Ketamine: A Drug at War with Itself

Authors: Paul Garcia, M.D., Ph.D. et al

Anesthesiology 3 2017, Vol.126, 371-372.

KETAMINE has always been the odd one out. Like an eccentric uncle who always turns up at the holiday season with a new partner, ketamine has never really comfortably fitted in to simple classifications of anesthetic drugs. Obviously, the anesthesia produced by ketamine is qualitatively very different, as compared to the more traditional γ-aminobutyric acid–mediated (GABAergic) hypnotics. Despite clear cardiopulmonary advantages (i.e., minimal hypotension or hypoventilation), its use has waxed and waned for the past 50 yr, due to concerns over postanesthetic neurocognitive behaviors. Currently, it is experiencing a minirenaissance and is increasingly used as an adjunct on top of the volatile-opioid–based anesthesia, for analgesic and antiinflammatory reasons. The interactions between ketamine and GABAergic hypnotics have not been thoroughly investigated. In this month’s edition of Anesthesiology, Hambrecht-Wiedbusch et al  show that intraperitoneal ketamine changes the electroencephalogram from slow waves to a burst suppression pattern when given in a dose of about one sixth required for loss of righting reflex to rats, on top of 1.1 minimum alveolar concentration isoflurane. Paradoxically, when the isoflurane was stopped about 90 min later, the ketamine caused the rats to wake up twice as fast as the saline controls. Ketamine had both deepened the anesthesia and simultaneously speeded up emergence. Further, the investigators also measured the concentrations of acetylcholine in the extracellular fluid of the medial prefrontal cortex. They found that isoflurane caused a marked decrease in acetylcholine levels that was not immediately reversed by the ketamine. However, when the isoflurane was stopped, the acetylcholine concentrations in the ketamine-injected rats rapidly rebounded to double that of the controls—which supports the notion that this was the mechanism for the quicker recovery observed in the ketamine-treated animals.