Page 469 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 25 General Anesthetics 455

therapeutic procedures. Midazolam has a more rapid onset, with reduction of CMRO , etomidate has failed to show neuroprotec-
2
greater amnesia and less postoperative sedation, than diazepam. tive properties in animal studies, and human studies are lacking.
Midazolam is also the most commonly used oral premedication The frequency of excitatory spikes on the EEG after the admin-
for children; 0.5 mg/kg administered orally 30 minutes before istration of etomidate is greater than with thiopental. Similar to
induction of anesthesia provides reliable sedation and anxiolysis methohexital, etomidate may activate seizure foci, manifested as
in children without producing delayed awakening. fast activity on the EEG. In addition, spontaneous movements
The synergistic effects between benzodiazepines and other characterized as myoclonus occur in more than 50% of patients
drugs, especially opioids and propofol, can be used to achieve bet- receiving etomidate, and this myoclonic activity may be associated
ter sedation and analgesia but may also greatly enhance their com- with seizure-like activity on the EEG.
bined respiratory depression and may lead to airway obstruction
or apnea. Because benzodiazepine effects are more pronounced B. Cardiovascular Effects
with increasing age, dose reduction and careful titration may be A characteristic and desired feature of induction of anesthesia with
necessary in elderly patients. etomidate is cardiovascular stability after bolus injection. In this
General anesthesia can be induced by the administration of regard, decrease in systemic blood pressure is modest or absent
midazolam (0.1–0.3 mg/kg IV), but the onset of unconsciousness and principally reflects a decrease in systemic vascular resistance.
is slower than after the administration of thiopental, propofol, or Therefore, the systemic blood pressure-lowering effects of etomi-
etomidate. Delayed awakening is a potential disadvantage, limiting date are probably exaggerated in the presence of hypovolemia, and
the usefulness of benzodiazepines for induction of general anesthesia the patient’s intravascular fluid volume status should be optimized
despite their advantage of less pronounced circulatory effects. before induction of anesthesia. Etomidate produces minimal
changes in heart rate and cardiac output. Its depressant effects on
ETOMIDATE myocardial contractility are minimal at concentrations used for
induction of anesthesia.
Etomidate (Figure 25–6) is an intravenous anesthetic with hypnotic C. Respiratory Effects
but not analgesic effects and is often chosen for its minimal hemody-
namic effects. Although its pharmacokinetics are favorable, endocrine The depressant effects of etomidate on ventilation are less pro-
side effects limit its use for continuous infusions. Etomidate is a nounced than those of barbiturates, although apnea may occasion-
carboxylated imidazole derivative that is poorly soluble in water and ally follow rapid intravenous injection of the drug. Depression of
is therefore supplied as a 2 mg/mL solution in 35% propylene glycol. ventilation may be exaggerated when etomidate is combined with
The solution has a pH of 6.9 and does not cause problems with pre- inhaled anesthetics or opioids.
cipitation as thiopental does. Etomidate appears to have GABA-like
effects and seems to act primarily through potentiation of GABA - D. Endocrine Effects
A
mediated chloride current, like most other intravenous anesthetics. Etomidate causes adrenocortical suppression by producing a dose-
dependent inhibition of 11β-hydroxylase, an enzyme necessary for
Pharmacokinetics the conversion of cholesterol to cortisol (see Figure 39–1). This
suppression lasts 4–8 hours after an induction dose of the drug.
An induction dose of etomidate produces rapid onset of anesthe- Despite concerns regarding this finding, no outcome studies have
sia, and recovery depends on redistribution to inactive tissue sites, demonstrated an adverse effect when etomidate is given in a bolus
comparable to thiopental and propofol. Metabolism is primarily by dose. However, because of its endocrine effects, etomidate is not
ester hydrolysis to inactive metabolites, which are then excreted in used as continuous infusion.
urine (78%) and bile (22%). Less than 3% of an administered dose
of etomidate is excreted as unchanged drug in urine. Clearance of Clinical Uses & Dosage
etomidate is about five times that of thiopental, as reflected by a
shorter elimination half-time (Table 25–2). The duration of action Etomidate is an alternative to propofol and barbiturates for the
is linearly related to the dose, with each 0.1 mg/kg providing about rapid intravenous induction of anesthesia, especially in patients
100 seconds of unconsciousness. Because of etomidate’s minimal with compromised myocardial contractility. After a standard
effects on hemodynamics and short context-sensitive half-time, induction dose (0.2–0.3 mg/kg IV), the onset of unconsciousness
larger doses, repeated boluses, or continuous infusions can safely be is comparable to that achieved by thiopental and propofol. Similar
administered. Etomidate, like most other intravenous anesthetics, is to propofol, during intravenous injection of etomidate, there is a
highly protein bound (77%), primarily to albumin. high incidence of pain, which may be followed by venous irrita-
tion. Involuntary myoclonic movements are also common but
Organ System Effects may be masked by the concomitant administration of neuromus-
cular blocking drugs. Awakening after a single intravenous dose of
A. CNS Effects etomidate is rapid, with little evidence of any residual depressant
Etomidate is a potent cerebral vasoconstrictor, as reflected by effects. Etomidate does not produce analgesia, and postoperative
decreases in cerebral blood flow and ICP. These effects are similar nausea and vomiting may be more common than after the admin-
to those produced by comparable doses of thiopental. Despite its istration of thiopental or propofol.