Pharmacology for Anaesthesia and Intensive Care

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9780521704632c08 CUFX213A/Peck 9780521618168 December 28, 2007 10:38

Section IICoredrugs in anaesthetic practice

lower concentrations used. Methohexitone was associated with a greater incidence

of hypersensitivity reactions although these did not appear to be as severe. Its main

metabolite hydroxymethohexitone had only limited hypnotic activity (Table8.3).

Non-barbiturates

Propofol

Presentation

This phenolic derivative (2,6 diisopropylphenol) is highly lipid-soluble and is pre-

sented as a 1% or 2% lipid–water emulsion (containing soya bean oil and purified

egg phosphatide) due to poor solubility in water. It is a weak organic acid with a

pKa = 11 so that it is almost entirely unionized at pH 7.4.

Uses

Propofol is used for the induction and maintenance of general anaesthesia and for

sedation of ventilated patients in intensive care. The induction dose is 1–2 mg.kg−^1

while a plasma concentration of 4–8μg.ml−^1 will maintain anaesthesia.

Effects


Cardiovascular – the systemic vascular resistance falls resulting in a drop in blood

pressure. A reflex tachycardia is rare and propofol is usually associated with a

bradycardia especially if administered with fentanyl or alfentanil. Sympathetic

activity and myocardial contractility are also reduced.


Respiratory – respiratory depression leading to apnoea is common. It is rare to

observe cough or laryngospasm following its use and so it is often used in anaes-

thesia for ease of placement of a laryngeal mask.


Central nervous system – excitatory effects have been associated with propofol

in up to 10% of patients. They probably do not represent true cortical seizure

activity; rather they are the manifestation of subcortical excitatory–inhibitory cen-

tre imbalance. The movements observed are dystonic with choreiform elements

and opisthotonos. Propofol has been used to control status epilepticus.


Gut–some evidence exists to suggest that propofol possesses anti-emetic prop-

erties following its use for induction, maintenance or in subhypnotic doses post-

operatively. Anatagonism of the dopamine D 2 receptor is a possible mechanism.


Pain – injection into small veins is painful but may be reduced if lidocaine is mixed

with propofol or if a larger vein is used.


Metabolic – a fat overload syndrome, with hyperlipidaemia, and fatty infiltration

of heart, liver, kidneys and lungs can follow prolonged infusion.


Miscellaneous – it may turn urine and hair green.