J Oral Maxillofac Surg

64:215-222, 2006

Comparison of Remifentanil With

Fentanyl for Deep Sedation in Oral
Surgery
Gabriel F. Lacombe, DMD, MSc(Anesthesia),*
James L. Leake, DDS, DDPH, MSc, FRCD(C),†
Cameron M.L. Clokie, DDS, PhD, FRCD(C),‡ and
Daniel A. Haas, DDS, PhD, FRCD(C)§

Purpose: The aim of this study was to compare recovery for oral surgery patients given a deep sedation
regimen of midazolam, propofol, and remifentanil with a standard control of fentanyl in place of
remifentanil.
Materials and Methods: This investigation was designed as a randomized, prospective, single-blinded
controlled study. Group 1, the control, received midazolam 0.03 mg/kg, fentanyl 1 ␮g/kg, and propofol
initially at 140 ␮g/kg/min. Group 2 received midazolam 0.03 mg/kg, remifentanil: propofol (1:500) given
at an initial propofol infusion rate of 40 ␮g/kg/min. Outcome measures included time to response to
verbal command, Aldrete score ⫽ 9, Postanesthesia Discharge Scoring System ⫽ 7, and assessment by the
Digit Symbol Substitution Test.
Results: Forty-seven subjects were entered in the study. Baseline findings were homogenous between
the 2 groups. Subjects in group 2 recovered earlier (P ⬍ .005) and required less propofol for both the
induction (0.8 ⫾ 0.4 versus 1.2 ⫾ 0.6 mg/kg; mean ⫾ SD, P ⬍ .01) and maintenance of deep sedation
(46 ⫾ 9 versus 131 ⫾ 17 ␮g/kg/min; P ⬍ .005). There were minor differences in vital signs.
Conclusions: This study demonstrated that this remifentanil regimen provided significantly more rapid
recovery and used significantly less propofol compared with the fentanyl regimen.
© 2006 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg 64:215-222, 2006

Many anesthetics are administered yearly for oral sur-
gery as well as general dentistry, the vast majority of
which are performed in the outpatient setting. The
ideal outpatient anesthetic should provide rapid onset
*Private Practice, Montréal, Canada.
†Professor and Head of Community Dentistry, Faculty of Den-
tistry, University of Toronto, Toronto, Ontario, Canada.
‡Professor and Head of Oral and Maxillofacial Surgery, Faculty of
Dentistry, University of Toronto, Toronto, Ontario, Canada.
§Professor and Head of Anesthesia, Chapman Chair in Clinical
Sciences, Faculty of Dentistry, University of Toronto, Toronto,
Ontario, Canada.
The results of this study were originally presented in June 2003
at the International Association of Dental Research Meeting in
Göteborg, Sweden.
Funding was provided by Abbott Pharmaceutical Canada.
Address correspondence and reprint requests to Dr Haas: Fac-
ulty of Dentistry, University of Toronto, 124 Edward St, Toronto,
Ontario, M5G 1G6, Canada; e-mail: daniel.haas@utoronto.ca
© 2006 American Association of Oral and Maxillofacial Surgeons
0278-2391/06/6402-0010$32.00/0
doi:10.1016/j.joms.2005.10.026
and stable operating conditions, while ensuring a fast,
predictable recovery of protective reflexes, cognitive
and psychomotor function, with a minimum of side
effects. Remifentanil is one such drug that has the
potential to significantly change currently accepted
protocols in outpatient anesthesia for dentistry and
oral and maxillofacial surgery.
Compared with fentanyl, which is the most com-
monly used opioid in anesthesia, remifentanil demon-
strates a more rapid onset and offset of action. This
can be explained in part by remifentanil’s smaller
volume of distribution, shorter half-time for equilibra-
tion between plasma and its effect compartment
(t½keo), and high clearance. Also, lower protein bind-
ing and increased percentage of the un-ionized frac-
tion of remifentanil will accelerate uptake in the tar-
get effective site, brain. In contrast to other opioids,
remifentanil is hydrolyzed by nonspecific plasma and
tissue cholinesterases.1,2 The context-sensitive half-
time of remifentanil is independent of the duration of
infusion, with recovery from the effects of remifen-
tanil occurring within 3 to 4 minutes irrespective of
the duration of the infusion.3 The pharmacokinetic

215
216 REMIFENTANIL VS FENTANYL FOR DEEP SEDATION

Table 1. PHARMACOKINETIC PROFILE OF FENTANYL

approached to participate in this study. Inclusion cri-
AND REMIFENTANIL teria included ASA Class I and II patients between the
ages of 16 and 50 years scheduled for extraction of
Fentanyl Remifentanil
third molars under intravenous sedation. Every partic-
Time to peak effect (min) 3 1.5 ipant signed an informed consent form. Patients sat-
t1/2 keo (min) 4 1 isfying the inclusion criteria and agreeing to partici-
Alpha half-life: rapid pate were divided randomly into 2 groups using a
distribution (min) 1.7 1
Beta half-life: intermediate lottery-type draw.
phase (min) 13 6 All drugs were prepared and administered by the
Terminal half-life: terminal principal investigator (G.F.L.). Adding 0.4 mg of
phase (min) 219 15 remifentanil for every 200 mg of propofol created the
Volume of distribution of
the central compartment admixture of remifentanil and propofol. This concen-
(L/kg) 0.5–1.0 0.1–0.2 tration was determined from the literature4 and pre-
Clearance (mL/min/kg) 10–20 40–60 clinical trials. The drug name, quantity, and the time-
Protein binding (%) 80 70 line of injections are described in Table 2. No oral
pKa 8.43 7.07
Un-ionized at pH 7.4 (%) 9 67
premedication was permitted. All patients received
100% oxygen through a nasal hood. All patients re-
Lacombe et al. Remifentanil vs Fentanyl for Deep Sedation. J Oral ceived lactated Ringer’s after intravenous access was
Maxillofac Surg 2006.
established. Appropriate doses of midazolam and fen-
tanyl were injected slowly over a 10-second period.
profiles of remifentanil and fentanyl are summarized Propofol was given at a rate of 10 mg/10 sec for
in Table 1. induction until loss of eyelash reflex, and if needed as
The purpose of this study was to compare remifen- a bolus of 20 mg to control signs of light anesthesia.
tanil with fentanyl in 2 balanced deep sedation tech- Dexamethasone, 8 mg, was given intravenously at
niques. The main outcome to be evaluated was the the beginning of the surgical procedure as part of this
speed of recovery. The control group was one well- clinic’s normal practice for third molar extraction.
established regimen using midazolam, propofol infu-
Local anesthetic was given 45 seconds after loss of
sion, and fentanyl by bolus administration. This was
consciousness (induction). A period of 5 minutes af-
compared with a similar regimen in which remifen-
ter the start of the injections was allowed to ensure
tanil by infusion was substituted for fentanyl.
complete local anesthesia. The oropharynx was suc-
tioned to remove any secretions, and an oropharynx
Patients and Methods partition consisting of a 4 ⫻ 4-inch gauze was posi-
This was a prospective, randomized, controlled tioned to secure the airway. A nasopharyngeal airway
study approved by the Research Ethics Committee of was used if needed in cases of obstruction. In the
the University of Toronto and the Faculty of Dentist- event of an inability to maintain a proper airway, this
ry’s Research Committee. Patients scheduled to be was constituted as a failure of deep sedation, and the
seen in the oral and maxillofacial surgery clinic of the patient would be awakened to a lighter level of seda-
Faculty of Dentistry at the University of Toronto were tion.

Table 2. DRUG ADMINISTRATION FLOWCHART

Drug Group
Fentanyl Remifentanil

Premedication (time ⫽ 0 min) Midazolam 0.03 mg/kg Midazolam 0.03 mg/kg

Fentanyl 1 ␮g/kg Infusion of admixture 100 ␮g/kg/min
Induction (time ⫽ 2 min) Propofol 10 mg/10 sec until loss of eyelash Propofol 10 mg/10 sec until loss of
reflex eyelash reflex
Maintenance Propofol infusion started at 140 ␮g/kg/min Admixture infusion started at 40 ␮g/
kg/min
Rescue propofol Propofol bolus 20 mg
At time ⫽ 30 min Fentanyl 0.5 ␮g/kg if surgical time is
expected to last another 30 min
NOTE. Premedication is the period from the beginning of the injections until time ⫽ 2 minutes. Induction starts at the 2-minute mark and
ends at the time of loss of eyelash reflex. Maintenance started after the loss of consciousness.
Lacombe et al. Remifentanil vs Fentanyl for Deep Sedation. J Oral Maxillofac Surg 2006.
LACOMBE ET AL
Standard monitoring consisted of an automatic non-
invasive blood pressure device, electrocardiogram (3-
lead), pulse oximeter (model 507; Criticare System
Inc, Wausheka, WI) and pretracheal stethoscope. The
patient was covered with a blanket to reduce the risk
of hypothermia. Physiologic parameters, including
blood pressure, respiratory rate, and oxygen satura-
tion measured via pulse oximetry, were recorded at
time 0 (baseline), time 2 minutes (premedication),
time 5 minutes, and then every 5 minutes (mainte-
nance) until the end of the procedure. The end-point
of the anesthetic regimen was a level of deep sedation
defined as a controlled state of depressed conscious-
ness, accompanied by partial loss of protective re-
flexes, including inability to respond purposefully to
verbal command.
Light anesthesia requiring rescue medication
(propofol boluses) was defined as increases in systolic
blood pressure more than 20% from baseline lasting 1
or more minutes, heart rate more than 90 beats per
minute for 1 minute or longer, patient movement
disruptive to the surgery procedure, eye opening,
grimacing, lacrimation, or sweating.
The starting infusion rates in the fentanyl and
remifentanil groups were adjusted to maintain the
patient spontaneously breathing, with no airway ob-
struction, and physiologic parameters within 20% of
baseline by increasing or decreasing the infusion rate
by 10% to 20% increments. Adequate ventilation was
defined as a respiratory rate of 8 or more breaths per
minute while maintaining oxygen saturation above
90%. Two first-year oral and maxillofacial surgery res-
idents rendered all surgical procedures.
RECOVERY PERIOD
The surgical procedure was defined as finished
when the last suture was tied, the oral cavity cleaned
of all visible debris and fluids, the oropharyngeal par-
tition removed, and the oropharynx suctioned. At this
point, the infusion pump was stopped and recovery
began. The recovery period was divided into early,
intermediate, and late recovery.5
T1 was defined as the time from termination of
drug infusion to patient response to verbal command:
“Mr. Jones, open your eyes” said once in a normal
tone repeated every 30 seconds. T2 was defined as
the time from discontinuation of anesthesia until pa-
tients recovered their protective reflexes and motor
function as assessed by the Aldrete Score.6 This score
is used widely with minor modifications in postanes-
thesia care units for patient evaluation and is shown
in Table 3.7-9 This system assigns a score of 0, 1, or 2
to activity, respiration, circulation, consciousness,
and oxygen saturation, giving a maximum score of 10.
A score of 9 or more indicates recovery sufficient for
217
Table 3. ALDRETE SCORING SYSTEM (MODIFIED)7-9
Activity: Able to move voluntary or on command
2 ⫽ Four extremities
1 ⫽ Two extremities
0 ⫽ None
Respiration:
2 ⫽ Able to deep breathe and cough freely
1 ⫽ Dyspnea, shallow or limiting breathing
0 ⫽ Apnea
Circulation:
2 ⫽ BP ⫾ 20 mm Hg of preanesthetic level
1 ⫽ BP ⫾ 20–50 mm Hg of preanesthetic level
0 ⫽ BP ⫾ 50 mm Hg of preanesthetic level
Consciousness:
2 ⫽ Fully awake
1 ⫽ Rousable on calling
0 ⫽ Not responding
O2 saturation:
2 ⫽ Able to maintain O2 saturation ⬎92% on room air
1 ⫽ Needs O2 inhalation to maintain O2 saturation
⬎90%
0 ⫽ O2 saturation ⬍90% even with O2 supplementation
NOTE. A score of ⱖ9 is required for discharge.
Abbreviation: BP, blood pressure.
Lacombe et al. Remifentanil vs Fentanyl for Deep Sedation. J Oral
Maxillofac Surg 2006.
the patient to be transferred to the ambulatory surgi-
cal unit in a hospital setting.
Patients were transferred into the recovery room
when they were able to walk with little or no assis-
tance. We used a modified version of the Postanesthe-
sia Discharge Scoring System (PADSS)10 that assigns a
score of 0, 1, or 2 to vital signs, activity-mental status,
pain, and nausea-vomiting. This is shown in Table 4. A
score of 7 or greater indicated completion of interme-
diate recovery, or T3 (ie, home readiness).
The Digit Symbol Substitution Test (DSST) has been
used to evaluate intermediate recovery after anesthe-
sia.11-13 The DSST consists of a sheet of paper, at the
top of which appears a key, numbered 1 through 9,
with each number being ascribed a different symbol.
Beneath the key are 5 rows of 25 randomly distributed
numbers without their corresponding symbol. The
patient is asked to substitute as many symbols as
possible in a 2-minute period starting with the first
row and working from left to right. The test is scored
by counting the number of correct symbols insert-
ed.14 The DSST was performed at the preoperative
assessment appointment, or the morning of the sur-
gery, and postoperatively, 4 times at 15-minute inter-
vals.
Twenty-four hours after the surgery, the principal
investigator (G.F.L.) called the patients via telephone
to answer any questions they had. A questionnaire
composed of 11 questions and a measuring scale of
the patient’s self-evaluation of overall recovery was
also completed.15 Two of those questions related to
218 REMIFENTANIL VS FENTANYL FOR DEEP SEDATION

Table 4. POSTANAESTHESIA DISCHARGE SCORING

IL). Mean and standard deviation were listed unless
SYSTEM (PADSS) otherwise indicated.

Vital signs
2 ⫽ Within 20% of preoperative value
1 ⫽ 20%–40% of preoperative value
Results
0 ⫽ 40% of preoperative value Of the 51 consecutive patients approached for the
Activity, mental status
2 ⫽ Oriented and steady gait
study, 4 did not meet the inclusion/exclusion criteria.
1 ⫽ Oriented or steady gait Forty-seven patients were then randomized to receive
0 ⫽ Neither either the standard anesthetic regimen (fentanyl) or
Pain, nausea, vomiting the study regimen (admixture remifentanil-propofol).
2 ⫽ Minimal Intraoperatively, 3 cases were aborted and trans-
1 ⫽ Moderate
0 ⫽ Severe
formed into conscious sedation because of either ex-
Surgical bleeding travascular injection or airway concerns, resulting in
2 ⫽ Minimal 44 patients completing the study. It was difficult to
1 ⫽ Moderate adequately maintain an open airway in one obese
0 ⫽ Severe male patient in the remifentanil group, and another
NOTE. The total score is 8; patients scoring ⱖ7 are considered fit male patient in the remifentanil group hypoventilated
for discharge. Modified from Marshall and Chung.10 (without desaturation) even at a very low infusion
Lacombe et al. Remifentanil vs Fentanyl for Deep Sedation. J Oral rate. Exclusion of these subjects did not change the
Maxillofac Surg 2006. results of this study.
The 2 study groups were comparable with respect
to demographic variables and clinical characteristics
general comments about the whole experience. Four such as number of teeth extracted, as well as anes-
questions related especially to surgical adverse reac- thesia time, surgical time, and apnea during induc-
tions the patient may have encountered, namely tion, as shown in Table 5. We found a statistical
bleeding, fever, pain, and headache. Five questions difference for the duration of the apneic episode on
addressed anesthesia issues such as nausea and vom- induction. No patients desaturated during induction.
iting, sleepiness, light-headedness, and weakness. Any No other apneic episodes were seen during mainte-
positive answer of at least one item in each category nance and recovery.
confirmed the presence of an adverse reaction to that Fewer patients in the remifentanil group required
specific category. rescue medication for signs of light anesthesia (14
A sample size calculation was done based on the versus 17). This did not reach statistical significance.
existing literature in this field. Song et al16 studied
early recovery from a balanced anesthetic with mida-
zolam (2 mg), fentanyl (2 ␮g/kg), propofol (100 ␮g/
Table 5. PATIENT DEMOGRAPHICS AND CLINICAL
kg/min), and nitrous oxide, finding that time to reach PROFILE
an Aldrete score of 9 or more was 15.7 ⫾ 4.6 minutes
(n ⫽ 40). From a study by Larson et al,8 early recovery Drug Group
defined by an Aldrete score of 9 or more, from a total Fentanyl Remifentanil
intravenous anesthesia technique with remifentanil No. of patients 22 22
and propofol was 7.2 ⫾ 2.7 minutes (n ⫽ 20). Power Age (yr) 26.0 ⫾ 6.9 25.6 ⫾ 7.5
was set at 90% at a significance level of .05. The Weight (kg) 61 ⫾ 9.5 68 ⫾ 14.7
sample size calculation estimated that in order to find Height (cm) 167 ⫾ 8.2 169 ⫾ 10.2
a difference of 8.5 minutes, it would take 22 patients Body mass index 22 ⫾ 4.2 23 ⫾ 2.1
Gender (male/female) 9/13 13/9
in each group. ASA1/ASA2 18/4 14/8
Ratio data analysis was done with the Student’s t No. of teeth extracted 3.6 ⫾ 0.9 3.6 ⫾ 0.7
test. In order to verify the normal distribution of the Anesthesia time (min) 54.5 ⫾ 12.8 56.8 ⫾ 18.5
groups, Levene’s test for equality of variances was Surgical time (min) 40.5 ⫾ 12.2 42.0 ⫾ 18.7
Duration of apneic
performed. Analysis that detected a statistically signif-
episode (sec) 51 ⫾ 20 83 ⫾ 37*
icant difference as determined by P ⬍ .05 was further No. of patients with
analyzed by analysis of covariance with a Bonferroni apneic episodes 9 13
correction in order to show interaction. Nominal data NOTE. Data are shown as mean ⫾ SD.
were analyzed with a ␹2 test or Fisher’s exact test as *Significantly different from fentanyl group, P ⫽ .03.
needed. All statistical analysis was performed with the Lacombe et al. Remifentanil vs Fentanyl for Deep Sedation. J Oral
aid of SPSS software version 10 (SPSS Inc, Chicago, Maxillofac Surg 2006.
LACOMBE ET AL 219

COMPARISON OF MEAN DIASTOLIC BLOOD PRESSURE

Table 6. AVERAGE DOSE OF DRUG ADMINISTERED
90

Mean Diastolic Blood Pressure

Drug Group
80
Fentanyl Remifentanil
70

(mm Hg)
Fentanyl (mg) 0.08 ⫾ 0.02 60

Remifentanil (mg) 0.33 ⫾ 0.12 50

Propofol induction 40
dose (mg/kg) 1.2 ⫾ 0.6 0.8 ⫾ 0.4* 30
Propofol infusion rate

5
15

25

35

45

55

65

75

85

95
0

5
(␮g/kg/min) 131 ⫾ 17 46 ⫾ 9†

10
Time (min)

NOTE. Data are shown as mean ⫾ SD. Fentanyl Remifentanil

Comparison of average dosage of drugs administered between
the fentanyl and remifentanil groups. FIGURE 2. Effect of the fentanyl and remifentanil regimens on the
*Significantly different from fentanyl group, P ⫽ .01. mean diastolic blood pressure. Data are shown as mean ⫾ SD.
†Significantly different from fentanyl group, P ⬍ .005.
Lacombe et al. Remifentanil vs Fentanyl for Deep Sedation. J Oral
Lacombe et al. Remifentanil vs Fentanyl for Deep Sedation. J Oral Maxillofac Surg 2006.
Maxillofac Surg 2006.

There was no difference in the mean number of the remifentanil group exhibited a significant lower-
interventions per patient (1.7). ing in respiratory rate compared with fentanyl (16 ⫾
Table 6 shows that the patients in the remifentanil 4.7 versus 23 ⫾ 4.3, P ⬍ .001). A statistically signifi-
group required 33% less propofol to achieve the end- cant difference was found in the mean heart rate
point of loss of eyelash reflex. Patients receiving the during maintenance between the 2 groups (fentanyl
admixture of propofol and remifentanil were main- 80 ⫾ 11.1 compared with remifentanil 73 ⫾ 10.5, P ⬍
tained in a deep sedation state at an average infusion .001). There were no significant differences between
rate of 46 ␮g/kg/min compared with 131 ␮g/kg/min the 2 groups in regard to the number of patients who
in the control group (P ⬍ .005). required propofol to control signs of light anesthesia
Figures 1 and 2 illustrate the effect on mean systolic or need to manage hypotension.
blood pressure and mean diastolic blood pressures, The effect on speed of recovery is shown in Table
respectively, with Figure 3 showing the effect on 7. The times to open eyes, reach an Aldrete score of
heart rate. Figure 4 shows the effect on respiratory at least 9, and reach a PADSS of at least 7 were
rate. Before induction, no significant differences in significantly shorter for the remifentanil group. The
baseline vital signs were found. Except for respiratory absolute value of the standard deviation was also
rate, parameters were within 20% of preoperative smaller for the study group indicating better predict-
values throughout the surgical procedure. Patients in ability of awakening and early recovery.

COMPARISON OF MEAN SYSTOLIC BLOOD PRESSURE

COMPARISON OF MEAN HEART RATE

160
150
140
100
Mean Systolic Blood Pressure

130

120 90
( m m Hg )

110
(beats per minute)
Mean Heart Rate

80
100

90
70
80

70 60

60
50
50
40
15

25

35

45

55

65

75

85

95
0

5
10

15

25

35

45

55

65

75

85

95

Time (min)
10

Time (min)
Fentanyl Remifentanil Fentanyl Remifentanil

FIGURE 1. Effect of the fentanyl and remifentanil regimens on the FIGURE 3. Effect of the fentanyl and remifentanil regimens on the
mean systolic blood pressure. Data are shown as mean ⫾ SD. mean heart rate. Data are shown as mean ⫾ SD.
Lacombe et al. Remifentanil vs Fentanyl for Deep Sedation. J Oral Lacombe et al. Remifentanil vs Fentanyl for Deep Sedation. J Oral
Maxillofac Surg 2006. Maxillofac Surg 2006.
 220 REMIFENTANIL VS FENTANYL FOR DEEP SEDATION

Comparison of Respiratory Rate between Fentanyl and Remifentanil Groups

35

30

25
FIGURE 4. Effect of the fentanyl and
Resp per minutes

20 remifentanil regimens on respiratory rate.

Data are shown as mean ⫾ SD.
15
Lacombe et al. Remifentanil vs Fentanyl
10
for Deep Sedation. J Oral Maxillofac Surg
2006.
5

0
0 2 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105
Time (minutes)

Fentanyl Remifentanil

The scores of the DSST were transformed as a
percentage of their respective baseline result in order
to compare between patients’ performances. As seen
in Figure 5, there was a trend in the remifentanil
group for higher scores, but it was statistically signif-
icant only for the first test performed 15 minutes after
the end of anesthesia.
As can be seen in Table 8, responses from the late
recovery evaluation questionnaire did not reveal any
statistical differences between the control and the
study groups. The distribution of anesthesia related
adverse events is almost identical between the 2
groups; approximately 50% of all the patients experi-
enced those problems within this 24-hour period. The
most frequently reported side effect to surgery was
pain, followed by headaches. Anesthesia-related side
effects were reported most often as sleepiness and
light-headedness in the fentanyl group, whereas
weakness and nausea were more frequent in the
remifentanil group.
Discussion
This study showed that the admixture of remifen-
tanil and propofol reduced the induction dose of
propofol as well as the maintenance rate. In addition,
Table 7. TIME FOR PATIENTS TO REACH T1, T2, AND
T3 AFTER TERMINATION OF INFUSION
Drug Group
Parameters Fentanyl
Open Eyes (T1) 10 ⫾ 6 min
Aldrete (T2) 13 ⫾ 7 min
PADSS (T3) 19 ⫾ 9 min
*Statistically significant difference from fentanyl group, P ⬍ .005.
Lacombe et al. Remifentanil vs Fentanyl for Deep Sedation. J Oral
Maxillofac Surg 2006.
it led to a more rapid awakening from deep sedation,
without increased adverse reactions.
Double-blindness represents one of the strongest
study designs. It would have been extremely difficult
to create such a design for this particular study. The 2
anesthetic regimens have to be considered as 2 dis-
tinct modalities of treatment. We did not aim to eval-
uate the addition of remifentanil to a propofol-based
anesthesia for deep sedation. The admixture of
remifentanil and propofol as used in this study is in
itself a totally different regimen. The mean infusion
rate observed in the study supports that assumption.
We tried to overcome this weakness by gathering data
in the form of highly objective measurements and
well-defined objectives.
Deep sedation was induced in both study groups
with an average dose of propofol less than the 2
mg/kg reported to be needed for general anesthesia.
This may have been due to the synergistic effect of
the benzodiazepines and opioids given prior to
propofol.17-19 Studies have shown that slow injection
of propofol can reduce the total amount needed for
loss of consciousness.20-22 At a rate of 10 mg/10 sec,
patients in this study were induced in an average of 1
minute.
Patients in the remifentanil group required less
propofol for induction. Because remifentanil and fen-
tanyl may be considered equipotent,23,24 this reduc-
tion can be explained either by the priming effect of
the 2-minute infusion of propofol, or perhaps a higher
brain concentration of the opioid, because of remifen-
Remifentanil tanil’s pharmacokinetic properties. The more pro-
4 ⫾ 3 min* nounced apnea in the remifentanil group may lend
6 ⫾ 4 min* support to the latter hypothesis. Alternatively,
11 ⫾ 6 min* remifentanil may be considered to be more potent
than fentanyl. The same is true with the remarkably
lower infusion rate for maintenance of deep sedation.
The lower respiratory rate may suggest that we
LACOMBE ET AL 221

Comparison of DSST as a percentage from baseline between Fentanyl and Remifentanil

160.0

140.0

Score Percentage from baseline

120.0
FIGURE 5. Effect of the fentanyl and
remifentanil regimens on the DSST scores. 100.0

Data are shown as mean ⫾ SD. Fentanyl

80.0
Remifentanil
Lacombe et al. Remifentanil vs Fentanyl
for Deep Sedation. J Oral Maxillofac Surg 60.0
2006.
40.0

20.0

0.0
DSST perc15 DSST perc30 DSST perc45 DSST perc60
Time

achieved and maintained a higher brain concentration tors.27,28 The amount of propofol boluses needed to
of opioid. control signs of light anesthesia was similar in both
Because opioids display very stable hemodynamics, groups. They manifested themselves most of the time
even at high concentrations, it is not surprising to see as gross bodily movement, likely due to failure of local
no difference in vital signs between the groups.25,26 anesthesia.
As shown in Figure 3, the lower heart rate found in Our results are in agreement with previous re-
the remifentanil group may be interpreted as better search showing remifentanil-based anesthetic regi-
pain control, although it did not reach clinical signif- mens yield faster emergence and earlier recovery
icance. It appears that the limiting factor for the compared with similar regimens with fentanyl.4,8,29,30
administration of remifentanil for deep sedation is the Our results are quite similar to the computer simula-
potential for respiratory depression. In our study, only tion published by Vuyk et al31 indicating awakening
one incident can be related to the potential side effect time of 10 minutes versus 4 minutes in favor of
of the medication. One patient showed high sensitiv- remifentanil. We were able to keep the infusion
ity to the respiratory depression of remifentanil. Even scheme to a lower rate than that proposed in this
though respiratory rate was low, patient safety was computer simulation and other clinical studies be-
not compromised and it did not represent a clinically cause our end-point was a state of deep sedation and
significant event. control of noxious stimuli was achieved with the use
A major concern of measuring recovery in this of local anesthetic. This is why the propofol infusion
study is maintaining equivalent depths of anesthesia. rate could be lowered below 80 ␮g/kg/min, which is
It has been reported that vital signs are good indica- considered to be the ED50 for unconsciousness.
Return of consciousness is achieved when the brain
concentration of hypnotic agent reaches a critical
Table 8. DESCRIPTION AND QUANTIFICATION OF level. This is equivalent to the MAC awake for inha-
POSTOPERATIVE SIDE EFFECTS AS DETERMINED BY lation agents or the ED50 awake for intravenous drugs.
THE 24 HOURS POSTOPERATIVE QUESTIONNAIRE
The rate of decay of a drug will influence the awak-
Drug Group ening time. The drug with the smallest context-sensi-
Fentanyl Remifentanil tive half-time in our study was remifentanil, followed
by propofol and fentanyl. It seems logical that in order
Overall to achieve faster emergence, propofol should be the
satisfaction Problems 1 3
Complaints 0 0
main anesthetic agent when combined with fentanyl
Surgery Bleeding 0 0 because the decay of propofol is steeper. In contrast,
Fever 3 2 return of consciousness is more rapid with relatively
Pain 11 15 high remifentanil concentration because remifentanil
Headache 5 6 concentration decreases faster than that of propofol.
Nausea 1 4
Anesthesia Vomiting 0 0
The DSST is reported to be a sensitive test of re-
Sleepiness 6 3 covery of cognitive function and fine motor
Light-headedness 5 2 activity.11-13 We could not find any statistically signif-
Weakness 3 6 icant difference between the 2 groups at 60 minutes
Lacombe et al. Remifentanil vs Fentanyl for Deep Sedation. J Oral after the end of anesthesia as demonstrated by the
Maxillofac Surg 2006. DSST. Our study lacked power to detect any statisti-
222
cally significant difference after 15 minutes in recov-
ery even if the trend indicated a better outcome in the
remifentanil group. We can speculate that a learning
curve may artificially increase the results after repeat-
ing a test, because the patients were not able to
practice the test before anesthesia. Changing the sym-
bols altogether instead of the order of presentation
could have compensated for the lack of practice.
Postoperative side effects were not different be-
tween the two groups and were mostly surgery re-
lated. Our study combining propofol with low dose of
opioid showed a low incidence of postoperative nau-
sea and vomiting. Those findings matched other re-
ports in the literature combining propofol with opi-
oids in low-risk procedures.32
In conclusion, the anesthetic regimen composed of
midazolam with an admixture of propofol/remifen-
tanil (ratio, 1:500) provided faster emergence and
recovery without increased adverse reactions com-
pared with a standard regimen where fentanyl is ad-
ministered by bolus.
Acknowledgment
This study formed the basis for a thesis submitted in conformity
with the requirements for the degree of Master of Science (Dental
Anaesthesia), Graduate Department of Dentistry, University of To-
ronto.
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