Use of alfentanil and propofol for outpatient monitored anesthesia care: Determining the optimal dosing regimen

Article (PDF Available)inAnesthesia & Analgesia 85(3):566-72 · September 1997with26 Reads
DOI: 10.1213/00000539-199709000-00015 · Source: PubMed
Abstract
Unlabelled: Propofol and alfentanil are both rapid and short-acting drugs that can be used for sedation and analgesia during monitored anesthesia care (MAC). This study was designed to determine the optimal infusion rates of propofol and alfentanil when administered during local anesthesia. In this randomized, double-blind study, we evaluated the effects of different propofol infusion rates on the alfentanil requirement, level of sedation, intraoperative recall, respiratory and cardiovascular variables, and recovery. Seventy-two consenting ASA physical status I or II female outpatients undergoing breast biopsy procedures with local anesthesia were randomly assigned to one of four treatment groups. All patients received midazolam, 2 mg intravenously (I.V.) for premedication. Propofol was infused at 0, 25, 50, or 75 microg x kg(-1) x min(-1) during the operation. Sedation was evaluated using the Observer's Assessment of Alertness/Sedation (OAA/S) scale at 5-min intervals by a blinded observer. Two minutes before the infiltration of the local anesthetic solution, a bolus of alfentanil, 2.5 microg/kg I.V., was administered, followed by a maintenance infusion of 0.5 microg x kg(-1) x min(-1). The alfentanil infusion rate was subsequently varied to maintain patient comfort and stable cardiovascular and respiratory function. Pictures were shown at the start of the propofol infusion, upon initiating the alfentanil infusion, and at 45 min after the skin incision to evaluate recall of intraoperative events. Propofol produced dose-dependent increases in the level of sedation (with median OAA/S scores of 2-4, P < 0.05). Higher infusion rates of propofol (50-75 microg x kg(-1) x min(-1)) produced significant amnesia, opioid-sparing effects (alfentanil 0.3 +/- 0.2 vs 0.6 +/- 0.2 microg x kg(-1) x min(-1)), and less postoperative nausea and vomiting (P < 0.05). However, episodes of transient hemoglobin oxygen desaturation were more common in the deeply sedated patients. Thus, in healthy outpatients premedicated with midazolam, 2 mg I.V., a propofol infusion of 25-50 microg x kg(-1) x min(-1) in combination with an alfentanil infusion of 0.2-0.4 microg x kg(-1) x min(-1) is recommended for sedation and analgesia during MAC in the ambulatory setting. Implications: Sedation is often given during local anesthesia. This study demonstrated that administration of an intravenous anesthetic, propofol, in combination with an opioid infusion (i.e., alfentanil) to provide sedation analgesia and amnesia with a low incidence of side effects, such as nausea and vomiting and respiratory depression in outpatients premedicated with midazolam.
Use of Alfentanil and Propofol for Outpatient Monitored
Anesthesia Care: Determining the Optimal Dosing Regimen
Michail N. Avramov,
MD, PhD,
and Paul F. White,
PhD, MD, FANZCA
Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas,
Dallas, Texas
Propofol and alfentanil are both rapid and short-acting
drugs that can be used for sedation and analgesia dur-
ing monitored anesthesia care (MAC). This study was
designed to determine the optimal infusion rates of
propofol and alfentanil when administered during lo-
cal anesthesia. In this randomized, double-blind study,
we evaluated the effects of different propofol infusion
rates on the alfentanil requirement, level of sedation,
intraoperative recall, respiratory and cardiovascular
variables, and recovery. Seventy-two consenting ASA
physical status I or II female outpatients undergoing
breast biopsy procedures with local anesthesia were
randomly assigned to one of four treatment groups. All
patients received midazolam, 2 mg intravenously (IV)
for premeditation. Propofol was infused at 0,25,50, or
75 pg. kg-’ * rnin~r during the operation. Sedation
was evaluated using the Observer’s Assessment of
Alertness / Sedation (OAA / S) scale at 5-min intervals
by a blinded observer. Two minutes before the infiltra-
tion of the local anesthetic solution, a bolus of alfentanil,
2.5 pLg/ kg IV, was administered, followed by a mainte-
nance infusion of 0.5 PLg * kg-i * min-r. The alfentanil
infusion rate was subsequently varied to maintain pa-
tient comfort and stable cardiovascular and respiratory
function. Pictures were shown at the start of the
propofol infusion, upon initiating the alfentanil infu-
sion, and at 45 min after the skin incision to evaluate
recall of intraoperative events. Propofol produced
dose-dependent increases in the level of sedation (with
median OAA/S scores of 2-4, P < 0.05). Higher infu-
sion rates of propofol (50-75 PLg * kg-’ . min-I) pro-
duced significant amnesia, opioid-sparing effects (al-
fentanil 0.3 i 0.2 vs 0.6 2 0.2 PLg * kg-’ . mini’), and
less postoperative nausea and vomiting (P < 0.05).
However, episodes of transient hemoglobin oxygen de-
saturation were more common in the deeply sedated
patients. Thus, in healthy outpatients premeditated
with midazolam, 2 mg IV, a propofol infusion of 25-50
pg * kg-* * min PI in combination with an alfentanil in-
fusion of 0.2-0.4 pg * kg-’ * mini is recommended for
sedation and analgesia during MAC in the ambulatory
setting. Implications: Sedation is often given during lo-
cal anesthesia. This study demonstrated that adminis-
tration of an intravenous anesthetic, propofol, in com-
bination with an opioid infusion (i.e., alfentanil) to
provide sedation analgesia and amnesia with a low in-
cidence of side effects, such as nausea and vomiting and
respiratory depression in outpatients premeditated
with midazolam.
(Anesth Analg 1997;85:566-72)
U
ntil recently, midazolam
and fentanyl have been
the most frequently used drugs to enhance pa-
tient comfort during local anesthesia. However,
this combination can produce clinically significant in-
traoperative respiratory depression (l), as well as re-
sidual amnesia and impairment of cognitive function
in the postoperative period (2). As a result of its fa-
vorable pharmacokinetic characteristics and recovery
profile (3), propofol has increasingly become the drug
Supported by a research grant from the Society for Ambulatory
Anesthesia, Park Ridge, IL, and the Ambulatory Anesthesia Re-
search Foundation, Dallas, TX.
Accepted for publication June 4, 1997.
Address correspondence and reprint requests to Paul F. White,
I’hD, MD, Department of Anesthesiology and Pain Management,
University of Texas Southwestern Medical Center at Dallas, 5161
Harry Hines Blvd., CS 2.126, Dallas, TX 75235-9068.
566 Anesth Analg 1997;85:566-72
of choice for the maintenance of sedation during mon-
itored anesthesia care (MAC) (2-4). Premeditation
with a small dose of midazolam, 2 mg intravenously
(IV), provides additional sedation and anxiolysis, as
well as greater amnesia with respect to intraoperative
events (4). However, to enhance patient comfort and
reduce pain during MAC, opioid analgesics are often
administered as IV adjuvants (5).
Alfentanil, an opioid analgesic with a rapid onset of
action, is well suited to administration by a continu-
ous variable-rate infusion (6). Satisfactory intraopera-
five conditions during MAC have been reported when
alfentanil was used alone (7~3) or in combination with
propofol (9). However, when used alone, alfentanil
was associated with more intra- and postoperative
respiratory depression (10). A synergestic effect with
respect to ventilatory depression occurs when opioids
01997 by the International Anesthesia Research Society
0003-2999/97/$5.00
ANESTH ANALG
1997:85:566-72
AMBULATORY ANESTHESIA AVRAMOV AND WHITE 567
USE OF ALFENTANIL AND PROPOFOL DURING MAC
are combined with either sedative-hypnotics (1,11,12)
or potent inhaled anesthetics (13-15). In a recent vol-
unteer study, Pavlin et al. (16) also demonstrated a
synergistic interaction between propofol and alfen-
tanil with regard to sedation and analgesia. However,
the interactions between propofol and alfentanil have
not been carefully evaluated during surgical proce-
dures under MAC.
Therefore, we examined the hypothesis that the use
of a minimally effective propofol infusion rate would
provide a greater safety margin when administered in
combination with an alfentanil infusion during local
anesthesia. Using a double-blind study design, we
assessed the effect of propofol infusion rates from 25
to 75 pg * kg-‘mini on the alfentanil requirement,
level of sedation, cardiorespiratory stability, recall of
intraoperative events, and recovery times in outpa-
tients undergoing breast biopsy procedures.
Methods
Seventy-two consenting ASA physical status I or II
female outpatients undergoing breast biopsy proce-
dures under local anesthesia were randomly assigned
to receive one of four different propofol infusion rates
in combination with a variable-rate infusion of alfen-
tanil according to a double-blind, institutional review
board-approved protocol. Before beginning the study,
a power analysis was performed to determine the
group sizes (n = 15) necessary to detect a 50% differ-
ence in the incidence of perioperative side effects with
a power of 0.8 (01 = 0.05). Patients with clinically
significant cardiovascular, respiratory, and / or hepatic
diseases were excluded from participating. In addi-
tion, patients with a history of drug or alcohol abuse,
as well as those currently taking sedative or analgesic
drugs, were also excluded.
Before midazolam premeditation, patients com-
pleted 100 -mm visual analog scales (VAS) for discom-
fort, pain, sleepiness, anxiety, and nausea anchored by
the following word pairs: no discomfort to worst dis-
comfort ever experienced, no pain to severe pain, not
sleepy to extremely sleepy, not nervous to extremely
nervous, and no nausea to severe nausea, respectively
(17). On arrival in the operating room, an IV cannula
was placed under local anesthesia in the nondominant
arm for administration of fluids and IV medications.
Standard monitoring devices included noninvasive
blood pressure (using the limb contralateral to the IV
infusion), heart rate, electrocardiogram, pulse oxime-
ter, and a capnograph for end-expiratory carbon diox-
ide (CO,) and respiratory rate (RR) monitoring. A
nasal cannula was positioned at the external nares to
deliver 3-4 L/min of oxygen, with a gas-sampling
catheter attached as described previously (18).
Baseline measurements of heart rate, mean arterial
blood pressure, hemoglobin oxygen saturation (Spa,),
and RR were obtained, and patients were asked to
verbally evaluate their level of discomfort (on an ll-
point numerical rating scale, with 0 = none to 10 =
extreme) and pain (on a descriptive scale: 0 = none,
1 = mild, 2 = moderate, or 3 = severe). The patients’
level of sedation was assessed using the Observer’s
Assessment of Alertness/Sedation (OAA / S) (19) scale
(modified by reversing the scale, i.e., 1 = awake/alert
to 5 = asleep/unarousable [Appendix 11) by the same
investigator (MNA).
All patients received midazolam, 2 mg IV, for pre-
medication. Five minutes after the administration of
midazolam, the degree of sedation was reassessed, the
patient was shown a picture (a drawing of a cat), and
the propofol infusion was initiated at a rate of either 0,
25, 50, or 75 pg * kg-* * mini, using a Bard Infus
O.R.@ pump (C. R. Bard, Inc. North Reading, MA). The
face of the pump and the IV tubing were covered to
prevent the investigator conducting the OAA/ S as-
sessments from identifying the propofol infusion rate.
Five minutes after the start of the propofol infusion,
the level of sedation was reassessed, a second picture
(a drawing of a desk) was shown, and the patient was
administered alfentanil, 2.5 pg/ kg IV bolus, followed
by a continuous infusion at an initial infusion rate of
0.5 PLg * kg-l * mini. Two to three minutes after the
opioid bolus, the surgeons began infiltrating the op-
erative field with local anesthetic (1% lidocaine), and
l-2 min later, the skin incision was performed.
The patient’s assessment of discomfort and pain
during the local anesthetic infiltration and at skin
incision was recorded. Vital signs, discomfort, pain,
and sedation scores were subsequently recorded at 5-
to 10 -min intervals until the end of the procedure. The
alfentanil infusion rate was adjusted in 0.25 -
FLg * kg-i * mini increments to maintain patient com-
fort (discomfort score ~4) and analgesia (pain score
<l) while avoiding clinically significant respiratory
depression (i.e., RR <8 bpm and/or Spo, ~90% last-
ing >30 s) or “excessive” sedation (OAA/ S score of 5).
Verbal complaints of pain were treated by administer-
ing a small bolus of alfentanil(2.5 PLg / kg) and increas-
ing the infusion rate. Moderate to severe pain not
responding to two bolus/infusion rate increases of
alfentanil over a 3-min period were treated by the
injection of additional local anesthetic solution. Ap-
proximately 45 min after the start of surgery, patients
were shown a third picture (a drawing of a ship).
The alfentanil and propofol infusions were discon-
tinued after placement of the final skin suture. Aldrete
scores (20) were assessed 5 min after discontinuation
of the sedative-hypnotic and opioid infusions. Patients
achieving an Aldrete score 29 in the operating room
were transferred directly from the operating room to
the Phase II “step-down” unit, where they remained
until they were ready to get dressed. The patient care
providers in the recovery units were blinded as to the
568 AMBULATORY ANESTHESIA AVRAMOV AND WHITE
ANESTH ANALG
USE OF ALFENTANIL AND I’ROPOFOL DURING MAC
1997;85:566-72
Table 1. Patient Demographic Characteristics and Analgesic Requirements for the Four MAC Treatment Groups
Propofol infusion rate (~g * kg-l * min-I)
Age (yr)
Weight (kg)
ASA physical status I/II (n)
Sedation time (min)
Local anesthetic (mL)
Alfentanil infusion rate (pg * kg-’ * min-‘)
Average rate
Minimal rate
Maximal rate
Supplemental alfentanil
bolus doses (n)
0
25 50
75
43
-c
12 45
t
16 40
2
14 39
+ 11
69
2
13 69
2
14 70? 16
68
-c
16
4114 4114 6112 6112
70
t
20 78
I+_
21 78
t
37 71-c 31
21 + 9 17 -c 9 18 + 8
18 t 14
0.6
k
0.2 0.3
t 0.1*
0.4
5
0.2* 0.3
f
0.2*
0.4
+-
0.2 0.3
+
0.2 0.2
?
0.2
0.2
?
0.2
0.6
I+_ 0.1
0.5
+ 0.1
0.5
5 0.1
0.5
+ 0.1
1.6 t 1.9 1.0 2
1.4 0.9
5
0.8
0.3
k
0.6%
Values are numbers or means I+_ SD.
n = 18 for each group.
MAC = monitored anesthesia care.
* Significantly different from propofol 0 group, P CO.05.
doses of the study medications. Patients were consid-
ered suitable for discharge when they had stable vital
signs, were alert and oriented,
were
able to
ambulate
unassisted, had no intractable nausea or vomiting/
retching, and had minimal wound drainage and pain.
Immediately before discharge, a second set of VAS
was administered, and recall of intraoperative events
was assessed using a standard picture recall test. Re-
call was graded as “free” (i.e., the patient correctly
named the picture shown), “cued” (i.e., the patient
recognized the object in a group of objects), “visual”
(i.e., the patient recognized the object on the picture),
and “none” (i.e., the patient did not recall the object
even after being shown the picture).
In a telephone interview on the first postoperative
day, all patients were asked about pain, nausea, vom-
iting, and other adverse events after their discharge
from the day-surgery unit. Patients were also asked to
rate their satisfaction with the analgesic management
during the period of local anesthetic infiltration and
with the overall surgical experience using a 7-point
verbal rating scale (7 = extremely satisfied, 6 = satis-
fied, 5 = somewhat satisfied, 4 = neither satisfied nor
dissatisfied, 3 = somewhat dissatisfied, 2 = dissati.s-
fied, and 1 = extremely dissatisfied), as well as
whether they would choose to receive the same
sedative-analgesic medications should they require a
similar surgical procedure in the future.
Data from the four study groups were compared
using one-way analysis of variance followed by post
hoc pairwise comparisons (Tukey’s test). Discrete vari-
ables were compared using the 2 test, with P values
<0.05 considered statistically significant.
Results
The four study groups were comparable with respect
to demographic characteristics and the duration of
surgery (Table 1). Similar volumes of local anesthetic
were infiltrated during the operation in all four treat-
ment groups. Midazolam produced comparable levels
of sedation in all four groups (Fig. 1). Because mida-
zolam (2 mg IV) was administered for premeditation,
a loading dose of propofol was not used in the study.
The infusion of propofol produced a dose-dependent
increase in the median OAA/S sedation score com-
pared with the control (alfentanil only) group (P
<0.05). The propofol effect was evident within 5 min
in the 50- and 75 -pg * kg-’ * mine1 groups, the peak
effect was achieved within 15-20 min, and a stable
level of sedation was maintained for the duration of
the operation (Fig. 1). However, approximately 45 min
after the start of the propofol infusion, the level of
sedation decreased in the 0- and 25 -pg * kg-* * mine1
propofol infusion groups (Fig. l), presumably as a
result of the declining effect of midazolam.
Propofol produced an opioid-sparing effect and de-
creased the alfentanil dose requirements by 30%-50%
(i.e., infusion rates of 0.3 + 0.2-O-4 f
0.2 pg * kg-l * mine1
in the propofol groups versus
0.6 C 0.2 PLg * kg-’ * min
-I in the alfentanil alone
group) (P ~0.05) (Table 1). There were no clinically
significant differences in pain and discomfort scores
among the four treatment groups. After discontinua-
tion of the study drug infusions, recovery was equally
rapid among the groups, with all patients being trans-
ferred directly from the operating room to the Phase II
(step-down) unit. Although different levels of seda-
tion were maintained until the end of the surgery in
the four treatment groups, sedation scores in all four
groups returned to baseline values within 15 min after
discontinuing the infusions (Fig. 1). There were no
significant differences in the times to ambulation and
to being judged fit for discharge. Actual discharge
times were also similar in all four treatment groups
(Table 2).
ANESTH ANALG
1997;85:566-72
AMBULATORY ANESTHESIA AVRAMOV AND WHITE 569
USE OF ALFENTANIL AND PROPOFOL DURING MAC
01 ‘I
I’* I* C’S I”,’ 1
BL Mdz P A 5 10 15 20 25 30 35 40 45 50 55 60 Ret
Figure 1. Median Observer’s Assessment of Alertness/Sedation
(&A/S) Scale scores for the four treatment groups: preoperatively
(BL). 5 min after midazolam (Mdz). 5 min after start of urouofol (I’).
2 mm after alfentanil (A), and at’ the indicated inter;als’after the
beginning of surgery, at the end of surgery, and during recovery
(Ret). P 0 = propofol 0 pg. kg-’
. min-‘,
25 pg * kg-’ - min-‘, P 50 = propofol
P 25 = propofol
propofol 75 pg * kg-’ * min- .
pg. kg-’ * min-‘, P 75 =
*P ~0.05 versus the propofol
0- pg * kg-’ * mine1 group. n = 18 for each group.
Midazolam premeditation produced amnesia for
the first picture in approximately one third of patients
in all four treatment groups (Table 2). The amnestic
effect of midazolam, however, was no longer apparent
in the control group at the time the third picture test
was shown. In contrast, the administration of propo-
fol, 50-75 pg * kg-’ * min-*, significantly reduced in-
traoperative free recall (P ~0.05) (Table 2).
The dose-dependent increase in sedation produced
by propofol was paralleled by an increase in the inci-
dence of episodes of bradypnea (i.e., transient de-
crease in RR <8 bpm) and Spo, ~90% in the larger
dose (50-75 pg * kg-’ * mini) propofol groups (Table
2). However, the hemodynamic variables were main-
tained within 10% of the preoperative baseline values
and did not differ among the four treatment groups.
In the control (alfentanil alone) group, the VAS nau-
sea scores were significantly increased at discharge
compared with the preoperative values (16.5 +- 27.4 vs
1.3 t 3.7 mm, P ~0.05). At discharge, patients in the
propofol groups reported increased VAS pain and
lower VAS anxiety scores compared with baseline
values (P < 0.05). Although there were no complaints
of intraoperative nausea, six patients in the control
group had emetic episodes after surgery that required
antiemetic treatment versus none in the propofol 50-
and 75 -pg * kg-i * min-l groups (Table 2). None of the
patients reported nausea, vomiting, or any other ad-
verse events after discharge from the ambulatory fa-
cility. More than 90% of patients in all four treatment
groups expressed satisfaction (verbal rating scale
score ~5) with their intraoperative sedative-analgesic
medications and expressed a willingness to receive the
same technique again in the future.
Discussion
The use of a continuous infusion of propofol, 25-
75 PLg * kg-’ * min-‘, in patients premeditated with
midazolam, 2 mg IV, produced increasing levels of
sedation and amnesia during breast biopsy proce-
dures performed under local anesthesia. The addition
of a low-dose alfentanil infusion, 0.3-
0.4 pg * kg-i * min-‘, enhanced patient comfort and
was associated with a low incidence of adverse effects.
Compared with alfentanil alone, the combined use of
alfentanil with propofol for MAC significantly re-
duced the opioid dose requirement and the incidence
of postoperative nausea and vomiting (PONV).
Although the combination of propofol and alfen-
tanil is frequently used for IV anesthesia (3,12,21,22),
there is little information on the use of this drug
combination for IV sedation (9). Propofol infusions
can be easily titrated to produce the desired level of
sedation during procedures performed under local
(23) or regional anesthesia (24), and they are associ-
ated with less postoperative sedation, drowsiness,
confusion, clumsiness, and amnesia, as well as a more
rapid recovery of cognitive function, compared with
midazolam (2). However, even “sedative” doses of
propofol can depress the hypoxic ventilatory response
(25). The administration of a small dose of midazolam
(2 mg IV) at the outset of the propofol infusion results
in increased sedation, anxiolysis, and amnesia without
compromising the rapid recovery from propofol seda-
tion (4).
Opioid analgesics are often used during local anes-
thetic infiltration to reduce the pain associated with
the injection of local anesthetic solutions and traction
on deeper tissues. When used alone during local an-
esthesia, opioid analgesics do not provide adequate
sedation and may produce undesirable side effects
(e.g., ventilatory depression, nausea, itching) (10,26).
The combination of even small doses of an opioid
analgesic (e.g., fentanyl) and a sedative-hypnotic (e.g.,
midazolam) can produce significant respiratory de-
pression (1). The combined use of midazolam, propo-
fol, and alfentanil produces enhanced sedation, amne-
sia, and analgesia compared with their effects when
administered separately (16), which suggests a syner-
gistic (or supraadditive) interaction between these
centrally active drugs (21,22). Nevertheless, the results
of the present study indicate that the safe and effective
use of this triple drug regimen is possible during
surgical procedures performed under local anesthesia,
provided the opioid analgesic is carefully titrated, ex-
cessive sedation is avoided, and the patients are ade-
quately monitored. The lack of clinically significant
hemodynamic and respiratory depression with this
drug combination supports the findings in the re-
cently published volunteer study (16).
In the present study, the plasma levels of alfentanil
and propofol were not measured. Therefore, it is not
possible to accurately predict the plasma and effect
site concentrations of propofol and alfentanil that pro-
vide optimal sedation and analgesia in this clinical
570 AMBULATORY ANESTHESIA AVRAMOV AND WHITE
USE OF ALFENTANIL AND PROPOFOL DURING MAC
ANESTH ANALG
1997;85:566-72
Table 2.
Sedation Levels, Intraoperative Free Recall, Side Effects, and Discharge Times for the Four Treatment Groups
Propofol infusion rate (pg. kg-’ * min-‘)
0
25
50
75
Sedation level (score)
0 min
5 min
During surgery
Picture recall (%)
First picture
Second picture
Third picture
Perioperative side effects?
RR <8 breaths/min
spo, <90%
Nausea/vomiting
Discharge time (min)
1.8 t 0.4 1.8 + 0.4
2.0 2 0.5 1.9 2 0.6
2.0
2
0.6 2.3
2
0.8
3.1
2 1.1*
3.5
? 1.1*
1.9
k
0.5
2.3
+-
0.6% 2.9 -c 0.8* 3.6 -c 0.8%
33
39
100
3
1
0
1
6 3
81 2 29
79
+
37
50
33
44
33 61
17* 17*
11+ 11*
4 6*
3 6%
0* 0"
79
+
37 84
+
35
Values are numbers, means 2 SD, or percentages.
RR = respiratory rate.
a Number of patients with specified events.
*Significantly different from propofol 0 group, P CO.05.
setting. However, a pharmacokinetic simulation of al-
fentanil (bolus of 2.5 PL& * kg-‘. min-‘, infusion of
0.5 pg * kg-’ * min-* for 15 min, followed by
0.3 pg * kg-’ * mini)
and
75 pg * kg-r * mine*,
propofol (50-
after >15 min of the infusion)
(12) should produce plasma alfentanil levels of 30-
60 ng/mL and propofol levels of 400-600 ng/mL,
consistent with the findings in the volunteer study
(16). It is possible that the use of computer-assisted
continuous infusions of propofol and alfentanil may
have improved the titration of these drugs and re-
duced perioperative side effects (27).
After midazolam premeditation, patients receiving
propofol, 50-75 PLg * kg-r . mini, experienced little
intraoperative recall. Although less effective in pro-
ducing intraoperative amnesia than midazolam (2),
propofol’s amnestic effect was evident when the pre-
medicant effect of midazolam had dissipated (as indi-
cated by the free recall of the third picture by all
patients who did not receive propofol). There is con-
troversy regarding the amnestic properties of propo-
fol, with some studies reporting little amnesia (2,5,24),
whereas others have reported significant amnesia (28).
Confounding factors, including the level of sedation,
type of memory tests, intensity of the surgical stimu-
lation, and type of anesthesia (regional versus local
infiltration) contribute to the variable results. Studies
that have controlled for the effect of sedation report
that significant amnesia is produced by propofol (29)
independent of its sedative effects (30). Although it is
difficult to delineate the effect of sedation on intraop-
erative recall, amnesia was consistently maintained
for the duration of the propofol infusion only in the
two larger dose infusion groups in the current study.
These findings suggest that the triple drug regimen of
midazolam, propofol, and alfentanil provides effective
intraoperative amnesia during MAC.
Compared with an opioid analgesic, a nonopioid
analgesic is associated with a lower incidence of
PONV when administered as part of a MAC technique
(26). In our study, 33% of the patients who received
alfentanil alone developed PONV. The addition of
propofol significantly reduced PONV, consistent with
the findings after propofol anesthesia (31) and sup-
porting the report that subhypnotic doses of propofol
possess antiemetic activity (32). Although the mecha-
nism of propofol’s antiemetic action remains un-
known, it has recently been suggested that deeper
levels of sedation per se may be associated with less
PONV (33-35). Additionally, the opioid-sparing effect
of propofol would be expected to further reduce
PONV. Avoiding opioid analgesics would be expected
to further decrease the incidence of PONV (26). How-
ever, when a midazolam-propofol combination was
administered without an opioid analgesic for sedation
during MAC, fentanyl was often required as a rescue
analgesic during the surgical procedures (36,37).
In the present study, the evaluation of the respira-
tory effects of the different treatment regimens was
based on the continuous measurement of end-
expiratory CO, concentrations at the external nares
using the side port of the nasal oxygen cannula. Al-
though this is a frequently used clinical method for
monitoring the RR during MAC (18), this technique
underestimates the true end-tidal CO, concentration
and its impact on central ventilatory drive. However,
the use of pulse oximetry should facilitate the detec-
tion of any clinically significant respiratory depression
produced by this sedative-opioid drug combination.
During propofol sedation, use of the lowest effective
infusion rate of alfentanil would be expected to pro-
duce the best balance between patient comfort, ade-
quate ventilation, and a low incidence of PONV. It is
possible that the use of a larger dose of propofol and
ANESTH ANALG AMBULATORY ANESTHESIA AVRAMOV AND WHITE
571
1997;85:566-72 USE OF ALFENTANIL AND PROPOFOL DURING MAC
a smaller dose of alfentanil would have proven to be
ambulatory procedures performed under local
an even better drug combination for MAC. anesthesia.
In summary, in healthy patients premeditated with
midazolam (2 mg IV), a continuous propofol infusion
(25-50 pg * kg-’ * min-‘) and a variable-rate alfentanil
infusion (0.2-0.4 hg * kg-l * min-‘) provided excellent
intraoperative sedation, analgesia, and amnesia with a
low incidence of perioperative side effects during
The authors express appreciation to the faculty, residents, and
CRNAs in the Department of Anesthesiology and Pain Manage-
ment (especially Dr. Scott Wansbrough).
Appendix 1. Modified Observer’s Assessment of Alertness/Sedation Scale (19)
Responsiveness
Responds readily to name
spoken in normal tone
Lethargic response to name
spoken in normal tone
Responds only after name is
called loudly and/or
repeatedly
Responds only after mild
prodding or shaking
Does not respond to mild
prodding or shaking
Speech
Normal
Mild slowing or
thickening
Slurring or prominent
slowing
Few recognizable
words
-
Facial expression Eyes
Score
Normal Clear, no ptosis 1 (alert)
Mild relaxation Glazed or mild ptosis 2
(less than half the
eye)
Marked relaxation Glazed and marked 3
(slacked jaw) ptosis (half the eye
and more)
- -
4
- -
5 (asleep)
References
1.
2.
3.
4.
5.