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Electroencephalographic changes with hypothermia and cardiopulmonary bypass in children
J THORAC
CARDIOVASC SURG
81:781-786, 1981
Electroencephalographic changes with hypothermia and cardiopulmonary bypass in children Our experience of EEG changes associated with hypothermia, induced predominantly by core cooling, is presented. Easily recognizable, repeatable patterns emerge and four different types of changes are seen, from generalized slowing and loss offaster rhythms progressing to discontinuous activity, burst suppression activity, and finally loss of all cerebral potentials. These patterns were not altered significantly by anesthetic agents or by patient age or weight differences. Abnormalities of various kinds can be distinguished from the hypothermic changes. In particular, continuous epileptiform activity can be recognized and therefore abolished.
R. G. Hicks* and J. L. Poole, M.B., B.S., F.F.A.R.A.C.S.,** Little Bay, N. S.
T he electroencephalogram (EEG) reflects the sum of multiple factors affecting cerebral perfusion and is (1)
routinely employed in this hospital during all operations involving cardiopulmonary bypass (CPB) in children. Hypothermia is commonly used to protect vital organs during CPB, and if the adequacy of cerebral perfusion and the protective effect of cooling are to be reliably assessed, a guide to the normal or acceptable EEG during these situations is essential. Abnormal features have to be distinguished from innocent changes induced purely by hypothermia.
Patients EEG monitoring was carried out on 326 children and infants undergoing hypothermic perfusions from 1972 to 1979. Of these 26 have been excluded from this series because (1) artifact made accurate assessment impossible (two patients), (2) temperature monitoring was considered to be grossly inaccurate (six patients), and (3) severe to gross EEG abnormalities for the age were present in the operative recording prior to CPB From the Prince Henry Hospital, Little Bay, N. S. W., Australia. Received for publication June 10, 1980. Accepted for publication Sept. 16, 1980. Address for reprints: R. G. Hicks, Chief Electroencephalographer, C.N.P.D., Prince Henry Hospital, Little Bay, 2036. N. S. W., Australia. *Division of Neurology. **Division of Anaesthesia.
w.,
Australia
(18 patients). In these last 18 patients no EEG activity was present during cooling on CPB. The EEG at the start of the operation was composed only of (1) intermittent irregular slow activity which all ceased either before CPB (six patients) or immediately after the start of CPB (four patients), (2) of irregular slow activity with frequent epileptiform features which again all ceased shortly after the start of CPB (three patients), (3) or of no cerebral activity at all (five patients). Three hundred patients, 150 boys and 150 girls, with ages ranging from 3 days to 15 years are included. Eighty of these were cooled below 20° C and underwent total circulatory arrest and 220 patients had continuous cold perfusion, the degree of hypothermia ranging from 32° to 20° C.
Methods Nasopharyngeal temperatures were accepted as the closest approximation of brain temperatures available to us. 2 Midesophageal and venous blood temperatures were also recorded. Membrane oxygenators and continuous flow roller pumps were used for all patients. Surface cooling commenced after intubation: Initially in the series this was by means of ice bags packed around the head and trunk; The majority, however, were cooled by a water cooling blanket placed beneath the patient. All patients listed for elective operation had a preoperative EEG 1 or 2 days beforehand. Many of the emergency cases had an EEG prior to operation, but
0022-5223/81/050781+06$00.60/0 © 1981 The C. V. Mosby Co.
781
782
The Journal of Thoracic and Cardiovascular Surgery
Hicks and Poole
h
2.
32C
3.
no
h
h
h
5. 22C
6. 20e Fig. 1. Top line is time marker in 1 second divisions. Channel 1 shows a baseline tracing at 36° C. Channel 2 showsthe slowing of the dominant rhythms from 10to 5 Hz, at 32° C. In channel 3 there has beenfurther slowing and loss of superimposed low-voltage fast rhythms at 26° C. Channel 4 shows the periodic bursts seen at 24° C, and channel 5 shows periodic bursts with flat periods, at 22° C. Burst-suppression activity at 20° C is seen in channel 6. Each channel is taken from two electrodes placed over the anteriorquadrant of the right hemisphere.
this was not always practical for some of the neonatal cases. For the operative EEGs, subdermal needle electrodes were used and a bipolar montage in the parasagittal plane was chosen to avoid as much artifact as possible and to conform with the position of the patient's head and the anesthetic requirements. Children more than I year old were premedicated with omnopon, scopolamine (0.3 mg/kg), and droperidol (0.1 mg/kg). Anesthesia was induced with nitrous oxide, oxygen, and halothane in most cases. Anesthesia was maintained with nitrous oxide/oxygen or nitrous oxide/oxygen/halothane mixtures and in approximately 10% of cases nitrous oxide/oxygen/ enflurane. Pancuronium bromide was administered as the muscle relaxant and positive-pressure ventilation was maintained to establish an arterial PC02 of 35 to 45 torr. The EEGs were monitored on eight-channel recorders using a paper speed of 3 ern/sec, a time constant of 0.3 second, and a sensitivity of 100 JL V/cm. The sensitivity was increased to 70 and 50 JL V/em when cerebral activity diminished in amplitude, and the paper speed was then slowed to 1.5 em/sec. EEG monitoring routinely commenced after the patient had been anesthetized and positioned on the operating room table. Extensive prebypass tracing made it possible to establish an accept-
able normothermic base line, with all other parameters stabilized." In the early part of the series ice packs were used for topical cooling, and in these cases, about 5% of the total, the EEG was started when the temperature had been reduced to about 32° C.
Findings In an ideal perfusion there is no discernible change in the EEG between 37° and 35° C. 4 Between 35° and 30° C there was progressive slowing of the dominant rhythms. The usual 8 to 12 Hz rhythms of nitrous oxide/halothane anesthesia slowed to 5 to 6 Hz and faster rhythms, from 15 to 25 Hz, slowed to 9 to 13 Hz. Below 32° C the amplitude of the EEG diminished. Between 29° and 24° C the amount of faster rhythms decreased as slow activity increased, until by 24° C fast rhythms had disappeared altogether. At about 24° C periodic bursts of higher voltage activity were seen and flat periods of brief duration (0.5 to 1.5 second) first appeared. These increased in duration and occurred more frequently, until at 23° to 22° C the EEG was composed only of periodic bursts." Below these temperatures the pattern changed to burst-suppression activity, with ever-lengthening isoelectric periods (Fig. l). With rare exceptions all cerebral potentials ceased below 18° C, although there were a few instances when isolated bursts persisted at lower temperatures and even
Volume 81 Number 5 May, 1981
EEG changes with hypothermia and CPR
783
....J~:: ---_
.'"
Fig. 2. Composite tracing showing the start of epileptiform activity (0943), progressing to continuous generalized spike and wave complexes (0948), and then spike and wave with flat periods (0950). The top channel is a time marker, with 1 second divisions. T = Time. The first section (T = 0943) occurred 16 minutes after the onset of cardiopulmonary bypass, at 26° C.
for some seconds after total circulatory arrest was instituted.
EEG abnormalities There were abnormal features in a number of the EEGs before CPB was established. These were most often short-lived, reflecting transient hypotension or hypoxia, but there were some persistent mild changes, consisting of asymmetry of the dominant rhythms or a bilateral excess of theta waves (4 to 7 Hz) which continued after the start of CPB. At the start of CPB transient abnormalities were frequently seen. These ranged from a slight loss of faster rhythms with the appearance of slower waves between 5 and 7 Hz to a gross slowing with 1.5 to 3 Hz delta activity replacing all other activity. However, the time and mode of onset and relatively quick resolution of these abnormalities made it easy to discriminate them from the start of the progressive changes resulting from hypothermia alone. 6 In 70 patients epileptiform activity was seen, first appearing 26° to 24° C. In most cases the initial manifestation was of lateralized or bilateral single sharp waves. These developed into paroxysmal bursts of sharp and slow wave complexes and then generalized runs of spike and wave activity. At this time background activity ceased and the EEG was composed
only of continuous epileptiform activity with intervening flat periods (Fig. 2). In most cases appropriate drugs were given and this activity was reduced or totally abolished. At temperatures below 26° C inadequate cerebral perfusion tended to abolish cerebral activity rather than to alter the waveforms or frequencies. Lateralized abnormalities were seen rarely. On two occasions an abrupt slowing of all frequencies leading to irregular delta activity (less than 4 Hz) of low amplitude over only one hemisphere was assumed to have been caused by gaseous emboli. The gradual improvement and return to acceptable frequencies by the end of CPB in each case tended to support this. Comment The EEG is widely used to monitor CPB because it is a direct index of cerebral function. Recording can be carried on continuously without harm to the patient, and it reflects accurately and rapidly any change in the cerebral status of the patient. The electrical activity of the brain is depressed during hypothermia. The EEG reflects this by patterns of progressive slowing of the dominant activity, then intermittent activity, and finally loss of all potentials below certain temperatures. This reduction of cerebral
7 84
Hicks and Poole
activity is mostly a physiological phenomenon consistent with the reduced metabolic activity induced by cold, but the possibility that cellular hypoxia plays a part has to be considered. Reduced cerebral blood flow, a shift in the oxygen-hemoglobin dissociation curve to the left, increased cerebrovascular resistance, and depression of enzyme activity may all act to produce cerebral hypoxia even though the oxygen demand of the brain is simultaneously reduced.' It was always considered of primary importance to maintain the patient's biochemistry and blood gases as close as possible to those levels prevailing at normal temperatures, and these were monitored at frequent intervals and immediately corrected when necessary. It has been shown that incidental transient changes in acid-base balance which occur during CPB do not significantly affect the EEG,8-10 and in particular the changes in Pco, do not affect the cold-induced depression of the EEG.7 In this clinical study it was not possible to measure brain temperature directly. The temperatures available to us were recorded from the nasopharynx, midesophagus, and venous blood return line. Midesophageal temperatures in the circumstances of CPB will not correlate well with brain temperature": venous blood temperature was not considered to be very reliable, and tympanic membrane temperature monitoring was not available for our use in children. Nasopharyngeal temperatures were accepted as the most consistent and closest available approximation of brain temperature and the least affected during CPB, when the ventilator was turned off. Thus the EEG patterns that have been described may be said to form acceptable changes for various temperatures. There were, of course, wide inter-individual differences, and these were most obvious during cooling between 35° and 25° C. A slowing of the dominant (anesthetic-induced) rhythms always occurred and became more marked with lower temperatures. There were quite often differences between comparable patients on the same regimen, sometimes expressed in terms of amplitude as well as slowing. In part this may have been due to the rate of cooling, which frequently was variable. A rapid rate, 1° C per minute or faster, causes a greater amount of slowing earlier on, although at lower temperatures individual differences were less apparent. The abnormalities seen in the EEGs were of three kinds: those reflecting inadequate cerebral perfusion, epileptiform activity, and embolic phenomena. EEG abnormalities caused by cerebral embolism were seen on only two occasions and were clearly lateralized. Epileptiform activity has occurred in an increasing number of cases recently from less than 10% 4 years
The Journal of Thoracic and Cardiovascular Surgery
ago to over 60% at present. The reason for this increased incidence is not clear and is not related to drug administration or any alteration in anesthetic technique. A possible explanation might be that the absence of any significant slow surface cooling has resulted in more rapid and unequal core cooling during the early stage of perfusion. Areas of cerebral vasoconstriction and hypoxia could be possible triggering mechanisms. It has been postulated that reduction of the desynchronizing drive of the reticular activating system (brain stem) might be an important factor in creating in both hemispheres a diffuse excitatory condition which renders the cortex prone to produce rapidly disseminating paroxysmal discharges." Since the brain stem is perfused predominantly by the vertebrobasilar system and the cortex by the carotid arteries, differential rates of cooling during CPB might cause early depression of the brain stem, which thereby would allow the cortex to respond with epileptiform activity of the spike and wave type. This activity certainly does not appear to be related to preoperative EEG epileptiform activity, which has been seen in only 22 patients (7%) in this series. Thirteen of them did not exhibit any epileptiform activity at all in the operative EEG: The other nine patients had epileptiform features in the EEG before, during, and after CPB. In those patients who did not have any predisposing electrical signs, the epileptiform activity was first seen in the EEG during CPB cooling at about 26° C and worsened with further cooling. The spike and wave activity persisted for most of the time at low temperatures, although in some cases it ceased at about 20° C, with the abolition of background activity. Otherwise the epileptiform changes always ended in the early part of rewarming before 26° C was reached. Despite the descriptions of enflurane as a potentially epileptogenic agent.P in the earlier part of the series when it was used for anesthesia there was only a very small incidence of epileptiform activity in the EEGs during CPB. A number of patients had hypoxic or anoxic episodes during CPB, usually at the start when flows become apulsatile and pressures may be inadequate. Such abnormalities usually improved after a short while and the EEG then presented an acceptable pattern again. The significance of these abnormalities and the epileptiform activity is hard to assess in terms of postoperative neurologic disability. Operative EEG abnormalities do not necessarily indicate postoperative neurologic complications.!" and it has not been possible to provide psychometric testing for any of our patients to assess minor neurologic abnormalities. A recent report suggested that there might be a higher incidence of de-
Volume 81 Number 5 May, 1981
velopmental abnormality in children undergoing hypothermic circulatory arrest compared with those who had continuous perfusion, although there was no obvious correlation between operative EEG abnormalities and later developmental abnormality. 14 However, a significant proportion of patients who develop epileptic seizures in infancy later have learning difficulties in school, and some even become institutionalized for mental retardation. IS It has been hypothesized that the developing brain might be more vulnerable to the metabolic consequences of seizure than the brain of older organisms. Mental retardation is three times more common in children who have convulsions with fever than in the general population;" Following prolonged epileptic seizures in animals or man, loss of nerve cells and gliosis may be found in the cerebellum, hippocampus, amygdala, cerebral cortex, or thalamus.": 18 A history of prolonged febrile convulsions in infancy is found in a very high proportion of adolescent children operated upon for temporal lobe epilepsy who show hippocampal sclerosis;" Early vigorous management of seizures is mandatory if the survivor is to be spared the real possibility of brain damage." We recently have used thiopentone sodium to abolish all epileptiform activity in the EEG during CPB. Although it is tempting to suggest that the systemic complications of convusions (hypoxia, hypocarbia, and hypotension) may be the cause of cerebral damage, there is increasing evidence that seizure discharges in the brain can induce ischemic neuronal damage in the absence of secondary systemic effects." Therefore, on the basis of this evidence, fairly large doses of thiopentone sodium (10 to 25 mg/kg) have been used successfully with no serious hemodynamic consequences during or after CPB. Large doses are required to abolish completely all spike and wave activity in the EEG, which usually is rendered isoelectric in the process. Barbiturates have been used in preference to diazepam, since they have an additive effect with cooling for cerebral protection. Hypothermia alone is probably not adequate to protect the brain fully during periods of circulatory arrest or cerebral ischemia when electrical activity is stilI present in the EEG. The mechanism whereby barbiturates and hypothermia protect the brain differ; in particular, barbiturates probably stabilize electrically active membranes in a more specific fashion than does hypothermia. 21 Cellular damage is often permanent, whether it be gross or subtle. Perception or abstract thinking are functions which are seldom checked following perfusion, although return of normal intellectual function is the crux of the matter in developing extracorporeal circulation into a
EEG changes with hypothermia and CPR
7 85
physiological and nontraumatic procedure. The goal for the brain must be perfect recovery. 22 The ability to distinguish EEG abnormalities from the changes resulting from hypothermia does allow the rational use of other forms of cerebral protection such as barbiturates. We wish to thank Associate Professor J. S. Wright for access to his patients, Dr. T. A. Torda for his helpful advice, Professor J. W. Lance for his suggestions, and Miss V. J. Foster for typing the manuscript. REFERENCES Hansotia PL, Myers WO, Ray JE, Greehling C, Sautter RD: Prognostic value of electroencephalography in cardiac surgery. Ann Thorac Surg 19:127-134, 1975 2 Whitby JD, Dunkin LJ: Cerebral, oesophageal and nasopharyngeal temperatures. Br J Anaesth 43:673-676, 1971 3 Wright JS, Lethlean AK, Hicks RG, Torda TA, Stacey RB: Electroencephalographic studies during open-heart surgery. J THORAC CARDIOVASC SURG 63:631-638, 1972 4 Arfel G, Weiss J, DuBouchet N: EEG findings during open-heart surgery with extra-corporeal circulation, Cerebral Anoxia and the Electroencephalogram, H Gastaut, JS Meyer, eds., Springfield, Ill., 1961, Charles C Thomas, Publisher, pp 231-249 5 Van Leeuwen SW, Nechelse K, Kok L, Zierfuss E: EEG during heart operations with artificial circulation, Cerebral Anoxia and the Electroencephalogram, H Gastaut, JS Meyer, eds .• Springfield, Ill., 1961, Charles C Thomas, Publisher, pp 268-278 6 Salerno TA, Lince DP, White DN, Lynn RB, Charrette EJ: Monitoring of the electroencephalogram during open-heart surgery. J THORAC CARDIOVASC SURG 76:97100, 1978 7 Ichiyanagi K, Matsuki M, Matsuko K, Nishisaka T, Watanabe R, Horikawa H: Effect of altered arterial carbon dioxide tensions on the electroencephalogram during hypothermia. Acta Anaesth Scand 13: 173-183, 1969 8 Harden A, Ashton BM: EEG studies during acidaemia and alkalaemia in children undergoing cardiac surgery. Electroencephalogr Clin Neurophysiol 22: 128-135, 1967 9 Juneja I, Flynn RE, Berger RL: The arterial pH, pC0 2 and the electroencephalogram during open-heart surgery. Acta Neurol Scand 48:169-175, 1972 10 Juneja I, Flynn RE, Berger RL: The arterial, venous pressures and the electroencephalogram during open-heart surgery. Acta Neurol Scand 48: 163-168, 1972 11 Gloor P: Generalized spike and wave discharges. A consideration of cortical and subcortical mechanisms of their genesis and synchronization, Synchronization of EEG Activity in Epilepsies, H Petsche, MA Brazier, eds., New York/Wein, 1975, Springer-Verlag, pp 381-405 12 Fleming DC, Fitzpatrick J, Fariello RG, DuffT, Hellman D, Hoff BH: Diagnostic activation of epileptogenic foci by enflurane. Anesthesiology 52:431-433, 1980
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13 Calanchini PR: EEGs during open-heart surgery. Electroencephalogr Clin Neurophysiol 28:9, 1970 14 Wright JS, Hicks RG, Newman DC: Deep hypothermic arrest. Observations on later development in children. J THORAC CARDIOVASC SURG 77:466-468, 1979 15 Wasterlain CG: Neonatal seizures and brain growth. Neuropadiatrie 9:213-228, 1978 16 Wallace SJ: Febrile fits. Br Med J 1:333-334, 1976 17 Meldrum B: Physiological changes during prolonged seizures and epileptic brain damage. Neuropadiatrie 9:203212, 1978 18 Blennow G, Brierley JB, Meldrum BS, Siesjo BK:
Thoracic and Cardiovascular Surgery
19 20 21 22
Epileptic brain damage. The role of systemic factors that modify cerebral energy metabolism. Brain 101:687-700, 1978. Falconer MA: Mesial temporal sclerosis as a common cause of epilepsy. Lancer 2:767-770, 1974 Truhubovich RV: Management of severe or intractable convulsions including eclampsia. Int Anesthesiol Clin 17:201-238, 1979 Michenfelder JD: Hypothermia plus barbiturates. Apples plus oranges? Anesthesiology 49: 157-158, 1978 Hill JD: Blood filtration during extracorporeal circulation. Ann Thorac Surg 15:313-316, 1973
CARDIOVASC SURG
81:781-786, 1981
Electroencephalographic changes with hypothermia and cardiopulmonary bypass in children Our experience of EEG changes associated with hypothermia, induced predominantly by core cooling, is presented. Easily recognizable, repeatable patterns emerge and four different types of changes are seen, from generalized slowing and loss offaster rhythms progressing to discontinuous activity, burst suppression activity, and finally loss of all cerebral potentials. These patterns were not altered significantly by anesthetic agents or by patient age or weight differences. Abnormalities of various kinds can be distinguished from the hypothermic changes. In particular, continuous epileptiform activity can be recognized and therefore abolished.
R. G. Hicks* and J. L. Poole, M.B., B.S., F.F.A.R.A.C.S.,** Little Bay, N. S.
T he electroencephalogram (EEG) reflects the sum of multiple factors affecting cerebral perfusion and is (1)
routinely employed in this hospital during all operations involving cardiopulmonary bypass (CPB) in children. Hypothermia is commonly used to protect vital organs during CPB, and if the adequacy of cerebral perfusion and the protective effect of cooling are to be reliably assessed, a guide to the normal or acceptable EEG during these situations is essential. Abnormal features have to be distinguished from innocent changes induced purely by hypothermia.
Patients EEG monitoring was carried out on 326 children and infants undergoing hypothermic perfusions from 1972 to 1979. Of these 26 have been excluded from this series because (1) artifact made accurate assessment impossible (two patients), (2) temperature monitoring was considered to be grossly inaccurate (six patients), and (3) severe to gross EEG abnormalities for the age were present in the operative recording prior to CPB From the Prince Henry Hospital, Little Bay, N. S. W., Australia. Received for publication June 10, 1980. Accepted for publication Sept. 16, 1980. Address for reprints: R. G. Hicks, Chief Electroencephalographer, C.N.P.D., Prince Henry Hospital, Little Bay, 2036. N. S. W., Australia. *Division of Neurology. **Division of Anaesthesia.
w.,
Australia
(18 patients). In these last 18 patients no EEG activity was present during cooling on CPB. The EEG at the start of the operation was composed only of (1) intermittent irregular slow activity which all ceased either before CPB (six patients) or immediately after the start of CPB (four patients), (2) of irregular slow activity with frequent epileptiform features which again all ceased shortly after the start of CPB (three patients), (3) or of no cerebral activity at all (five patients). Three hundred patients, 150 boys and 150 girls, with ages ranging from 3 days to 15 years are included. Eighty of these were cooled below 20° C and underwent total circulatory arrest and 220 patients had continuous cold perfusion, the degree of hypothermia ranging from 32° to 20° C.
Methods Nasopharyngeal temperatures were accepted as the closest approximation of brain temperatures available to us. 2 Midesophageal and venous blood temperatures were also recorded. Membrane oxygenators and continuous flow roller pumps were used for all patients. Surface cooling commenced after intubation: Initially in the series this was by means of ice bags packed around the head and trunk; The majority, however, were cooled by a water cooling blanket placed beneath the patient. All patients listed for elective operation had a preoperative EEG 1 or 2 days beforehand. Many of the emergency cases had an EEG prior to operation, but
0022-5223/81/050781+06$00.60/0 © 1981 The C. V. Mosby Co.
781
782
The Journal of Thoracic and Cardiovascular Surgery
Hicks and Poole
h
2.
32C
3.
no
h
h
h
5. 22C
6. 20e Fig. 1. Top line is time marker in 1 second divisions. Channel 1 shows a baseline tracing at 36° C. Channel 2 showsthe slowing of the dominant rhythms from 10to 5 Hz, at 32° C. In channel 3 there has beenfurther slowing and loss of superimposed low-voltage fast rhythms at 26° C. Channel 4 shows the periodic bursts seen at 24° C, and channel 5 shows periodic bursts with flat periods, at 22° C. Burst-suppression activity at 20° C is seen in channel 6. Each channel is taken from two electrodes placed over the anteriorquadrant of the right hemisphere.
this was not always practical for some of the neonatal cases. For the operative EEGs, subdermal needle electrodes were used and a bipolar montage in the parasagittal plane was chosen to avoid as much artifact as possible and to conform with the position of the patient's head and the anesthetic requirements. Children more than I year old were premedicated with omnopon, scopolamine (0.3 mg/kg), and droperidol (0.1 mg/kg). Anesthesia was induced with nitrous oxide, oxygen, and halothane in most cases. Anesthesia was maintained with nitrous oxide/oxygen or nitrous oxide/oxygen/halothane mixtures and in approximately 10% of cases nitrous oxide/oxygen/ enflurane. Pancuronium bromide was administered as the muscle relaxant and positive-pressure ventilation was maintained to establish an arterial PC02 of 35 to 45 torr. The EEGs were monitored on eight-channel recorders using a paper speed of 3 ern/sec, a time constant of 0.3 second, and a sensitivity of 100 JL V/cm. The sensitivity was increased to 70 and 50 JL V/em when cerebral activity diminished in amplitude, and the paper speed was then slowed to 1.5 em/sec. EEG monitoring routinely commenced after the patient had been anesthetized and positioned on the operating room table. Extensive prebypass tracing made it possible to establish an accept-
able normothermic base line, with all other parameters stabilized." In the early part of the series ice packs were used for topical cooling, and in these cases, about 5% of the total, the EEG was started when the temperature had been reduced to about 32° C.
Findings In an ideal perfusion there is no discernible change in the EEG between 37° and 35° C. 4 Between 35° and 30° C there was progressive slowing of the dominant rhythms. The usual 8 to 12 Hz rhythms of nitrous oxide/halothane anesthesia slowed to 5 to 6 Hz and faster rhythms, from 15 to 25 Hz, slowed to 9 to 13 Hz. Below 32° C the amplitude of the EEG diminished. Between 29° and 24° C the amount of faster rhythms decreased as slow activity increased, until by 24° C fast rhythms had disappeared altogether. At about 24° C periodic bursts of higher voltage activity were seen and flat periods of brief duration (0.5 to 1.5 second) first appeared. These increased in duration and occurred more frequently, until at 23° to 22° C the EEG was composed only of periodic bursts." Below these temperatures the pattern changed to burst-suppression activity, with ever-lengthening isoelectric periods (Fig. l). With rare exceptions all cerebral potentials ceased below 18° C, although there were a few instances when isolated bursts persisted at lower temperatures and even
Volume 81 Number 5 May, 1981
EEG changes with hypothermia and CPR
783
....J~:: ---_
.'"
Fig. 2. Composite tracing showing the start of epileptiform activity (0943), progressing to continuous generalized spike and wave complexes (0948), and then spike and wave with flat periods (0950). The top channel is a time marker, with 1 second divisions. T = Time. The first section (T = 0943) occurred 16 minutes after the onset of cardiopulmonary bypass, at 26° C.
for some seconds after total circulatory arrest was instituted.
EEG abnormalities There were abnormal features in a number of the EEGs before CPB was established. These were most often short-lived, reflecting transient hypotension or hypoxia, but there were some persistent mild changes, consisting of asymmetry of the dominant rhythms or a bilateral excess of theta waves (4 to 7 Hz) which continued after the start of CPB. At the start of CPB transient abnormalities were frequently seen. These ranged from a slight loss of faster rhythms with the appearance of slower waves between 5 and 7 Hz to a gross slowing with 1.5 to 3 Hz delta activity replacing all other activity. However, the time and mode of onset and relatively quick resolution of these abnormalities made it easy to discriminate them from the start of the progressive changes resulting from hypothermia alone. 6 In 70 patients epileptiform activity was seen, first appearing 26° to 24° C. In most cases the initial manifestation was of lateralized or bilateral single sharp waves. These developed into paroxysmal bursts of sharp and slow wave complexes and then generalized runs of spike and wave activity. At this time background activity ceased and the EEG was composed
only of continuous epileptiform activity with intervening flat periods (Fig. 2). In most cases appropriate drugs were given and this activity was reduced or totally abolished. At temperatures below 26° C inadequate cerebral perfusion tended to abolish cerebral activity rather than to alter the waveforms or frequencies. Lateralized abnormalities were seen rarely. On two occasions an abrupt slowing of all frequencies leading to irregular delta activity (less than 4 Hz) of low amplitude over only one hemisphere was assumed to have been caused by gaseous emboli. The gradual improvement and return to acceptable frequencies by the end of CPB in each case tended to support this. Comment The EEG is widely used to monitor CPB because it is a direct index of cerebral function. Recording can be carried on continuously without harm to the patient, and it reflects accurately and rapidly any change in the cerebral status of the patient. The electrical activity of the brain is depressed during hypothermia. The EEG reflects this by patterns of progressive slowing of the dominant activity, then intermittent activity, and finally loss of all potentials below certain temperatures. This reduction of cerebral
7 84
Hicks and Poole
activity is mostly a physiological phenomenon consistent with the reduced metabolic activity induced by cold, but the possibility that cellular hypoxia plays a part has to be considered. Reduced cerebral blood flow, a shift in the oxygen-hemoglobin dissociation curve to the left, increased cerebrovascular resistance, and depression of enzyme activity may all act to produce cerebral hypoxia even though the oxygen demand of the brain is simultaneously reduced.' It was always considered of primary importance to maintain the patient's biochemistry and blood gases as close as possible to those levels prevailing at normal temperatures, and these were monitored at frequent intervals and immediately corrected when necessary. It has been shown that incidental transient changes in acid-base balance which occur during CPB do not significantly affect the EEG,8-10 and in particular the changes in Pco, do not affect the cold-induced depression of the EEG.7 In this clinical study it was not possible to measure brain temperature directly. The temperatures available to us were recorded from the nasopharynx, midesophagus, and venous blood return line. Midesophageal temperatures in the circumstances of CPB will not correlate well with brain temperature": venous blood temperature was not considered to be very reliable, and tympanic membrane temperature monitoring was not available for our use in children. Nasopharyngeal temperatures were accepted as the most consistent and closest available approximation of brain temperature and the least affected during CPB, when the ventilator was turned off. Thus the EEG patterns that have been described may be said to form acceptable changes for various temperatures. There were, of course, wide inter-individual differences, and these were most obvious during cooling between 35° and 25° C. A slowing of the dominant (anesthetic-induced) rhythms always occurred and became more marked with lower temperatures. There were quite often differences between comparable patients on the same regimen, sometimes expressed in terms of amplitude as well as slowing. In part this may have been due to the rate of cooling, which frequently was variable. A rapid rate, 1° C per minute or faster, causes a greater amount of slowing earlier on, although at lower temperatures individual differences were less apparent. The abnormalities seen in the EEGs were of three kinds: those reflecting inadequate cerebral perfusion, epileptiform activity, and embolic phenomena. EEG abnormalities caused by cerebral embolism were seen on only two occasions and were clearly lateralized. Epileptiform activity has occurred in an increasing number of cases recently from less than 10% 4 years
The Journal of Thoracic and Cardiovascular Surgery
ago to over 60% at present. The reason for this increased incidence is not clear and is not related to drug administration or any alteration in anesthetic technique. A possible explanation might be that the absence of any significant slow surface cooling has resulted in more rapid and unequal core cooling during the early stage of perfusion. Areas of cerebral vasoconstriction and hypoxia could be possible triggering mechanisms. It has been postulated that reduction of the desynchronizing drive of the reticular activating system (brain stem) might be an important factor in creating in both hemispheres a diffuse excitatory condition which renders the cortex prone to produce rapidly disseminating paroxysmal discharges." Since the brain stem is perfused predominantly by the vertebrobasilar system and the cortex by the carotid arteries, differential rates of cooling during CPB might cause early depression of the brain stem, which thereby would allow the cortex to respond with epileptiform activity of the spike and wave type. This activity certainly does not appear to be related to preoperative EEG epileptiform activity, which has been seen in only 22 patients (7%) in this series. Thirteen of them did not exhibit any epileptiform activity at all in the operative EEG: The other nine patients had epileptiform features in the EEG before, during, and after CPB. In those patients who did not have any predisposing electrical signs, the epileptiform activity was first seen in the EEG during CPB cooling at about 26° C and worsened with further cooling. The spike and wave activity persisted for most of the time at low temperatures, although in some cases it ceased at about 20° C, with the abolition of background activity. Otherwise the epileptiform changes always ended in the early part of rewarming before 26° C was reached. Despite the descriptions of enflurane as a potentially epileptogenic agent.P in the earlier part of the series when it was used for anesthesia there was only a very small incidence of epileptiform activity in the EEGs during CPB. A number of patients had hypoxic or anoxic episodes during CPB, usually at the start when flows become apulsatile and pressures may be inadequate. Such abnormalities usually improved after a short while and the EEG then presented an acceptable pattern again. The significance of these abnormalities and the epileptiform activity is hard to assess in terms of postoperative neurologic disability. Operative EEG abnormalities do not necessarily indicate postoperative neurologic complications.!" and it has not been possible to provide psychometric testing for any of our patients to assess minor neurologic abnormalities. A recent report suggested that there might be a higher incidence of de-
Volume 81 Number 5 May, 1981
velopmental abnormality in children undergoing hypothermic circulatory arrest compared with those who had continuous perfusion, although there was no obvious correlation between operative EEG abnormalities and later developmental abnormality. 14 However, a significant proportion of patients who develop epileptic seizures in infancy later have learning difficulties in school, and some even become institutionalized for mental retardation. IS It has been hypothesized that the developing brain might be more vulnerable to the metabolic consequences of seizure than the brain of older organisms. Mental retardation is three times more common in children who have convulsions with fever than in the general population;" Following prolonged epileptic seizures in animals or man, loss of nerve cells and gliosis may be found in the cerebellum, hippocampus, amygdala, cerebral cortex, or thalamus.": 18 A history of prolonged febrile convulsions in infancy is found in a very high proportion of adolescent children operated upon for temporal lobe epilepsy who show hippocampal sclerosis;" Early vigorous management of seizures is mandatory if the survivor is to be spared the real possibility of brain damage." We recently have used thiopentone sodium to abolish all epileptiform activity in the EEG during CPB. Although it is tempting to suggest that the systemic complications of convusions (hypoxia, hypocarbia, and hypotension) may be the cause of cerebral damage, there is increasing evidence that seizure discharges in the brain can induce ischemic neuronal damage in the absence of secondary systemic effects." Therefore, on the basis of this evidence, fairly large doses of thiopentone sodium (10 to 25 mg/kg) have been used successfully with no serious hemodynamic consequences during or after CPB. Large doses are required to abolish completely all spike and wave activity in the EEG, which usually is rendered isoelectric in the process. Barbiturates have been used in preference to diazepam, since they have an additive effect with cooling for cerebral protection. Hypothermia alone is probably not adequate to protect the brain fully during periods of circulatory arrest or cerebral ischemia when electrical activity is stilI present in the EEG. The mechanism whereby barbiturates and hypothermia protect the brain differ; in particular, barbiturates probably stabilize electrically active membranes in a more specific fashion than does hypothermia. 21 Cellular damage is often permanent, whether it be gross or subtle. Perception or abstract thinking are functions which are seldom checked following perfusion, although return of normal intellectual function is the crux of the matter in developing extracorporeal circulation into a
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physiological and nontraumatic procedure. The goal for the brain must be perfect recovery. 22 The ability to distinguish EEG abnormalities from the changes resulting from hypothermia does allow the rational use of other forms of cerebral protection such as barbiturates. We wish to thank Associate Professor J. S. Wright for access to his patients, Dr. T. A. Torda for his helpful advice, Professor J. W. Lance for his suggestions, and Miss V. J. Foster for typing the manuscript. REFERENCES Hansotia PL, Myers WO, Ray JE, Greehling C, Sautter RD: Prognostic value of electroencephalography in cardiac surgery. Ann Thorac Surg 19:127-134, 1975 2 Whitby JD, Dunkin LJ: Cerebral, oesophageal and nasopharyngeal temperatures. Br J Anaesth 43:673-676, 1971 3 Wright JS, Lethlean AK, Hicks RG, Torda TA, Stacey RB: Electroencephalographic studies during open-heart surgery. J THORAC CARDIOVASC SURG 63:631-638, 1972 4 Arfel G, Weiss J, DuBouchet N: EEG findings during open-heart surgery with extra-corporeal circulation, Cerebral Anoxia and the Electroencephalogram, H Gastaut, JS Meyer, eds., Springfield, Ill., 1961, Charles C Thomas, Publisher, pp 231-249 5 Van Leeuwen SW, Nechelse K, Kok L, Zierfuss E: EEG during heart operations with artificial circulation, Cerebral Anoxia and the Electroencephalogram, H Gastaut, JS Meyer, eds .• Springfield, Ill., 1961, Charles C Thomas, Publisher, pp 268-278 6 Salerno TA, Lince DP, White DN, Lynn RB, Charrette EJ: Monitoring of the electroencephalogram during open-heart surgery. J THORAC CARDIOVASC SURG 76:97100, 1978 7 Ichiyanagi K, Matsuki M, Matsuko K, Nishisaka T, Watanabe R, Horikawa H: Effect of altered arterial carbon dioxide tensions on the electroencephalogram during hypothermia. Acta Anaesth Scand 13: 173-183, 1969 8 Harden A, Ashton BM: EEG studies during acidaemia and alkalaemia in children undergoing cardiac surgery. Electroencephalogr Clin Neurophysiol 22: 128-135, 1967 9 Juneja I, Flynn RE, Berger RL: The arterial pH, pC0 2 and the electroencephalogram during open-heart surgery. Acta Neurol Scand 48:169-175, 1972 10 Juneja I, Flynn RE, Berger RL: The arterial, venous pressures and the electroencephalogram during open-heart surgery. Acta Neurol Scand 48: 163-168, 1972 11 Gloor P: Generalized spike and wave discharges. A consideration of cortical and subcortical mechanisms of their genesis and synchronization, Synchronization of EEG Activity in Epilepsies, H Petsche, MA Brazier, eds., New York/Wein, 1975, Springer-Verlag, pp 381-405 12 Fleming DC, Fitzpatrick J, Fariello RG, DuffT, Hellman D, Hoff BH: Diagnostic activation of epileptogenic foci by enflurane. Anesthesiology 52:431-433, 1980
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13 Calanchini PR: EEGs during open-heart surgery. Electroencephalogr Clin Neurophysiol 28:9, 1970 14 Wright JS, Hicks RG, Newman DC: Deep hypothermic arrest. Observations on later development in children. J THORAC CARDIOVASC SURG 77:466-468, 1979 15 Wasterlain CG: Neonatal seizures and brain growth. Neuropadiatrie 9:213-228, 1978 16 Wallace SJ: Febrile fits. Br Med J 1:333-334, 1976 17 Meldrum B: Physiological changes during prolonged seizures and epileptic brain damage. Neuropadiatrie 9:203212, 1978 18 Blennow G, Brierley JB, Meldrum BS, Siesjo BK:
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Epileptic brain damage. The role of systemic factors that modify cerebral energy metabolism. Brain 101:687-700, 1978. Falconer MA: Mesial temporal sclerosis as a common cause of epilepsy. Lancer 2:767-770, 1974 Truhubovich RV: Management of severe or intractable convulsions including eclampsia. Int Anesthesiol Clin 17:201-238, 1979 Michenfelder JD: Hypothermia plus barbiturates. Apples plus oranges? Anesthesiology 49: 157-158, 1978 Hill JD: Blood filtration during extracorporeal circulation. Ann Thorac Surg 15:313-316, 1973