New iv induction anaesthetics.

Abstract

The history of intravenous (iv) anaesthetic induction agents almost mirrors that of the 50 years of the Canadian Anaesthetists' Society. ~ While other agents were available before its introduction, thiopentone has been used for slightly more than 50 yr. 2 In fact, Since its introduction, up until the present day, thiopentone has been considered as the standard against which other/v induction agents have to be judged. 3 Over the past 50 yr many agents have been used to induce anaesthesia intravenously; however, only a few can be considered true/v induction agents. An ideal /v induction agent should include the following properties.4 1 Predictable, rapid /v induction (one arm-to-brain circulation). 2 Lack of cardiovascular and respiratory depression. 3 Rapid awakening (recovery). 4 Minimal side-effects. 5 Minimal anaphylactic reactions. Intravenous agents No iv agent that has been available is able to meet all these criteria. In fact, some have been withdrawn, such as alfathesin; 5 never been available in Canada, i.e., etomidate; 6 or never been used to a major extent - methohexitone.7 It is interesting to look at the reasons for the unavailability of the above. Alfathesin, 5 a mixture of two steroids, was widely used in Europe and Canada before being withdrawn 'in the 1980's. Alfathesin, as with most of the other agents since thiopentone was not water soluble and, therefore, required a solvent. Alfathesin was formulated in cremophor EL and this formulation led to an unacceptably high incidence of anaphylactoid reactions. 8,9 Etomidate, also water insoluble, has a number of undesirable features, i.e., pain on injection, involuntary movements, nausea and vomiting but causes little cardiovascular depression. 6.~0 However, it has never been released in Canada and probably will not be because of its ability to cause adrenal suppression. ~ Another steroidbased agent, minaxolone, appeared promising especially as it was water soluble, but was never released due to problems with carcinogenesis in rats and relatively slow recovery times. ~2 A number of other iv drugs have been used to induce anaesthesia including benzodiazepines - diazepam, midazolam; narcotics - fentanyl, morphine and ketamine. However, none of these really meet the criteria of a true /v induction agent particularly with regard to predictability and rapidity of induction, and speed of recovery and so will not be considered in this presentation. Propofol The recent introduction of propofol (2,6-disoprophylfenol) has provided competition for thiopentone as the standard /v induction agent. R3 Propofol is again not water soluble but its formulation in a lipid emulsion (10% soya bean oil, 1.2% egg phosphatide and 2.25% glycerol) has not produced the same anaphylactoid reactions as for alfathesin. 14 Propofol will be examined under the criteria of an ideal '/v induction agent and as compared primarily with thiopentone.