Characteristics of Anesthetic Agents Used for Induction and Maintenance of General Anesthesia

Edmond I. Eger, II, MD


Am J Health Syst Pharm. 2004;61(20) 

In This Article

Intravenous Anesthetics

Intravenous (i.v.) anesthetics include etomidate, midazolam, propofol, thiopental, ketamine, and opioid agonists. The first four agents act by enhancing the activity of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the CNS. Ketamine antagonizes the effect of the excitatory neurotransmitter N-methyl-D-aspartate (NMDA) on NMDA receptors, and opioid agonists stimulate opioid receptors.

The ideal i.v. anesthetic agent has a rapid onset of action and is quickly cleared from the bloodstream and CNS, facilitating control of the anesthetic state (e.g., allowing titration of effect). The ideal agent also protects vital tissues, has other desirable pharmacologic effects (e.g., an antiemetic effect), does not affect the circulatory system or cause other adverse effects, and is inexpensive. Propofol is the most widely used i.v. anesthetic agent for induction. It is highly lipophilic and distributes rapidly into the CNS and other tissues, which accounts for its rapid onset of action.[1] Propofol produces unconsciousness within the time it takes for the drug to travel from the injection site to the brain, which is referred to as one "arm-brain circulation time" and requires less than one minute.[1] The onset of anesthesia is smooth, although the drug can cause pain at the injection site.[1] Propofol is rapidly and extensively metabolized in the liver and at extrahepatic sites, which means it has a high rate of total body clearance. The drug has a direct antiemetic effect through an unknown mechanism.[1] It also is euphorigenic, but does not have residual psychotic effects as does ketamine.

Adult patients often prefer that anesthesia be induced by i.v. injection because induction occurs more quickly and smoothly and is associated with less claustrophobia. In 40 patients undergoing ophthalmic surgery using either inhaled sevoflurane plus nitrous oxide or i.v. propofol for induction, satisfaction with induction of anesthesia was assessed afterward by asking patients whether they would be willing to receive the same anesthetic agent again.[2] More patients given propofol (90%) were willing to receive the same anesthetic again than was the case with sevoflurane (50%). The difference may be attributed to claustrophobia. However, children often prefer an inhalation induction of anesthesia because of a fear of needles. Inhalation induction also may be useful in patients with a lack of venous access.

Several reasons suggest the use of i.v. anesthetics for anesthesia induction but not for anesthesia maintenance. Administration of multiple doses by i.v. injection or a continuous i.v. infusion can result in drug accumulation and delays in recovery from anesthesia. The higher cost of i.v. therapy compared with the costof inhaled therapy also is a consideration. The lack of a means for continuously measuring the depth of anesthesia is perhaps the most important reason for avoiding the use of i.v. anesthetics for anesthesia maintenance. The use of inhaled anesthetics for maintenance of anesthesia provides greater control of the depth of anesthesia because sophisticated devices are available for monitoring the concentration of the inhaled anesthetic agent delivered to the patient. In 90 patients randomized to receive i.v. propofol or one of two inhaled anesthetic agents (isoflurane or desflurane) for maintenance of anesthesia after induction during an office-based procedure, the percentage of patients with purposeful movement during surgery was significantly higher with propofol than with either of the inhaled anesthetic agents.[3] Movement reflects a shallow depth of anesthesia and can interfere with and delay surgery.