FRCA Notes

Context Sensitive Half-Time

  • Context sensitive half-time can be defined as:

    • The time taken for the plasma concentration of a drug to fall by half, after the cessation of an infusion designed to maintain a steady plasma concentration

  • There is no definition for 'context' but it is generally used to identify the fact that the half time of a drug is usually altered by the duration of its infusion
  • NB, context sensitive half life predicts the time that it takes for the plasma concentration to fall by half, not the time until the patient wakes up

CSHT graph

Adapted from WFSA

Remifentanil

  • Remifentanil is the exceptional drug because it is context insensitive
  • Its half-time remains fairly constant despite long infusion times
  • This is because it is rapidly cleared by plasma esterases

Fentanyl

  • Fentanyl's CSHT curve is more complex; it is sigmoid in shape
  • At 2hrs it has the same CSHT as alfentanil (50mins)
  • It continues to rise such that at 8hrs it has a CSHT of 280mins
  • By 48hrs of infusion, it has a CSHT of 10 - 12hrs
  • As the duration of the infusion continues to rise, fentanyl does not because context-insensitive

Alfentanil

  • The CSHT rises such that it is 50mins after 2hrs
  • However after 2hrs the curve is horizontal i.e. after 2hrs of infusion, alfentanil is relatively context insensitive
  • After 8hrs, its CSHT is only 64mins

Propofol

  • The CSHT curve rises smoothly such that it is 15mins after a 2hr infusion
  • This rises to a CSHT of 40mins after 8hrs
  • Propofol does not become context insensitive; it's CSHT continues to rise with ongoing infusion
  • However the CSHT remains fairly short even after long infusions

Thiopentone

  • The CSHT rises rapidly such that it is 50mins after only 30mins of infusion
  • It continues to rise like a build-up exponential curve
  • At 8hrs it is 150mins
  • Does not become context insensitive

  • The patient may need the plasma concentration to fall by a certain percentage in order to awaken
  • Decrement time can be defined as:

    • The time taken for the plasma concentration of a drug to fall to a specified percentage of its formed value after cessation of an infusion designed to maintain steady plasma concentration

  • Context senstive half-time is therefore the decrement time when the specified percentage is 50%
  • For propofol, the decrement time is commonly quoted as the time taken to reach a plasma concentration of 1.2μg/ml, as this is the level that patient wake up is thought to occur at (in the absence of other sedative/anaesthetic agents)