GENERAL ARTICLES
The Effect of Remifentanil on the Bispectral Index Change
and Hemodynamic Responses After Orotracheal Intubation
Bruno Guignard, MD, Christophe Menigaux, MD, Xavier Dupont,
Dominique Fletcher, MD, and Marcel Chauvin, MD
Department of Anesthesiology, Hôpital Ambroise Pare, Boulogne-Billancourt, France
In order to examine whether changes in the bispectral
index (BIS) may be an adequate monitor for the analge-
sic component of anesthesia, we evaluated the effect of
remifentanil on the BIS change and hemodynamic re-
sponses to laryngoscopy and tracheal intubation. Fifty
ASA physical status I patients were randomly assigned,
in a double-blinded fashion, to one of five groups (n !
10/group) according to the remifentanil target effect
compartment site concentration (0, 2, 4, 8, or 16 ng/mL).
The target-controlled infusion (TCI) of remifentanil
was initiated 3 min after the TCI of propofol that was
maintained at the effect-site concentration of 4 !g/mL
throughout the study. After the loss of consciousness
and before the administration of vecuronium 0.1 mg/
kg, a tourniquet was applied to one arm and inflated
above the systolic blood pressure in order to detect any
gross movement within the first minute after tracheal
intubation, which was performed 3 min after remifen-
tanil TCI began. A BIS value was generated every 10 s.
Arterial blood pressure and heart rate (HR) were mea-
sured every minute, noninvasively. Measures of mean
arterial pressure (MAP), HR, and BIS were obtained be-
fore the induction, before the start of remifentanil TCI,
before laryngoscopy, and 5 min after intubation. The
relationships between remifentanil effect-site concen-
trations and BIS change or hemodynamic responses
G
eneral anesthesia combines several components:
unconsciousness, amnesia, and immobility in
response to a painful stimulus. An electroen-
cephalogram (EEG) indicator, the bispectral index
(BIS) that measures interfrequency phase relationships
in the EEG, was proposed as a measure of anesthetic
depth (1). In healthy volunteers, BIS values correlate
with hypnotic drug concentrations (2,3). In contrast,
alfentanil at a plasma concentration "300 ng/mL did
not affect BIS (3). Moreover, at target concentrations of
Accepted for publication September 20, 1999.
Address correspondence and reprint requests to Marcel Chauvin,
MD, Department of Anesthesiology, Hôpital Ambroise Pare, 9 Ave.
Charles de Gaulle, Boulogne-Billancourt, 92100, France. Address
e-mail to marcel.chauvin@apr.ap-hop-paris.fr.
©2000 by the International Anesthesia Research Society
0003-2999/00
MD,
(changes in MAP and HR) to intubation were deter-
mined by logarithmic regression. BIS values were not
affected by remifentanil before laryngoscopy. During
this period, MAP and HR decreased significantly (P "
0.01) in the remifentanil 8 and 16 ng/mL groups.
Changes in BIS, MAP, and HR were negatively corre-
lated with remifentanil effect-site concentration (P "
0.0001). The number of movers in the remifentanil 0-, 2-,
4-, 8-, and 16-ng/mL groups was, respectively, 10, 9, 7,
1, and 0. Hypotensive episodes (MAP " 60 mm Hg)
were noted in 1, 2, and 5 patients in the remifentanil 4-,
8-, and 16-ng/mL groups, respectively. We conclude
that the addition of remifentanil to propofol affects BIS
only when a painful stimulus is applied. Moreover,
remifentanil attenuated or abolished increases in BIS
and MAP after tracheal intubation in a comparable
dose-dependent fashion. Implications: Bispectral in-
dex change is as sensitive as hemodynamic responses
after a painful stimulus for detecting deficits in the an-
algesic component of anesthesia. It may, therefore, be a
useful monitor of the depth of anesthesia in patients
who are incapable of HR and MAP responses to nox-
ious stimuli because of medications or cardiovascular
disease.
(Anesth Analg 2000;90:161–7)
50 and 100 ng/mL, alfentanil added to propofol did
not decrease BIS (4). However, at larger alfentanil
doses that decreased spectral edge 95, BIS decreased to
"50 (5).
BIS is a predictor of patient response to skin incision
during propofol/nitrous oxide anesthesia (1,6). How-
ever, with the addition of opioids, the BIS correlation
with patient movement was less significant (7). In
contrast, the change in BIS after a painful stimulus in
healthy volunteers is decreased by increased opioid
doses, suggesting that BIS variability produced by a
nociceptive input may be inversely correlated with the
level of analgesia (4). We hypothesized that, under
certain levels of unconsciousness, BIS variability may
reflect the degree of opioid-induced inhibition of nox-
ious stimuli.
Anesth Analg 2000;90:161–7 161
162 GUIGNARD ET AL.
REMIFENTANIL AND CHANGE OF BIS AFTER INTUBATION
The purpose of this prospective study was to eval-
uate the effect of different remifentanil concentrations
on BIS: 1) during a steady level of propofol when no
painful stimulation was applied and 2) with laryngos-
copy and orotracheal intubation. Throughout this
study, hemodynamic values were recorded and move-
ments of the arm were noted. We then compared the
ability of remifentanil to prevent movements and to
decrease BIS and hemodynamic changes with endo-
tracheal intubation.
Methods
After obtaining institutional review board approval
and written, informed patient consent, 50 ASA phys-
ical status I patients, ranging in age from 18 to 70 yr,
scheduled for elective noncranial surgical procedures,
were studied. Patients with known neurologic, car-
diac, or metabolic disease, including those requiring
anticonvulsant therapy and those taking cardiovascu-
lar medication, were excluded.
Patients were randomly allocated, in a double-
blinded fashion, to five groups (10 per group) accord-
ing to which remifentanil concentration they received:
0, 2, 4, 8, or 16 ng/mL. Figure 1 describes the time line
for the study. No sedative premedication was admin-
istered before surgery. After breathing oxygen, anes-
thesia was induced and maintained with IV propofol.
The patients’ lungs were ventilated to normocapnia
with a mixture of oxygen and air fraction of inspired
oxygen 0.4. The IV drugs (propofol, remifentanil) were
administered via two computer-assisted infusion de-
vices (Becton Dickinson Pilote!, Fresenius Vial Medi-
cal, Brezins, France) to target effect site concentration.
A computer program, written in Visual Basic 5® (Mi-
crosoft Corporation, Santa Rosa, CA) by one of the
investigators (BG), simultaneously controlled the in-
fusion pumps and acquired the other variables. The
pharmacokinetic sets used to calculate target effect-
site concentrations of propofol and remifentanil were
those published respectively by Marsh et al. (8) and by
Minto et al. (9). The Keo values used for propofol and
remifentanil were, respectively, 0.638/min and 0.516/
min (9). Propofol was administered at a target effect-
site concentration of 4 !g/mL (e.g., 2 mg/kg bolus
followed by 225 !g " kg#1 " min#1) during the period
of study. Three minutes after the propofol target-
controlled infusion (TCI) began, remifentanil was
given at a target effect-site concentration of 0, 2
(e.g., 0.5 !g/kg bolus over 30 s followed by
0.1 !g " kg#1 " min#1), 4 (e.g., 1 !g/kg bolus over 30 s
followed by 0.2 !g " kg#1 " min#1), 8 (e.g., 2 !g/kg
bolus over 30 s followed by 0.4 !g " kg#1 " min#1), or
16 (e.g., 4 !g/kg bolus over 30 s followed by
0.8 !g " kg#1 " min#1) ng/mL according to a random-
ization schedule. After loss of consciousness, a tour-
niquet was inflated over an arm to a pressure of
ANESTH ANALG
2000;90:161–7
150 mm Hg higher than systolic blood pressure, as
described previously (10). Vecuronium 0.1 mg/kg was
administered. The trachea was intubated 3 min after
the start of remifentanil infusion. A positive response
was defined as a gross purposeful movement of the
arm within the first minute after tracheal intubation.
The duration of laryngoscopy and tracheal intubation
was noted for each patient. A hypotensive episode
was defined as mean arterial blood pressure (MAP) "
60 mm Hg. These episodes were corrected by the
administration of IV ephedrine as a bolus of 6 mg.
The study was terminated 11 min after the start
of the propofol TCI.
Before the induction of anesthesia, silver/silver
chloride pregelled electrodes (Zipprep®; Aspect Med-
ical Systems, Natick, MA) were applied to the left and
right frontal (Fp1 and Fp2) regions and referred to a
vertex electrode (CZ). Electrode impedance was main-
tained "2 k$. The EEG was recorded continuously
using an Aspect A-1000 EEG monitor (Aspect Medical
Systems), which also computed the BIS (revision 3.12)
in real time. A BIS value was generated every 10 s.
MAP and heart rate (HR) were measured every
minute, noninvasively, by using a Cardiocap (Datex,
Helsinki, Finland) and acquired simultaneously with
the EEG by using multi serial interfaces between the
monitors and the personal computer. All acquired
data were stored on disk for subsequent analysis.
BIS values before tracheal intubation were defined
as the mean of six measures obtained 1 min before the
induction, before the start of remifentanil TCI, and
before laryngoscopy. BIS change with intubation (%
BIS) was defined as the difference between BIS before
laryngoscopy and the maximal BIS value obtained
within the first 5 min after intubation. HR and MAP
changes with intubation (% HR and % MAP) were
defined as the difference between the HR and the
MAP 1 min before laryngoscopy and the maximal
value within the first 5 min after intubation.
All statistical analyses were performed by using
NCSS 6.0 (Statistical Solution, Cork, Ireland). Demo-
graphic data, durations of laryngoscopy and tracheal
intubation, and maximal changes in BIS, HR, and
MAP during the 5 min after intubation were analyzed
by using analysis of variance (ANOVA). The BIS, HR,
and MAP at each time and changes in BIS, HR, and
MAP from baseline were analyzed by using ANOVA
and repeated measures ANOVA. To attest to the sta-
bility of BIS, the coefficients of variation of the BIS
values obtained within the 1-min periods were calcu-
lated for each individual. Fisher’s exact and "2 tests
were used to compare the proportion of patients with
movement and hypotension in each group. When a
difference in proportions was found among the
groups, pairwise comparisons were done, and a Bon-
ferroni adjustment was made for multiple compari-
sons. An # level of 5% (P " 0.05) was used to establish
ANESTH ANALG
2000;90:161–7
Figure 1. Time line of the study.
statistical significance. In addition, the relationships
between remifentanil effect-site concentrations and %
BIS, % HR, and % MAP were determined by logarith-
mic regression and Spearman’s rank correlation coef-
ficient for each group.
Results
No significant difference was found among the groups
concerning age, weight, height, sex ratio (Table 1), BIS
(Fig. 2), HR (Table 2), or MAP (Table 3) values during
the period preceding induction or the duration of
laryngoscopy and tracheal intubation (Table 1).
In all patients, BIS values obtained within each 1-min
period before laryngoscopy were stable, with a coeffi-
cient of variation that did not exceed 12%. BIS values
before the remifentanil infusion began showed no sig-
nificant differences among the five groups (Fig. 2). BIS
values remained comparable before remifentanil and be-
fore laryngoscopy, regarding mean in each group and
individual measures (Fig. 2). Maximal BIS values were
significantly (P " 0.01) increased by laryngoscopy and
orotracheal intubation in the remifentanil 0- and
2-ng/mL groups (Fig. 2). The maximal increase in BIS
was noted within the first 2 min in all cases. Figure 3
shows the logarithmic regression between remifentanil
concentration and % BIS for each of the individual pa-
tients. % BIS, expressed as the percentage of BIS value
obtained before laryngoscopy, was inversely correlated
with target effect-site concentration of remifentanil (P "
0.0001).
During the 3-min period of propofol infusion with-
out remifentanil, no significant changes occurred in
HR and MAP for all five treated groups (Tables 2 and
3). Before laryngoscopy, HR and MAP decreased sig-
nificantly (P " 0.01) in the remifentanil 8- and 16-
ng/mL groups and remained unchanged in the
remifentanil 0-, 2- and 4-ng/mL groups in comparison
with the preinduction values (Tables 2 and 3). Orotra-
cheal intubation was associated with a significant (P "
0.01) increase in HR and MAP only in the remifentanil
0- and 2-ng/mL groups in comparison with the pre-
laryngoscopy values (Tables 2 and 3). The maximal
increase in HR and MAP was always observed during
the first 2 min after intubation. The logarithmic regres-
sion between remifentanil concentration and hemody-
namic variables are shown in Figure 3 for % HR and %
GUIGNARD ET AL. 163
REMIFENTANIL AND CHANGE OF BIS AFTER INTUBATION
MAP, expressed as the percentage of values obtained
before laryngoscopy. % HR and % MAP were inversely
correlated with target effect-site concentration of
remifentanil (P " 0.0001). % BIS correlated with %
MAP (r2 ! 0.71, P " 0.0001) and % HR (r2 ! 0.41, P "
0.003).
The number of movers in remifentanil 0-, 2-, 4-, 8-,
and 16-ng/mL groups was respectively 10, 9, 7, 1, and
0. Hypotensive episodes requiring ephedrine were
noted before and/or after orotracheal intubation in 0,
0, 1, 2, and 5 patients in the remifentanil 0-, 2-, 4-, 8-,
16-ng/mL groups, respectively. All patients had no
recall of the procedure when questioned later.
Discussion
The results of this study demonstrate that remifen-
tanil, even at the maximal target effect-site concentra-
tion of 16 ng/mL, did not modify BIS values corre-
sponding to a constant target effect-site concentration
of propofol 4 !g/mL. In contrast, remifentanil caused
a dose-related decrease in the % BIS after the stimula-
tion of laryngoscopy and orotracheal intubation.
Blood concentrations of propofol and remifentanil
were not measured, but were calculated by using a
pharmacokinetic model. The variable sets of Marsh et
al. (8) selected for propofol and of Minto et al. (9)
selected for remifentanil have been shown to perform
well (11,12). In the present study, and according to the
findings of Wakeling et al. (13), propofol and remifen-
tanil were administered to a target effect-site concen-
tration rather than to a target plasma concentration to
minimize the hysteresis between blood concentration
and drug effect, leading to rapidly achieving and
maintaining stable drug concentrations at the site of
drug effect. The Keo values that we selected for propo-
fol and remifentanil probably do provide a rapid de-
sired effect-site concentration. Wakeling et al. (13)
demonstrated that a Keo of 0.63/min for propofol
determined a loss of responsiveness in 1.23 minutes,
and the simulation indicated that the desired effect
site concentration was reached in a delay of 2 minutes.
All these delays are consistent with the timeline of our
study protocol.
We observed that remifentanil, even at large doses,
produced no modification of BIS obtained under a
164 GUIGNARD ET AL. ANESTH ANALG
REMIFENTANIL AND CHANGE OF BIS AFTER INTUBATION 2000;90:161–7

Table 1. Demographic Data

Remifentanil effect-site concentration (ng/mL)
0 2 4 8 16
Age (yr) 39 & 17 42 & 15 54 & 15 54 & 15 43 & 19
Weight (kg) 69 & 9 67 & 16 65 & 12 66 & 16 62 & 11
Height (cm) 173 & 8 165 & 9 169 & 9 168 & 11 167 & 7
Sex (m/f) 8/2 4/6 6/4 5/5 3/7
OTI duration (s) 35 & 16 30 & 21 30 & 12 41 & 21 26 & 11
Values are mean & sd.
OTI ! orotracheal intubation.

Figure 2. Individual bispectral index values, before induction, 1 min before remifentanil target-controlled infusion (TCI), 1 min before
laryngoscopy and after orotracheal intubation (OTI) (maximal value) in each group. The horizontal bars denote mean values for each group.
*P " 0.01 compared with preinduction values. &P " 0.01 compared with prelaryngoscopy values.

constant level of propofol infusion. However, the
range of remifentanil concentrations that we studied
did not affect spectral edge (5,14). This confirms that
opioids, even combined with propofol, do not seem to
modify the BIS level when there is no painful stimu-
lation (4) and at doses that do not modify EEG fre-
quency (5). These results are in agreement with other
studies that reported a small reduction in sevoflurane
(15) or propofol (16) requirements for loss of con-
sciousness by fentanyl. The difference in sites of action
between opioids and hypnotics may explain the dif-
ference in the effect on BIS. Hypnotics affect the EEG
by an action on the cerebral cortex, whereas opioids
exert their analgesic action through an inhibition of
subcortical structures, including the spinal cord.
In contrast, we observed a hemodynamic interac-
tion between propofol and remifentanil when no no-
ciceptive stimulation was applied (i.e., before laryn-
goscopy and from two minutes after endotracheal
intubation) in the two larger remifentanil concentra-
tion groups. Others have evaluated the hemodynamic
responses to the induction of large remifentanil doses
with propofol. The amplitudes of the decreases in HR
and MAP were similar to those observed by Thomp-
son et al. (17) with a regimen of remifentanil of
1 !g/kg bolus over 30 s, followed by an infusion of
0.5 !g " kg#1 " min#1 started three minutes before oro-
tracheal intubation. These authors reported an inci-
dence of hypotension (systolic arterial pressure "
80 mm Hg), and bradycardia (HR " 50 bpm) of 50%.
ANESTH ANALG GUIGNARD ET AL. 165
2000;90:161–7 REMIFENTANIL AND CHANGE OF BIS AFTER INTUBATION

Table 2. Mean (& sd) of Heart Rate (bpm)

Remifentanil effect-site concentration (ng/mL)
0 2 4 8 16
Preinduction 81.4 & 9.3 78.5 & 10.2 72.0 & 9.6 74.3 & 9.7 77.8 & 12.8
Preremifentanil TCI 74.4 & 13.4 83.6 & 12.8 72.9 & 12.8 71.4 & 13.0 67.7 & 15.1
Prelaryngoscopy 73.8 & 10.2 79.1 & 18.7 69.1 & 8.8 56.3 & 10.3*† 56.8 & 11.7*†
1 min postOTI 92.6 & 16.3‡ 97.5 & 18.7‡ 72.4 & 14.2 65.8 & 6.8 53.8 & 7.2*†
2 min postOTI 85.7 & 17.9 92.2 & 20.3 69.8 & 9.9 58.2 & 6.2*† 58.6 & 10.3*†
5 min postOTI 79.7 & 13.8 88.8 & 18.5 65.7 & 7.5 58.2 & 6.6† 57.3 & 8.2†
TCI ! target-controlled infusion, OTI ! orotracheal intubation.
* P " 0.05 compared with Group 0.
† P " 0.01 compared with preinduction values.
‡ P " 0.01 compared with prelaryngoscopy values.

Table 3. Mean (& sd) of Mean Arterial Pressure (mm Hg)

Remifentanil effect-site concentration (ng/mL)
0 2 4 8 16
Preinduction 99.3 & 9.8 98.2 & 13.5 91.7 & 10.8 98.7 & 13.3 93.9 & 11.4
Preremifentanil TCI 90.2 & 11.9 88.3 & 10.8 88.3 & 15.0 82.9 & 10.6 84.1 & 11.1
Prelaryngoscopy 85.6 & 16.8 80.4 & 13.8 74.7 & 12.8* 66.6 & 11.4*† 62.3 & 6.8*†
1 min postOTI 121.9 & 25.5‡ 113.0 & 26.3‡ 79.6 & 19.0* 67.9 & 12.2*† 55.7 & 8.2*†
2 min postOTI 119.2 & 25.0‡ 98.1 & 14.8*‡ 76.2 & 16.6* 67.8 & 12.3*† 57.8 & 10.2*†
5 min postOTI 94.1 & 11.9 89.0 & 22.5 73.3 & 10.9* 67.2 & 9.4* 62.5 & 5.4*
TCI ! target-controlled infusion, OTI ! orotracheal intubation.
* P " 0.05 compared with Group 0.
† P " 0.01 compared with preinduction values.
‡ P " 0.01 compared with prelaryngoscopy values.

Remifentanil 3 and 4 !g/kg, infused over 90 seconds,
before tracheal intubation produced a MAP decrease
of 28% and 26% without significant hypotension or
bradycardia (18). However, patients received saline
0.9% (7 mL/kg) before the induction of anesthesia.
Although the administration of a crystalloid solution
(19) or of a vagolytic drug (17) may minimize the
incidence of bradycardia and hypotension, it appears
more appropriate to use smaller doses of remifentanil.
In the present study, the efficacy of the smallest
remifentanil concentrations to attenuate the hemody-
namic responses to laryngoscopy and orotracheal in-
tubation with fewer incidences of hypotension sup-
ports this assumption. Indeed, remifentanil prevents
the movement and the increases in hemodynamic
variables associated with laryngoscopy and intubation
in a concentration-dependent fashion with a signifi-
cant reduction of % HR, % MAP, and % BIS observed
from the two smallest remifentanil target concentra-
tions of 2 and 4 ng/mL. This marked effect produced
with relatively small concentrations of opioids was
well documented in other studies (18,20,21) that re-
ported attenuation or abolition of the cardiovascular
responses to intubation with the dose of remifentanil
1 !g/kg over 30 seconds, which corresponds to a
concentration of 4 ng/mL
Blood propofol concentrations of 4 !g/mL are ad-
equate to produce loss of consciousness in 90% of
patients (16,22). In our study, this concentration was
associated with BIS values included in a range provid-
ing a deep level of hypnosis. However, this concen-
tration is notably insufficient in preventing patient
responsiveness to painful stimuli. Blood propofol con-
centrations to prevent movement in response to skin
incision in 50% and 90% of patients have been re-
ported to be 14.3 and 20.6 !g/mL, respectively (16,23).
Laryngoscopy and tracheal intubation are much more
painful than skin incision and require larger propofol
concentrations (24). Also, it was not surprising that all
the patients in the group with no remifentanil moved
and increased HR and MAP at laryngoscopy and in-
tubation. BIS was also increased by this painful stim-
ulation with 57.0% & 21.1% increase, although before
laryngoscopy, no patient had BIS ' 60%.
Our results highlight the BIS limitations in predicting
movements and hemodynamic responses to a major
painful stimulus such as laryngoscopy and endotracheal
intubation. The addition of an opioid to a hypnotic pre-
vents the somatic and autonomic responses to a noxious
stimulus. One interesting finding is that BIS change with
laryngoscopy and intubation was comparable to hemo-
dynamic changes, indicating that BIS is a measure of the
depth of anesthesia during painful stimuli as sensitive as
cardiovascular variables. Our data and a previous study
(25) that found no auditory-evoked response after intu-
bation, whereas diastolic arterial pressure and HR
166 GUIGNARD ET AL. ANESTH ANALG
REMIFENTANIL AND CHANGE OF BIS AFTER INTUBATION 2000;90:161–7

Figure 3. Correlation between remifentanil effect site concentration and changes of bispectral index value (% BIS), heart rate (% HR), and
mean arterial pressure (% MAP) after orotracheal intubation expressed in percentage of the values recorded before laryngoscopy, by using
the Spearman’s rank correlation. Each symbol represents an individual patient (X ! mover, O ! nonmover). Correlation coefficient (r2) was
used to express the correlation between the changes of the different variables and target effect site concentration of remifentanil. The
horizontal bars denote mean values for each group.

increased, suggest that BIS is a more accurate EEG pa-
rameter. We also observed that % BIS had a higher cor-
relation with remifentanil target effect-site concentra-
tions than did % HR and was as effective in correlating
with remifentanil target effect site concentration as %
MAP. These results may be explained by the parasym-
pathomimetic effect of opioids and/or the propofol-
induced reduction in the baroreflex control of HR (26).
According to these data, we conclude that the BIS value
as a measure of the depth of anesthesia is a result of a
balance between the depression caused by anesthetics
and arousal caused by stimuli such as the painful stim-
ulation of laryngoscopy and tracheal intubation. Thus,
when under a constant level of an anesthetic regimen
administration, BIS value suddenly increases to a noci-
ceptive stimulation, the BIS reflects a deficit in the anal-
gesic component of anesthesia that requires increasing
either the opioid or the hypnotic or both.
In the current study, there was no difference be-
tween % BIS and % MAP with laryngoscopy and oro-
tracheal intubation. However, all patients were ASA
physical status I, without apparent cardiovascular dis-
ease or medication able to modify HR or MAP. But, in
patients unable to mount a hemodynamic response to
painful stimulation because of medications or cardio-
vascular disease during anesthesia, BIS variability
with painful stimuli may be useful to titrate the anal-
gesic component of general anesthesia.
In conclusion, our study demonstrates that, under a
constant regimen of propofol administration, remifen-
tanil does not affect BIS values but prevents the in-
crease in BIS associated with laryngoscopy and oro-
tracheal intubation in a dose-dependent fashion.
Because % BIS is as sensitive as changes in hemody-
namic variables after a painful stimulus to detect a
deficit in the analgesic component of anesthesia, it
may be a useful monitor of depth of anesthesia when
HR and MAP are no longer accurate indicators.
References
1. Kearse LA, Manberg P, Chamoun N, et al. Bispectral analysis of
the electroencephalogram correlates with patient movement to
skin incision during propofol/nitrous oxide anesthesia. Anes-
thesiology 1994;81:1365–70.
2. Leslie K, Sessler DI, Schroeder M, Walters K. Propofol blood
concentration and the bispectral index predict suppression of
learning during propofol/epidural anesthesia in volunteers.
Anesth Analg 1995;81:1269 –74.
ANESTH ANALG
2000;90:161–7
3. Glass PS, Bloom M, Kearse L, et al. Bispectral analysis measures
sedation and memory effects of propofol, midazolam, isoflu-
rane, and alfentanil in healthy volunteers. Anesthesiology 1997;
86:836 – 47.
4. Iselin-Chaves IA, Flaishon R, Sebel PS, et al. The effect of the
interaction of propofol and alfentanil on recall, loss of con-
sciousness, and the bispectral index. Anesth Analg 1998;87:
949 –55.
5. Billard V, Gambus PL, Chamoun N, et al. A comparison of
spectral edge, delta power, and bispectral index as EEG meas-
ures of alfentanil, propofol, and midazolam drug effect. Clin
Pharmacol Ther 1997;61:45–58.
6. Leslie K, Sessler DI, Smith WD, et al. Prediction of movement
during propofol/nitrous oxide anesthesia. Anesthesiology 1996;
84:52– 63.
7. Sebel PS, Lang E, Rampil IJ, et al. A multicenter study of
bispectral electroencephalogram analysis for monitoring anes-
thetic effect. Anesth Analg 1997;84:891–99.
8. Marsh B, White M, Morton N, Kenny GNC. Pharmacokinetic
model driven infusion of propofol in children. Br J Anaesth
1991;67:41– 8.
9. Minto CF, Schnider TW, Egan TD, et al. Influence of age and
gender on the pharmacokinetics and pharmacodynamics of
remifentanil. Anesthesiology 1997;86:10 –23.
10. Tunstall ME. Detecting wakefulness during general anesthesia
for caesarean section. BMJ 1977;1:1321.
11. Coetzee JF, Glen JB, Wium CA, Boshoff L. Pharmacokinetic
model selection for target controlled infusions of propofol.
Anesthesiology 1995;82:1328 – 45.
12. Drover DR, Lemmens HJM. Population pharmacodynamics and
pharmacokinetics of remifentanil as a supplement to nitrous
oxide anesthesia for elective abdominal surgery. Anesthesiology
1998;89:869 –77.
13. Wakeling HG, Zimmerman JB, Howell S, Glass PSA. Targeting
effect compartment or central compartment concentration of
propofol. Anesthesiology 1999;90:92–7.
14. Egan TD, Minto CF, Hermann DJ, et al. Remifentanil versus
alfentanil: comparative pharmacokinetics and pharmacody-
namics in healthy adult male volunteers. Anesthesiology 1996;
84:821–33.
GUIGNARD ET AL. 167
REMIFENTANIL AND CHANGE OF BIS AFTER INTUBATION
15. Katoh T, Ikeda K. The effects of fentanyl on sevoflurane require-
ments for loss of consciousness and skin incision. Anesthesiol-
ogy 1998;88:18 –24.
16. Smith C, McEwan AI, Jhaveri R, et al. The interaction of fentanyl
on the CP50 of propofol for loss of consciousness and skin
incision. Anesthesiology 1994;81:820 – 8.
17. Thompson JP, Hall AP, Russell J, et al. Effect of remifentanil on
the haemodynamic response to orotracheal intubation. Br J An-
aesth 1998;80:467–9.
18. Stevens JB, Wheatley L. Tracheal intubation in ambulatory sur-
gery patients: using remifentanil and propofol without muscle
relaxants. Anesth Analg 1998;86:45–9.
19. Philip BK, Scuderi PE, Chung F, et al. Remifentanil compared
with alfentanil for ambulatory surgery using total intravenous
anesthesia. Anesth Analg 1997;84:515–21.
20. McAtamney D, O’Hare R, Hughes D, et al. Evaluation of
remifentanil for control of haemodynamic response to tracheal
intubation. Anaesthesia 1998;53:1209 –27.
21. O’Hare R, McAtamney D, Mirakhur RK, et al. Bolus dose
remifentanil for control of haemodynamic response to tracheal
intubation during rapid sequence induction of anaesthesia. Br J
Anaesth 1999;82:283–5.
22. Vuyk J, Engbers FHM, Burm AGL, et al. Pharmacodynamic
interaction between propofol and alfentanil when given for
induction of anesthesia. Anesthesiology 1996;84:288 –99.
23. Andrews DT, Leslie K, Sessler DI, Bjorksten AR. The arterial
blood propofol concentration preventing movement in 50% of
healthy women after skin incision. Anesth Analg 1997;85:414 –9.
24. Kazama T, Ikeda K, Morita K. Reduction by fentanyl of the CP50
values of propofol and hemodynamic responses to various nox-
ious stimuli. Anesthesiology 1997;87:213–27.
25. McGregor RR, Allan LG, Sharpe RM, et al. Effect of remifentanil
on the auditory evoked response and haemodynamic changes
after intubation and surgical incision. Br J Anaesth 1998;81:
785– 6.
26. Ebert TJ, Muzi M, Berens R, et al. Sympathetic responses to
induction of anesthesia in humans with propofol or etomidate.
Anesthesiology 1992;76:725–33.