Neurotoxicity

Neurotoxicity
Rodent and monkey research strongly supports the
observation that ketamine can induce accelerated programmed
nerve cell death (apoptosis) when administered in high doses or
for prolonged periods. Concern about potential human
neurotoxicity has prompted ongoing investigations by the Food
and Drug Administration and National Institutes of Health,
with consideration given to removing ketamine from the market
or substantially restricting it.109
Although it is beyond dispute that ketamine can induce
neuronal death in rodents and other animals, the literature is
silent about such an effect in humans. Indeed, such a premise is
at complete odds with the wealth of human experience with this
agent. This animal research indicates that the minimum single
dose of ketamine required to produce neuroapoptosis is 40 mg/
kg, more than an order of magnitude higher than typical clinical

use. This research involves animals neurodevelopmentally much
younger than the children who typically might receive ED
ketamine.109 Resolution of this question in humans will not be
easy and will appear to require case-control studies of ED
ketamine sedation with long-term neuropsychological
follow-up.109
Isomers
The 2 optimal isomers of ketamine, R( ) and S( ), have
different properties, but the literature is inconclusive about
whether this might be clinically important.4,12,15,16,110 The
S( ) ketamine may exhibit enhanced dissociative/analgesic
potency, greater amnesia, faster elimination, and fewer recovery
reactions and may have neuroprotective effects.110 The S( )
formulation is available in Europe but not the United States or
Canada.
Optimized IV Delivery
Emergency physicians typically administer IV ketamine in
single or sequential doses. Although this delivery style is simple,
it will frequently exceed the minimum amount of drug required.
It may be possible to decrease the total amount of ketamine
delivered, and thus potentially shorten recoveries, through the
use of pharmacokinetic infusion models.111,112 Targetcontrolled
infusion in particular has shown promise with
ketamine and other drugs and deserves further study.111