Ketamine
Isomers
PK
dosages
effects
100

derived from

phencyclidine (PCP)

"angel dust"

100

R-ketamine

right-handed optical isomer

100

onset/peak

30 sec - 1min

IV - 1 min

IM - 5 min

100

induction

0.5-1.5 mg/kg IV

4-8 mg/kg IM

100

CV

SNS stimulation, increases plasma EPI and Norepi levels

*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

200

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

200

Racemic Mixture

inhibit uptake of catecholamines back into the postganglionic sympathetic nerve endings

*cocaine-like effect

less fatigue and cognitive impairment

200

duration

10-20 minutes

full consciousness 60-90 min

200

maintenance

0.2-0.5 mg/kg IV
4-8 mg/kg IM

200

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

300

advantages of ketamine over propofol and etomidate

no pain on injection (no lipid emulsion vehicle)

profound analgesia at subanesthetic doses

300

S(+) ketamine

left-handed optical isomer

more intense analgesia

more rapid metabolism and recovery

less salivation

lower incidence of emergence reaction

300

Vd

3L/kg

highly lipid soluble (5-10x thiopental)


300

subanesthetic 

0.2-0.5 mg/kg

300

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

400

disadvantages of ketamine

frequency fo emergence delirium

abuse potential

400

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

400

clearance

1L per minute

400

postop sedation - pedi <3 surgery

1-2 mg/kg/hr

400

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

500

perservative of ketamine

benzethonium chloride - inhibits the neuronal ACh

500

other receptors 

opioid (mu, delta, kappa, weak sigma), monoaminergic, muscarinic, VG Na+, L-type Ca++ and neuronal nicotinic ACh

weak GABA-A receptor

500

metabolism/excretion

CYP450 -> norketamine: active metabolite (1/3 potency)

E 1/2 = 2-3 hrs

kidneys

500

neuraxial 

epidural 30 mg

spinal 5-50 mg in 3 mL of saline

500

other systems

inhibits platelet aggregation

inhibits cytosolic free calcium concntrations (enhanves Non-depolarizing NMBDs)

inhibits plasma cholinesterases (prolongs Sux)

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