Download Propofol versus Remifentanil Patient Controlled Sedation for Awake

Alexandria Journal of Anaesthesia and Intensive Care
34
Propofol versus Remifentanil Patient Controlled Sedation
for Awake Craniotomy During Epileptic Surgeries
Ashraf A Moussa, MD*, Saad A Sheta, MD**, Essam A Eid, MD*
Department of Anaesthesia, * National Liver Institute, Menofiya University, Egypt;
**Faculty of Medicine, Alexandria University, Egypt.
ABSTRACT
Background: Anaesthesia for neurosurgical procedures, specifically craniotomies requiring
patient participation presents a challenge to both the neuroanaesthesiologist and the
neurosurgeon. Despite the popularity of general anaesthesia for these procedures, there has
been a renewed interest in this technique of awake craniotomy due to its definite advantages
in specific patient populations. This study evaluate two anaesthetic regimens for propofol
and remifentanil for awake craniotomy in epileptic surgeries.
Methods:Total drug administered, incidence of complications, sedation score and patient
satisfaction were assessed in 20 patients, randomely assigned into 2 equal groups, aged 1855 years undergoing awake craniotomy for epileptic surgeries. Sedation was induced via
propofol patient controlled sedation in group I and via remifentanil patient controlled sedation
in group II,
Results : five patients in the remifentanil group versus two patients in propofol group
experienced nausea and /or vomiting. Respiratory rate depression, desturation were more
frequent in remifentanil group while pain and hypotension were more frequent in propofol
group. Both groups achieved a good level of sedation and patient satisfaction.
Conclusion : Propofol and remifentanil are almost ideal drugs for conscious sedation during
awake craniotomy.
Key wards: Awake craniotomy; epilepsy; propofol; remifentanil.
INTRODUCTION
Victor Horsley in 1886 performed the
first surgical resection for epilepsy (1),
since then, the role of the neuroanaesthesiologist has been redefined
from one merely administering a general
anaesthesia that does not trigger
seizures, to providing monitored anaesthesia care for “ awake craniotomy”(2).
Anaesthesia is usually provided using
a combination of local anaesthesia (local
infiltration and regional blockade) and
intravenous medications to provide
sedation, anxiolysis, and supplemental
analgesia during these long procedures(3).
Traditionally, neurolept analgesia using a
combination of opioid (often fentanyl) and
droperidol has been popular technique (4).
Regional blockade of the scalp is
achieved by blocking four pairs of
nerves. The supraorbital and supratrochlear nerves which are the terminal
branches of the ophthalmic division of
the trigeminal nerve. The auriculo-
AJAIC-Vol. (8) No. 2 June 2005
temporal nerve, which is the terminal
branch of the mandibular division of the
trigeminal nerve, the greater and lesser
occipital nerves which are branches
from the cervical plexus. Plus blockade
of the terminal portions of the temporal
branches of the maxillary division of the
trigeminal nerve (3) .
Recently, the use of propofol
sedation during these procedures has
been reported (5). However, several
reports suggest that propofol has a
potent anticonvulsant effect and may
depress epileptic activity (6,7). Fortunately, because of its short duration of
action, propofol administration could be
suspended in advance of neurophysiological monitoring to minimize
drug-induced adverse effects.
Remifentanil is a novel ultra short
acting estrase metabolized synthetic
opioid. It is highly selective μ opioid
agonist and has an ester linkage
rendering it susceptable to rapid meta-
Alexandria Journal of Anaesthesia and Intensive Care
bolism by non-specific blood and tissue
estrases.Adult pharmacokinetic studies
have shown a rapid onset of peak effect
(blood-brain equilibration time :1.2 – 1.4
min), a short duration of action independent of the duration of infusion
(context-insensitive, half-time :3 min)
and rapid clearance (40 ml/kg/min).
From the time the infusion switch off, the
duration of action of the usual plasma
concentration is 3-6 minutes with no
residual effects. These pharmacokinetic
values make it ideal sedo-analgesia for
awake craniotomy (8) .
The purpose of this study is to
compare propofol versus remifentanil in
patient controlled sedation technique
during the long procedures of awake
craniotomy for epeliptic surgeries.
PATIENTS
After institutional ethics approval
from King Faisal Specialist Hospital &
Research Centre (KFSH&RC) and
acquisition of written, informed consent,
20 adult patients aged 18-55 years,
presented for awake craniotomy for
intractable epilepsy. Each patient was
randomly assigned into one of two equal
groups using a computer – generated
list (MS Excel 7.0 ), to receive propofol
or remifentanil. Group P received
propofol as a patient controlled sedation
(PCS), and group R received remifentanil as PCS .
Exclusion criteria included 100%
above ideal body weight, patients who
are suffering from any significant
arrhythmia, uncontrolled hypertension,
severe CNS, lung, liver, renal or
endocrine diseases. The chronic use of
of anxiolytic, antidepressants or analgesic drugs, or any such use of within
12 h of surgery, was also considered as
an exclusion criterion.
All patients were receiving anticonvulsant therapy, but the dose was
tapered or the drug was discontinued
before surgery.Ondansteron 4mg was
AJAIC-Vol. (8) No. 2 June 2005
35
given prophylactically i.v on call to OR,
the patients were unpremeditated.
Regional blockade of the scalp was
performed by the surgeon in the holding
bay area, 30-60 minutes before the
patient arrived in the operating room
using bupivacaine 0.5% with epinephrine. Supplemental local anaesthetic
solution (bupivacaine 0.25% with epinephrine) was used to infiltrate along the
incision lines prior to surgery. During
craniotomy, dura mater was anaesthetized using a mixture of lidocaine
1% and 0.25% bupivacaine without
epinephrine (9) .
On arrival, the patient was placed as
comfortable as possible on the operating table. The monitors used included
an ECG (lead II), non-invasive automated blood pressure and a pulse
oximeter. Supplemental oxygen was
given using nasal prongs that were
adapted for the monitoring of end tidal
CO2 and respiratory rate (Marquette
Electronics, Solar 8000, UK). Maintenance intravenous fluid consisted of
Ringers lactate at 70 ml/hr through
minimum 18-gauge cannula, plus the
deficits, and a 20-gauge i.v. cannula
was also inserted for the study drug
PCA device.
Preoperatively, all patient were shown
how to use the standard patient controlled
analgesia device (Baxter PCA II,
Deerfield, USA). and were instructed to
administer sedation if they wished to be
more “sleepy” or if they experienced
anxiety or discomfort.Patients were encouraged to use the PCS device early in
the operative procedure( to ensure that
they understood how to use it and what
effect it would have on them) and were
reminded that they could use the pump if
they requested more sedation or became
restless during the operation. They were
also told that supplemental sedation was
available from their anaesthesiologist if
they were uncomfortable and that the
anaesthesiologist would take over administration of sedation if they were unable
Alexandria Journal of Anaesthesia and Intensive Care
or unwilling to do so at any point in the
operation.
Sedation for group P consisted of an
initial bolus dose of propofol 0.5 mg/kg,
a lockout interval of 3 minutes, and
patient controlled boluses of 0.25 mg/kg
(one half of the initial bolus dose) via a
standard PCA device. A basal infusion
of 3mg/kg/hr (50 µg/kg/min), was
adjusted via a standard syringe pump
(Diprifusor TM, Grasepy 3500, by SIMS,
Waterford, Herts, UK).
Sedation for group R consisted of
remifentanil hydrochloride using an
initial bolus dose of 0.5 μg/kg over 30 60 seconds, patient contolled boluses of
0.25 μg/kg, a lockout time of 2 min using
the standard PCA device. Basal infusion
of 0.1 μg/kg/min was used via the
standard syringe pump. Remifentanil
dosage had been determined by an
early open label dose – ranging study(10)
To avoid potential interference with
the neurophysiological monitoring in
group P, propofol administration was
suspended 15 minutes prior to
neurophysiological recording.
ll complications such as nausea,
vomiting, seizures, excessive sedation,
pain, oxygen desaturation less than 90%,
increase end tidal C02 (≥ 45mmHg),
decrease respiratory rate (< 8/min.),
inability to cooperate, induction of general
anaesthesia, airway obstruction, hypotension and hypertension (± 20% from the
basal readings) were documented.
At anytime during the procedure, if a
patient developed seizures, they were
treated by a small intravenous dose of
thiopentone (25-50mg), and if developed nausea and/or vomiting, they
were treated by ondansteron 4mg iv.
Intraoperative sedation was assessed prior to surgery (baseline) and then
hourly by the attending anaesthesiologist based on a 5-point scale
(Appendix I). The technical difficulty
associated with each surgical procedure
was evaluated by the surgeon based on
a 5-point scale(technically easy = 1,
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36
technically difficult = 5). Patient satisfaction was evaluated using a short
questionnaire completed by each patient
in the recovery room and on the
postoperative days 1 and 3 (Appendix
II).
The total doses of all drugs required
and the incidence of complications were
tabulated for each patient. Statistical
analysis was performed using analysis
of variance. Where significance was
found, Student t-test was performed. P >
0.05 was considered significant. Fisher’s
or Chi-square test was used for the
analysis of complications. Calculations
were performed on a personal computer, using a standard software package (Winstat TM 3.0, Kalmia, US)
RESULTS
There were no difference among the
two groups in age, sex, weight and
length of surgery (table 1). The majority
of patients underwent temporal lobectomy. The duration of anaesthesia and
surgery averaged 4-5 hours and surgical
difficulty was comparable between the
both groups.
The total requirements of drugs by
each group of patients are shown in
table 2. In the propofol group, the mean
total propofol dose for the initial bolus
doses and the basal infusion was
15.8±2mg/kg. All patients in group P
required additional PCS boluses of
propofol with a mean value of 4.2 ± 4
mg/kg.
In the remifentanil group, the mean
total remifentanil dose including the
initial and basal infusion doses was
28.65 ± 4 µg /kg .All patients in group R
required additional PCS boluses of
remifentanil with a mean value of 1.9 ±2
µg/kg.
The incidence of complications is
shown in table 3. Five patients in
remifentanil group (50%) experienced
nausea and / or vomitting during the
surgery, all of them received at least
one dose of ondansteron 4 mg iv, this
Alexandria Journal of Anaesthesia and Intensive Care
was statistically significantly higher than
propofol group where two patients only
(20 %) had nausea and / or vomitting. p‹
0.05. One patient in group R had a
neurological deficit immediately post
operatively in the form of dysphasia that
was improving by the time of discharge
from hospital.
During the first 15 min after initiation
of study drug administration and prior to
scalp incision, a reduction in systolic
blood pressure was observed in patients
receiving propofol (from 134 ± 11 to 121
± 21 mmHg) and a reduction in the
respiratory rate per minute in patient
receiving remifentanil (from 14 ± 4 to 10
± 8) and both reductions were
statistically significant from the other
group, with stable values (P < 0.001,
analysis of covariance).
No statistically significant difference
were observed between propofol and
remifentanil groups in the incidence of
hypotension (10% in both groups ), or
bradycardia (20% and 10 % respectively) throughout the procedure.
Compared with baseline, sedation
scores increased in a similar fashion in
both groups with higher score values for
propofopl group during the whole period
of surgery when compared to the
sedation score values in the remifentanil
group but these values did not reach the
levels of statistical significance (Figure 1).
Patient satisfaction was similar in the
two groups with respect to the general
level of comfort and willingness to repeat
the procedure using the same sedation
technique (Table 4). Satisfaction with the
option of self administered sedation was
high and maintained through out the third
postoperative day.
DISCUSSION
Awake craniotomy requires: (1)
sufficient depth of anaesthesia during
opening and closing the bone flap; (2) full
consciousness during cortical mapping;
(3) smooth transition between anaesthesia and consciousness; (4) adequate
ventilation; and (5) patients immobility and
comfort throughout surgery. In attempt to
satisfy these requirements,some techniques have been established. These are
summarized as sedation and local
anaesthesia(11) and asleep-awake-asleep
technique(12) .
The combination of various drugs
have been tried for conscious sedation.
In 1950s, codeine was the favoured
drug. The “lytic cocktail” (13) consisting of
a combination of pethedine, promethazine and chlorpromazine was used
by many anaesthesiologist as multipurpose sedative agent. The concept of
neuroleptanalgesia was started in 1959
using a combination of droperidol and
fentanyl (14).
Table 1: Demographic Data ; Surgical charactristics
Characteristic
Group P
Age (yr)
32 ± 11
Sex (M/F)
4: 6
Weight (kg)
71 ± 10
Length of surgery (Hr)
4.4 ± 1.0
Surgical Site T/F
8/2
Surgical difficulty (1-5)
3 ± 0.9
Local anaesthetic scalp block (Bupivacaine 0.5%
20 ± 1
with epinephrine 1/200.000) (ml)
Local anaesthetic scalp infiltration (Bupivacaine
35 ± 18
0.25% with epinephrine 1/200.000) (ml)
Data are presented as mean ± SD or number of patients.
T/F = Temporal / Frontal.
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37
Group R
30 ± 17
5: 5
77 ± 12
4.5 ± 1.4
8/2
3 ± 0.7
20 ± 1
41 ± 11
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Table 2: Drug Administered in the two groups of patients.
Characteristic
Group P
Total dose of propofol (mg/kg)
15.8 ± 2
(Initial + basal infusion )
mg/kg
Total dose of PCS propofol (mg/kg)
4.2 ± 4
mg/kg
21±2
PCS Demand ratio (%) (success : total demand)
22±20
Total Dose ondansteron (mg)
Number of patients given intraoperative
3
Ondansteron
Group R
28.65 ± 4
mg/kg
1.9 ± 2
mg/kg
6±8
39±28
5
PCS = Patient controlled Sedation.
P < 0.05 between groups.
Table 3: The Icidence of Intraoperative Complications in the two groups of
patients.
Characteristic
Group P
Group R
Nausea / Vomiting
2
5*
Pain
2
1
Excessive Sedation
0
0
Uncooperative
0
0
Induction of General Anaesthesia
0
0
Seizures
1
1
Airway Obstruction
0
1`
Transient Respiratory Rate Depression
1
4*
Desaturation
1
2
Hypercapnia
2
5
Hypotension
1
1
Bradycardia
2
1
Neurological Deficits
0
1
* statistically significant (p ≥ 0.05).
PATIENT SEDATION SCORES (APPENDIX 1)
SEDATION SCORE
5
4
GROUP P
3
GROUP R
2
1
1
2
3
4
5
TIME FROM PRE OPERATIVE (HRS)
Fig. 1. patient sedation scores in the two groups at different time Intervals.
AJAIC-Vol. (8) No. 2 June 2005
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Table 4: Patient Satisfaction Questionaire Results
Questionaire score (1-4 )
Satisfaction index
PACU
POD 1
POD 3
General level of comfort
Group P
2.9±1.1
2.9±0.9
3.0±1.1
Group R
2.9±0.9
2.8±1.2
2.9±1.1
Willingness to use same technique
In the future
Group P
3.0±0.8
3.0±0.9
3.0±1.1
Group R
2.9±1.1
3.0±1.2
3.1±0.7
Satisfaction with
patient-administration
Group P
3.2±0.9
3.5±0.4
3.5±0.4
Group R
3.1±0.8
3.4±0.2
3.4±0.2
Data are presented as mean = SD
PACU = post operative care unit
POD = Post operative day.
The introduction of ultra-short acting
synthetic opioids opened a new door to
the anaethetist whereby the drugs given
in the infusion form can be titrated to
effect. The choice of anaesthetic drugs
depend on the individual anaesthesiologist. For conscious sedation, virtually all
rely on some combination of a short
acting opioid and a non narcotic sedative.
The commonly used opioid include
fentanyl, sufentanil and remifentanil and
the sedatives used include midazolam,
droperidol and propofol(15,16).
Propofol offers the advantage of being
a short acting sedative with antiemetic
and amnestic properties. Considerable
controversy regarding its anticonvulsant
properties was easily overcomed by its
stopping 15-20 minutes before neurophysiological monitoring to ensure minimal
impact(16).
This comparative study of propofol
versus remifentanil for sedation during
awake craniotomy showed more respiratory depression and perioperative nausea
and / or vomiting with remifentanil. With
propofol, there was more sedation, pain
and hyoptension.
Most of these side effects, as well as
the depth of sedation, are dosedependent; thus the the titration of the
AJAIC-Vol. (8) No. 2 June 2005
drugs by the use of patient controlled
administration were attempted to be at
an equi-sedative level in both groups.
The chosen infusion rate of propofol
(3mg/kg/h) in this study is in good
accordance with the data previously
published for sedation during regional
blockade(17,18). Conversely, the initial
remifentanil infusion rate was probably
too high reflected by lower rate of PCS
administration in group R when
compared to group P.
Sa Rego and coworkers(19) recommend
remifentanil rather given as bolus
increments of 0.25 µg/kg when needed
instead of continuous infusion. However,
when respiratory depression occurred,
normalisation could be achieved rapidly
by dose reduction because of the very
rapid degradation of remifentanil(20). All
the remifentanil patients were breathing
adequately upon shortlasting stimulation.
The optimal infusion rate for remifentanil
during regional blockade can therefore
be estimated around 0.075 µg/kg/min.
The inclusion of a basal infusion is
also advantageous during propofol for
long procedures during which the patients
often become restless or fatigued as the
procedure progresses(21). A basal infusion
provides a baseline level of sedation that
Alexandria Journal of Anaesthesia and Intensive Care
patients may augment by using PCS or
asking for a bolus in response to clinical
circumestances.
As the number of patients in our
study was small, the power of the study
was calculated. The power was greater
than 0.80 for all. Although, our centre is
the most well known hospital in the
whole middle east for awake craniotomies, the turn over number of cases is
still very limited and a multi-centres
study should be planned for future for
this kind of surgeries.
Nausea and vomiting are documented
side–effects of opioids in general, including remifentanil, whereas propofol is
known to have antiemetic properties (22). In
this study, 5 patients experinced nausea
and/or vomiting during surgery in the
remifentanil group but only two in the
propofol group. This is unpleasant for the
patient and may induce movements
disturbing the surgeon or even increase
the risk of aspiration of gastric content in
the sedated patients. The reported incidence of nausea and vomiting ranges
from 8% to 50%. The different causative
factors exacerbating nausea and vomittin
include use of opioids, surgical stimulation
such as stripping of dura, temporal lobe,
meningeal vessle manipulation also
insufficient analgesia combined with
hypovolaemia. Various drugs have been
tried to prevent and treat nausea and
vomitting including ondansteron, dropridol
and propofol(23).
Two patients in group P (20 %)
experienced intraoperative pain, one of
them was due to irritation at the study
drug iv site, that was overcomed by
infusion to a larger bore iv cannula while
the other patient experienced pain at the
time of dural reflection and suturing and
was overcomed by asking the surgion to
infiltrtate the site of dural suturing. Only
one patient in group R (10%), experienced pain during dural retraction that
was treated by informing the surgeon to
decrease the retraction. This difference
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40
did not reach statistical significance
(logistic regression analysis ).
One patient in the propofol group
(10%) experienced an episode of respiratory depression defined as respiratory
rate < 8 breaths / min or SaO2 <95% for
at least 1 min, compared to four patients
in the remifentanil group (40%), (P <
0.01, Fisher’s Exact test). One patient in
the propofol group and two patients in
the remifentanil group experienced
episodes of oxygen desaturation ≤ 90%.
These episodes were of short duration
and only in one case did study drug
administration have to be inturrupted
(remifentanil) for 3 minutes.
In both groups, but more often in the
remifentanil group, some patients experienced respiratory depression (defined as a
respiratory rate of less than eight breaths
per minute or oxygen saturation below
95%). When this problem was specifically
addressed in a previous study(24) the
administration of low doses of propofol to
maintain concscious sedation or light
sleep did not cause respiratory depression. The use of opioids for sedation
carries with it a well known risk of
respiratory depression(25) Due to rapid
elimination and short context sensitive
half-time with remifentanil(26) the episodes
were shortlasting. Nevertheless, this
study confirms that the administration of
sedative or analgesic agents during
regional anaesthesia necessiates close
monitoring of repiratory function and
provision of oxygen supplementation(27).
However, opioids depress both the
hypoxic and the hypercapnic ventilatory
responses(22). Thus, oxygen supplementation and pulse oximeter monitoring
may not protect against dangerous, high
carbon dioxide levels. For this reason,
continuous clinical assessment of respiratory function or endtidal carbon
dioxide measurements should be applied
when opioids are used for sedation.
Patients achieved similar levels of
sedation and were similarly satisfied
with both techniques. Sedation score
Alexandria Journal of Anaesthesia and Intensive Care
values were higher in propofol than in
remifentanil group during the whole
period of surgery, but did not reach a
value of statistical significance. Continuous basal infusion for both drugs
maintain this level of sedation during the
whole period of surgery in a relatively
low dose of drugs administration.
Propofol may exert a positive effect
on mood(28,29), which has been postulated to contribute to the high levels of
patient satisfaction which was noted in
group P. Our results suggest that patient
satisfaction is independent on this
effects, if they exist, since satisfaction is
maintained well into the third postoperative day.
In conclusion, both propofol as a
sedative, with antiemetic, euphoric and
short duration of action, and remifentanil
as an analgesic, sedative and ultra-short
duration of action, is almost ideal agent
for concious sedation in cases of awake
craniotomy for epileptic surgeries. The
method of their administration is for the
anaethesiologist preference taking into
consideration the utmost advantage of a
continuous basal infusion for both drugs
for these long procedures. The combination of both agent for this type of
surgery may be the future study cocktail
with lower doses and consequently,
lesser side effects.
Acknowledgements
We deeply thanks Prof John Grivin(9),
consultant of neurosurgery, King Faisal
Specialist Hospital & Research Centre
for his unlimited guidance, advises and
co-operation .
Appendix 1
Intraoperative Sedation Score
Score Criteria
1. Fully awake and oriented
2. Drowsy, eyes open
3. Drowsy,
eyes
closed,
but
arousable to command
4. Drowsy, eyes closed arousable to
mild physical stimulation
5. Unrousable to mild physical
stimulation
Appendix 2
Patient Satisfaction Questionaire
Please help us evaluate your anaesthetic by completing the following
questions. We are interested in your
honest opinion, positive or negative. We
also welcome your comments and
suggestions.
Circle your answer:
1. How satisfied were you with your pain management and overall level of
comfort?
______4______ ______3_______ _________2________ __________ 1 _______
very satisfied mostly satisfied mildy satisfied or quite dissatified
indifferent
2.If you were to have surgery again, would opt for the same method of
management?
____ 1 ______ _____ 2 _______ ______ 3 ________ _________ 4 _______
no, definitely not no, I don’t think so yes, I think so yes, definitly
3. Did you like the method of self-administeration of sedative medication?
____ 4 ____ _____ 3 ______ _______ 2 _______ _________ 1 ________
yes, definitly yes, I think so no, I don’t think so no, definitly not
AJAIC-Vol. (8) No. 2 June 2005
41
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