changes in catecholamines during total intravenous
TRANSCRIPT
483 一
J. Tokyo Med. Univ., 60(6): 483r-488, 2002
Changes in catecholamines during
by propofol for neurological
total intravenous anesthesia
endovascular surgery
Kazumi IKEDA, Toshiaki IKEDA, Toshiaki ONIZUKA
Division of Critical Care and Emergency Medicine, Hachioji Medical Center of Tokyo Medical University
Abstract
Purpose To i nvestigate changes in hemodynamics and catecholamines during total intravenous anesthesia
(TIVA) by propofol for neurological endovascular surgery and to evaluate the usefulness of propofol anesthesia
for this type of surgery.
Methods The subjects were 15 patients who received neurological endovascular surgery in our hospital.
Induction and maintenance ofanesthesia were performed with propofol infusion in the angiography room. The
patients were intubated and ventilated during surgery. We determined hemodynamics and serum concentrations
of propofol and catecholamines (adrenaline and noradrenaline) during anesthesia. We also examined required
doses of propofol and awareness, as well as other complications during anesthesia.
Results The required dose of propofo1 for induction was 1.18±O.3 mg/kg (mean±S.D) and the dose for
maintenance was 2.94±O.6 mg/kg/h. Serum concentration of propofol at 30 minutes after induction was 1.09±
O.63pt g/ml, 2 hours later it was 1.88±O.52 pt g/ml. Serum concentration of catecholamines decreased after
induction, but these changes were not significant. Hemodynamics (blood pressure and heart rate) were stable
and no major complications were observed during operation.
Conclusion We obtained hemodynamical stability and decrease of catecholamines during TIVA by
propofol for neurological endovascular surgery. Concentrations and required doses of propofol were less than
those of general anesthesia for intracranial surgery.
Introduction
Propofol is a usefu1 agent for induction and mainte-
nance of anesthesia in adults. lt has a short half-life
and provides a smooth and fast recovery. Total intra-
venous anesthesia (TIVA) for intracranial surgery is
increasing in popularity, and propofol is considered a
suitable hypotonic agent to induce and maintain anes-
thesia in neurological patients. lt suppresses brain
electrical activity and decreases the cerebral metabolic
rate of oxygen (CMRO,) and cerebral blood flow.
We attempted to induce and maintain TIVA by
propofol for neurological endovascular surgery in the
angiography room. We wanted to manage anesthesia
with hemodynamic stability, adequate sedation and fast
recovery after the surgery.
We examined changes in hemodynamics and cate-
cholamines during anesthesia, required doses and con-
centrations of propofol and time for recovery. We also
later inteiviewed the patients about their impression
about the anesthesia. The aim of this study was to
determine the usefulness of TIVA by propofol for
endovascular surgery in the field of neurology.
Patients and methods
Informed consent was obtained for all patients in this
study, but not including the later interview.
We studied 15 patients in ASA physical state 1 or II
Received J uly 24, 2002, Accepted December 7, 2002
Key words: Propofol, Catecholamine, Endovascular Surgery
Reprint requests to: Kazumi lkeda, Division of Critical Care and Emergency Medicine,
Medical University, Tatemachi 1163, Hachioji shi, Tokyo 193-0998, Japan
Hachioji Medical Center of Tokyo
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一 484 THE JOURNAL OF TOKYO MEDICAL UNIVERSITY VoL 60 No.6
Table l Patient characteristics
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Age Sex Diagnosis Duration of
Anesthesia (min)
Duration ofOperation (min)
44
64
73
56
53
52
72
77
63
61
67
61
55
80
62
F
MF
MMF
F
MF
F
F
F
MF
F
Unruptured aneurysm
AVMSAHSAHUnruptured aneurysm
Unruptured aneurysm
AVMCCFSA H
AVMSA H
AVMSA H
CCFSA H
300
435
453
160
405
320
500
480
360
615
480
840
360
630
240
165
255
285
90
270
195
390
360
240
540
420
765
265
585
190
AVM (arteriovenous malformation) CCF (carotid cavernous fistula)
undergoing neurological endovascular surgery (Table 1).
The diagnosis was subarachnoid hemorrhage (SAH)
with ruptured aneurysm in 6 cases, unruptured aneurysm
in 3 cases, arteriovenous malformations (AVM) in 4
cases and carotid cavernous fistula (CCF) in 2 cases.
The duration of operations was 331.1± 176.1 min and
the duration of anesthesia was 438.1±164.1 min.
(mean±S.D). Cases No. 10 and No. 12 were the same
patient who received the same operation twice in a week.
Atropine sulfate (O.5 mg) was given to the patients 15
minutes before induction of anesthesia. Upon arrival
in the angiography room, a radial arterial catheter was
inserted into all patients for blood pressure monitoring,
ECG and SaO, monitoring were obtained. Anesthesia
was induced with ln一一2 mg/kg propofol to obtain the
loss of eyelash refiex and tracheal intubation was
facilitated by vecuronium O.2 mg/kg, and maintained by
1-v4 mg/kg propofol and O.08 mg/kg vecuronium per
hour. Mechanical ventilation was controlled with air
and oxygen at O.6 Fio, to maintain PaCO2 around 35
mm Hg. Bolus injection of perdipine lrv2 mg was
performed to maintain systolic arterial pressure (SAP)
below 170 mmHg as required. The patients were trans-
ferred to the ICU after operation. We stopped infusion
of propofol and vecuronium and examined the gag refiex
and gave 1 mg atropine and 2 mg vagostigmine. The
tracheal tube was extubated after observation of enough
spontaneous breathing. We interviewed the patients
about the existance of awareness or dreams during
anesthesia and the impression about anesthesia 15
minutes after extubation and one day after operation.
We examined the required dose of propofol for induc-
tion and maintenance, and the required time to obtain a
response to orders (open eyes and gasping), time for
extubation after cessation of propofol. Blood pressure
and heart rate (HR) were checked during anesthesia.
Serum concentrations of propofol were determined by
high performance liquid chromatography (HPLC) at 30
minutes, 2 hours after induction and immediately after
extubation. The serum concentrations of adrenaline
and noradrenaline were determined by HPLC before, 30
minutes and 2 hours after induction and immediately
after extubation.
Data were expressed as means ±standard deviations
(SD). Statistical evaluation was performed using Stu-
dents t-test. A p value of less than O.05 was considered
to indicate a statistically significant difference.
Results
Results of individual cases are shown in Table 2.
The average required dose of propofol for induction was
1.18±O.3mg/kg, that for maintenance was 2.94±O.6
mg/kg. The average time for obtain awareness from
cessation of infusion of propofol was 6.60±4.9 min, that
for extubation was 16.4±9.4 min. Seven patients
required perdipine for control of blood pressure. Case
8 became hypothermic spontaneously and case 11 need-
ed hypothermia therapy because cerebral infarction
occurred during surgery. According to the interview of
the patients, one patient was aware, two patients had
good dreams, and one had a pain on injection. One
showed sinus bradycardia (minimum HR was 38 bpm)
during anesthesia.
The changes in mean arterial pressure (MAP) and HR
are shown in Fig.1. We did not observe any significant
change in MAP and HR decreased after induction but
this change was not significant. The changes in cate-
cholamines are shown in Fig. 2 and 3. The concentra一
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Nov., 2002 Ikeda, et al: Catecholamines during propofol anesthesia
Table 2 Results of anesthesia
一 485 一
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Induction dose (mg/kg)
Maintenance dose (mg/kg/h)
Time for Time for Drugsawareness(min) extubation(min)
Comments
1.0
1.41
1.5
1.58
1.0
1.5
1.0
1.0
1.0
2.0
1.46
1.52
1.63
1.0
1.0
1.98
2.98
3.5
3.0
3.1
3.96
2.61
2.24
2.1
3.82
2.86
2.92
3.12
3.00
3.00
3
5
10
4
5
3
3
Not reversed
5
5
Not reversed
5
20
8
12
10
15
18
8
10
6
8
18
18
15
40
18
30
None
NonePerdipine
None
NonePerdipine
None
NonePerdipine
NonePerdipine
Perdipine
Perdipine
NonePerdipine
Awareness
None
None
None
Good dream
Good dream
Bradycardia
None
None
Venous pain
None
None
None
None
None
120
100
80
60
圓MAP mmHg
40 1 =一 一一 一一 =一 一 HR bpm
20
0
Bef。re A盛er A翫er 30 min皿te、 a血er
induction induction intubation induction
Fig. 1 Changes in mean arterial pressure (MAP) and heart rate (HR) (n: 15)
No significant change of MAP and HR
pg/ml
80
70
60
50
40
30
20
10
0
Before 30 minutes after 2 hours after After extubation
induction induction induction
Fig.2 Changes in serum concentration of adrenaline(n: 15)
The concentrations of adrenaline decreased after induction, but this change was not significant.
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一 486 一 THE JOURNAL OF TOKYO MEDICAL UNIVERSITY VoL 60 No.6
P91m璽
500
450
400
350
300
250
200
150
100
50
o
Before 30 minutes after 2 hours after After
induction induction induction extubation
Fig.3 Changes in serum concentration of noradrenaline(n: 15)
The concentrations of noradrenaline decreased after induction, but this change was not significant.
u g/ml
2
1.8
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
;.甕
s・t
蕪.ll
30minutes after 2 hours after After
induction intubation extubation
Fig.4 Changes in serum concentration of propofol(n: 15)
tions of adrenaline and noradrenaline decreased after
induction, but these changes were not significant. The
changes in serum concentration of propofol are shown
in Fig.4 All of the values were within the normal
range. The serum concentration of propofol 30 min-
utes after induction was 1.09±O.63 pt g/ml, 2 hours after
induction it was 1.88±O.52 pt g/ml and after extubation
it was O.63±O.21 pt g/ml.
Discussion
Propofol which is solubilized in a soybean emulsion
is suitable as an infusion for either maintenance of
anesthesia or sedation. lt has a short half life and
provides a smooth and fast recovery. lndeed, propofol
has proven to be a satisfactory agent for TIVA or
sedation of critically ill patients. TIVA for intracranial
surgery is gaining increasing popularity, and propofol is
considered a suitable hypnotic agent in neurosurgical
Patients.ie-3)
The ideal anesthetic for neuroanesthesia should pro一
vide cerebroprotective effects, hemodynamic stability,
and short recovery time to allow postoperative neuro-
logic assessment. Luc et al demonstrated that 2 mg/kg
of propofol produced significant decrease of arterial
pressure, intracranial pressure, and cerebral perfusion
pressure.‘) Michel et al showed that anesthetic blood
concentration of propofol (3-5 mg/kg) was associated
with a decrease in cerebral perfusion pressure and intra-
cranial pressure. Cerebrovascular resistance and cere-
bral arteriovenous oxygen content difference were un-
changed.5) lt has also been reported that propofol
improved neurologic outcome and decreased neuronal
damage from incomplete cerebral ischemia in rats,
because propofol suppressed brain electrical activity and
decreased cerebral oxygen consumption and cerebral
blood flow.6’一g)
Propofol was considered to have anticonvulsion
effect. Udo et al demonstrated that burst suppression
pattern on EEG was achieved by infusion of 15 mg/kg/
h propofol (maximal serum concentration was 9.2±2.9
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Nov., 2002 Ikeda, et al: Catecholamines during propofol anesthesia 一 487 一
pt g/dl), and demonstrated significant decrease of mean
arterial pressure, cardiac index, and left ventricular
stroke work index. They concluded that this dose of
propofol was suflicient to eliminate EEG changes as-
sociated with venodilation and myocardial depressant
propenies.iO) Otherr reports also demonstrated th at
propofol induced electrical silence on the EEG.iiNi3)
Ravussion et al showed that the propofol dose for
induction was 1.8±O.1mg/kg, for maintenance was
86±3.5 ptg/kg and for burst suppression was 500 ptg/
kg/min during a clipping operation.i4) According to
these reports, propofol was considered to reduce cerebral
blood flow and the cerebral metabolic rate of oxygen
and these effects were accompanied by a reduction in
cerebral electrical activity as evidenced by burst suppres-
sion patterns with periods of isoelectricity in the
electroencephalogram (EEG).
Hans et al showed that target controlled anesthesia
maintained with a constant calculated plasma concentra-
tion of 4 ptg/ml propofol and O.5 ng/ml sufentanil
prevents an increase in aiterial pressure and heart rate
following application of a Mayfield head holder.i5)
They also showed that propofol could be administered
as a bolus of 1.5 mg/kg at induction followed by 6 mg/
kg for maintenance, obtaining hemodynamical stability
for neurosurgical patients.i6) Taniguchi et al demon-
strated that a new anesthetic protocol consisting of
propofol and alfentanjl was usefu1 for intraoperative
somatosensory evoked potential (SEP) monitoring and
was safe to use during aneurysmal surgery.i7)
In our study we observed hemodynamic stability and
prevented an increase in catecholamines with TIVA by
propofol. The average required dose of propofol for
induction was 1.18±O.3 mg/kg, and that for mainte-
nance was 2.94±O.6 mg/kg. Serum concentration of
propofol during anesthesia was 1.88±O.52 pt g/ml.
These required doses and concentrations of propofol
were less than those for general intracranial surgery with
craniotomy.i6) We obtained fast recovery, at which
point the concentration was O.63±O.21 ptg/ml, which
was less than that for intracranial surgery. Koh et al
showed that the average serum concentration of
propofol at awareness was 1.07 pt g/ml.i) The recovery
time was also faster than in anesthesia by barbiturate
and Enada showed a lower frequency of vomiting by
propofol coinpared with barbiturate.3) The benefit of
TIVA by propofol is that it does not require an anes-
thetic machine for inhalational anesthetic gas and anes-
thesia can be managed in the angiography room.
Deutschman et al showed that propofol anesthesia
induced sinus bradycardia in response to parasympa-
thetic stimulii8) and another study showed pain on
injection.i9) ln our patients, some had sinus bradycar-
dia or pain on injection. Case No. 1 remembered aware一
ness during anesthesia with less than 2 mg/kg concentra-
tion of propofol for maintenance, and we changed the
infusion dose of propofol for subsequent patients.
Conclusions
We concluded that TIVA by propofol is a safe and
usefu1 method of anesthesia for neurological endovas-
cular surgery. Also we were able to perform anesthesia
in the angiography room without an anesthetic machine.
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References
Shingu K, Osawa M, Mori K: Clinical study of
propofol in male volunteers. Anesthesiology 39:
219-228, 1990
Nakamoto T: Propofol. LISA 1: 2-9, 1994
1nada E: Newcomer vs oldtimes propofol. LISA
1: 10-23, 1994
Herregods L, Verbeke J, Rolly G, Colardyne F:
Effect of propofol on elevated intracranial pressure.
Anesthesia 43: S IO7m lO9, 1988
Pinaud M, Lelausque JN, Chetanneau A, Fauchoux
N, Menegalli D, Souron R: Effect of propofol on
cerebral hemodynamics and metabolism in patients
with brain tumor. Anesthesiology 73:404-409,
1990
Kochs E, Hoffmann WE, Werner C, Thomas C,
Albrecht R, Esch JS: The effect of propofol on
brain electrical activity, neurological outcome and
neurological damage following incomplete ischemia
in rats. Anesthesiology 76: 245-252, 1992
Ridenour TR, Warner DS, Todd MM, Gionet TX:
Comparative effects of propofol and halothane on
outcome from temporary middle cerebral artery
occlusion in the rats. Anesthesiology 76:807-812,
1992
Pittman J, Sheng H, Pearistein R, Brinkous A,
Dexter F, Warner DS: Comparison of the effects of
propofol and pentobarbital on neurologic outcome
and cerebral infarct size after temporary focal is一一
chemia in the rats. Anesthesiology 87: 1139-1144,
1997
Alkire MT, Haier RJ, Barker SJ, Shah NK, Wu JC,
Kao YJ:Cerebral metabolism during propofol
anesthesia in humans studied with positron emissio
tomography. Anesthesiology 82: 393-403, 1995
1ilievich UM, Petricek W, Schramm W, Weindlmary
M, Crech T, Spiss CK: Electroencephalographic
burst suppression by propofol infusion in humans,
hemodynamics consequences. Anesth Analg 77:
166-160, 1993
Kalkman CJ, Drummond JC, Ribberink AA, Patel
PM, Sano T, Bickfold RG: Effects of propofol,
etomodate, midazolam, and fentanyl on motor evok-
ed response to transcranial electrical or magnetic
stimulation in humans. Anesthesiology 76: 502-
509, 1992
Matta BF, Lam AM, Mayberg TS: Cerebral pres-
sure autoregulation and carbon dioxide reactivity
during propofbl induced EEG sしlpression. British
(5)
一 488 一 THE JOURNAL OF TOKYO MEDICAL UNIVERSITY VoL 60 No.6
13)
14)
15)
16)
Journal of Anesthesia 74: 159-163, 1995
Wang B, Bai Q, Jiao X, Wang E, White P: Effect of
sedative and hypotonic doses of propofol on the
EEG activity ofpatients with or without a history of
seizure disorders. Journal of Neurosurgical Anesth-
esiology 9: 335-340, 1997
Ravussian P, Tribolet N: Total intravenous anes-
thesia with propofol for burst suppression in cere-
bral aneurysm surgery, preliminary report of 42
patients. Neurosurgery 32: 236-240, 1993
Hans P, Coussaert E, Dewandre PY, Brichant JF,
Grevesse M, Lamy M: Effect of target controlled
anesthesia with propofol and sufentanyl on the
hemodynamics response to Mayfield head holder
application. Acta Anaesthe Belg 49: 7-11, 1998
Hans P, Coussaert E, Cantraine F, Pieron F, Dewan-
dre PY, Hollander A, Lamy M: Predictive accuracy
of continuous propofol infusions in neurological
patients: comparison of pharmacokinetics models.
Journal of Neurosurgical Anesthesiology 9: 112L
117, 1997
17) Taniguchi M, N adstawek J, Pechstein U, Schramm
J: Total intravenous anesthesia for improvement of
intraoperative monitoring of somatosensory evoked
potentials during aneurysmal surgery. Neurosur-
gery 31: 891-897, 1992
18) Clifford SD, Harris AP, Fleisher LA: Changes in
heart rate variability under propofol anesthesia: a
possible explanation for propofo1 explanation for
propofol induced bradycardia. Anesth Analg 79:
373-377, 1997
19) Borgeat A, Dessiburg C, Popovic V, Meier D,
Blanchard M, Schwander D: Propofol and sponta-
neous movements: an EEG study. Anesthesiology
74: 24-27, 1991
脳外科.血管内手術におけるプロポフォールによる完全静脈麻酔中の
カテコラミンの変動について
池 田 一 美 池 田 寿 昭 鬼 塚 俊 朗
東京医科大学八王子医療センター 救命救急部
【要旨】 我々は脳外科血管内手術においてプロポフォールによる完全静脈麻酔を施行し、循環動態とカテコラミンの変化
を測定し、その有用性について検討した。対象は当センターで脳外科領域の血管内手術を受けた15例であり、内訳はSAH
(subarachnoid hemorrhage)6例、 Unruptured aneurysm 3イ 1、 AVM(arteriovenous malf()rmation)4例、 CCF(carotid
cavernous fistula)2例であった。
麻酔の導入及び維持は血管内手術室でプロポフォールの静脈内投与によって行ない、患者は挿管されて呼吸器により人
工呼吸されたが、麻酔ガスの吸入は行なわなかった。我々は麻酔中の血圧、心拍数、血中カテコラミン、プロポフォール
濃度、および覚醒に要した時間について測定し、患者の麻酔についての感想も調査した。プロポフォールの投与量は導入
は1.18±0.3mg/kg、維持は2.94±0.6 mg/kgであり、血中プロポフォール濃度は導入30分後はLO9±0.63μg/ml、2時間後
は188±052μg/mlであった。麻酔中循環動態は安定し、血中カテコラミン濃度は導入後有意に低下し、麻酔中は有意の
変化は無かった。術中覚醒が1例、洞性二王が1例にみられたが、その他は特に問題は無く、2名は術中良い夢をみたと
の感想であり、覚醒も速やかであった。
以上の結果より、プロポフォールによる完全静脈麻酔は脳外科領域の血管内手術においては有用であると思われた。
〈Key words>脳血管内手術、完全静脈麻酔、プロポフォール
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