Repetitive administration of highly lipid-soluble barbiturates (eg, infusion of thiopental for “barbiturate coma” and brain protection) saturates the peripheral compartments, minimizing any effect of redistribution and rendering the duration of action more dependent on elimination. This is an example of context sensitivity.
Barbiturates constrict the cerebral vasculature, causing a decrease in cerebral blood flow, cerebral blood volume, and intracranial pressure.
Although apnea may be relatively uncommon after benzodiazepine induction, even small intravenous doses of these agents have resulted in respiratory arrest.
In contrast to other anesthetic agents, ketamine increases arterial blood pressure, heart rate, and cardiac output, particularly after rapid bolus injections.
Induction doses of etomidate transiently inhibit enzymes involved in cortisol and aldosterone synthesis. When used for sedation in the intensive care unit, etomidate was reported to produce consistent adrenocortical suppression.
Propofol formulations can support the growth of bacteria, so sterile technique must be observed in preparation and handling. Propofol should be administered within 6 h of opening the ampule.
General anesthesia began with the inhaled agents ether, nitrous oxide, and chloroform, but in current practice, anesthesia can be induced and maintained with drugs that enter the patient through a wide range of routes. Preoperative or procedural sedation is usually accomplished by way of oral or intravenous routes. Induction of general anesthesia is usually accomplished by inhalation or intravenous drug administration. Alternatively, general anesthesia can be induced and maintained with intramuscular injection of ketamine. General anesthesia is maintained with a total intravenous anesthesia (TIVA) technique, an inhalation technique, or a combination of the two. This chapter focuses on the injectable agents used to produce narcosis (sleep), including barbiturates, benzodiazepines, ketamine, etomidate, propofol, and dexmedetomidine.
Barbiturates depress the reticular activating system in the brainstem, which controls consciousness. Their primary mechanism of action is believed to be through binding to the γ-aminobutyric acid type A (GABAA) receptor. Barbiturates potentiate the action of GABA in increasing the duration of openings of a chloride-specific ion channel.
Barbiturates are derived from barbituric acid (Figure 9–1). Substitution at carbon C5 determines hypnotic potency and anticonvulsant activity. The phenyl group in phenobarbital is anticonvulsive, whereas the methyl group in methohexital is not. Thus methohexital is useful for providing anesthesia for electroconvulsive therapy when a seizure is desired. Replacing the oxygen at C2 (oxybarbiturates) with a sulfur atom (thiobarbiturates) increases lipid solubility. As a result, thiopental and thiamylal have a greater potency, more rapid onset of action, and shorter durations of action (after a single “sleep dose”) than pentobarbital. The sodium salts of the barbiturates are water soluble but markedly alkaline (pH of 2.5% thiopental ≥10) and relatively unstable (2-week shelf-life for 2.5% thiopental solution).
Barbiturates share the structure of barbituric acid and ...