KETAMINE

QUESTION: A patient has been given an injection of ketamine in a dose calculated to be sufficient for anesthesia.  His eyes remain open, and there is slight nystagmus and occassional purposeless movements.  This is an indication that:
a. the dose is inadequate
b. more ketamine should be given to stop the movements
c. the dose is excessive
d. the dose is adequate for anesthesia
e. the patient is having a seizure

HIGHLIGHTS ON KETAMINE:
Dose: 1-2 mg/kg IV (induction) 4-8 mg/kg IM
0.2-0.5 mg/kg IV (analgesia)
15-30 mcg/kg/min (infusion)

Overview:
Phencyclidine derivative that produces "dissociative anesthesia" - dissociation between the thalamocortical and limbic system.  Resembles a cataleptic state in which the eyes remain open with a slow nystagmic gaze.  Pt is noncommunicative; wakefulness may appear to be present.  Varying degrees of hypertonus and purposeful skeletal muscle movements occur independent of surgical stimulation. 
*Has amnestic and analgesic properties.  (however, no retrograde amnesia)

Structure Activity Relationships:
Two optical isomers (racemic mixture):
left-handed = S(+) --> more intense analgesia, rapid metabolism and recovery, less emergence rxn
right-handed = R (-)

Mechanism:
Binds noncompetitively (allosteric site) to N-methyl-D-aspartate (NMDA) receptors.  (Also exerts effects on several other receptors, including opioid and GABA receptors)
NMDA receptors are ligand-gated ion channels.  Endogenous ligands to NMDA are glutamate and glycine.  Presynaptic release of glutamate is also decreased by ketamine.

Pharmacokinetics/dynamics:
Onset: 1 min
Duration: 5-15 min
water-soluble
Metabolism: by hepatic microsomal enzymes; demethylation of ketamine by CYP450  enzymes to form norketamine - an active metabolite (1/5-1/3 as potent as ketamine)

Clinical Use:
*ketamine increases salivary secretions - administer antisialagogue (0.2 mg glyco) preop
*has been mixed with propofol to decrease occurance of hypotension
*No pain on injection

System Effects/SE:
CNS: Increases CBF & CMRO2 but not ICP (potent cerebral vasodilator)
Neuroprotective role (although not strongly supported by research)
Does not induce seizures (controversial)

CV: direct central SNS stimulation, incr catecholamine [ ], but negative cardiac inotropic effect
Increase in ABP, HR, CO and myocardial O2 requirements

Pulm: *maintains intact airway muscle tone and reflexes, and ventilation
Breathing frequency may decrease for several minutes after admin; apnea can occur if given too quickly or admin with opioid
bronchodilatory activity - has been used to treat bronchospasm and status asthmaticus

Heme: Inhibits platelet aggregation (impt in bleeding disorder)
Inhibits plasma cholinesterase activity (may see prolonged duration of succs)

Psych: Emergence delirium (5-30%; misinterpretation of auditory and visual stimuli) - typically in young and middle aged adults; decreased incidence with preop Versed; usually only given to very young and very old patients.
hallucinations can occur 24 hr post admin

Other: does not affect hepatic/renal systems; does not cause histamine release so rarely causes allergic rxns

ANSWER: (d) Traditional signs of the anesthetic state are not seen with ketamine administration. Purposeless movements are seen, and these do not indicate the need for more anesthetic.

REFERENCES:
Stoelting, Hillier. Pharmacology & Physiology in Anesthetic Practice (4th ed). pg. 167-174
Dershwitz. McGraw-Hill Specialty Board Review: Anesthesiology Examination & Board Review (6th ed)