Metabolism, Induction, and Maintenance of Anesthesia
Etomidate is metabolized in the liver primarily by ester hydrolysis
to the corresponding carboxylic acid of etomidate (major metabolite) or by N-dealkylation.
[582]
The main metabolite is inactive.[585]
Only 2% of the drug is excreted unchanged, the rest being excreted as metabolites
by the kidney (85%) and in bile (13%).[585]
Figure 10-22
Structure of etomidate, an imidazole derivative.
TABLE 10-12 -- Uses and doses of etomidate
|
Induction of general anesthesia |
0.2–0.6 mg/kg IV |
|
Maintenance of general anesthesia |
10 µg/kg/min IV with N2
O and an opiate |
|
Sedation |
5–10 µg/kg/min IV. Prolonged periods of sedation
are contraindicated because of inhibition of corticosteroid synthesis |
Etomidate has been used for both induction and maintenance of
anesthesia ( Table 10-12
).
The induction dose of etomidate varies from 0.2 to 0.6 mg/kg,[575]
[583]
[586]
[587]
and it is reduced by premedication with an opiate, a benzodiazepine, or a barbiturate.
[575]
The onset of anesthesia after a routine induction
dose of 0.3 mg/kg etomidate is rapid (one arm-brain circulation) and equivalent to
that obtained with an induction dose of thiopental or methohexital.[575]
[583]
[588]
The
duration of anesthesia after a single induction dose is linearly related to the dose—each
0.1 mg/kg administered provides about 100 seconds of loss of consciousness.[589]
Repeat doses of etomidate, either by bolus or infusion, prolong the duration of
hypnosis. Recovery after multiple doses or an infusion of etomidate is still usually
rapid.[575]
[586]
[590]
[591]
[592]
[593]
[594]
The
addition of small doses of fentanyl with etomidate for short surgical procedures
reduces the required dose of etomidate and allows earlier awakening. In children,
induction by rectal administration of etomidate has been achieved with 6.5 mg/kg.
Hypnosis occurs in 4 minutes. At this dose the drug's hemodynamics is unaltered,
and recovery is still rapid.[595]
Various infusion schemes have been devised to use etomidate as
a maintenance agent for the hypnotic component of anesthesia (see Chapter
12
). Most regimens aim to achieve a plasma level of 300 to 500 ng/mL,
which is the concentration necessary for hypnosis.[24]
[25]
[596]
[597]
Both two- and three-stage infusions have been used successfully. These regimens
consist of an initial rapid infusion of 100 µg/kg/min for 10 minutes followed
by 10 µg/kg/min thereafter[597]
or 100 µg/kg/min
for 3 minutes, 20 µg/kg/min for 27 minutes, and 10 µg/kg/min thereafter.
[24]
Loss of consciousness with these techniques
occurs after 100 to 120 seconds.[24]
The infusion
is usually terminated 10 minutes before the desired awakening time.[24]
