100
Electroencephalography and Clinical Neurophysiology, 1978, 4 5 : 1 0 0 - - 1 0 6 © Elsevier/North-Holland Scientific Publishers, Ltd.
Clinical note VISUAL EVOKED POTENTIALS DURING HYPOTHERMIA CIRCULATORY ARREST
AND PROLONGED
E.L. REILLY *, C. KONDO **, J.A. BRUNBERG *** and D.B. DOTY §
Departments of Psychiatry, Neurology and Surgery, University of Iowa, Iowa City, Iowa (U.S.A.) (Accepted for publication: March 2, 1978)
The response of the brain following intermittent light stimulation has been of interest since the early days of EEG. Gross changes following flashes are identifiable by visual analysis at normal sensitivities and are used clinically (Walter et al. 1946; Gastaut 1950; Bickford et al. 1952; Reilly and Peters 1973). More subtle changes demonstrated only by special techniques have been investigated since Dawson (1947) used an overtrace method to accentuate lower voltage responses not easily seen or not seen at all after a single stimulus. A major drawback retarding routine clinical use of evoked potentials has been the variability between subjects over time and particularly as age changes (Dustman and Beck 1969). The problem is greater in the newborn where even more variability occurs (Ellingson 1958, 1960, 1966, 1968, 1970, 1973, Ferriss et al. 1967). These potentials provide information about CNS function. In the unresponsive patient, presently available neurophysiological studies such as EEG are not sensitive enough to predict recovery and may not provide early warning of the individual who has significant CNS stress from changes in cerebral perfusion or increased metabolic demand. Open heart surgery is generally delayed until children gain weight. Palliative temporary surgical corrections are often made to allow survival with the expectation that definitive procedures will be carried out when the patient approaches maturity. Palliative
procedures are usually delayed if possible until the child is 35 lb or more. Due to the basic illness such weight may not be reached until 4--5 years of age. The smaller child at this age may also be unable to survive the ill effects sustained from a long procedure which demands a heart-lung machine. The side effects of the heart-lung machine in small children may contraindicate conventional surgery. As a result, the young (less than 2 years) light (less than 10 kg) child may require the use of hypothermia (16--20°C) which allows full cessation of all circulation for periods up to 60--70 rain. In this time period complete rather than palliative open heart procedures can be carried out. The total cessation of all circulation certainly has an effect on the CNS (Brunberg et al. 1973) but if the duration is limited, permanent effects are minimal. Only a few children sustain significant side effects (Brunberg et al. 1974a). Nonetheless it would be useful to find a means of detecting the child who is sustaining more profound CNS stress during the procedure and who is likely to be the patient who develops permanent side effects. The present study does not attempt to evaluate evoked potentials in relation to predetermined normative values, but examines the changes of the visual evoked potential in the same individuals over a few hours during hypothermia, surgery and recovery.
Material and Method * Associate Professor of Psychiatry and Chief of EEG and Clinical Neurophysiology Laboratories, The University of Texas Medical School at Houston, Houston, Texas 77030, U.S.A. (Reprint address). ** Now at the University of Kentucky, Lexington, Ky., U.S.A. *** Now in private practice of Neurology in Fresno, Calif., U.S.A. § Professor of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, U.S.A.
Eight children (Table I) undergoing open heart cardiac surgery using hypothermia and total circulatory arrest had visual evoked potentials recorded before, during and after the period of arrest. These children were very ill and often the decision to use surgery to correct otherwise fatal problems was made within hours of the procedure. The condition of the patient was brought to optimal level by a variety of methods and the patients only became relatively homogeneous as surgery was begun. The operative procedure (Brunberg et al. 1974b), neurological and metabolic changes (Brunberg et al. 1973, 1974a), and
VEPs DURING HYPOTHERMIA
101
the EEG changes (Reilly et al. 1974) have been reported elsewhere for a larger group of patients which included those described here. Only late in the study of this larger series were evoked potentials investigated. Case numbers have been kept the same as in the earlier study if more detail about specific children is desired (Reilly et al. 1974). Halothane anesthesia was used in the early portion of the surgical procedure and up to the arrest of circulation. It was generally unnecessary thereafter, even during recovery. Nasopharyngeal temperature was monitored as an approximation of cerebral temperature. The patient's body temperature was
lowered to 32°C by packing ice bags around the body. The operation was performed through a midsternal incision, and the patient was placed on cardiopulmonary bypass using a single right arterial cannula for venous drainage with oxygenated blood returned to the ascending aorta. A heat exchanger was placed in the oxygenator circuit and the temperature of the blood perfusing the patient was at 25°C for about 1--2 rain, after which the perfusate was cooled to establish a 12°C gradient with the body temperature. The perfusate temperature was thus between 10 and 15°C in the final minutes of bypass cooling. One hundred percent oxygen was used in the
IP2 NI*
~
'~NI
~P2 ~e2
3& EX41 suv.L
EX5
EX
IX6
5&6
NIt
l~P2 Ex7
5UV
Nlf
SUV~
~P2
Fig. I. The legend demonstrates evoked potentials of patient 22 (19 days of age) on the 7 occasions they were collected during the surgery. Measurable latencies could not be determined for example 5 which is the last 3 rain of circulatory arrest. In the figure negative is up.
102
E.L. REILLY ET AL.
oxygenator during the final 60--90 see of bypass cooling. Cardiopulmonary bypass was discontinued and total circulatory arrest established when the nasopharyngeal temperature reached 20-- 23°C. The period of circulatory arrest lasted 10--57 min. Following intracardiac repair of the congenital cardiac defect, eardiopulmonary bypass was re-established with the perfusate initially at 30°C with the temperature subsequently increased to 42°C. Cardiopulmonary bypass was terminated when the patient's nasopharyngeal temperature reached 35°C.
TABLE I Diagnosis: VSD, ventricular septal defect; ASD, atrial septal defect; PDA, patient ductus arteriosus; TGA, transposition of the great arteries; PS, pulmonary stenosis.
T h e visual e v o k e d p o t e n t i a l s
The EEGs were recorded on a 10-channel Grass Model 6 EEG machine and stored on a Precision Instrument tape recorder. Averaging was done with a Tectronic Computer of Average Transients (CAT). The N1 and P2 latencies were measured as was the amplitude between these two peaks. These parameters were compared on 7 occasions during the procedure (Fig. 1). These occasions were: (1) early anesthesia while surface cooling was being initiated; (2) early bypass cooling (first 3 min); (3) late bypass cooling (last 3 min); (4) early circulatory arrest; (5) last 3 rain of circulatory arrest; (6) early bypass rewarming; (7) the record immediately after bypass warming was terminated (35°C). Flashes were presented by means of Grass Instruments Model 2 photic stimulator at a rate of 1/sec. Sixty responses were averaged in each period. Ten pV calibration pulses were recorded from a Grass $4 stimulator at each of the sensitivity and filter settings. The responses were written out on a Houston X-Y plotter.
Age
Defect
9 11 14 15
3 months 9 months 11 months 2.5 months
22 26 27 28
19 5 16 5
ASD Tetrology of Fallot VSD TGA, VSD, PDA, Coarctation TGA TGA, VSD, PS VSD, ASD ASD, VSD, PDA, Coarctation
days months days weeks
period, the latency of the N1 potential became longer than it had been in the surface cooling stage in four of the seven children where results were available. The P2 latency was longer in three. In only one child did the latency of b o t h the P2 and N1 component actually become shorter at this point (Tables II and III). By late cooling bypass, the latency of both the N1 and P2 potential was increased for all but one of the children. The variability of the N1 and P2 latency increased during the procedure but the variability was greater for the P2 co m p o n en t where the standard deviation increased from 33 to 101 msec. The variability of the P2 wave component exceeds that of N1 wave to a significant degree (P < 0.005; F = 3.0.53; d f = 37) (Tables II and III). Amplitude was variable in all portions of the procedure but there was a progressive decrease in amplitude during cooling (Table IV). Following cooling
Results T h e eight children in the study range in age from 16 days to 11 m o n t h s (Table I). In the early bypass TABLE
Patient no.
II
0 = not recorded; -- = no response present.
NI latency
Surface cooling Early bypass Late bypass Early arrest Late arrest Bypass rewarm 35°C
9
11
14
15
22
26
86 98 144 200 0 83 94
115 127 84
71 60 165
149 223 0
137 113 178
113 134 175
86
--
183
149
97
--
107
82
55
179
27
28
Means
S.D.
68 ---
82 0 0
102.6 110.8 149.2
30.5 28.4 38.8
--
--
0
154.5
50.3
172
125
133
58
110.7
37.0
57
97
67
27
82.5 112.71
45.3 43.08
VEPs D U R I N G H Y P O T H E R M I A
103
T A B L E III 0 = not recorded; -- = no response present. P2 l a t e n c y
S u r f a c e cooling Early b y p a s s Late b y p a s s Early arrest Late arrest Bypass r e w a r m 35°C
9
11
14
15
22
26
27
28
Mean
S.D.
151 149 267 375 0 134 148
173 164 114 131 . 135 124
122 100 323 -. -100
215 359 0 255
174 205 307 -. 152 163
215 ----
142 0 0 0
169.3 192.5 263.6 263.0
32.9 82.7 86.2 101.4
242 266
162 178 307 291 . 240 114
22
.
.
.
.
.
171 94
155 72
175.6 177.6 191.81
46.4 55.6 75.27
26
27
28
Average
S.D.
8.1 7.3 4.8 2.4 . 0.7 19.0
3.8 ----
4.4 0 0 0
1.1 0.9
0.9 1.1
6.5 4.0 3.2 1.4 0.6 3.2 11.9
5.2 2.4 2.3 1.0 0.5 0.5 12.7
T A B L E IV 0 = not recorded;-
= no response present. Amplitude (pV)
S u r f a c e cooling Early b y p a s s Late bypass Early arrest L a t e arrest Bypass rewarm 35°C
9
11
14
15
5.6 4.3 7.1 2.5 0 1.6 8.3
4.0 4.9 1.9 -. 2.2 3.8
18.0 3.5 2.0 -. -10.70
7.6 1.2 0 0.9 . 3.0 29.6
.
b y p a s s c o m p l e t e c i r c u l a t o r y a r r e s t was i n i t i a t e d a n d t h e average a m p l i t u d e was o n l y a q u a r t e r o f t h e initial values. O n e o f t h e c h i l d r e n lost m e a s u r a b l e e v o k e d p o t e n t i a l s d u r i n g early b y p a s s cooling, a n d t w o m o r e lost t h e i r e v o k e d p o t e n t i a l s in early circul a t o r y arrest. E v o k e d p o t e n t i a l s were a b s e n t in all seven c h i l d r e n r e c o r d e d in t h e late a r r e s t period. A n e i g h t h child did n o t have a s e c o n d e v o k e d p o t e n t i a l r e c o r d e d d u r i n g c i r c u l a t o r y arrest since t h e p e r i o d o f his arrest was o n l y 10 rain. T h e r e c o r d i n g ' n o i s e ' level d u r i n g t h e final p e r i o d o f c i r c u l a t o r y a r r e s t averaged o n e - t e n t h o f t h e initial a m p l i t u d e a n d a c t i v i t y in a n y way d i s c e r n i b l e as visual e v o k e d p o t e n t i a l s was a b s e n t in all seven c h i l d r e n r e c o r d e d . S e v e n o f t h e eight children had prompt return of evoked potentials during w a r m i n g bypass, a n d all eight r e c o v e r e d e v o k e d p o t e n t i a l s b y t h e t i m e t h e y w e r e r e w a r m e d t o 35°C.
Discussion It h a s b e e n p r e v i o u s l y felt t h a t t h e m o s t reliable wave b o t h for ' i n t e r - i n d i v i d u a l c o m p a r i s o n ' a n d f o r
5.0 6.1 2.7 2.5 .
. 0.4 12.0
use as a n 'age m a r k e r ' is t h e P2 wave (Ferriss et al. 1 9 6 7 ; Ellingson 1 9 7 0 , 1 9 7 3 ) . This wave is t h e IV wave of Ciganek ( 1 9 6 1 ) or Kooi a n d Bagchi ( 1 9 6 4 ) . T h e r e is a m a r k e d c h a n g e in t h e l a t e n c y of t h e P2 c o m p o n e n t f r o m b i r t h t o m a t u r i t y (Ferriss et al. 1967; Elingson 1968, 1973; Fogarty and Reuben 1 9 6 9 ) . T h e l a t e n c y decreases r a p i d l y in t h e first 4--5 weeks (Ferriss et al. 1 9 6 7 ) a n d s h o w s signific a n t m a t u r a t i o n over t h e first 2--3 m o n t h s o f life ( F o g a r t y a n d R e u b e n 1 9 6 9 ; Ellingson et al. 1 9 7 3 ) . I n this series o f c h i l d r e n , t h e l a t e n c y o f t h e P2 p o t e n t i a l o f t h e t h r e e c h i l d r e n u n d e r 2 m o n t h s o f age was n o t significantly d i f f e r e n t f r o m t h a t of t h e five c h i l d r e n over t h a t age ( 1 7 3 msec vs. 167 msec, respectively). All t h e s e c h i l d r e n were severely ill w i t h v a r y i n g degrees o f h y p o x i a a n d all h a d d e l a y e d d e v e l o p m e n t . I t is likely t h a t e x p e c t e d age r e l a t e d c h a n g e s were b l u r r e d b y illness, a n d e x p e c t e d m a t u r a t i o n h a d n o t o c c u r r e d . D u r i n g t h e p r o c e d u r e , t w o t r e n d s were seen. T h e N1 a n d P2 latencies d e m o n s t r a t e d a s t e a d y progressive increase w i t h loss o f t h e e v o k e d p o t e n t i a l b y t h e t i m e o f c i r c u l a t o r y a r r e s t or earlier (Tables II a n d III). I n a n i m a l studies t h e visual e v o k e d p o t e n -
104 tials of both the cortex and retina decrease in amplitude and increase in latency during hypothermia (Wolin et al. 1964). Studies using cats showed a period o f evoked potential hyper-responsiveness with a temperature in the range of 35--24°C (Suda et al. 1957). In our patients, the response during the early bypass cooling was different than that during anesthesia and surface cooling and some of the variation may represent such stimulation effect. Equally likely is the possibility that the variability in early bypass may be partially explained by the marked improvement in oxygenation of bypass blood compared to the blood available to these children from their spontaneous circulation. By the late cooling bypass stage latencies were increased for all but one of the children. The variability of the P2 wave over the course of bypass cooling and after recovery (Table III) suggests that its latency may be influenced by factors other than temperature alone. The possibilities include relative hypoxia and the rate of temperature change. N1 has lesser variability raising the possibility that N1 may be of greater value in assessing early change in hypoxia and other CNS stresses than the more variable P2 component. In this study N1 could be identified with the same frequency as the P2 component. In contrast to the loss of evoked potentials, EEG activity persisted at very low levels in six of the eight patients even in the period of circulatory arrest (Reilly et al. 1974). Early studies suggested that EEG activity was lost even at temperatures as high as 20°C (McQueen 1956) but later studies found persistence of activity in man with total loss of EEG activity only at 7--17°C (Pagni and Courjon 1964). When circulatory arrest was carried out during hypothermia, it has been reported that activity is lost in i or 2 min (Harden et al. 1966; Weiss et al. 1975) but the amplification used in these studies was less than is necessary even for simple determination of electrocerebral inactivity (American EEG Society 1976) and is certainly less than current equipment allows. The present series involves records with a sensitivity of 2 p V / m m or more and demonstrated persistence of very low voltage activity in eight of fourteen children (Reilly et al. 1974). Weiss et al. (1975) suggested this low voltage activity recorded in hypothermia was subcortical in origin but does not substantiate this belief. Reilly et al. (1974) found return of normal cortical voltage in those with residual low voltage (1--2 pV) discharges more quickly than in those without. This does not prove a cortical origin of the voltage but is consistent with the general feeling that scalp recorded potentials are of surface cortex origin and demonstrates a direct relationship of faster return of clearly cortical activity with the very low voltage seemingly cortical residual activity seen during hypothermia. In these children, EEG activity was never lost
E.L. REILLY ET AL. during hypothermia alone and loss w h e n it occurred, followed circulatory arrest. The difference with more frequent loss of the evoked potential than E E G activity is significant (P < 0.02, X 2 = 6.0, df = 1). Following rewarming the evoked potential latencies tended to be shorter than in the initial records. Postoperatively all but one of the children had better cardiac function and better oxygenation. The exceptional child (child 15) was unable to maintain adequate cardiac output. The latency of both N 1 and P2 was longer than in the initial portion of the procedure and the child died shortly after the last value was obtained. Another child had an N 1 latency 8 msec longer than at the start of the procedure but the P2 latency was not significantly changed. This child did well.
Summary Visual evoked potentials were recorded in eight children during hypothermia and circulatory arrest. The potentials were lost in all children recorded in late arrest. The evoked potential is a more sensitive indicator of C N S stress as provoked by combined hypothermia and hypoxia than is the E E G . E E G activity persisted in six of the eight children in this series even during circulatory arrest. The E E G had been seen to do the same in more than half of a larger series of children recorded at that stage. The results suggest that evoked potentials m a y be a sensitive indicator of early impairment of cerebral function and m a y demonstrate useful changes sooner than the E E G . The examination m a y be useful in following children with illnesses producing hypoxia or anoxia. The N 1 c o m p o n e n t was as easily and as frequently identifiable as the P2 component. Under the stress of this procedure, the latency of the P2 c o m p o n e n t became more variable than the N 1 peak. The results suggest the N 1 c o m p o n e n t m a y be as useful and perhaps more useful than the P2 wave in following the effect of s o m e C N S stresses in children.
R~sum~
Potentiels ~voqu~s visuels au cours de l'hypothermie et de l'arr~t circulatoire prolong$ Des potentiels ~voqu~s visuels ont ~t~ enregistrds chez huit enfants en cours d'hypothermie et d'arr~t circulatoire. Ces potentiels disparaissent chez tons les enfants enregistr~s en arr~t prolongS. Le potentiel ~voqu~ est un indicateur plus sensible de stress du S N C produit par la combinaison d'hypothermie et d'hypoxie que ne l'est I'EEG. L'activit6 E E G persiste chez six des huit enfants de cette s~rie m ~ m e en cours
VEPs DURING HYPOTHERMIA d'arr~t circulatoire. Ceci a ~t~ 4galement observ4 dans plus de la moiti~ des cas d'une s~rie plus grande d'enfants ~ ce stade. Les r~sultats sugg~rent q u e les potentiels ~voqu~s puissent ~tre un indicateur sensible d'une atteinte pr~coce des fonctions c~r~brales et qu'ils puissent montrer des changements utiles plus tSt que I'EEG. L'examen peut ~tre utile pour suivre l'~volution des enfants atteints de maladies qui provoquent l'hypoxie ou l'anoxie. La composante N1 est aussi ais~ment et aussi fr~quemment identifiable que ne l'est la composante P2. En situation de stress, la latence de la composante P2 devient plus variable que le pic N1. Ces r~sultats sugg~rent que la composante N1 puisse ~tre aussi utile et peut ~tre plus utile que l'onde P2 pour suivre l'~volution des effets de certain stress du SNC chez l'enfant.
References American EEG Society Minimum Technical Standards for EEG Recording in Suspected Cerebral Death. American EEG Society, 1976. Bickford, R.G., Sem-Jacobsen, C.W., White, P.T. and Daly, D. Some observations on the mechanism of photic and photometrazol activation. Electroenceph, clin. Neur
Electroencephalography and Clinical Neurophysiology, 1978, 4 5 : 1 0 0 - - 1 0 6 © Elsevier/North-Holland Scientific Publishers, Ltd.
Clinical note VISUAL EVOKED POTENTIALS DURING HYPOTHERMIA CIRCULATORY ARREST
AND PROLONGED
E.L. REILLY *, C. KONDO **, J.A. BRUNBERG *** and D.B. DOTY §
Departments of Psychiatry, Neurology and Surgery, University of Iowa, Iowa City, Iowa (U.S.A.) (Accepted for publication: March 2, 1978)
The response of the brain following intermittent light stimulation has been of interest since the early days of EEG. Gross changes following flashes are identifiable by visual analysis at normal sensitivities and are used clinically (Walter et al. 1946; Gastaut 1950; Bickford et al. 1952; Reilly and Peters 1973). More subtle changes demonstrated only by special techniques have been investigated since Dawson (1947) used an overtrace method to accentuate lower voltage responses not easily seen or not seen at all after a single stimulus. A major drawback retarding routine clinical use of evoked potentials has been the variability between subjects over time and particularly as age changes (Dustman and Beck 1969). The problem is greater in the newborn where even more variability occurs (Ellingson 1958, 1960, 1966, 1968, 1970, 1973, Ferriss et al. 1967). These potentials provide information about CNS function. In the unresponsive patient, presently available neurophysiological studies such as EEG are not sensitive enough to predict recovery and may not provide early warning of the individual who has significant CNS stress from changes in cerebral perfusion or increased metabolic demand. Open heart surgery is generally delayed until children gain weight. Palliative temporary surgical corrections are often made to allow survival with the expectation that definitive procedures will be carried out when the patient approaches maturity. Palliative
procedures are usually delayed if possible until the child is 35 lb or more. Due to the basic illness such weight may not be reached until 4--5 years of age. The smaller child at this age may also be unable to survive the ill effects sustained from a long procedure which demands a heart-lung machine. The side effects of the heart-lung machine in small children may contraindicate conventional surgery. As a result, the young (less than 2 years) light (less than 10 kg) child may require the use of hypothermia (16--20°C) which allows full cessation of all circulation for periods up to 60--70 rain. In this time period complete rather than palliative open heart procedures can be carried out. The total cessation of all circulation certainly has an effect on the CNS (Brunberg et al. 1973) but if the duration is limited, permanent effects are minimal. Only a few children sustain significant side effects (Brunberg et al. 1974a). Nonetheless it would be useful to find a means of detecting the child who is sustaining more profound CNS stress during the procedure and who is likely to be the patient who develops permanent side effects. The present study does not attempt to evaluate evoked potentials in relation to predetermined normative values, but examines the changes of the visual evoked potential in the same individuals over a few hours during hypothermia, surgery and recovery.
Material and Method * Associate Professor of Psychiatry and Chief of EEG and Clinical Neurophysiology Laboratories, The University of Texas Medical School at Houston, Houston, Texas 77030, U.S.A. (Reprint address). ** Now at the University of Kentucky, Lexington, Ky., U.S.A. *** Now in private practice of Neurology in Fresno, Calif., U.S.A. § Professor of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, U.S.A.
Eight children (Table I) undergoing open heart cardiac surgery using hypothermia and total circulatory arrest had visual evoked potentials recorded before, during and after the period of arrest. These children were very ill and often the decision to use surgery to correct otherwise fatal problems was made within hours of the procedure. The condition of the patient was brought to optimal level by a variety of methods and the patients only became relatively homogeneous as surgery was begun. The operative procedure (Brunberg et al. 1974b), neurological and metabolic changes (Brunberg et al. 1973, 1974a), and
VEPs DURING HYPOTHERMIA
101
the EEG changes (Reilly et al. 1974) have been reported elsewhere for a larger group of patients which included those described here. Only late in the study of this larger series were evoked potentials investigated. Case numbers have been kept the same as in the earlier study if more detail about specific children is desired (Reilly et al. 1974). Halothane anesthesia was used in the early portion of the surgical procedure and up to the arrest of circulation. It was generally unnecessary thereafter, even during recovery. Nasopharyngeal temperature was monitored as an approximation of cerebral temperature. The patient's body temperature was
lowered to 32°C by packing ice bags around the body. The operation was performed through a midsternal incision, and the patient was placed on cardiopulmonary bypass using a single right arterial cannula for venous drainage with oxygenated blood returned to the ascending aorta. A heat exchanger was placed in the oxygenator circuit and the temperature of the blood perfusing the patient was at 25°C for about 1--2 rain, after which the perfusate was cooled to establish a 12°C gradient with the body temperature. The perfusate temperature was thus between 10 and 15°C in the final minutes of bypass cooling. One hundred percent oxygen was used in the
IP2 NI*
~
'~NI
~P2 ~e2
3& EX41 suv.L
EX5
EX
IX6
5&6
NIt
l~P2 Ex7
5UV
Nlf
SUV~
~P2
Fig. I. The legend demonstrates evoked potentials of patient 22 (19 days of age) on the 7 occasions they were collected during the surgery. Measurable latencies could not be determined for example 5 which is the last 3 rain of circulatory arrest. In the figure negative is up.
102
E.L. REILLY ET AL.
oxygenator during the final 60--90 see of bypass cooling. Cardiopulmonary bypass was discontinued and total circulatory arrest established when the nasopharyngeal temperature reached 20-- 23°C. The period of circulatory arrest lasted 10--57 min. Following intracardiac repair of the congenital cardiac defect, eardiopulmonary bypass was re-established with the perfusate initially at 30°C with the temperature subsequently increased to 42°C. Cardiopulmonary bypass was terminated when the patient's nasopharyngeal temperature reached 35°C.
TABLE I Diagnosis: VSD, ventricular septal defect; ASD, atrial septal defect; PDA, patient ductus arteriosus; TGA, transposition of the great arteries; PS, pulmonary stenosis.
T h e visual e v o k e d p o t e n t i a l s
The EEGs were recorded on a 10-channel Grass Model 6 EEG machine and stored on a Precision Instrument tape recorder. Averaging was done with a Tectronic Computer of Average Transients (CAT). The N1 and P2 latencies were measured as was the amplitude between these two peaks. These parameters were compared on 7 occasions during the procedure (Fig. 1). These occasions were: (1) early anesthesia while surface cooling was being initiated; (2) early bypass cooling (first 3 min); (3) late bypass cooling (last 3 min); (4) early circulatory arrest; (5) last 3 rain of circulatory arrest; (6) early bypass rewarming; (7) the record immediately after bypass warming was terminated (35°C). Flashes were presented by means of Grass Instruments Model 2 photic stimulator at a rate of 1/sec. Sixty responses were averaged in each period. Ten pV calibration pulses were recorded from a Grass $4 stimulator at each of the sensitivity and filter settings. The responses were written out on a Houston X-Y plotter.
Age
Defect
9 11 14 15
3 months 9 months 11 months 2.5 months
22 26 27 28
19 5 16 5
ASD Tetrology of Fallot VSD TGA, VSD, PDA, Coarctation TGA TGA, VSD, PS VSD, ASD ASD, VSD, PDA, Coarctation
days months days weeks
period, the latency of the N1 potential became longer than it had been in the surface cooling stage in four of the seven children where results were available. The P2 latency was longer in three. In only one child did the latency of b o t h the P2 and N1 component actually become shorter at this point (Tables II and III). By late cooling bypass, the latency of both the N1 and P2 potential was increased for all but one of the children. The variability of the N1 and P2 latency increased during the procedure but the variability was greater for the P2 co m p o n en t where the standard deviation increased from 33 to 101 msec. The variability of the P2 wave component exceeds that of N1 wave to a significant degree (P < 0.005; F = 3.0.53; d f = 37) (Tables II and III). Amplitude was variable in all portions of the procedure but there was a progressive decrease in amplitude during cooling (Table IV). Following cooling
Results T h e eight children in the study range in age from 16 days to 11 m o n t h s (Table I). In the early bypass TABLE
Patient no.
II
0 = not recorded; -- = no response present.
NI latency
Surface cooling Early bypass Late bypass Early arrest Late arrest Bypass rewarm 35°C
9
11
14
15
22
26
86 98 144 200 0 83 94
115 127 84
71 60 165
149 223 0
137 113 178
113 134 175
86
--
183
149
97
--
107
82
55
179
27
28
Means
S.D.
68 ---
82 0 0
102.6 110.8 149.2
30.5 28.4 38.8
--
--
0
154.5
50.3
172
125
133
58
110.7
37.0
57
97
67
27
82.5 112.71
45.3 43.08
VEPs D U R I N G H Y P O T H E R M I A
103
T A B L E III 0 = not recorded; -- = no response present. P2 l a t e n c y
S u r f a c e cooling Early b y p a s s Late b y p a s s Early arrest Late arrest Bypass r e w a r m 35°C
9
11
14
15
22
26
27
28
Mean
S.D.
151 149 267 375 0 134 148
173 164 114 131 . 135 124
122 100 323 -. -100
215 359 0 255
174 205 307 -. 152 163
215 ----
142 0 0 0
169.3 192.5 263.6 263.0
32.9 82.7 86.2 101.4
242 266
162 178 307 291 . 240 114
22
.
.
.
.
.
171 94
155 72
175.6 177.6 191.81
46.4 55.6 75.27
26
27
28
Average
S.D.
8.1 7.3 4.8 2.4 . 0.7 19.0
3.8 ----
4.4 0 0 0
1.1 0.9
0.9 1.1
6.5 4.0 3.2 1.4 0.6 3.2 11.9
5.2 2.4 2.3 1.0 0.5 0.5 12.7
T A B L E IV 0 = not recorded;-
= no response present. Amplitude (pV)
S u r f a c e cooling Early b y p a s s Late bypass Early arrest L a t e arrest Bypass rewarm 35°C
9
11
14
15
5.6 4.3 7.1 2.5 0 1.6 8.3
4.0 4.9 1.9 -. 2.2 3.8
18.0 3.5 2.0 -. -10.70
7.6 1.2 0 0.9 . 3.0 29.6
.
b y p a s s c o m p l e t e c i r c u l a t o r y a r r e s t was i n i t i a t e d a n d t h e average a m p l i t u d e was o n l y a q u a r t e r o f t h e initial values. O n e o f t h e c h i l d r e n lost m e a s u r a b l e e v o k e d p o t e n t i a l s d u r i n g early b y p a s s cooling, a n d t w o m o r e lost t h e i r e v o k e d p o t e n t i a l s in early circul a t o r y arrest. E v o k e d p o t e n t i a l s were a b s e n t in all seven c h i l d r e n r e c o r d e d in t h e late a r r e s t period. A n e i g h t h child did n o t have a s e c o n d e v o k e d p o t e n t i a l r e c o r d e d d u r i n g c i r c u l a t o r y arrest since t h e p e r i o d o f his arrest was o n l y 10 rain. T h e r e c o r d i n g ' n o i s e ' level d u r i n g t h e final p e r i o d o f c i r c u l a t o r y a r r e s t averaged o n e - t e n t h o f t h e initial a m p l i t u d e a n d a c t i v i t y in a n y way d i s c e r n i b l e as visual e v o k e d p o t e n t i a l s was a b s e n t in all seven c h i l d r e n r e c o r d e d . S e v e n o f t h e eight children had prompt return of evoked potentials during w a r m i n g bypass, a n d all eight r e c o v e r e d e v o k e d p o t e n t i a l s b y t h e t i m e t h e y w e r e r e w a r m e d t o 35°C.
Discussion It h a s b e e n p r e v i o u s l y felt t h a t t h e m o s t reliable wave b o t h for ' i n t e r - i n d i v i d u a l c o m p a r i s o n ' a n d f o r
5.0 6.1 2.7 2.5 .
. 0.4 12.0
use as a n 'age m a r k e r ' is t h e P2 wave (Ferriss et al. 1 9 6 7 ; Ellingson 1 9 7 0 , 1 9 7 3 ) . This wave is t h e IV wave of Ciganek ( 1 9 6 1 ) or Kooi a n d Bagchi ( 1 9 6 4 ) . T h e r e is a m a r k e d c h a n g e in t h e l a t e n c y of t h e P2 c o m p o n e n t f r o m b i r t h t o m a t u r i t y (Ferriss et al. 1967; Elingson 1968, 1973; Fogarty and Reuben 1 9 6 9 ) . T h e l a t e n c y decreases r a p i d l y in t h e first 4--5 weeks (Ferriss et al. 1 9 6 7 ) a n d s h o w s signific a n t m a t u r a t i o n over t h e first 2--3 m o n t h s o f life ( F o g a r t y a n d R e u b e n 1 9 6 9 ; Ellingson et al. 1 9 7 3 ) . I n this series o f c h i l d r e n , t h e l a t e n c y o f t h e P2 p o t e n t i a l o f t h e t h r e e c h i l d r e n u n d e r 2 m o n t h s o f age was n o t significantly d i f f e r e n t f r o m t h a t of t h e five c h i l d r e n over t h a t age ( 1 7 3 msec vs. 167 msec, respectively). All t h e s e c h i l d r e n were severely ill w i t h v a r y i n g degrees o f h y p o x i a a n d all h a d d e l a y e d d e v e l o p m e n t . I t is likely t h a t e x p e c t e d age r e l a t e d c h a n g e s were b l u r r e d b y illness, a n d e x p e c t e d m a t u r a t i o n h a d n o t o c c u r r e d . D u r i n g t h e p r o c e d u r e , t w o t r e n d s were seen. T h e N1 a n d P2 latencies d e m o n s t r a t e d a s t e a d y progressive increase w i t h loss o f t h e e v o k e d p o t e n t i a l b y t h e t i m e o f c i r c u l a t o r y a r r e s t or earlier (Tables II a n d III). I n a n i m a l studies t h e visual e v o k e d p o t e n -
104 tials of both the cortex and retina decrease in amplitude and increase in latency during hypothermia (Wolin et al. 1964). Studies using cats showed a period o f evoked potential hyper-responsiveness with a temperature in the range of 35--24°C (Suda et al. 1957). In our patients, the response during the early bypass cooling was different than that during anesthesia and surface cooling and some of the variation may represent such stimulation effect. Equally likely is the possibility that the variability in early bypass may be partially explained by the marked improvement in oxygenation of bypass blood compared to the blood available to these children from their spontaneous circulation. By the late cooling bypass stage latencies were increased for all but one of the children. The variability of the P2 wave over the course of bypass cooling and after recovery (Table III) suggests that its latency may be influenced by factors other than temperature alone. The possibilities include relative hypoxia and the rate of temperature change. N1 has lesser variability raising the possibility that N1 may be of greater value in assessing early change in hypoxia and other CNS stresses than the more variable P2 component. In this study N1 could be identified with the same frequency as the P2 component. In contrast to the loss of evoked potentials, EEG activity persisted at very low levels in six of the eight patients even in the period of circulatory arrest (Reilly et al. 1974). Early studies suggested that EEG activity was lost even at temperatures as high as 20°C (McQueen 1956) but later studies found persistence of activity in man with total loss of EEG activity only at 7--17°C (Pagni and Courjon 1964). When circulatory arrest was carried out during hypothermia, it has been reported that activity is lost in i or 2 min (Harden et al. 1966; Weiss et al. 1975) but the amplification used in these studies was less than is necessary even for simple determination of electrocerebral inactivity (American EEG Society 1976) and is certainly less than current equipment allows. The present series involves records with a sensitivity of 2 p V / m m or more and demonstrated persistence of very low voltage activity in eight of fourteen children (Reilly et al. 1974). Weiss et al. (1975) suggested this low voltage activity recorded in hypothermia was subcortical in origin but does not substantiate this belief. Reilly et al. (1974) found return of normal cortical voltage in those with residual low voltage (1--2 pV) discharges more quickly than in those without. This does not prove a cortical origin of the voltage but is consistent with the general feeling that scalp recorded potentials are of surface cortex origin and demonstrates a direct relationship of faster return of clearly cortical activity with the very low voltage seemingly cortical residual activity seen during hypothermia. In these children, EEG activity was never lost
E.L. REILLY ET AL. during hypothermia alone and loss w h e n it occurred, followed circulatory arrest. The difference with more frequent loss of the evoked potential than E E G activity is significant (P < 0.02, X 2 = 6.0, df = 1). Following rewarming the evoked potential latencies tended to be shorter than in the initial records. Postoperatively all but one of the children had better cardiac function and better oxygenation. The exceptional child (child 15) was unable to maintain adequate cardiac output. The latency of both N 1 and P2 was longer than in the initial portion of the procedure and the child died shortly after the last value was obtained. Another child had an N 1 latency 8 msec longer than at the start of the procedure but the P2 latency was not significantly changed. This child did well.
Summary Visual evoked potentials were recorded in eight children during hypothermia and circulatory arrest. The potentials were lost in all children recorded in late arrest. The evoked potential is a more sensitive indicator of C N S stress as provoked by combined hypothermia and hypoxia than is the E E G . E E G activity persisted in six of the eight children in this series even during circulatory arrest. The E E G had been seen to do the same in more than half of a larger series of children recorded at that stage. The results suggest that evoked potentials m a y be a sensitive indicator of early impairment of cerebral function and m a y demonstrate useful changes sooner than the E E G . The examination m a y be useful in following children with illnesses producing hypoxia or anoxia. The N 1 c o m p o n e n t was as easily and as frequently identifiable as the P2 component. Under the stress of this procedure, the latency of the P2 c o m p o n e n t became more variable than the N 1 peak. The results suggest the N 1 c o m p o n e n t m a y be as useful and perhaps more useful than the P2 wave in following the effect of s o m e C N S stresses in children.
R~sum~
Potentiels ~voqu~s visuels au cours de l'hypothermie et de l'arr~t circulatoire prolong$ Des potentiels ~voqu~s visuels ont ~t~ enregistrds chez huit enfants en cours d'hypothermie et d'arr~t circulatoire. Ces potentiels disparaissent chez tons les enfants enregistr~s en arr~t prolongS. Le potentiel ~voqu~ est un indicateur plus sensible de stress du S N C produit par la combinaison d'hypothermie et d'hypoxie que ne l'est I'EEG. L'activit6 E E G persiste chez six des huit enfants de cette s~rie m ~ m e en cours
VEPs DURING HYPOTHERMIA d'arr~t circulatoire. Ceci a ~t~ 4galement observ4 dans plus de la moiti~ des cas d'une s~rie plus grande d'enfants ~ ce stade. Les r~sultats sugg~rent q u e les potentiels ~voqu~s puissent ~tre un indicateur sensible d'une atteinte pr~coce des fonctions c~r~brales et qu'ils puissent montrer des changements utiles plus tSt que I'EEG. L'examen peut ~tre utile pour suivre l'~volution des enfants atteints de maladies qui provoquent l'hypoxie ou l'anoxie. La composante N1 est aussi ais~ment et aussi fr~quemment identifiable que ne l'est la composante P2. En situation de stress, la latence de la composante P2 devient plus variable que le pic N1. Ces r~sultats sugg~rent que la composante N1 puisse ~tre aussi utile et peut ~tre plus utile que l'onde P2 pour suivre l'~volution des effets de certain stress du SNC chez l'enfant.
References American EEG Society Minimum Technical Standards for EEG Recording in Suspected Cerebral Death. American EEG Society, 1976. Bickford, R.G., Sem-Jacobsen, C.W., White, P.T. and Daly, D. Some observations on the mechanism of photic and photometrazol activation. Electroenceph, clin. Neur
