Propofol context sensitive half life

[Soparklion]

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I'm interested in published data regarding the context sensitive half life of propofol at different infusion rates... I believe that there is a limit, below which there is zero accumulation. But I don't know that limit.

 

[Radetzky]

The maximum context sensitive half time is 40 minutes. Don’t have literature on hand for that sorry.

 

[deleted697535]

Have you searched any of this? There's lots published on this.

And what do you mean by different infusion rates? Csht's definition implies steady state not increasing or decreasing infusions

I have 20 mins in my head for propofol csht but thats UK anesthesia and we're usually drunk and haven't a notion what's going on

 

[epidural man]

Already done by many people. What is your angle that would be different?

 

[BLADEMDA]

Propofol has a context-sensitive half-time that varies between 3 min for a very short infusion to about 18 min after a 12-h infusion. This relatively small variation in context-sensitive half-time, despite a large V3, occurs because excretion is rapid compared with redistribution

Pharmacokinetics of drug infusions

Abstract. In clinical practice, drugs are given by continuous infusion to maintain a predictable pharmacodynamic action. In anaesthesia, the most common ro

academic.oup.com

 

[BLADEMDA]

Propofol
Pharmacology
Propofol is distributed rapidly and induces sedation within 30 to 60 seconds. The context-sensitive half-life is only 2 to 8 minutes. Metabolism is by hepatic conjugation with renal excretion of inactive metabolites. Propofol is a centrally acting neural depressant without any analgesic properties and rapidly crosses the blood-brain barrier to potentiate GABA activity.

Context-Sensitive Half-Life - an overview | ScienceDirect Topics

www.sciencedirect.com

 

[woopedazz]

Not quite sure what you're asking, maybe this helps though:

There is no mathematical "limit" (floor effect) when it comes to the CSHT of propofol, because by definition CSHT is a PK model where the infusion of any amount of drug will produce a positive value (>0 time units). Unless you're actually measuring plasma concentration and not modelling it, in which case, why? Doesn't seem to have any clinical application?
From a clinical perspective: The CSHT is dependent on the effect-site concentration that is being targetted. I assume this is what you're talking about re: lowest infusion rate where the effect-site concentration will approach 0/awake independent of the context (time/duration) of the infusion?
From that, it depends if you want the CSHT of propofol for hypnosis; or the CSHT of propofol for amnesia; or the CSHT of propofol for anxiolysis, etc, etc. You won't find any published data on this because it is too broad and irrelevant when you can do a standardised, high concentration model, and then extrapolate from there. The existing studies only really assess the CSHT of propofol for "MAC" equivalency/BIS scores.

Have a play around with this: Effect Site Concentrations to see if it answers your question.

 

[epidural man]

What you should study, which has not been elucidated well, is how multi drugs effect this multi-compartment model.
In other words, does adding precedex change the pharmacokinetics of propofol? Or visa Versa?