Revising a Dogma: Ketamine for Patients with Neurological Injury?

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.

Study at a glance

Abstract

UNLABELLED: We evaluated reports of randomized clinical trials in the perioperative and intensive care setting concerning ketamine's effects on the brain in patients with, or at risk for, neurological injury. We also reviewed other studies in humans on the drug's effects on the brain, and reports that examined ketamine in experimental brain injury. In the clinical setting, level II evidence indicates that ketamine does not increase intracranial pressure when used under conditions of controlled ventilation, coadministration of a gamma-aminobutyric acid (GABA) receptor agonist, and without nitrous oxide. Ketamine may thus safely be used in neurologically impaired patients. Compared with other anesthetics or sedatives, level II and III evidence indicates that hemodynamic stimulation induced by ketamine may improve cerebral perfusion; this could make the drug a preferred choice in sedative regimes after brain injury. In the laboratory, ketamine has neuroprotective, and S(+)-ketamine additional neuroregenerative effects, even when administered after onset of a cerebral insult. However, improved outcomes were only reported in studies with brief recovery observation intervals. In developing animals, and in certain brain areas of adult rats without cerebral injury, neurotoxic effects were noted after large-dose ketamine. These were prevented by coadministration of GABA receptor agonists. IMPLICATIONS: Ketamine can be used safely in neurologically impaired patients under conditions of controlled ventilation, coadministration of a {gamma}-aminobutyric acid receptor agonist, and avoidance of nitrous oxide. Its beneficial circulatory effects and preclinical data demonstrating neuroprotection merit further animal and patient investigation.