Propofol

By | 2011-06-13

Propofol belongs to a class of drugs known as the hindered phenols, and is unrelated to all other anesthetic agents. The drug is poorly soluble in water and is supplied as an emulsion containing 10 mg propofol, 100 mg soyabean oil, 22.5 mg glycerol and 12 mg purified egg phosphatide per ml. This emulsion contains no preservative and strongly supports bacterial growth. Consequently, ampoules must be disposed of within 8 hours of being opened. Multidose vials with rubber bungs are now licensed for veterinary use, but the only advantage of these over conventional ampoules is that the possibility of shards of glass entering the emulsion and subsequently being drawn up into a syringe is eliminated. Once the rubber has been penetrated, the emulsion still has to be disposed of within 8 hours. A novel, lipid free micro-emulsion of propofol with antimicrobial preservatives is now available in multidose bottles with a shelf life of 28 days (PropoClear®).

Central nervous effects: Experimentally, propofol has a slightly slower onset time than thiopental, but this is not usually particularly obvious in the clinical setting. Induction of general anesthesia is usually smooth, although muscle twitching and tremors can occur under propofol anesthesia, but usually diminish with time or with administration of inhalational agents. Although the drug is non-irritant with perivascular administration, pain on intravenous injection is common in humans. This appears to be less problematic in animals and occurs only rarely. Propofol appears to have both pro-convulsant and anticonvulsant effects and, although it has been suggested that the drug be avoided in epileptic patients, it has been used for the treatment of status epilepticus. Current opinion appears to be that propofol can be used safely in epileptic animals.

Cardiovascular effects: The cardiovascular effects of propofol in both dogs and cats are similar to those of thiopental; dose-related vasodilation occurs with a lesser contribution from direct myocardial depression. Unlike thiopental, propofol does not sensitise the heart to catecholamines. Respiratory effects: The degree of respiratory depression with propofol is, again, similar to that of thiopental, but post-induction apnoea is more common with the former. Propofol may also result in transient cyanosis at induction in a minority of patients, and this is attributed to opening up of vascular shunts within the lungs.

Propofol has a quick onset and smooth, rapid recovery, due both to redistribution and rapid metabolism. Although the latter occurs primarily in the liver, there is evidence that extrahepatic metabolism of propofol also occurs, probably in the lungs, but possibly also in the kidneys. It is useful for anesthesia of sighthounds, since recovery is not delayed, unlike the situation with thiopental. Due to the rapid clearance from the body, propofol is not only suitable for use as a single intravenous induction agent, but can also be used in dogs for maintenance of anesthesia, either by ‘top-up’ injection or constant intravenous infusion. In addition, the drug can be delivered at subanesthetic infusion rates to maintain sedation for prolonged periods (for instance, in dogs in intensive care). It is less suitable for maintenance of anesthesia in cats, since the feline liver is much slower at metabolising the drug. Indeed, Heinz body formation, due to oxidative injury of red blood cells, has been reported in cats following consecutive day anesthesia with propofol, resulting in anorexia, malaise and diarrhoea, and is due to the cats’ relative inability to metabolise phenolic compounds.

Propofol is licensed for use in dogs and cats, and has largely superseded thiopental as the commonest induction agent in small animal practice, due both to the potential advantages of propofol (e.g. smoother recovery) and the inability to obtain adequate supplies of thiopental. In the UK, propofol is also more commonly used than alfaxalone, possibly due to a relative lack of familiarity with the latter, but probably also due to the significantly higher cost of alfaxalone.

The main advantage of propofol is the rapid, smooth recovery with minimal ‘hangover’ – particularly useful for short procedures – while the main disadvantage is the potential for contamination of the ampoule or vial.

In no way should propofol be considered a ‘safe’ anesthetic agent; in terms of its cardiovascular and respiratory effects, it is no better than many of the other agents currently available.

Propofol – Summary

Indications

Induction of general anesthesia

Long-term sedation in dogs

Side effects

Cardiovascular depression

Respiratory depression

Occasional muscle twitching or tremors

Heinz body formation (cats)

(Contamination of ampoule or vial)

Contra-indications

Inability to secure airway

Egg allergy (emulsion formulation)