Barbiturates are respiratory depressants, and a usual induction dose of thiopental or methohexital typically produces transient apnea, which will be more pronounced if other respiratory depressants are also administered. Barbiturates lead to decreased minute ventilation through reduced tidal volumes and respiratory rate and also decrease the ventilatory responses to hypercapnia and hypoxia. Resumption of spontaneous breathing after an anesthetic induction dose of a barbiturate is characterized by a slow breathing rate and decreased tidal volume. Suppression of laryngeal reflexes and cough reflexes is probably not as profound as after an equianesthetic propofol administration, which makes barbiturates an inferior choice for airway instrumentation in the absence of neuromuscular blocking drugs. Furthermore, stimulation of the upper airway or trachea (eg, by secretions, laryngeal mask airway, direct laryngoscopy, tracheal intubation) during inadequate depression of airway reflexes may result in laryngospasm or bronchospasm. This phenomenon is not unique to barbiturates but is true whenever the drug dose is inadequate to suppress the airway reflexes.
D. Other Effects
Accidental intra-arterial injection of barbiturates results in excruciating pain and intense vasoconstriction, often leading to severe tissue injury involving gangrene. Approaches to treatment include blockade of the sympathetic nervous system (eg, stellate ganglion block) in the involved extremity. If extravasation occurs, some authorities recommend local injection of the area with 0.5% lidocaine (5–10 mL) in an attempt to dilute the barbiturate concentration. Life-threatening allergic reactions to barbiturates are rare, with an estimated occurrence of 1 in 30,000 patients. However, barbiturate-induced histamine release occasionally is seen.
The principal clinical use of thiopental (3–5 mg/kg IV) or methohexital (1–1.5 mg/kg IV) is for induction of anesthesia (unconsciousness), which usually occurs in less than 30 seconds. Patients may experience a garlic or onion taste after administration. Solutions of thiopental sodium for intravenous injection have a pH range of 10–11 to maintain stability. Rapid co-injection with depolarizing and nondepolarizing muscle relaxants, which have much lower pH, may cause precipitation of insoluble thiopentone acid. Barbiturates such as methohexital (20–30 mg/kg) may be administered per rectum to facilitate induction of anesthesia in mentally challenged patients and uncooperative pediatric patients. When a barbiturate is administered with the goal of neuroprotection, an isoelectric EEG indicating maximal reduction of CMRO2 has traditionally been used as the end point. More recent data demonstrating equal protection after smaller doses have challenged this practice. The use of smaller doses is less frequently associated with hypotension, thus making it easier to maintain adequate cerebral perfusion pressure, especially in the setting of increased ICP.
Benzodiazepines commonly used in the perioperative period include midazolam, lorazepam, and less frequently, diazepam. Benzodiazepines are unique among the group of intravenous anesthetics in that their action can readily be terminated by administration of their selective antagonist, flumazenil. Their most desired effects are anxiolysis and anterograde amnesia, which are extremely useful for premedication.
The chemical structure and pharmacodynamics of the benzodiazepines are discussed in detail in Chapter 22.
Pharmacokinetics in the Anesthesia Setting
The highly lipid-soluble benzodiazepines rapidly enter the CNS, which accounts for their rapid onset of action, followed by redistribution to inactive tissue sites and subsequent termination of the drug effect. Additional information regarding the pharmacokinetics of the benzodiazepines may be found in Chapter 22.