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9780521704632c08 CUFX213A/Peck 9780521618168 December 28, 2007 10:38
Section IICoredrugs in anaesthetic practiceKinetics
Propofol is 98% protein bound to albumin and has the largest volume of distribution
of all the induction agents at 4 l.kg−^1 .Following bolus administration, its duration
of action is short due to the rapid decrease in plasma levels as it is distributed to
well-perfused tissues.
Metabolism is largely hepatic; about 40% undergoing conjugation to a glu-
curonide and 60% metabolized to a quinol, which is excreted as a glucuronide
and sulphate, all of which are inactive and excreted in the urine. Its clearance
exceeds hepatic blood flow suggesting some extra-hepatic metabolism. Owing to
this high clearance, plasma levels fall more rapidly than those of thiopental fol-
lowing the initial distribution phase. Its terminal elimination half-life is 5–12 hours
although it has been suggested that when sampling is performed for longer than
24 hours the figure approaches 60 hours and may reflect the slow release of propo-
fol from fat. During prolonged infusion its context-sensitive half-time increases,
although where the infusion has been titrated carefully, waking may still be relatively
rapid.Toxicity
Propofol has been associated with the unexpected deaths of a small number of
children being ventilated for respiratory tract infection in intensive care. Progressive
metabolic acidosis and unresponsive bradycardia lead to death. The serum was
noted to be lipaemic. While further small studies failed to demonstrate a worse
outcome when propofol was used as sedation for critically ill children, a more recent
study showed a higher overall death rate and the Committee on Safety of Medicines
(CSM) has advised that propofol should be contraindicated for sedation in intensive
care units in children 16 years and younger.
Patients allergic to eggs are usually allergic to egg protein or albumin. The egg
component of the propofol preparation is lecethin, which is a phosphatide, therefore
it is unlikely that allergic reactions are due to these components of its preparation.
Propofol does not appear to be allergenic in patients who are sensitive to soya beans
because all protein within the soya bean oil is removed.
Itdoes not appear to cause any adverse effects when given intra-arterially, although
onset of anaesthesia is delayed.Ketamine
Ketamine is a phencyclidine derivative.Presentation and uses
Ketamine is presented as a racemic mixture or as the single S(+)enantiomer, which
is 2 to 3 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