Context-Sensitive Half-Time in Anaesthetic Practice

Anaesthesia essentials, half time versus half life

1. Context-Sensitive Half-Time (CSHT) in Anaesthetic Practice Dr. Monica Jain Sr. Professor And Head Department Of Pharmacology SMS Medical College, Jaipur

2. Definition The context-sensitive half-time is the time required for blood or plasma concentrations of a drug to decrease by 50% after discontinuation of drug administration. It is a useful concept because it helps explain the duration of action of a drug given by infusion after stopping the infusion.

3. Why is it needed? It reflects several pharmacokinetic principles: First , 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.

4. Second , every drug accumulates to differing extents, which is largely influenced by the physicochemical properties of the drug. Third , 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 metabolized (e.g., by the liver) or excreted from the body unchanged (e.g., in urine). Whether or not the metabolites are active is also important

5. Where is it needed? The context-sensitive half-time is determined by the interaction of all these principles. It is mainly important to know in Anesthetic Practice 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

6. How is it possible to determine? The context-sensitive half-time is a function of the duration of drug administration and may only be estimated by computer simulation It is more relevant than other isolated pharmacokinetic parameters to understanding the kinetics of drug concentrations

7. How is CSHT different from half-life?

8. The Truth: Two half-lives viz , Alpha and Beta Two  half - lives  can be described: the alpha half - life , the rate of decline in plasma concentrations due to the process of drug redistribution from the central to the peripheral compartment, and the  beta half - life , the rate of decline due to the process of drug elimination due to metabolism (it is the elimination half-life)

9. From this, it is clear that the α half-life  and the β half-life are going to be substantially different. This has substantial relevance to the kinetics of drug infusions, specifically to their context-sensitive half time. The closer the infusion is to steady-state concentration, the closer to the β half-life its context sensitive half time.

10. The context-sensitive half-time cannot be predicted by the elimination half-life (a measure of the time needed for actual drug metabolism or elimination) because it also depends on drug distribution

11. Half - life :  Propofol  is bi- phasic with its initial  half - life  being relatively quick, around 40 minutes, and its terminal  half - life  usually being 4 to 7 hours.  Context - sensitive half -time may be up to 1-3 days after a 10-day infusion. The clinical effect of  propofol  is much shorter in duration