Ketamine is a unique anesthetic that induces a dissociative state with profound analgesia and amnesia without necessarily causing loss of consciousness. Introduced over 30 years ago as a potential 'monoanesthetic,' its use diminished due to side effects like psychotomimetic reactions, but it remains valuable for specific indications such as induction in hemodynamic shock or asthma, and sedation for painful procedures. Its primary mechanism is noncompetitive antagonism of NMDA glutamate receptors, though it also interacts with opioid, cholinergic, and monoaminergic systems. The S(+) enantiomer has greater potency and may offer faster recovery and fewer side effects than the racemic mixture. Small doses provide preemptive analgesia, reducing postoperative opioid requirements by 40-60%. Ketamine may also have neuroprotective properties, and concerns about increasing intracranial pressure are mitigated by maintaining normocapnia.
Ketamine does not increase intracranial pressure in neurologically impaired patients when used with controlled ventilation, a GABA receptor agonist, and without nitrous oxide (level II evidence). Its hemodynamic stimulation may improve cerebral perfusion, making it a preferred sedative after brain injury. In laboratory studies, ketamine shows neuroprotective effects, and S(+)-ketamine may have neuroregenerative effects, even when given after a cerebral insult, though improved outcomes were only seen in studies with brief recovery periods. Large-dose ketamine caused neurotoxic effects in developing animals and certain brain areas of adult rats without injury, but these were prevented by coadministering GABA receptor agonists.