Revising a dogma: ketamine for patients with neurological injury?
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.


CONCLUSIONS
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.
Himmelseher
Sabine
S
*Klinik fuer Anaesthesiologie, Klinikum rechts der Isar, Technische Universität, München, Germany; and †Department of Anesthesiology, University of Virginia Health System, Charlottesville, Virginia.
Durieux
Marcel E
ME
D000778:Anesthetics, Dissociative / Q000009:adverse effects / Q000627:therapeutic use*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003422:Critical Care; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007649:Ketamine / Q000009:adverse effects / Q000627:therapeutic use*; D009422:Nervous System Diseases / Q000188:drug therapy; D018696:Neuroprotective Agents; D020258:Neurotoxicity Syndromes; D016032:Randomized Controlled Trials as Topic; D013237:Stereoisomerism; D020196:Trauma, Nervous System / Q000188:drug therapy*
D000778:Anesthetics, Dissociative; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D007649:Ketamine