Vol. 87 No.

5 May 1999

ORAL SURGERY
ORAL MEDICINE
ORAL PATHOLOGY

ORAL AND MAXILLOFACIAL SURGERY

Editor: Larry J. Peterson

Propofol anesthesia for outpatient oral and maxillofacial surgery

Joseph E. Cillo, Jr, DMD,a Buffalo, NY
ERIE COUNTY MEDICAL CENTER

Propofol is a sedative-hypnotic intravenous anesthetic agent that has gained wide use in outpatient oral and maxillofacial surgery since its clinical introduction in 1985. Propofol has several therapeutic advantages that make it an excellent
choice for use in all phases of general anesthesia and conscious sedation. It is associated with minimal side effects, a controllable anesthetic state, and rapid recovery. This review of propofol discusses its pharmacologic character, administration, and
side effects and presents anesthetic drug interaction information and comparisons. (Oral Surg Oral Med Oral Pathol Oral

Radiol Endod 1999;87:530-8)

Since its clinical introduction in 1985, the use of

propofol (Diprivan; Zeneca Inc, Wilmington, Del), a
sedative-hypnotic intravenous (IV) anesthetic agent, in
outpatient oral and maxillofacial surgery has significantly increased.1 Propofol has qualities that make it an
effective and excellent agent for use in all phases of
sedation and general anesthesia, and it has several
characteristics that make it superior to more commonly
used anesthetic agents in outpatient oral and maxillofacial surgery. It produces minimal side effects and offers
a quick onset, rapid emergence from general anesthesia, and rapid recovery of psychomotor and cognitive function, even after prolonged administration.
Propofol is most commonly available in 20-mL and 50mL (10 mg/mL) vials in an emulsion of Intralipid 10%,
an aqueous emulsion containing (weight in volume)
10% soya bean oil, 2.25% glycerol, and 1.2% purified
egg phosphatide. This emulsion does not contain any
preservatives or antimicrobial agents, so aseptic techniques during handling are necessary.

CLINICAL PHARMACOKINETICS OF
PROPOFOL
Propofol pharmacokinetics involve a 3-compartment
linear model; the compartments represent plasma,
rapidly equilibrating tissues, and slowly equilibrating
tissues.2 The rapid onset of anesthesia and sedation
after an IV bolus of propofol is due to the rapid equilibration between plasma and the highly perfused tissue
aGeneral Practice Resident.
Received for publication May 29, 1998; returned for revision July 2,
1998; accepted for publication Dec. 2, 1998.
Copyright 1999 by Mosby, Inc.
1079-2104/99/$8.00 + 0 7/12/96477

530

of the brain. The effects of anesthesia and sedation are

generally seen 40 seconds after administration. Plasma
levels initially decline rapidly as a result of both rapid
distribution, which accounts for half of the decline, and
high metabolic clearance.2 This distribution begins to
decrease over time in a manner that is dependent on the
rate and duration of infusion. As bodily tissues begin to
equilibrate with plasma, there is no longer a transfer of
propofol between tissues and plasma. Propofol has a
clearance of 30 to 60 mL/kg/min and a volume of
distribution of 3.5 to 4.5 L/kg. It has an elimination
half-life of 3 to 12 hours, a rapid distribution half-life
of 2 to 4 minutes, and a slower distribution half-life of
30 to 64 minutes. It is metabolized in the liver into 4
inactive metabolites1-quinol glucuronide, 4-quinol
glucuronide, propofol glucuronide, and 4-quinol
sulphateand eliminated in the urine.2

CLINICAL PHARMACOLOGY OF PROPOFOL

The pharmacologic characteristics of propofol are
summarized in Table I and discussed in the sections
that follow.
Hepatorenal system
Propofol is extensively metabolized in the liver by the
cytochrome P450 enzyme system into 4 inactive metabolites.2 Elimination from the body occurs mainly in the
urine, whereas feces contain minimal amounts.2 Propofol
is a weakly acidic anesthetic agent that is highly bonded
to serum protein, predominantly albumin. Because of the
absence of significant changes in protein binding in
patients with renal and liver disease, it is unlikely that
there will be an exaggerated pharmacologic response in
such a patient after the administration of a standard

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY

Volume 87, Number 5

Cillo 531

Table I. Summary of propofol pharmacology

System

Effect(s)

Cardiovascular

Hypotension with decreases in systolic, diastolic, and mean arterial pressures

Decreases cardiac contractility (negative inotropy)
Dose-dependent respiratory depression, including apnea, changes in breathing patterns, and ventilatory depression
Decreases cerebral glucose metabolism
GABA-ergic anesthetic agent
Metabolized by cytochrome P450 system in liver
Eliminated from body in urine
Feces contain minimal amounts of drug
Reduced incidences of postoperative nausea and vomiting
No effect on adrenal steroidogenesis
Not immunosuppresive
Does not stimulate histamine release
Supports rapid microbial growth at room temperature

Respiratory
Central nervous
Hepatorenal

Gastrointestinal
Endocrine
Immune

propofol dose.3 There has been no statistical evidence to

show that propofols induction dose or clearance is
altered in patients with renal failure3,4 or uncomplicated
cirrhosis of the liver3; this is in contrast to other anesthetic agents, such as midazolam, that show impairment
of protein binding in patients with renal failure.4 Costela
et al3 suggest 2 theories to explain this event. First,
competitive binding between other serum proteins, such
as 1-acid glycoprotein, may explain why changes in
albumin levels in patients with renal or hepatic disease do
not alter propofol binding. Second, conformational
changes in albumin in diseased states may expose additional sites, leading to increased binding. In geriatric
patients, however, lower doses may be required inasmuch
as there is a significantly lower rate of clearance in such
patients than in younger patients, possibly because of
decreased cardiac output and hepatic blood flow.5,6

Central nervous system

Unlike other anesthetic agents such as barbiturates,
propofol significantly decreases cerebral metabolism,
showing a reduction in whole brain glucose metabolism.7 It specifically reduces metabolism in the frontal,
parietal, and occipital lobes, which involve areas
belonging to the sensory (auditory, visual, and
somatosensory), motor, and limbic systems.7
Gamma aminobutyric acid (GABA) is the main
inhibitory neurotransmitter in the central nervous system.
Propofol, which is believed to be a GABA-mimic anesthetic agent, enhances GABA activity and induces
hypnosis through its effect on the alpha subunit of GABA
receptors.8 Propofol modifies the receptor/chloride
channel so that it remains open longer after the binding
of endogenously released GABA.8
Gastrointestinal system
Postoperative nausea and vomiting (PONV) are side
effects of some anesthetic agents. In comparison with
management of postoperative pain, management of

PONV is a factor judged to be critical in the acceptance

of an anesthetic by the patient population. PONV can
be as debilitating as the pain associated with a surgical
procedure and is the most important factor in determining the length of stay after ambulatory anesthesia.
In comparison with inhalation anesthetics, such as
sevoflurane,9 and IV anesthetic agents, such as methohexital,10 propofol is associated with significantly
fewer incidents of PONV.

Endocrine system
Surgery provokes a generalized stress response that
leads to profound changes in endocrine function and
metabolism, resulting in the release of hormones
such as adrenaline, noradrenaline, and cortisol. In
surgical situations, endocrine stress responses are
undesirable because they may delay recovery to
normal metabolic states and impair defense mechanisms and wound healing, particularly in patients
with preexisting disease. Like other anesthetic
agents, such as benzodiazepines, propofol does not
induce adrenal steroidogenesis.11
Patients with hyperthyroidism may suffer from
tachycardia, increased stroke volume, increased
cardiac output, and decreased peripheral resistance. In
these patients, propofol is a beneficial anesthetic agent
because it does not stimulate the sympathetic nervous
system and because it decreases heart rate and blood
pressure.12 However, distribution volume and clearance of propofol are increased in patients with hyperthyroidism; increased infusion rates are thus required
for the sake of achieving therapeutic levels.12
Respiratory system
Respiratory depression is a usual side effect of some
commonly used anesthetic agentsspecifically,
benzodiazepines and barbiturates. Although hypoxia
may occur when these agents are used, deaths from
respiratory arrest are rare. Propofol produces dose-

532 Cillo

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY

May 1999

Table II. Comparison of IV agents

Propofol
Class
IV induction dose
GA maintenance
Sedation
Onset
Duration (min)
Clearance (mg/kg/min)
Volume of distribution (L/kg)
Half-life (h)
Plasma protein binding (%)
Supplied

Methohexital

Sedative-hypnotic
Ultra-shortacting barbiturate
1-2.5 mg/kg
0.5-2.5 mg/kg
80-150 g/kg/min IV
0.25-1 mg/kg IV
10-50 g/kg/min IV
5-25 mg IV bolus
<40 s
<60 s
4-8
5-7
30-60
10.9-12.1
3.5-4.5
1.1-2.2
0.5-1
1
95-99
73
Liquid, 20-mL and
Powder, 5g/500-mL
50-mL ampule, 10 mg/mL
multidose vial

Midazolam

Ketamine

Benzodiazepine
0.1-0.2 mg/kg
150-300 g/kg IV
1-2.5 mg IV bolus
3-5 min
10-20
7.5
1.1-1.7
2-4
80
Liquid, 5-mL vial,
1 mg/mL

Phencyclidine derivative
0.25-0.75 mg/kg
10-50 g/kg/min IV
0.2-8 mg/kg IV
30 s
7-11
16-18
2.5-3.5
1-2
12
Liquid, 5-mL
vial, 100 mg/mL

GA, General anesthesia.

dependent respiratory depression, with apnea, changes

in breathing patterns, and ventilatory depression being
the most widely reported respiratory effects.13 These
complications are relatively minor and can be well
managed if they are properly monitored.

Cardiovascular system
Most pharmacologic investigation into the administration of propofol has concerned hemodynamic factors
involving heart rate, heart contractility, and blood pressure. Propofol does not directly induce bradyarrhythmias
because it does not depress sinoatrial node activity or
atrioventricular conduction at therapeutic doses.14
However, propofol shows a simultaneous decrease in
heart contractility (negative inotropy) and afterload
reduction, which leads to hypotension.15 This resulting
hypotension involves significant reductions in systolic,
diastolic, and mean arterial pressures that are not
followed by the less-than-expected increase in heart rate
or cardiac output.14 In comparison with other anesthetic
agents, such as methohexital,16 propofol IV infusion is
associated with reductions in arterial blood pressure that
are more marked and hypotensive reactions that are more
frequent. There are 2 proposed mechanisms for propofolinduced hypotension. Mackenzie and Grant17 speculate
that propofol-induced hypotension is mediated by an
inhibition of the sympathetic nervous system and impairment of the baroreflex regulatory mechanism. Li et al18
postulate that the disturbance in Ca2+ transport and availability may cause a decrease in energy production and
produce propofols negative inotropic effect.
Immune system
Many anesthetic agents and adjuvants, such as
opioids and muscle relaxants, can cause the release of
histamine from mast cells. This can lead to several
undesirable consequences, including hypotension,
tachycardia, urticaria, pruritis, and bronchospasm. In

some instances, these events can lead to life-threatening reactions during anesthetic administration.
Although propofol can cause allergic reactions in
patients who are allergic to this agent, it is generally
safe from anaphylactoid reactions because when
administered at therapeutic doses it does not promote
the release of histamine from mast cells.19 However,
because propofol and its lipid emulsion, Intralipid, do
not contain preservatives or antimicrobial agents, they
support rapid microbial growth at room temperature.20
The use of improper aseptic techniques in handling
propofol vials has resulted in numerous reported cases
of postoperative bloodstream and surgical site infections.20,21 The etiologic agents in these infections have
been Staphylococcus aureus, Candida albicans,
Moraxella osloensis, Enterobacter agglomerans, and
Serratia marcescens.20

ADMINISTRATION TECHNIQUES OF
PROPOFOL ANESTHESIA FOR OUTPATIENT
ORAL AND MAXILLOFACIAL SURGERY
Propofols acceptance in outpatient oral and maxillofacial surgery is due to its favorable safety and efficacy
for general anesthesia and sedation. Propofol has both
rapid onset and psychomotor recovery characteristics;
these implicate it for use in an ambulatory anesthesia
and sedation. For this reason, and because of its
extremely low occurrence of postoperative nausea and
vomiting, it is particularly useful in pediatric,22 geriatric,5,23 and mentally and/or physically handicapped24
patients who benefit from expeditious recovery without
numerous postoperative complications.
Methods of administration
Several techniques for the administration of propofol
anesthesia have been reported: continuous infusion,
patient-controlled infusion, and manual bolus infusion.
Continuous infusion. Continuous infusion of

Cillo 533

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY

Volume 87, Number 5

Table III. Interactions between propofol and other anesthetic agents

Anesthetic combination

Results

Propofol/methohexital

No significant differences in induction properties, intraoperative variables, rate of recovery, or postoperative

sequelae
Reduces propofol dose requirement
Produces no additional consequences to recovery characteristics, postoperative mood or patient satisfaction
Provides hemodynamic stability
Additive effect at endpoints of hypnosis and anesthesia
Lower occurrence of apnea
Decreases induction time
Reduces propofol dose requirement
Does not improve recovery time
Reduces propofol dose requirement
Increases sedative and analgesic effects
Reduces emetic potential of alfentanil
Alfentanil may potentiate hemodynamic depressant effects of propofol
Faster recovery time
Less postoperative nausea and vomiting
Tremendously reduces the required rate of propofol infusion
Provides reliable sedation with no change in recovery time
Reduces incidences of postoperative shivering
Reduces incidences of postoperative nausea and vomiting
Reduces propofol dose requirements
No effect on postoperative analgesia and recovery time

Propofol/midazolam
Propofol/ketamine

Propofol/fentanyl

Propofol/alfentanil

Propofol/sufentanil
Propofol/remifentanil
Propofol/diazepam
Propofol/nitrous oxide

propofol at variable rates minimizes the peaks and

valleys of blood concentrations of IV anesthetics that
are seen with incremental bolus techniques. By maintaining a constant plasma concentration of propofol,
this technique decreases the amount of drug administered, stabilizes the level of anesthesia, and shortens
recovery time. Continuous infusion of propofol minimizes the risks of hypotension and bradycardia and
produces improved hemodynamic stability.5 In elderly
patients, slow continuous infusionin contrast with
bolus administration, which has a greater effect on
diminishing cardiac output, greater negative inotropic
effects, and a greater decrease in systemic vascular
resistance caused by vasodilatationis more beneficial because of these patients increased risk of and
exaggerated response to hypotension.5 Slower infusion
in nonpremedicated elderly patients results in lower
plasma concentrations, less hemodynamic derangement, less slowing of the heart rate, and a reduction in
the amount of drug required to induce anesthesia.25
Patient-controlled sedation. Patient-controlled
sedation (PCS), which has been widely reported as safe
and effective, is a favorable method of intraoperative
anesthesia for surgery performed with a patient under
local or regional anesthesia.23,26 PCS allows the patient
to establish and maintain his or her own desired level
of sedation. This is accomplished through an IV
connection to an infusion pump that is controlled by
the patient during the surgical procedure. Each patientinitiated dose allows the self-administration of a prede-

termined amount of anesthetic, usually over a 5-second

interval. A delay mechanism in the infusion pump
prevents oversedation by blocking administration for
several minutes. Patients have different sensitivities to
sedative drugs and different preferences with respect to
the level of sedation required during a procedure.
Additionally, the level of perceived surgical stress may
change during the course of a procedure. These individual factors may make it difficult to provide optimal
sedation for each patient. PCS provides a mechanism
by which to compensate for individual pharmacokinetic and pharmacodynamic differences.
Midazolam PCS produces similar levels of sedation
and anxiolysis, but propofol PCS provides more beneficial characteristics. These include rapid response to fluctuating patient requirements, less occurrence of apnea,
faster recovery of memory and mental performance, and
a more beneficial effect on patient mood; with propofol,
there may be a feeling of well-being and less postoperative depression.26 Methohexital PCS compares favorably with propofol PCS because it is eliminated rapidly
and is less expensive.26 Although a patient receiving
methohexital PCS feels more drowsy and experiences
less psychomotor skill recovery immediately after a
procedure, there are no significant clinical differences in
recovery time.26 Methohexital PCS is considered to be a
suitable alternative to propofol PCS.23
Propofol PCS bolus doses are generally from 5 to 10
mg (0.5 to 1 mL). Because these doses tend to produce
deeper levels of sedation in elderly patients, it is

534 Cillo

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY

May 1999

Table IV. Comparisons between propofol and other anesthetic agents

Anesthetic agents

Comparison

Propofol vs methohexital

Recovery characteristics identical after 20 min

Methohexital increases heart rate
Propofol produces greater percentage of episodes of hypotension
No difference in patient cooperation or comfort, cardiopulmonary stability, recovery time, amnesia,
and postoperative nausea and vomiting
Cost-effectiveness superior with methohexital
At equal sedation levels, propofol produces similar degree of memory impairment
Propofol produces less respiratory depression
Propofol produces more episodes of hypotension
Propofol produces faster cognitive and psychomotor recovery
Propofol produces faster recovery times and better amnesia
Propofol produces more episodes of hypotension
Patients prefer propofol
Sevoflurane produces significantly slower induction rates
Sevoflurane produces more frequent nausea and vomiting
No significant difference in emergence times
Propofol produces more episodes of hypotension
Sevoflurane is more irritating, leading to patient preference for propofol
Similar psychomotor recovery times
Propofol produces less nausea and vomiting
Propofol produces more episodes of bradycardia and hypotension
Both agents suitable for maintenance of anesthesia in pediatric patients
Propofol decreases minute ventilatory rate more frequently
Propofol produces less nausea and vomiting
Halothane produces faster recovery of psychomotor function in pediatric patients

Propofol vs midazolam

Propofol vs diazepam

Propofol vs sevoflurane

Propofol vs isoflurane

Propofol vs halothane

suggested that such a patient receive a reduced dose.23

Suggested propofol PCS doses for the elderly are 0.3
mg/kg for patients between the ages of 60 and 69 years
and 0.15 mg/kg for patients between the ages of 70 and
79 years.23
Manual bolus infusion. Manual infusion by bolus
administration typically provides satisfactory sedation
for the performance of oral and maxillofacial procedures, as do techniques such as continuous infusion.25,27,28 However, incremental bolus administration
of propofol tends to produce variable plasma concentrations, thereby increasing the occurrence of hypotension and respiratory depression and increasing the
amount of drug that must be administered.25,27,28

Dosage
Propofol is compared with other IV anesthetic agents
in Table II and in the sections that follow.
The induction dose of 1% propofol is 1 to 2.5 mg/kg
IV. For the maintenance of general anesthesia, propofol
should be administered at a rate of 80 to 150 g/kg/min.
This can be combined with an opiate and/or nitrous
oxide or volatile anesthetic. For conscious sedation,
propofol should be administered at 10 to 50 g/kg/min,
either alone or in combination with an opiate. Because
propofol is a lipid-soluble anesthetic agent, it is
expected to have a prolonged effect in patients in whom
the proportion of fat is significant with respect to total

body weight. Reduced clearance and slower distribution

in peripheral compartments may result from propofol
infusion because it reduces cardiac output and liver
blood flow.28 Therefore, when increased concentrations
are needed, the change in dosage should be made in
proportion to propofols depressant effect on hemodynamic function.28 These regimens are effective and safe
in establishing a well-sedated patient capable of undergoing outpatient oral and maxillofacial surgery.

Recovery
One of the more beneficial aspects reported for
propofol is its rapid recovery time.16,29-31 The fastest
reported recovery times after propofol general anesthesia were 5 minutes16 and 30 minutes.31 Whereas
patients undergoing deep sedation with either propofol
or methohexital recover psychomotor performance
faster with propofol, both agents produce similar
recovery characteristics 20 minutes postoperatively.32
Propofol is a safe and effective anesthetic agent in
both short-duration and long-duration procedures, with
recovery rates similar to those of some volatile anesthetics.10,31 Propofol has lower incidences of postoperative shivering than do other anesthetic agents, such as
methohexital33 and halothane.34 In addition, patients
are reported to be clear-headed and well oriented and to
experience fewer postoperative complications on
awakening after propofol anesthesia and sedation.33,34

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY

Volume 87, Number 5

Cillo 535

ANESTHETIC DRUG INTERACTIONS AND

COMPARISONS
Interactions between propofol and other anesthetic
agents (summarized in Table III) and comparisons of
propofol and other agents (summarized in Table IV)
are discussed in the sections that follow.

Ketamine
Ketamine (Ketalar, Parke-Davis) is an anesthetic agent
that is known to reduce hypotension by increasing heart
rate, cardiac output, and arterial blood pressure through
sympathetic nervous system activation.41 The combination of ketamine and propofol has been used in an
attempt to balance the cardiostimulatory effects of ketamine with the cardiodepressant effects of propofol for the
sake of achieving improved cardiovascular stability.42
The sedative effects of these 2 drugs have an additive
effect at endpoints of hypnosis and anesthesia, and there
is less probability of apnea. This combination of propofol
with ketamine for total IV anesthesia provides greater
intraoperative hemodynamic stability than does the
administration of propofol alone.42

Methohexital
Methohexital (Brevital, Jones Medical) is a nonanalgesic short-acting barbiturate IV anesthetic agent
commonly used for sedation and anesthesia. Propofols
influences on immediate postoperative mood state are
different from and more favorable than those of methohexital. Propofol is associated with a more elated, more
agreeable, and less anxious patient (with better postoperative psychomotor performance on cessation of
anesthesia) than is methohexital.29 This is in the very
early recovery period, however; after 20 minutes,
recovery characteristics for the 2 anesthetics are essentially identical.31,35 Comparisons of the 2 agents with
respect to conscious sedation show that the significant differences are increases in heart rate with methohexital35 and a greater percentage of episodes of
hypotension with propofol.29 There are no significant
differences in cooperation, cardiopulmonary stability,
recovery time, amnesia, comfort, or incidence of
PONV after 24 hours.35 Methohexital administered
concomitantly with propofol, in comparison with
propofol alone, resulted in no significant differences
in induction properties and complications, intraoperative variables, rate of recovery, or postoperative
sequelae.36 The use of both anesthetic agents provides
safe and reliable anesthesia for outpatient oral and
maxillofacial surgery. However, propofol is significantly more expensive than methohexital, which makes
the cost-effectiveness of methohexital superior to that
of propofol.
Midazolam
Midazolam (Versed, Roche Labs) is a benzodiazepine indicated for use in sedation and general
anesthesia. In comparison with midazolam at equal
sedation levels, propofol was found to produce the
same degree of memory impairment 37 while
producing less respiratory depression and achieving
faster cognitive and psychomotor recovery. 38 The
addition of midazolam to the propofol regimen
decreases the propofol dose requirement while
producing no additional consequences with respect
to recovery characteristics, postoperative mood, incidence of postoperative dreams, and patient satisfaction. 39 Immediate premedication with 2 mg of IV
midazolam before propofol infusion produces
increased sedation, amnesia, and anxiolysis.40

Opioids
Fentanyl (Sublimaze), alfentanil (Alfenta), sufentanil
(Sufenta), and remifentanil (Ultivar) are opioid analgesics used as adjuncts for sedation and general anesthesia. These short-acting opioids are primarily used to
attenuate the response to the painful stimulus of local
anesthesia administration.
Premedication with a typical 100-g dose of
fentanyl decreases induction time and reduces
propofol requirements in very short procedures, but it
does not improve the recovery time or quality of anesthesia.43 Combined sufentanil-propofol anesthesia
results in less vomiting during the early postoperative
period than does propofol-induced isoflurane anesthesia.44 Alfentanil reduces the amount of propofol
required to achieve hypnotic effects and increases the
respective sedative and analgesic properties of both
drugs45; however, alfentanil does not assure more
hemodynamic stability during induction because in
some patients it may potentiate the hemodynamic
propofols depressant effects to nearly the same degree
that it potentiates its sedative effects.45 In comparison
with anesthesia with propofol alone, remifentanil
anesthesia provides comparable intraoperative conditions and patient comfort at a lower sedation level but
results in greater respiratory depression and longer
recovery times.46
Diazepam
Diazepam (Valium) is a benzodiazepine used as an
anxiolytic and anticonvulsant in sedation and general
anesthesia. Diazepam administration during propofol
anesthesia provides reliable sedation, the combination
being superior to separate administration of the 2 drugs,
with minimal side effects and no change in recovery
time.47 In comparison with IV diazepam alone, IV
propofol alone provides faster recovery times and better
amnesia and has a higher patient preference.48

536 Cillo

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY

May 1999

Nitrous oxide
Nitrous oxide is a colorless inorganic gas that is
nonirritating and has a pleasant odor. A nitrous
oxide/oxygen combination is commonly used in
mildly apprehensive individuals. Propofolnitrous
oxide sedation, in comparison with propofol-room air
sedation, decreases postanesthesia shivering49 and
causes less nausea and vomiting.50,51 In addition, this
combination decreases the propofol dose requirement50,51 while having no effect on postoperative
analgesia and recovery time.50

10%.30 Propofol-induced pain on injection can be

significantly reduced or eliminated with prior or
concomitant IV administration of lidocaine or meperidine.57 When 3 mL of 2% lidocaine or 40 mg of
meperidine is administered intravenously 1 minute
before propofol administration, propofol-induced pain
on injection is significantly reduced.57
As previously described, other common side effects
of propofol-based anesthesia are hypotension and
dose-dependent respiratory depression. If the patient is
properly monitored during propofol-based anesthesia,
these occurrences can be easily managed.
Another potential side effect of propofol administration is intraarterial injection. Early suggestion of
intraarterial injection of propofol occurs if a patient
complains of pain on injection that is not abolished by
lidocaine or meperidine administration or if blanching
of the injection site occurs. Unlike intraarterial injections of other IV anesthetics, such as methohexital,
which can have profound systemic effects, intraarterial
injection of propofol has been reported to result in
nothing more than a few hours of hyperemia.58 The
best precaution against intraarterial injection of
propofol is to establish a running IV line before the
administration of propofol.
Because propofol and its emulsion support rapid
microbial growth and are administered in large-dose
vials, the proper use of aseptic technique in the
handling of the vials is essential in preventing postoperative infections.21 Postoperative infections have
resulted solely from vials that were extrinsically contaminated as a result of mishandling by the persons
administrating the anesthetic.21

Volatile anesthetic agents

The volatile anesthetic agents sevoflurane (Ultane,
Abbott Hosp), isoflurane (Forane, Ohmeda), and
halothane (Fluothane, Wyeth-Ayerst) are nonflammable halogenated ethers indicated for use as inhalation anesthetics for the maintenance of general anesthesia. They are commonly used for outpatient
general anesthesia in oral and maxillofacial surgery
either alone or in combination with propofol or other
anesthetic agents. In comparisons between sevoflurane/nitrous oxide and propofol/nitrous oxide anesthesia, sevoflurane/nitrous oxide was found to have a
significantly slower induction rate while producing
more frequent nausea and vomiting without any
significant difference in emergence time.9,52 For
induction of anesthesia, patients preferred propofol to
sevoflurane, which was rated as unpleasant.52
In comparison with propofol-based anesthesia, isoflurane-based anesthesia produces similar psychomotor
recovery times53; the former produces less nausea and
vomiting, but it also produces more episodes of bradycardia and hypotension.54
Halothane is a safe and effective inhalation anesthetic agent that is most commonly used in pediatric
patients for maintenance of general anesthesia. In
comparisons between propofol and halothane-based
anesthesia in pediatric patients, both agents were found
to be suitable for maintenance of anesthesia.34
However, whereas propofol decreases the minute ventilatory rate in pediatric patients in comparison with
halothane,55 it produces less postoperative vomiting.56
The recovery of psychomotor function in pediatric
patients after general anesthesia with propofol was
significantly faster than after general anesthesia with
halothane.56 In combination with propofol, halothane
is safe to use on healthy and asthmatic children56 and
provides acceptable intubation conditions.22
SIDE EFFECTS
The most frequently reported side effect of propofol
administration is pain on injection.30,57 This painful
stimulus is attributed to propofols solvent, Intralipid

CONCLUSION
Propofol is an excellent anesthetic agent for use in
outpatient oral and maxillofacial surgery of short or
long duration. Propofol possesses many ideal anesthetic
agent characteristics, including rapid onset, fast and
clear recovery, reliability of action, and lack of allergic
responses. It is a beneficial anesthetic agent for patients
suffering from renal failure, cirrhosis, and hyperthyroidism. Intraoperatively, propofol does not induce
malignant hyperthermia, although it may cause
hypotension and dose-dependent respiratory depression. Aseptic technique is imperative during the
handling of propofol vials inasmuch as postoperative
infections have been traced to extrinsically contaminated vials. Whether it is used alone or in combination
with other anesthetic agents to produce balanced anesthesia, propofol provides reliable sedation. It causes
pain on injection that is diminished with prior administration of lidocaine or meperidine. Postoperatively, it
produces minimal confusion with comparably fast

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY

Volume 87, Number 5

Cillo 537

psychomotor recovery, considerably less nausea and

vomiting, and less postanesthetic shivering. Propofol is
significantly more expensive than other commonly used
agents, such as methohexital, and economic factors may
be a consideration in its use.

18. Li YC, Ridefelt P, Wiklund L, Bjerneroth G. Propofol induces a

lowering of free cystolic calcium in myocardial cells. Acta
Anaesthesiol Scand 1997;41:633-8.
19. Stellato C, Casolaro V, Ciccarelli A, Mastronardi P, Mazzarella
B, et al. General anaesthetics induce only histamine release
selectively from human mast cells. Br J Anaesth 1991;67:751-8.
20. Bennet SN, McNeil MM, Bland LA, Arduino MJ, Villarino ME,
et.al. Postoperative infections traced to contamination of an intravenous anesthetic, propofol. N Engl J Med 1995;333:147-54.
21. Seeberger MD, Staender S, Oertli D, Kindler CH, Marti W.
Efficacy of specific aseptic precautions for preventing propofolrelated infections: analysis by a quality-assurance program
using the explicit outcome method. J Hosp Infect 1998;39:6770.
22. Hansen D, Schaffartzik W, Dopjans D, Haeitz E, Striebel HW.
Halothane-propofol anaesthesia for tracheal intubation in young
children. Br J Anaesth 1997;78:366-9.
23. Ganapthy S, Herrick IA, Gelb AW, Kirby J. Propofol patientcontrolled sedation during hip or knee arthroplasty in elderly
patients. Can J Anaesth 1997;44:385-9.
24. Roelofse JA, van der Bijl P. Propofol for sedation in a mentally
retarded dental patient. Anesthesia Progress 1994;41:81-2.
25. Bennett J, Shafer DM, Elfaw, Goupil M. Incremental bolus
versus a continuous infusion of propofol for deep
sedation/general anesthesia during dentoalveolar surgery. J Oral
Maxillofac Surg 1998;56:1049-53.
26. Hamid SK, McCann N, McArdle L, Asbury AJ. Comparison of
patient-controlled sedation with either methohexitone or
propofol. Br J Anaesthes 1996;77:727-30.
27. Pratila MG, Fischer ME, Alagesan R, Alagesan R, Reinsel RA,
et al. Propofol versus midazolam for monitored sedation: a
comparison of intraoperative and recovery parameters. J Clin
Anesth 1993;5:268-74.
28. Struys M, Versichelen L, Thas O, Herregods L, Rolly G.
Comparison of computer-controlled administration of propofol
with two manually controlled infusion techniques. Anaesthesia
1997;52:41-50.
29. Sear JW, Glen JB. Propofol administered by a manual infusion
regimen. Br J Anaesth 1995;74:362-7.
30. Pastuovic MN, Cohen ME, Burton RG. Propofol: an alternative
general anesthetic for outpatient oral surgery. J Oral Maxillofac
Surg 1996;54:943-8.
31. Raeder J, Gupta A, Pederson FM. Recovery characteristics of
sevoflurane- or propofol-based anesthesia for day-care surgery.
Acta Anaesthesiol Scand 1997;41:988-94.
32. Cohen M, Eisig S, Kraut RA. Comparison of recovery of
propofol and methohexital sedation using an infusion pump.
Anesthesia Progress 1996;43:9-13.
33. Candelaria LM, Smith RK. Propofol infusion technique for
outpatient general anesthesia. J Oral Maxillofac Surg
1995;53:124-8.
34. Carpenter RD, Sikich N, Levine M, Lerman J. Anaesthesia for
insertion of ear tubes in children: comparison of propofol,
thiopentone, and halothane. Paediatr Anaesth 1997;7:25-31.
35. Johns FR, Sandler NA, Buckley MJ, Herlich A. Comparison of
propofol and methohexital continuous infusion techniques for
conscious sedation. J Oral Maxillofac Surg 1998;56:1124-7.
36. Thompson N, Robertson GS. Comparison of propofol and a
propofol-methohexitone mixture for induction of day-care
anaesthesia. Br J Anaesth 1996;77:213-6.
37. Veselis RA, Reinsel RA, Feshchenko VA, Wronski M. The
comparative amnestic effects of midazolam, propofol,
thiopental, and fentanyl at equisedative concentrations.
Anesthesiology 1997;87:749-64.
38. Sarasin DS, Ghoneim MM, Block RI. Effects of sedation with
midazolam or propofol on cognition and psychomotor functions.
J Oral Maxillofac Surg 1996;54:1187-93.
39. Oxorn DC, Ferris LE, Harrington E, Orser BA. The effects of
midazolam on propofol induced anesthesia: propofol dose
requirements, mood profiles, and perioperative dreams. Anesth
Analg 1997;85:553-9.
40. Taylor E, Ghouri AF, White PF. Midazolam in combination with

I thank Paul A. Moore, DMD, PhD, Professor, University

of Pittsburgh School of Dental Medicine, for his assistance in
the preparation of this manuscript.
REFERENCES
1. Pecaro BC, Houting T. Diprivan (ICI 35868, 2,6 diisopropophenol), a new intravenous anesthetic. Oral Surg Oral
Med Oral Pathol 1985;60:586-90.
2. Schnider TW, Minto CF, Gambus PL, Andresen C, Goodale DB,
et al. The influence of method of administration and covariates
on the pharmacokinetics of propofol in adult volunteers.
Anesthesiology 1998;88:1170-82.
3. Costela JL, Jimenez R, Calvo R, Suarez E, Carlos R. Serum
protein binding of propofol in patients with renal failure or
hepatic cirrhosis. Acta Anaesthesiol Scand 1996;40:741-5.
4. Morcos WE, Payne JP. The induction of anaesthesia with
propofol (Diprivan) compared in normal and renal failure
patients. Postgrad Med J 1985;61:61-3.
5. Chan VW, Chung FF. Propofol infusion for induction and maintenance in elderly: recovery and hemodynamic profiles. J Clin
Anesth 1996;8:317-23.
6. Fruen BR, Mickelson JR, Roghair TJ, Litterer LA, Louis CF.
Effects of propofol on Ca2+ regulation by malignant hyperthermia-susceptible muscle membranes. Anesthesiology
1995;82:1274-82.
7. Alkine MT, Haier RJ, Barker SJ, Shah NK, Wu JC, et al.
Cerebral metabolism during propofol anesthesia in humans
studied with positron emission tomography. Anesthesiology
1997;82:393-403.
8. Krasowski MD, OShea SM, Rick CE, Whiting PJ, Hadingham
KL, et al. Alpha subunit influences of GABA(A) receptor modulation by propofol. Neuropharmacology 1997;36:941-9.
9. Lien CA, Hemmings HC, Belmont MR, Abalos A, Hollmann C,
et al. A comparison: the efficacy of sevoflurane-nitrous oxide or
propofol-nitrous oxide for induction and maintenance of general
anesthesia. J Clin Anesthes 1996;8:639-43.
10. Best N, Traugott F. Comparative evaluation of propofol or
methohexitone as the sole anaesthetic agent for microlaryngeal
surgery. Anaesth Intensive Care 1991;19:50-6.
11. Aitkenhead AR, Pepperman ML, Willatts SM, Coates PD, Park
GR, et al. Comparison of propofol and midazolam for sedation
in critically ill patients. Lancet 1989;2(8665):704-9.
12. Tsubokawa T, Yamamoto K, Kobayashi T. Propofol clearance
and distribution volume increase in patients with hyperthyroidism. Anesth Analg 1998;87:195-9.
13. Sternlo JE, Sandin RH. Recurrent respiratory depression after
total intravenous anaesthesia with propofol and alfentanil.
Anaesthesia 1998;53:378-81.
14. Romano R, Ciccaglioni A, Fattorini A, Quaglione R, Favaro R,
et al. Effects of propofol on the human heart electrical system: a
transesophageal pacing electrophysiologic study. Acta
Anaesthesiol Scand 1994;8:30-2.
15. Gauss A, Heinrich H, Wilder-Smith OHG. Echocardiographic
assessments of the haemodynamic effects of propofol: a
comparison with etomidate and thiopentone. Anaesthesia
1991;46:99-105.
16. Sellgren J, Ejnell H, Elam M, Ponten J, Wallin BG. Sympathetic
muscle nerve activity, peripheral blood flows, and baroreceptor
reflexes in humans during propofol anesthesia and surgery.
Anesthesiology 1994;80:534-44.
17. Mackenzie N, Grant IS. Comparison of propofol with methohexitone in the provision of anaesthesia for surgery under
regional blockade. Br J Anaesth 1985;57:1167-72.

538 Cillo

41.
42.
43.
44.

45.

46.
47.

48.
49.
50.

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY

May 1999

propofol for sedation during local anesthesia. J Clin Anesthes

1992;4:213-6.
Hemmingen C, Klint-Neilsen JE. Intravenous ketamine for
prevention of severe hypotension during spinal anesthesia. Acta
Anaesthesiol Scand 1991;35:755-7.
Frizelle HP, Duranteau J, Samii K. A comparison of propofol
with a propofol-ketamine combination for sedation during
spinal anesthesia. Anesth Analg 1997;84:1318-22.
Smith C, McEwan AI, Jhaveri R. The interaction of fentanyl on
the CP50 of propofol for loss of consciousness and skin incision.
Anesthesiology 1994;81:820-8.
Standl T, Wilhelm S, von Knobelsdorff G, Schulte an Esch J.
Propofol reduces emesis after sufentanil supplemented anaesthesia in paedeatric squint surgery. Acta Anaesthesiol Scand
1996;40:729-33.
Vuyk J, Hannis PJ, Burm AG, de Voogt JW, Speierdijk L.
Comparison of midazolam and propofol in combination with
alfentanil for total intravenous anesthesia. Anesth Analg
1997;85:553-9.
Smith I, Avramov MN, White PF. A comparison of propofol and
remifentanil during monitored anesthesia care. J Clin Anesth
1997;9:148-54.
Hampl KF, Marsch SC, Erb T, Drewe J, Schneider MC.
Intravenous sedation for retrobulbar injection and eye surgery:
diazepam and/or propofol? Acta Anaesthesiol Scand
1996;40:53-8.
Valtonen M, Salonen M, Forsell H, Scheinin M, Viinamaki O.
Propofol infusion for sedation in outpatient oral surgery: a
comparison with diazepam. Anaesthesia 1989;44:730-4.
Lim BL, Low TC. Total intravenous anaesthesia versus inhalation anaesthesia for dental day surgery. Anaesth Intensive Care
1992;20:475-8.
Lindekaer AL, Skielboe M, Guldager H, Jensen EW. The influence of nitrous oxide on propofol dosage and recovery after total

51.

52.
53.

54.
55.
56.

57.
58.

intravenous anaesthesia for day-case surgery. Anaesthesia

1995;50:379-9.
Sukhani R, Lurie J, Jabamoni R. Propofol for ambulatory gynecologic laparascopy: does omission of nitrous oxide alter postoperative emetic sequelae and recovery? Anesth Analg
1994;78:831-5.
Thwaites A, Edmends S, Smith I. Inhalation induction with
sevoflurane: a double-blind comparison with propofol. Br J
Anaesth 1997;78:356-61.
Stebel S, Lam AM, Matta B, Mayberg TS, Aaslid R, Newell
DW. Dynamic and static cerebral autoregulation during isoflurane, desflurane, and propofol anesthesia. Anesthesiology
1995;83:66-76.
Jellish WS, Leonetti JP, Murdoch JR, Fowles S. Propofol-based
anaesthesia as compared with standard anesthetic techniques in
middle ear surgery. J Clin Anesth 1995;7:292-6.
Kulkarni P, Brown KA. Ventilatory parameters in children
during propofol anaesthesia: a comparison with halothane. Can
J Anaesth 1996;43:653-9.
Klockgether-Radke A, Piorek V, Crozier T, Kettler D. Nausea
and vomiting after laprascopic surgery: a comparison of
propofol and thiopentone/halothane anaesthesia. Eur J
Anaesthesiol 1996;13:3-9.
Pang WW, Mok MS, Huang S, Hwang MH. The analgesic effect
of fentanyl, morphine, meperidine, and lidocaine in the peripheral veins: a comparative study. Anesth Analg 1998;86:382-6.
Ang BL. Prolonged cutaneous sequelae after intra-arterial injection of propofol. Singapore Med J 1998;39:124-6.

Reprint requests:
Joseph E. Cillo, Jr., DMD
661 Terrace Blvd. Apt 1
Depew, NY 14043

AVAILABILITY OF JOURNAL BACK ISSUES

As a service to our subscribers, copies of back issues of Oral Surgery, Oral Medicine, Oral
Pathology, Oral Radiology, and Endodontics for the preceding 5 years are maintained and are
available for purchase from the publisher, Mosby, at a cost of $13.00 per issue until inventory is
depleted. The following quantity discounts are available: 25% off on quantities of 12 to 23; one
third off on quantities of 24 or more. Please write to Mosby, Inc, Subscription Services, 11830
Westline Industrial Drive, St Louis, MO 63146-3318, or call (800) 453-4351 or (314) 453-4351
for information on availability of particular issues. If unavailable from the publisher, photocopies of complete issues are available from UMI, 300 N Zeeb Rd, Ann Arbor, MI 48106;
(313) 761-4700.