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Favourable properties supporting propofol's use for continuous sedation:

  • Propofol has a rapid onset of action (approx. 30 seconds in a normal adult) though this may be slightly prolonged in low cardiac output states. It is short acting (a single dose will last approximately 5-10 minutes).

  • There is minimal accumulation with prolonged infusion, also making it the agent of choice where neurological assessment is of concern.

    • The reason for this is that propofol has a relatively stable and short context-sensitive half time (3-18 minutes, see below) and it has inactive metabolites.

  • There is no known change in propofol's pharmokinetic profile in patients with hepatic or renal dysfunction making it the preferred agent in these circumstances.

 

Context-sensitive half time

  • This is a useful concept to begin to become familiar with, though you do not need to know a lot about it at this stage.

  • It is defined as the time for the plasma concentration of a drug to fall by half after discontinuation of an infusion of the drug that was aimed at maintaining a steady state.

  • It is a useful concept because it helps explain the duration of action of a drug given by infusion after stopping the infusion.

  • It reflects several pharmacokinetic principles:

    • Firstly, that as any drug is infused into the body more of the drug will deposit in the body's tissues (i.e. accumulate) the longer the duration of infusion (or "context" as it is known) until the body's tissues are completely saturated. Once the drug infusion is stopped this stored drug will then redistribute back into the blood and maintain its effects.

    • Secondly, every drug of course accumulates to differing extents which is largely influenced by the physicochemical properties of the drug.

    • Thirdly, drugs are removed from the blood through two major mechanisms:

      • Distribution: where the drug moves from the blood into the tissues, e.g. fat.

      • Excretion: where the drug is either metabolised (e.g. by the liver) or excreted from the body unchanged (e.g. in urine). Whether the metabolites are active or not is also important.

  • The context-sensitive half time is determined by the interaction of all these principles.

  • It is mainly important to know whether a drug has a short, stable context-sensitive half time, e.g. remifentanil, which will wear off very quickly and predictably after stopping the infusion or a more prolonged, variable context-sensitive half time, e.g. fentanyl, which will take much longer to wear off and is less predictable.

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