Fentanyl DOA with multiple boluses

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agammaglobulin

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Question regarding Fentanyl and multiple boluses. I know Fentanyl has a S-shaped context sensitive half life with infusion, but more practically, after what dose of Fentanyl do you start to think of it as a more long acting drug? I assume there is a point in longer cases where additional Fentanyl will stay on longer than giving additional Hydromorphone. Is this after 250mcg? 500mcg?

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i think it would depend on the size and body composition of the patient - some people have large stores for lipid soluble drugs.

i suspect once you get to about 700mcg in the average 80kg patient ... you're probably getting offset by metabolism rather than distribution ... but I don't have any evidence for that, that's just what i think based on observation.
 
Not quite so simple.

When you give fentanyl, the drug goes to the central compartment (blood vessels space), then distributes to both the target space and peripheral compartments (most importantly the fat compartment for lipid soluble drug like fentanyl).

The initial central compartment concentration gives you the initial short lived potent analgesic effect. This concentration drops rapidly following an exponential decay pharmacokinetic, mostly due to redistribution to the fat. Once fentanyl bolus or infusion is stopped and the drug is allowed to redistribute, you now have a fentanyl depot in your fat, that slowly releases fentanyl to the bloodstream with a slow zero order kinetic.

There was a clinical study on this back from the 80s, Of a bolus of fentanyl, on top of the initial predicted short acting action, you get ~10% of that bolus sticking around as a long acting drug. So if you give 500mcg of fentanyl bolus straight up, you can expect ~50mcg equivalent of that drug to stick around for hours.

Infusion administration is time dependent. it takes hours to days to completely equilibrate a steady dose infusion of fentanyl, but the entire time, you're equilibrating with the fat store, and your context sensitive half life keeps getting longer.

Note though: your response to fentanyl will be modulated by developing tolerance. So... you may not actually get the full analgesic effect simply predicted by pharmacokinetics.
 
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