The amnestic, anxiolytic, and sedative effects of benzodiazepines make this class of drugs the most popular choice for preoperative medication. Midazolam (1–2 mg IV) is effective for premedication, sedation during regional anesthesia, and brief therapeutic procedures. Midazolam has a more rapid onset, with greater amnesia and less postoperative sedation, than diazepam. Midazolam is also the most commonly used oral premedication for children; 0.5 mg/kg administered orally 30 minutes before induction of anesthesia provides reliable sedation and anxiolysis in children without producing delayed awakening.
The synergistic effects between benzodiazepines and other drugs, especially opioids and propofol, can be used to achieve better sedation and analgesia but may also greatly enhance their combined respiratory depression and may lead to airway obstruction or apnea. Because benzodiazepine effects are more pronounced with increasing age, dose reduction and careful titration may be necessary in elderly patients.
General anesthesia can be induced by the administration of midazolam (0.1–0.3 mg/kg IV), but the onset of unconsciousness is slower than after the administration of thiopental, propofol, or etomidate. Delayed awakening is a potential disadvantage, limiting the usefulness of benzodiazepines for induction of general anesthesia despite their advantage of less pronounced circulatory effects.
Etomidate (Figure 25–6) is an intravenous anesthetic with hypnotic but not analgesic effects and is often chosen for its minimal hemodynamic effects. Although its pharmacokinetics are favorable, endocrine side effects limit its use for continuous infusions. Etomidate is a carboxylated imidazole derivative that is poorly soluble in water and is therefore supplied as a 2 mg/mL solution in 35% propylene glycol. The solution has a pH of 6.9 and does not cause problems with precipitation as thiopental does. Etomidate appears to have GABA-like effects and seems to act primarily through potentiation of GABAA-mediated chloride current, like most other intravenous anesthetics.
An induction dose of etomidate produces rapid onset of anesthesia, and recovery depends on redistribution to inactive tissue sites, comparable to thiopental and propofol. Metabolism is primarily by ester hydrolysis to inactive metabolites, which are then excreted in urine (78%) and bile (22%). Less than 3% of an administered dose of etomidate is excreted as unchanged drug in urine. Clearance of etomidate is about five times that of thiopental, as reflected by a shorter elimination half-time (Table 25–2). The duration of action is linearly related to the dose, with each 0.1 mg/kg providing about 100 seconds of unconsciousness. Because of etomidate’s minimal effects on hemodynamics and short context-sensitive half-time, larger doses, repeated boluses, or continuous infusions can safely be administered. Etomidate, like most other intravenous anesthetics, is highly protein bound (77%), primarily to albumin.
A. CNS Effects