KETAMINE

PRESENTATION
PK, PD
 KETAMINE
• Ketamine is a phencyclidine derivative
• Ketamine is presented as a racemic mixture or as the single
S(+) enantiomer, which is two to three times as potent as the
R(–) enantiomer.
• It is soluble in water forming an acidic solution (pH 3.5–5.5).
• Three concentrations are available: 10, 50 and 100 mg.ml−1 ,
and it may be given intravenously (1–2 mg.kg−1 ) or
intramuscularly (5–10 mg.kg−1 ) for induction of anaesthesia.
• Three concentrations are available: 10, 50 and 100 mg.ml−1 ,
and it may be given intravenously (1–2 mg.kg−1 ) or
intramuscularly (5–10 mg.kg−1 ) for induction of anaesthesia.

• It has gained popularity at low doses in combination with

other analgesics and may be particularly useful in those
with an element of chronic pain
EFFECTS OF KETAMINE

CVS

• Produces sympathetic nervous system stimulation,

increasing circulating levels of adrenaline and noradrenaline
• Heart rate, cardiac output, blood pressure and myocardial
oxygen requirements are all increased
• S(+) ketamine produces less direct cardiac depression in
vitro compared with R(−) ketamine
• Racemic ketamine has been shown to block ATP-sensitive
potassium channels; , S(+) ketamine does not
RESPIRATORY

• Respiratory rate may be increased and the laryngeal

reflexes relatively preserved.
• A patent airway is often, but not always, maintained, and
increased muscle tone associated with the jaw may
precipitate airway obstruction.
• It causes bronchodilation and may be useful for patients
with asthma
CNS

• Produces a state of dissociative anesthesia that is

demonstrated on EEG by dissociation between the
thalamocortical and limbic systems
• In addition, intense analgesia and amnesia are produced.
• The α rhythm is replaced by θ and δ wave activity
• Does not induce anaesthesia in one arm–brain circulation
time – central effects becoming evident 90 seconds after an
intravenous dose
• Cerebral blood flow, oxygen consumption and intracranial
pressure are all increased
Others

• When given by infusion at doses low enough to avoid side effects

ketamine may still retain useful analgesic effects and reduce morphine
consumption
• Nausea and vomiting occur more frequently than after propofol or
thiopental.
• Salivation is increased requiring anticholinergic premedication
• High-dose use has been associated with severe interstitial cystitis that
may require cystectomy
KINETICS
• Following an intravenous dose the plasma concentration falls in a bi-
exponential fashion.
• The initial fall is due to distribution across lipid membranes while the slower
phase is due to hepatic metabolism.
• Ketamine is the least protein-bound (about 25%) of the intravenous
anaesthetics and is demethylated to the active metabolite norketamine by
hepatic P450 enzymes.
• Norketamine (which is 30% as potent as ketamine) is further metabolized to
inactive glucuronide metabolites.
• The conjugated metabolites are excreted in the urine