=Acta-Nuro&irurgica

Acta Neurochir (Wien) (1992) 116:38-43

9 Springer-Verlag 1992
Printed in Austria

Isoflurane in the Management of Status Epilepticus After Surgery for Lesion Around
the Motor Area
T. Sakaki l, K. Abe 2, T. Hoshida ~, T. Morimoto 1, S. Tsunoda ~, K. Okuchi 3, S. Miyamoto 3, and H. Furuya 4
Departments of 1Neurosurgery, 3 Emergent Medicine and 4 Anesthesiology, Nara Medical University, Nara, and 2 Department of Anesthesiology, Osaka Police Hospital, Osaka, Japan

Summary

A

When conventional treatment for status epilepticus fails, general
anaesthesia is recommended. We present our experience with isoflurane, an inhalational anaesthetic, in the management of four patients with status epilepticus which occurred soon after surgery for
motor area lesion. The seizures were controlled with relatively small
concentrations of isoflurane. Hypotension, the only adverse effect
of isoflurane, was managed easily with the use of dopamine in physiological saline. Although status epilepticus occurring soon after
surgery is transient, it carries a risk of persistent brain damage if
active treatment is not instituted promptly. Isoflurane general anaesthesia may be recommended to control it in the intensive neurosurgical care.

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Keywords." Isoflurane; status epilepticus; motor area; postoperative complication.
Introduction

Status epilepticus is a neurological emergency.
When conventional intravenous agents prove unsuccessful, general anaesthesia is advocated 3. It has been
shown that both thiopental and isoflurane produce a
dose-related decrease in cerebral function as detected
by the electroencephalogram (EEG), with an attendant
decrease in cerebral oxygen metabolism (CMRO2),
with maximal metabolic depression occurring with onset of an isoelectric EEG 17' la. Although barbiturate
anaesthesia is good treatment for status epilepticus ~2'
25, 31 it is often difficult to keep the serum level steady,
and to maintain the blood pressure without performing
Fig. 1. Electroencephalography demonstrated spike discharges from
the hemisphere with the lesion preoperatively (A). But, status epilepticus occurred in spite of pre-operative administration of anticonvulsants soon after removal of the lesion and termination of
anaesthesia (B)

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T. Sakaki et al.: Isoflurane in the Management of Status Epilepticus After Surgery for Lesion Around the Motor Area

a continuous dopamine infusion2L Judging from these
shortcomings of barbiturate anaesthesia, isoflurane anaesthesia may be the best treatment for patients with
status epilepticus resulting from surgery for cerebral
organic lesions.
We report four cases whose status epilepticus occurred soon after surgery for cerebral lesions around
the motor area and treated effectively with isoflurane
general anaesthesia. We describe the effectiveness of
isoflurane, an inhalational anaesthetic, in the management of this condition to alleviate attacks and to protect
the brain from ischaemic damage during the attack.
Patients and Methods
Four patients had status epilepticus soon after the operation for
a lesion around the motor area (Fig. 1) and were subjected to iso-

A

flurane anaesthesia, because the seizure did not respond to the
prompt administration of therapeutic doses of phenobarbital or
phenytoin. Although intravenous diazepam administration alleviated the attacks, the effect was only transient. An administration of
thiopental was also effective, but marked hypotension occurred,
whenever the dose reached burst-suppression of the EEG pattern.
For these reasons, it was decided to administer isoflurane general
anaesthesia. Continuous isoflurane general anaesthesia was performed using a vaporizer (Isoflurane vaporizer 952, Siemens-elema,
Sweden) attached to the gas supply of the ventilator (Servo 900C,
Siemens-elema, Sweden). EEG activity was monitored continuously
until electroencephalographic suppression occurred (Fig.2), and
thereafter monitored every thirty minutes. Intracranial pressure
(ICP) was also monitored continuously using spinal drainage apparatus. The isoflurane was easily titrated to maintain burst suppression, but an increased volume of intravenous fluid and a transient
increase in the dopamine were given to maintain an adequate blood
pressure, if necessary. The patient was given concentration of 0.5 to
1 percent of inspired isoflurane. The end-tidal isoflurane concentra-

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Fig. 2. The remarkable spike discharges (A)
were suppressed completely after isoflurane
general anaesthesia (B)

40

T. Sakaki et aL: ]Isoflurane in the Management of Status Epilepticus After Surgery for Lesion Around the Motor Area

tion and endexpiratory CO2 were monitored continuously (M 1025A,
Hewlett Packard, U.S.A.). An anaesthetist and a neurosurgeon were
always present.
If the ICP exceeded 200 mmH20, instillation of mannitol or
glycerol was started in addition to the administration of steroid.
In all patients, seizures were controlled long term with oral administration of conventional anticonvulsants, and the prognosis of
the patients was excellent.

Case Reports
Case I

A 39 year-old woman was transferred on April 1, 1988 to our
hospital with generalized tonic-clonic convulsions which were soon
alleviated by the intravenous administration of diazepam. CT scan
performed on admission, demonstrated a large meningioma at the
left motor area without perifocal cerebral oedema (Fig. 3). Left external and internal angiography demonstrated a convexity meningioma indenting the brain between prerolandic and vein of Trolard's.
Surgical removal of the meningioma was performed on 18th April
1988, and she woke up from anaesthesia without neurological deficit.
But partial seizures of right upper extremity occurred two hours after
the surgery and developed into generalized status epilepticus in spite
of the intravenous administration of diazepam or thiopental. A lidocaine infusion at 4mg/min for 3 hours and 10% paraldehyde
solution in physiological saline infusion 30ml/h for 6 hours had no
effect. Therefore they were discontinued. Considering that maximal
therapy with conventional anticonvulsants had not controlled the
status epilepticus, it was decided to administer isoflurane general
anaesthesia. With the start of anaesthesia, suppression of epileptiform discharge was observed without blood pressure reduction. 12
hours later, valploic acid was administered at a dose of 4 mg/kg/6
hour transenterally through the nasal tube. Although the anaesthesia
was gradually withdrawn 24 hours after administration of isoflurane,
epileptiform discharges were seldom recognized in the EEG. The
patient regained consciousness slowly but steadily and showed monoparesis of the right upper extremity and motor aphasia at first.
These signs cleared after 2 days completely. The seizures were well
controlled by oral intake of valploic acid thereafter.

Fig. 4. Angiography of Case 2 showed a small arteriovenous maiformation (arrow) at the left post-rolandic gyrus (A), and it was
completely removed surgically (B)

Case 2

Fig. 3. CT scan demonstrating the meningioma involving the motor
area of the left hemisphere without perifocal oedema (A). After
surgery, the area of surgical removal demonstrated ring-like enhancement on CT scan with infusion of contrast material (B)

A 24 years-old man was admitted with sudden onset of generalized convulsions and loss of consciousness on 5th September 1989.
CT scan performed on admission, showed a calcified lesion which
was enhanced by the administration of the contrast material. Left
internal carotid angiography demonstrated a small arteriovenous
malformation at the left parietal motor area (Fig. 4). On 16th September, surgical removal of the arteriovenous malformation was
performed. Although the patient woke up from anaesthesia soon,
slight paresis of the right upper extremity was recognized. One hour
!ater, right hemiconvulsions occurred. These developed into status
epilepticus in spite of aggressive intravenous administration of anticonvulsants such as diazepam, phenytoin, phenobarbital, or lidocain. Although intravenous administration of thiopental was effective, the blood pressure could not be maintained without titration
of dopamine, and his spontaneous respiration disappeared whenever
the dose of thiopental was increased to stop the seizure completely.
Considering that infusion of conventional anticonvulsants was only
partially effective, it was decided to administer isofhirane general
anaesthesia under controlled ventilation. Anaesthesia was continued

T. Sakaki et al.: Isoflurane in the Management of Status Epilepticus After Surgery for Lesion Around the Motor Area
for 12 hours. With gradual withdrawal of anaesthesia, 30 mg/kg/day
of valproic acid, 120mg/day of phenobarbital, and 300rag/day of
phenytoin were given through nasogastric tube. His seizures were
well controlled after discontinuation of anaesthesia, and consciousness returned although the right hemiparesis which improved remarkably three months later, was obvious initially.
Case 3

A 34 year-old-woman was transferred to our hospital on 15th
March 1990, because of moderate headache, right hemiparesis and
speech disturbance. These symptoms and signs occurred gradually
over months and were not remarkable. On the next day, she had a
partial seizure involving the right upper extremity and thereafter she
could not move her right upper extremity and speak fluently. On
the CT scan and MRI performed at our hospital, a cystic tumour
with partial caltification was visualized.
On 27th March 1990, a left frontoparietal craniotomy was performed and the tumour was removed partially for histological diagnosis, and an Ommaya's reservoir was set up for the purpose of
evacuation of the tumour cyst from time to time. Soon after surgery,
the patient was conscious although she had increased right hemiparesis and speech disturbance. About three hours later, monoconvulsions of her right upper extremity started, and then status epilepticus with generalized convulsions developed over several hours
in spite of the intravenous administration of conventional anticonvulsants. On the basis of our past experience, we decided to perform
isoflurane general anaesthesia to control the status epilepticus. Although the inhalational anaesthesia was discontinued twelve hours
after start of isoflurane administration, her convulsions were controlled well with oral intake of valproic acid and phenobarbital
through the nasal tube.
Case 4

A 44-year-old woman was transferred to our hospital on 4th
August 1990, because she had an arteriovenous malformation
(AVM) involving the posterior part of the right frontal lobe.
On 13th August, surgical removal of the AVM was performed.
Aithough the patient regained consciousness soon after surgery, partial seizures of the left upper extremity started. At first the attacks
were confined to the left extremities, however, soon they developed
into the generalized tonic-clonic status epilepticus. In spite of the
intravenous administration of diazepam, phenytoin, and thiopental,
the attacks were very difficult to control. Because of our previous
excellent experience with three cases, and afraid of dangerous postoperative Needing secondary to hypertension accompanying the epileptic attacks, we decided to institute isoflurane general anaesthesia
under the EEG monitoring.
Soon after start of the anaesthesia, the status epilepticus was
controlled and the blood pressure got down to the normal range.
12 hours after the anaesthesia, conventional anticonvulsant drugs
(valploic acid 1200 rag/day, phenobarbital 150 rag/day) were administered via the nasogastric tube. The concentration of isoflurane was
gradually reduced and stopped 14 hours after the induction of anaesthesia. The patient recovered from the anaesthesia gradually and
did not show any epileptic attacks. After that, the seizures were well
controlled by the oral intake of 1200 rag/day of valpolic acid alone.

Discussion
C o n v u l s i o n s which occur early after n e u r o s u r g e r y
involving lesions a r o u n d the m o t o r area, are n o t so

41

rare. Even if the convulsion, develops into status epilepticus, initial t r e a t m e n t (i.e., i n t r a v e n o u s p h e n y t o i n
a n d / o r p h e n o b a r b i t a l following t r e a t m e n t with intravenous d i a z e p a m ) for the status is effective in m o s t
cases a n d o n l y a m i n o r i t y o f p a t i e n t s require further
t r e a t m e n t 12. But if status supervenes with fits r e c u r r i n g
at s h o r t intervals, the risk o f Persistent b r a i n d a m a g e
m a y increase a' 16, 17. Therefore, it is necessary to s t o p
this as s o o n as possible. W h e n status epilepticus does
n o t r e s p o n d to c o n v e n t i o n a l i n t r a v e n o u s anticonwflsant drugs, an i n h a l a t i o n a l a n a e s t h e t i c c a n be
e m p l o y e d 3,13. H a l o t h a n e was the o n l y i n h a l a t i o n a l anaesthetic available for this p u r p o s e b e f o r e the i n t r o d u c t i o n o f isoflurane 3. But h a l o t h a n e has m a n y shortc o m i n g s such as u n a c c e p t a b l e adverse h a e m o d y n a m i c
effects due to negative i n o t r o p i s m a n d systemic vasodilation, h e p a t o t o x i c i t y a n d so on 5. E n f l u r a n e has been
n o t e d to have anti-epileptic actions in l a b o r a t o r y
animalsZ2, 3o a n d h u m a n s 6' 19 But m a n y investigators
have s h o w n t h a t b y using relatively high c o n c e n t r a t i o n
(up to 3.5%) a n d h y p o c a r b i a , enflurane c a n induce
seizures 29, a n d some have advised a g a i n s t the use o f
this anaesthetic for epileptic p a t i e n t s 14' 26. I s o f l u r a n e
does n o t evoke such side effects a n d causes a doser e l a t e d r e d u c t i o n in cortical electrical activity with an
a t t e n d a n t decrease in c e r e b r a l o x y g e n m e t a b o l i s m witho u t c h a n g i n g cerebral b l o o d flow 4' 7, 17, 18
M a n y lesions which result in c h r o n i c focal epilepsy
are a s s o c i a t e d with focal b l o o d - b r a i n - b a r r i e r (BBB)
b r e a k d o w n 27. Thus, p a t h o l o g i c a l i n t r a c e r e b r a l l e a k a g e
o f quinolinic acid m i g h t result f r o m the BBB d i s r u p t i o n
following surgery. A l t h o u g h the m e c h a n i s m o f p o s t o p e r a t i v e status epilepticus is n o t k n o w exactly, hyp e r e x c i t a t i o n o f nerve cells a r o u n d the m o t o r cortex
m a y be e n h a n c e d b y surgical m a n i p u l a t i o n . M R I o r
C T scan o f these f o u r cases p e r f o r m e d p r e - o p e r a t i v e l y ,
d e m o n s t r a t e d no sign o f perifocal o e d e m a o r cerebral
d a m a g e . I t is s u p p o s e d t h a t the n e u r a l cells a r o u n d the
lesion are a l r e a d y b r o k e n d o w n p r e - o p e r a t i v e l y in cases
with perifocal a b n o r m a l i t y on M R I o r C T scan a n d
t h a t they d e m o n s t r a t e no t r a n s i e n t h y p e r a c t i v i t y in
their f u n c t i o n after surgery. But, n e u r a l cells a r o u n d
the lesion are still f u n c t i o n i n g actively in cases w i t h o u t
perifocal a b n o r m a l i t y d e m o n s t r a t e d o n M R I o r C T
scan. Therefore, in such cases the incidence o f status
epilepticus m a y be h i g h e r t h a n in cases with perifocal
oedema.
I s o f l u r a n e is a very useful agent for the m a n a g e m e n t
o f status epilepticus I~ 11,15 because it can p r o d u c e E E G
s u p p r e s s i o n at c o n c e n t r a t i o n s n o t o r d i n a r i l y associated

42

T. Sakaki etal.: Isoflurane in the Management of Status Epilepticus After Surgery for Lesion Around the Motor Area

with undesirable haemodynamic effects and because it
lacks known organ toxicity2' 24. Kofke et al. 1~ reported
that a 10-year-old girl who suffered from intractable
epilepsy, was treated with prolonged low flow isoflurane anaesthesia, and suggested that isoflurane may
have a role in the earlier management of refractory
status epilepticus in the future 1~ 11 Meeke e t a l . 15 reported that a 32-year-old woman with generalized
tonic-clonic status epilepticus was managed by isoflurane general anaesthesia using a vaporizer attached
to the gas supply of the ventilator, and concluded that
isoflurane may be preferable to halothane and possibly
thiopental in the management of status epilepticus.
Now, no data are available to guide the clinician
who is trying to decide how deeply to anaesthetize a
patient with status epilepticus. Barbiturates in animals
have been noted to produce maximal depression of
cerebral metabolism when a burst-suppression interval
of 30 secs is achieved 9. The dose regimen of barbiturate
is chosen empirically on the serum revels during burstsuppression state in the treatment of status
epilepticus12, 31. Thus a burst-suppression interval of
15 to 30 secs seems a reasonable goal in titrating isoflurane in such patients with intractable seizures.
Even if status epilepticus is transient after surgery,
it must be treated promptly and actively because of the
risk of persistent brain damage. We conclude that continuous isoflurane anaesthesia may be a good method
for the management of status epilepticus developing
soon after surgical treatment of lesions of the motor
area.
References
1. AminoffMJ, Simon RP (1980) Status epilepticus: causes, clinical
features and consequences in 98 patients. Am J Med 69: 657666
2. Baden JM, Rice SA (1986) Metabolism and toxicity of inhaled
anesthetics. In: Miller RD (eds) Anesthesia. Churchill Livingstone, New York, pp 701-744
3. Delgado-Escueta AV, Wasterlain C, Trieman DM, Porter RJ
(1982) Management of status epilepticus. N Engl J Med 306:
133%1340
4. Eger EI, Stevens WC, Cromwell TH (1971) The electroencephalogram in mean anesthetized with Forane. Anesthesiology 35:
504~508
5. Egar EI (1981) Isoflurane: a review. Anesthesiology 55:559-576
6. Gallagher TJ, Galindo A, Richey ET (1978) Inhibition of seizure
activity during euflurane anesthesia. Anesth Analg 57:130-132
7. Ito BM, Sato S, Kufta CV, Tran D (1987) Effect of isoflurane
and enflurane on the electrocorticogram (ECOG) of epileptic
patients (abstract). Neurology [Suppl] 37:91
8. Jennett WB (1969) Early traumatic epilepsy. Lancet 1: 10231026

9. Kasse11NF, Hitchon PW, Gerk MK, Sokoll MD, Hill TR (1980)
Alterations in cerebral blood flow, oxygen metabolism, and electrical activity produced by high dose sodium thiopental. Neurosurgery 7:598-603
10. Kofke WA, Snider MT, Young PSK, Ramer JC (1985) Prolonged low flow isoflurane anesthesia for status epilepticus.
Anesthesiology 62:653-656
11. Kofke WA, Young RS, Davis P, Woelfel SK, Gray L, Johnson
D, Gelb A, Meeke R, Warner DS, Pearson KS, Gibson JR,
Koncelik J, Wessel HB (1989) Isoflurane for refractory status
epilepticus: a clinical series. Anesthesiology 71:653-659
12. Lowenstein DH, Aminoff M J, Simon RP (1988) Barbiturate
anesthesia in the treatment of status epilepticus. Neurology 38:
395-400
13. Lowe HJ, Ernst EA (1981) The quantitative practice of anesthesia. Wilfiams and Wilkins, Baltimore/London
14. Marshall BE, Wollman H (1980) General anesthetics. In: Gilman
AG, Gilman LS (eds) The pharmacological basis of therapeutics,
5th Ed. Macmillan, New York, pp 276-299
I5. Meekre RI, Soifer BE, Gelf AW (1989) Isoflurane for the management of status epilepticus. DICP 23:579-581
16. Meldrum BS, Brierly JB (1973) Prolonged epileptic seizures in
primates: ischemic cell change and its relation to ictal physiological events. Arch Neurol 28:10-17
17. Michenfelder JD (1974) The interdependency of cerebral function and metabolic effects following massive doses of thiopental
in the dog. Anesthesiology 41:231-236
18. Newberg LA, Milde JH, Michenfelder JD (1983) The cerebral
metabolic effects ofisoflurane at and above concentration which
suppress cortical electrical activity. Anesthesiology 59:23-29
19. Opitz A, Oberwetter D (1979) Enflurane or halothane anesthesia
for patients with cerebral convulsive disorders? Acta Anesthesiol
Scand [Suppl] 71:43-47
20. Opitz A, Marschall M, Degan R, Koch D (1983) General anesthesia in patients with epilepsy and status epilepticus. In: Delgado-Escueta AV, Wasterlain CG, Treiman DM, Porter ILl (eds)
Mechanism of brain damage and treatment. Raven Press, New
York, pp 531-535
21. Orlowski JP, Erenberg G, Hans L (1984) Hypothermia and
barbiturate coma for refractory status epilepticus. Crit Care Med
12:362-372
22. Oshima E, Urabe N, Shingu K, Mori K (1985) Anticonvulsant
actions of enflurane on epilepsy models in cats. Anesthesiology
63:29-40
23. Pagni CA (1990) Posttraumatic epilepsy. Incidence and Prophylaxis. Acta Neurochir (Wien) [Suppl] 50:28-47
24. Pauca AL, Dripps RD (1973) Clinical experience with isoflurane
(Forane). Br J Anaesth 45:697-703
25. Rashkin MC, Youngs C, Penovich P (1987) Pentobarbital treatment of refractory status epilepticus. Neurology 37:500-503
26. Rosen I, Soederberg M (1975) Electroencephalographic activity
in children under enflurane anesthesia. Acta Anesthesiol Scand
19:361-369
27. Rougier A (1990) The epileptic focus versus the pathological
focus. Acta Neurochir (Wien) t-Suppl] 50:1-5
28. Schwarcz R, Whetsell WO Jr, Mangano RM (1983) Quinolinic
acid: an endogenous metabolite that produces axon-sparing lesions in rat brain. Science 219:316-318

T. Sakaki etal.: Isoflurane in the Management of Status Epilepticus After Surgery for Lesion Around the Motor Area
29. Steen PA, MichenfeIder JD (1979) Neurotoxicity of anesthetics.
Anesthesiology 50:437-453
30. Triner L, Vulliemoz Y, Verosky M, Woo S-Y (1980) Action of
volatile anesthetics in brain. In: Fink BR (ed) Molecular Mechanisms of Anesthesia, Vol 2. Raven Press, New York, pp 229239

43

31. Welty TE, Kreal RL (1985) Pentobarbital coma for treating
intractable seizures in a neonate. Clin Pharrn 4:330-32

Correspondence and Reprints: Dr. T. Sakaki, Department of
Neurosurgery, Nara Medical University, Nara, Japan.