Uses
Induction and Maintenance of Anesthesia
Propofol is suitable for both induction and maintenance of anesthesia
and has also been approved for use in neurologic and cardiac anesthesia ( Table
10-3
). The induction dose varies from 1.0 to 2.5 mg/kg,[77]
[233]
[234]
and
the
ED95
in unpremedicated adult patients is 2.25 to 2.5 mg/kg.[233]
[235]
Physiologic characteristics that best determine
the induction dose are age, lean body mass, and central blood volume.[236]
Premedication with an opiate or a benzodiazepine, or with both, markedly reduces
the induction dose.[79]
[80]
[237]
A dose of 1 mg/kg (with premedication) to
1.75 mg/kg (without premedication) is recommended for inducing anesthesia in patients
older than 60 years (also see Chapter
62
).[238]
To prevent hypotension in sicker
patients or those undergoing cardiac surgery, a fluid load should be administered
as tolerated, and propofol should be administered in small incremental doses (10
to 30 mg or as an infusion) until the patient loses consciousness. To limit the
dose and retain the fastest onset time, an infusion of 80 mg/kg/hr is optimal. Diluting
propofol to 0.5 mg/mL further reduces the impact of this induction dose on hemodynamics.
[239]
The ED95
(2.0 to 3.0 mg/kg) for
induction is increased in children, primarily because of pharmacokinetic differences
(also see Chapter 60
).[240]
[241]
When used for induction of anesthesia in briefer procedures, propofol
results in significantly quicker recovery and earlier return of psychomotor function
than
TABLE 10-3 -- Uses and doses of propofol
|
Induction of general anesthesia |
1–2.5 mg/kg IV; dose reduced with increasing age |
|
Maintenance of general anesthesia |
50–150 µg/kg/min IV combined with N2
O
or an opiate |
|
Sedation |
25–75 µg/kg/min IV |
|
Antiemetic |
10–20 mg IV; can repeat q5-10min or start infusion of 10
µg/kg/min |
thiopental or methohexital does, irrespective of the agent used for maintenance of
anesthesia.[242]
[243]
[244]
The incidence of nausea and vomiting when
propofol is used for induction is also markedly lower than after the use of other
intravenous induction agents, probably because of the antiemetic properties of propofol.
[235]
[243]
As a result of its pharmacokinetics, propofol provides rapid recovery
and is thus superior to barbiturates for maintenance of anesthesia,[244]
[245]
[246]
and
it
appears to be equal to enflurane and isoflurane.[79]
[242]
[247]
Recovery
from desflurane is slightly more rapid than recovery from propofol.[248]
Propofol can be given as intermittent boluses or as a continuous infusion for maintenance.
[214]
After a satisfactory induction dose, a bolus
of 10 to 40 mg is needed every few minutes to maintain anesthesia. Because these
doses need to be given frequently, it is more suitable to administer propofol as
a continuous infusion.
Several infusion schemes have been used to achieve adequate plasma
concentrations of propofol (see also Chapter
12
).[244]
[249]
After an induction dose, an infusion of 100 to 200 µg/kg/min is usually needed.
[79]
[139]
[140]
[188]
[242]
[244]
[245]
[246]
The
infusion rate is then titrated to individual requirements and the surgical stimulus.
When combined with propofol, midazolam, clonidine, morphine, fentanyl, sufentanil,
alfentanil, or remifentanil reduces its required infusion rate and concentration
(see also Chapter 12
).[84]
[137]
[139]
[140]
[250]
[251]
[252]
[253]
Because opioids alter the concentration of
propofol required for adequate anesthesia, the relative dose of either opioid or
propofol will markedly affect the time from termination of drug effect to awakening
and recovery. The infusion rate required to achieve the combination with the shortest
recovery is propofol, 1 to 1.5 mg/kg followed by 140 µg/kg/min for 10 minutes
and then 100 µg/kg/min, and alfentanil, 30 µg/kg followed by an infusion
of 0.25 µg/kg/min, or fentanyl, 3 µg/kg followed by 0.02 µg/kg/min.
Propofol has also been used as a single mixture with alfentanil at 1 mg alfentanil
(2 mL) to 400 mg propofol (40 mL). When this mixture was administered at infusion
rates commonly used for propofol (i.e., 166 µg/kg/min for 10 minutes, 133 µg/kg/min
for 10 minutes, and 100 µg/kg/min thereafter), it provided an outcome equal
to that obtained by administering the two drugs as separate infusions.[254]
Increasing age is associated with a decrease in propofol infusion
requirements,[255]
[256]
whereas these requirements are higher in children and infants.[55]
The blood levels of propofol alone needed to achieve loss of consciousness are 2.5
to 4.5 µg/mL, and the blood levels (when combined with nitrous oxide) required
for surgery are 2.5 to 8 µg/mL.[17]
[18]
[82]
[139]
[140]
[247]
Similar concentrations are necessary when
propofol is combined with an opioid for a total intravenous technique. Knowledge
of these levels and the pharmacokinetics of propofol has enabled the use of pharmacokinetic
model-driven infusion systems to deliver propofol as a continuous infusion for maintenance
of anesthesia (see also Chapter 12
).
[79]
[139]
[257]
[258]
For short (<1 hour) body surface procedures, the advantages
of more rapid recovery and decreased nausea and vomiting are still evident.[242]
However, if propofol is used only for induction in longer or major procedures, both
speed of recovery and the incidence of nausea and vomiting are similar to those after
thiopental/isoflurane anesthesia.[79]
[242]
Total intravenous anesthesia with propofol plus an opiate results in similar recovery
but reduces the incidence of postoperative nausea and vomiting in the first 72 hours
by 15% to 20% when compared with an isoflurane-based anesthetic.[259]
A meta-analysis of recovery data after either propofol for maintenance or the newer
volatile anesthetics indicated only minor differences in times to reach recovery
goals; however, the incidence of nausea and vomiting remained significantly lower
in patients administered propofol for maintenance.[260]
Several studies have investigated the utility of propofol as a
maintenance infusion regimen for cardiac surgery. The use of reduced and titrated
doses of propofol for induction and titrated infusion rates of 50 to 200 µg/kg/min
combined with an opioid for maintenance provided intraoperative hemodynamic control
and ischemic episodes similar to those with either enflurane/opioid or a primary
opioid technique.[261]
[262]
[263]
[264]
Sedation
Propofol has been evaluated for sedation during surgical procedures
[85]
[86]
[265]
[266]
and in mechanically ventilated patients in
the intensive care unit (ICU).[267]
[268]
[269]
Propofol by continuous infusion provides
a
readily titratable level of sedation and rapid recovery once the infusion is terminated,
irrespective of the duration of the infusion.[86]
[265]
[268]
[270]
In a study of patients sedated in the ICU for 4 days with propofol, recovery to
consciousness was rapid (≅10 minutes). Both the rate of recovery and the decrease
in plasma concentration were similar at 24 and 96 hours, when the infusion was discontinued.
In addition, the plasma concentrations required for sedation and for awakening were
similar at 24 and 96 hours, a finding implying that tolerance to propofol did not
occur.[270]
As noted earlier, there have been more
recent reports of tolerance with propofol. Infusion rates required for sedation
to supplement regional anesthesia in healthy patients are half or less than those
required for general anesthesia (i.e., 30 to 60 µg/kg/min).[85]
[265]
In elderly patients (older than 65 years)
and sicker patients, the infusion rates that are necessary are markedly reduced.
[85]
[267]
[268]
Thus, it is important to titrate the infusion individually to the desired effect.
A 1992 report[271]
linked propofol with several
deaths in children requiring sedation for mechanical ventilation secondary to upper
respiratory tract infections. This rare syndrome (see later) may also occur in adults.
A potential advantage of propofol for sedation of ICU patients is that it appears
to possess antioxidant properties.[272]
Generally, at propofol infusion rates more rapid than 30 µg/kg/min,
patients are amnesic.[265]
[268]
When compared with midazolam for maintenance of sedation, propofol provides equal
or better control and more rapid recovery.[86]
[265]
[268]
In mechanically ventilated patients, more
rapid recovery translates to more rapid extubation when sedation is terminated.[268]
The use of propofol for sedation after cardiac surgery to provide fast tracking
has shown that patients can be extubated rapidly with this technique.[273]
The incidence of unwanted cardiovascular changes and ischemic events was similar
when propofol or midazolam was used for sedation in patients after coronary artery
bypass surgery.[188]
Propofol has also been used
successfully in patient-controlled sedation. It was rated better than midazolam
when used by this technique, probably because of its much more rapid onset and offset.
[274]
