit postoperatively, while others may exhibit neurological changes postoperatively despite a normal EEG during operation. Among the survivors there was no significant correlation of EEG changes with neurological complications or with postoperative hypotension. All 7 (14 per cent) surviving patients who developed significant hypotension, however, did develop encephalopathy (p < 0.01). Group II (intraoperative death). All 5 patients who died during operation had isoelectric EEG recordings which lasted more than 5 minutes during the course of the operation. They all had prolonged perfusions with EEG evidence of deterioration
I
All with neurological changes
Per cent
No.
40
23 13 36
I
Per cent
92 65 80
as the procedure progressed beyond 2 hours. One patient developed EEG abnormalities associated with a retrograde dissection of the aorta early in the procedure. Despite rapid conversion to prograde arch perfusion, a return to normal EEG tracings was never achieved. Another patient developed EEG changes secondary to severe anoxia of the brain because of technical problems at the onset of bypass. The abnormal EEG continued to the conclusion of the procedure. Two of the 5 patients died of acute massive myocardial infarction and 1 from uncontrollable bleeding from the right atrium. In these patients EEG activity slowed to 3 cycles per second with low voltage just after completion of cardiopulmonary bypass: Group III (postoperative deaths). Table II shows the relationship between EEG changes, operative hypotension, and postoperative clinical disorders. Twenty-five of the 45 patients (55 per cent) in this group had alterations of the EEG during operation. Twenty-three (92 per cent) developed neurological changes. Twenty of the 45 patients in this group (44 per cent) did not develop EEG abnormalities during operation. Among this group only 13 (65 per cent) developed postoperative neurological defects. The difference between the two groups is statistically significant (p < 0.05). Thus patients with abnormalities in
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Table III. Operative and postoperative findings among patients who survived and patients who died Findings during and after operation
EEG changes Hypotension during operation Hypotension after operation Encephalopathy without motor changes Motor changes without encephalopathy Both encephalopathy and motor changes All neurological changes
Patients who Died (45 patients)
Patients who survived (50 patients) Per cent
No.
7 7 11
14 14 22
25 26 32
55 57 71
< <
<
0.02 0.01 0.01
14
28
14
31
>
0.05
0
0
8
17
< 0.01
11 25
22 50
14 36
31 80
>
No.
I
p value
Per cent
I
0.05
< 0.01
Table IV. Hypotension, clinical neurological changes, and postmortem findings in relation to electroencephalographic abnormalities after cardiac surgery (20 patients who died and had postmortem examination) Findings during and after operation and at postmortem examination
Hypotension during operation Hypotension after operation Encephalopathy without motor changes Motor changes without encephalopathy Both encephalopathy and motor changes All neurological changes Patients with anatomic brain damage
Table V. Pathological findings in 16 patients with brain damage No.
Severe diffuse cortical necrosis Anoxic neuronal degeneration Infarction of the brain Embolization due to particles of calcium Herniation of cerebral tonsils
6
13 8 3 2
the EEG during operation had a significantly higher incidence of encephalopathy with or without focal motor defects. Among the patients who did not survive, there was no correlation between the development of EEG changes during surgery and operative or postoperative hypotension as defined. There was no relationship of the EEG to localizing neurological defects, as such defects generally appeared to be more directly re-
EEG changes (/8 patients)
9 9 1 6 9
16 15
No EEG changes (2 patients)
o
o o o 1
1 1
A II (20 patients)
9 9 1 6
10 17 16
lated to embolic phenomena which were not detected by the EEG. Correlations between operative and postoperative disorders in the survival and nonsurvival groups (Groups I and II) are shown in Table III. It is clear that patients who died in the postoperative period, when compared with those who survived, were four times more likely to have developed intraoperative EEG abnormalities, four times more likely to have developed hypotension during operation, more likely to have developed hypotension postoperatively, and more likely to have developed neurological disorders of some kind. Pathological findings. A postmortem examination of the brain was performed in 20 patients. Clinical and EEG observations in these patients are summarized in Table IV. At least one histologic abnormality was noted in each of
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Fig. 1. Photomicrograph from the cerebellum of a 22-year-old woman who died 2 days after replacement of an old mitral prosthesis. Extensive necrosis of Purkinje cells can be seen. (Hematoxylin and eosin; original magnification x200.)
Fig. 2. Photomicrograph of the hippocampus from a 55-year-old woman who died 5 days after mitral valve replacement with a prosthesis. Severe ischemic degeneration of neuronal cells is apparent. (Hematoxylin and eosin; original magnification x200.)
16 cases. The changes are recorded in Table V. The most common histologic manifestation was the kind of neuronal degeneration commonly attributed to anoxia (13 patients) . Ten of the 13 had both encephalopathy and localizing motor changes. The lesions appeared as focal areas of tissue vacuolization, neuronal death, and loss of neuronal cells. They occurred most fre-
quently in the hippocampus, cerebral cortex, and cerebellar cortex (Figs. 1 and 2). Eight of the 16 had postoperative localizing motor defects; all of them showed evidence of cerebral infarction (Fig. 3). Calcium emboli were found in 3 of the 6 patients. In 1 case, basilar artery thrombosis with severe parenchymal damage was demonstrated (Fig. 4). In 6 patients, each
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Fig. 3. Photomicrograph from the same patient as in Fig . 2, showing the margin of an infarct in the cerebral cortex with cellular reaction. (Hematoxylin and eosin ; original magnification x200.)
Fig 4. Photomicrograph of the cerebellum in a 47-year-old woman who died 11/2 months after replacement of the mitral valve with a prosthesis. A calcified fragment can be seen in the lumen of a small artery (Hem atoxylin and eo sin: original magnification x200.)
of whom had hypotension at some time during the operation, the cerebral cortex was diffusely necrotic. Death in these 20 patients was ascribed to the following causes: Nine patients died as a direct result of brain damage. F ive died from cardiac complications, including 4 with acute massive myocardial infarction and I with acute mitral regurgitation following separation of a Magovern prosthesis
from the mitral annulus. Five died because of persistent hemorrhage and shock. One death resulted from embolism to the hepatic artery and necrosis of the liver. Discussion
Neurological disorders which follow open-heart procedures may manifest themselves by a variety of signs and symptoms. Behavioral and gnostic disorders are the
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most common, reported by Javid and colleagues' to occur in 43 per cent of patients who survive cardiac surgery. In their series, such disorders of intellectual function or disturbances of recognition or memory were usually transient and disappeared by the time the patient was discharged from the hospital. However, 15 per cent of their patients had signs of cerebral dysfunction at the time of discharge. Of patients not surviving surgery, up to 85 per cent have been noted to have gross or microscopic pathologic changes in the brains at autopsy.';' L' Diffuse cerebral injury and necrosis were often demonstrated among them. but localized or focal abnormalities appear to be the most common and are believed to be due to embolization by air or particular matter. Tufo" has postulated that cerebral damage is related to arterial hypotension during or after surgery and that its incidence is significantly increased with advanging age, particularly over 70 years. Aguilar reported that among 166 patients who did not survive extracorporeal circulation, the most significant changes were embolic (78 per cent) within the small cerebral vessels, resulting in acute ischemic neuronal damage, foci of infarction, and perivascular and focal subarachnoid hemorrhage. Earlier studies by Wright and associates' indicated that EEG monitoring was an essential adjunct to cardiopulmonary bypass since it provided early warning of unacceptable perfusion characteristics. In a study of 100 patients undergoing open-heart surgery, they concluded that careful EEG monitoring during the procedure could significantly decrease neurological abnormalities resulting from inadequate perfusion. On the other hand Coons and associates" concluded that a level of cerebral perfusion can exist during which irreversible hypoxic tissue damage does not result despite the fact that EEG activity may cease at some time during the course of the operation. In the present studies, patients were examined neurologically for major clinical changes after operation, and attempts were
made to relate them to the EEG alterations recorded during the operative procedure. The presence of EEG abnormalities during operation was found to correlate significantly with the development of postoperative neurological disorders. On the other hand, it became apparent that patients may develop neurological deficits despite normal EEG tracings, whereas postoperative neurological abnormalities may fail to develop in patients who demonstrated EEG changes. A relationship was also identified between operative hypotension, which was defined as a fall in the mean arterial pressure to less than 45 mm. Hg for at least 5 minutes, and the occurrence of postoperative neurological abnormalities. In the group of patients who died in the postoperative period and had a postmortem examination, 80 per cent had neuronal degeneration, which was clearly related to hypotension during operation and encephalopathy after the operation. Neuronal degeneration was observed in 13 patients who had tolerated the operative procedure poorly and whose postoperative course was complicated by a low cardiac output syndrome. Although cerebral cortical necrosis was often demonstrable, lesions were most commonly confined to the cerebellar cortex, the cornu Ammonis of the hippocampus, and to other areas known to be vulnerable to hypoxia. Focal infarction was observed in 8 of the 16 cases. Most of these may have been secondary to air embolism, since intravascular particulate matter could not be identified in relation to the lesions. Embolization by calcific particles was identified in only 3 of the cases. In the patients who died, the incidence of EEG abnormalities was high. Although the abnormalities generally occurred shortly after the institution of bypass, they often suddenly occurred later in the procedure without obvious relationship to alterations in the blood pressure. The flow-rate was maintained at about 2,100 ml. per square meter of body surface area, regardless of variations in the blood pressure. Abnor-
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malities in the EEG appeared to correlate with the duration of perfusion in the patients who died. Indeed, of the 5 patients who died during operation, all had gross abnormalities in the EEG prior to the conclusion of the procedure. The duration of cardiopulmonary bypass averaged 125 minutes in patients who died and 85 minutes in patients who lived. Despite numerous reports describing the neurological disorders which occur following open-heart surgery.:":':' no single etiologic factor has been identified. Certainly the level of tissue perfusion is critical because of the extreme sensitivity of neurons in the brain and cord to hypoxia levels of perfusion. Techniques for monitoring the level of tissue perfusion have not been developed to the point of general availability for the central nervous system. In both animals and man the EEG has been found to be a very sensitive indicator of carbon dioxide accumulation or oxygen depletion.':' Indeed, among the patients who died postoperatively and who had developed abnormalities of the EEG, 16 (64 per cent) had had hypotension during the course of the operation. An isoelectric ("flat") EEG was found in 28 per cent of patients who died (Group III) and in only 2 per cent of the patients who survived (Group I). This suggests that the severity of EEG changes correlates with postoperative prognosis and could provide early warning of organic cerebral alteration. Some of the EEG changes that occur during the operation could reflect alterations in metabolism resulting from the development of new and different flow relationships which, at the present time, are poorly understood. When cardiopulmonary bypass is discontinued, however, abrupt EEG changes may indicate the development of an inadequate cardiac output. Therefore, such EEG changes in the postperfusion period may indicate that continued mechanical circulatory support is necessary. The EEG can provide early warning of unacceptable perfusion characteristics which may give rise to neurological abnormalities.
Summary and conclusions
1. The EEG was recorded continuously in patients undergoing cardiopulmonary bypass for open-heart surgery. Observations of the EEG were correlated with survival, postoperative neurological abnormalities, and operative or postoperative hypotension in 50 surviving and 50 nonsurviving patients. 2. Abnormalities in the EEG during operation correlated with the development of neurological abnormalities in the surviving and nonsurviving groups of patients (Tables I and II). 3. Abnormalities of the EEG and neurological complications were more common among patients who died than among those who lived (Table III). 4. A significant correlation was observed between operative hypotension and the occurrence of postoperative neurological disorders. 5. Histopathological changes in the brain were demonstrated in 80 per cent of autopsied cases. Diffuse neuronal degeneration was the most common pathological manifestation of the encephalopathic syndrome after operation, while focal cerebral necrosis (8 patients) was most often associated with postoperative motor changes. 6. In nearly half the patients, brain injury was an important cause of death after openheart surgery. REFERENCES
2
3
4
5
Lorenz, R., and Hehrlein, F.: Electroencephalographic Findings in Heart Surgery, Minn. Med. 53: 1069, 1970. Davenport, H. T., Arfel, G., and Sanchez, E. R.: The Electroencephalogram in Patients Undergoing Open Heart Surgery With HeartLung By-pass, Anesthesiology 20: 674, 1959. Fisher-Williams, M., and Cooper, R. A.: Some Aspects of Electroencephalographic Changes During Open Heart Surgery, Neurology 14: 472, 1964. Snedecor, G. W.: Statistical Methods, Ames, Iowa, 1971, Iowa University Press, pp. 215219. Javid, H., Tufo, H., Najafi, H., Dye, W. S., Hunter, T. A., and Julian, O. c.: Neurological Abnormalities Following Open-Heart Surgery, J. THoRAc. CARDIOVASC. SURG. 58: 502, 1969.
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6 Tufo, H. M., Ostefeld, A. M., and Shekelle, R.: Central Nervous System Dysfunction Following Open-Heart Surgery, 1. A. M. A. 212: 1933, 1970. 7 Aguilar, M. 1., Gerbode, F., and Hill, D.: Neuropathological Complications of Cardiac Surgery, 1. THoRAc. CARDIOVASC. SURG. 61: 676, 1971. 8 Wright, 1. S., Lethlean, A. K., Hicks, R. G., Torda, T. A., and Stacey, R.: Electroencephalographic Studies During Open-Heart Surgery, 1. THORAC. CARDIOVASC. SURG. 63: 631, 1972. 9 Coons, R. E., Skeats, A. S., and Cooley, D. A.: Significance of Electroencephalographic Changes Occurring During Cardio-pulmonary Bypass, Anesthesiology 20: 674, 1959. 10 Gilman, S.: Cerebral Disorders After OpenHeart Operations, N. Engl. 1. Med. 272: 489, 1965. 11 Blachly, P. H., and Starr, A.: Post-cardiotomy Delirium, Am. 1. Psychiatry 121: 371, 1964. 12 Sachdev, N. S., Carter, C. C., Swank, R. L., and Blachly, P. H.: Relationship Between Post-cardiotomy Delirium, Clinical Neurological Changes, and EEG Abnormalities, 1. THoRAc. CARDIOVASC. SURG. 54: 557, 1967. I3 Brierley, 1. B.: Brain Damage Complicating Open-Heart Surgery (A Neuropathological Study), Proc. R. Soc. Med. 60: 858, 1967. 14 Juneja, 1., Flynn, R. E., and Berger, R. L.: The Arterial-Venous Pressure and the Electroencephalogram During Open-Heart Surgery, Acta Neurol. Scand. 48: 163, 1972. 15 Clowes, G. H., lr., Kretchmer, H. E., McBurney, R. W., and Simeone, F. A.: The Electroencephalogram in the Evaluation of the Effects of Anesthetic Agents and Carbon Dioxide Accumulation During Surgery, Ann. Surg. 138: 558, 1953. 16 Faulconer, A., lr.: Correlation of Concentration of Ether in Arterial Blood With Electroencephalographic Patterns Occurring During Ether-Oxygen and During Nitrous Oxide, Oxygen and Ether Anesthesia of Human Surgical Patients, Anesthesiology 13: 361, 1952.
Discussion DR. lAMES R. MALM New York. N. Y.
Dr. Kornfeld and Dr. Heller of our Department of Psychiatry at the Columbia Presbyterian Medical Center carried out a prospective study on a group of 96 patients undergoing heart surgery. Their investigations included preoperative electroencephalograms, personal interviews, and psychological testing. They found several interesting things. First, there was a high incidence of abnormal preopera-
tive electroencephalograms in the adult patients with acquired heart disease. Second, in the immediate postoperative period there was a 4 per cent incidence of organic neurological defects. An additional 20 per cent of the patients developed postperfusion delirium, a behavioral pattern which develops in the intensive care unit about the fourth or fifth day and clears promptly when the patient is removed from the intensive care environment and has periods of continued sleep. All the patients were restudied at 6 months and, almost without exception, their scores on the psychological testing showed improvement over the original scores. This was a rather uniform finding. The improvement was over and above that which one would expect from training or retaking the examination. Their conclusion was that there was no evidence of intellectual impairment or what is known as the coping index, i.e., a person's ability to deal with problems. Instead, there was a general improvement. DR. FRANK GERBODE San Francisco. Calif.
1 congratulate Dr. Simeone's group for being willing to analyze their results so straightforwardly. We should do this more often. We have not analyzed our own results so completely in this respect. However, fortunately, we haven't had quite the high incidence he has described, possibly because we haven't analyzed it so carefully as he has. We have found that microembolic picked up during perfusion are extremely important. Since we began using blood filters in the line-the Swank filter has been used exclusively in our unit-the incidence of neurological complications has decreased enormously. We have found it interesting to analyze the brains of patients who have died, determining what kind of microemboli have gone into the brain during operation. The Swank filter has reduced the number of fat emboli found in the cerebral microcirculation but hasn't eliminated them. Other types of microemboli have almost entirely been eliminated We are careful to wash the wound very thoroughly before initiating bypass. Before the start of bypass, after all the cannulation has been done, there is much free fat floating over the blood that is in the pericardium. Of course, as soon as one starts returning pericardial blood to the circulation, the fat, unless it has been removed, goes with it. These fat emboli go into the microcirculation. The incidence of postoperative delirium in older patients has almost been eliminated in the past 2 years. I believe this has been due to two things:
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(I) perhaps more careful psychological observations during and immediately after bypass; (2) the removal of microemboli during perfusion. DR. WITOSZKA (Closing) I would like to thank Drs. Gerbode and Maim for their comments. In our studies we were interested only in the severe EEG changes and
severe encephalopathies. Our study did not concern subtle psychological disorders. No extra filter was used until I \/2 years ago, when a second filter was placed in the venous return line. The use of the second filter may have influenced the prevalence of postoperative cerebral complications, but we have no data to indicate this.