Ketamine
derived from
phencyclidine (PCP)
"angel dust"
R-ketamine
right-handed optical isomer
onset/peak
30 sec - 1min
IV - 1 min
IM - 5 min
induction
0.5-1.5 mg/kg IV
4-8 mg/kg IM
CV
*blunted by premed benzos or inhaled anesthetics & N2O
increases SBP, PAP, HR, CO, MRO2
HR +33%
MAP +28%
PAP +44%
Unexpected drops in SBP and CO -> depleted catecholamine stores
**direct myocardial depressant
dissociative anesthesia
resembles a cataleptic state in which the eyes remain open with a slow nystagmus gaze
*noncommunicative, but wakefulness is present; hypertonus and purposeful skeletal muscle movements
Racemic Mixture
inhibit uptake of catecholamines back into the postganglionic sympathetic nerve endings
*cocaine-like effect
less fatigue and cognitive impairment
duration
10-20 minutes
full consciousness 60-90 min
maintenance
0.2-0.5 mg/kg IV
4-8 mg/kg IM
ventilation and airway
no signficant depression of ventilation
ventilatory response to CO2 maintained
**unlikely to increase more than 3 mmHg
Upper airway and skeletal muscle tone and reflexes maintained and intact
increased salivary and tracheobronchial mucous gland secretions
bronchodilator activity; no histamine release
advantages of ketamine over propofol and etomidate
no pain on injection (no lipid emulsion vehicle)
profound analgesia at subanesthetic doses
S(+) ketamine
left-handed optical isomer
more intense analgesia
more rapid metabolism and recovery
less salivation
lower incidence of emergence reaction
Vd
3L/kg
highly lipid soluble (5-10x thiopental)
subanesthetic
0.2-0.5 mg/kg
CNS
potent cerebral vasodilator
increases CBF by 60%
0.5-2 mg/kg no further increase in ICP
*excitatory activity in EEG does not alter seizure threshold
**myoclonus
* increased amplitude with SSEP -> reduced by N2O
disadvantages of ketamine
frequency fo emergence delirium
abuse potential
Receptors
Bind non-competitively to NMDA receptors. inhibits activation of NMDA receptors by glutamate and decreases the presynaptic release of glutamate
* glutamate (most abundant excitatory NT)
*glycine is an obligatory co-agonist
clearance
1L per minute
postop sedation - pedi <3 surgery
1-2 mg/kg/hr
emergence delirium
psychedelic effects in 5-30% of patients
visual, auditory, proprioceptive and confusional illusions
*morbid and vivid dreams in color and hallucinations up to 24hours
MOA: depression of the inferior colliculus and medial geniculate nucleus
prevention: benzo IV 5 min prior
perservative of ketamine
benzethonium chloride - inhibits the neuronal ACh
other receptors
opioid (mu, delta, kappa, weak sigma), monoaminergic, muscarinic, VG Na+, L-type Ca++ and neuronal nicotinic ACh
weak GABA-A receptor
metabolism/excretion
CYP450 -> norketamine: active metabolite (1/3 potency)
E 1/2 = 2-3 hrs
kidneys
neuraxial
epidural 30 mg
spinal 5-50 mg in 3 mL of saline
other systems
inhibits platelet aggregation
inhibits cytosolic free calcium concntrations (enhanves Non-depolarizing NMBDs)
inhibits plasma cholinesterases (prolongs Sux)