Ketamine: an update on the first twenty-five years of clinical experience

In nearly 25 years of clinical experience, the benefits and limitations of ketamine analgesia and anaesthesia have generally been well-defined. The extensive review of White et al. and the cardiovascular review of Reves et al. are broad in their scope and have advanced the understanding of dissociative anaesthesia. Nevertheless, recent research continues to illuminate different aspects of ketamine pharmacology, and suggests new clinical uses for this drug. The identification of the N-methylaspartate receptor gives further support to the concept that ketamine's analgesic and anaesthetic effects are mediated by separate mechanisms. The stereospecific binding of (+)ketamine to opiate receptors in vitro, more rapid emergence from anaesthesia, and the lower incidence of emergence sequelae, make (+)ketamine a promising drug for future research. Clinical applications of ketamine that have emerged recently, and are likely to increase in the future, are the use of oral, rectal, and intranasal preparations for the purposes of analgesia, sedation, and anaesthetic induction. Ketamine is now considered a reasonable option for anaesthetic induction in the hypotensive preterm neonate. The initial experience with epidural and intrathecal ketamine administration has not been very promising but the data are only preliminary in this area. The use of ketamine in military and catastrophic settings is likely to become more common. The clinical availability of midazolam will complement ketamine anaesthesia in several ways. This rapidly metabolized benzodiazepine reduces ketamine's cardiovascular stimulation and emergence phenomena, and does not have active metabolites. It is dispensed in an aqueous medium, which is usually non-irritating on intravenous injection, unlike diazepam. The combination of ketamine and midazolam is expected to achieve high patient acceptance, which never occurred with ketamine as a sole agent. Finally, it is necessary to point out the potential for abuse of ketamine. While ketamine is not a controlled substance (in the United States), the prudent physician should take appropriate precautions against the unauthorized use of this drug.