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Since its introduction in the early 1980s, propofol has been a cornerstone of anesthetic practice. Propofol is an intravenous anesthetic used for the induction and maintenance of general anesthesia and for sedation in and outside of the operating room.


The structure of propofol is 2, 6-diisopropylphenol (Figure 53-1). As an alkylphenol derivative, propofol exists as an oil at room temperature. Because it is highly lipophilic and insoluble in aqueous solution, propofol is formulated in a rather complicated 1% (10 mg/mL) lipid solution, containing 10% soybean oil, 2.25% glycerol, 1.2% purified egg phosphatide, and 0.0005% sodium edetate (antimicrobial).


Structure of propofol.

The incidence of anaphylactic reactions to propofol is around 1:20 000, but more common in patients with eczema and/or multiple food allergies. Common clinical practice is to avoid administering propofol to patients with soybean, peanut, and egg allergies due to its formulation with similar products. Despite this “clinical wisdom,” most egg allergies are to egg protein (whites) rather than the egg phosphatide (yolk) that makes up the propofol solution. Avoiding the use of propofol in those with egg allergy may not be warranted.


Propofol has a very favorable pharmacokinetic profile (Table 53-1). After a single bolus injection, it is quickly redistributed and eliminated. It is rapidly metabolized in the liver by conjugation to glucuronide and sulfate to produce inactive water-soluble compounds that are excreted by the kidneys. Clearance of propofol exceeds liver metabolism, suggesting extra-hepatic metabolism. This fact is confirmed during the anhepatic phase of liver transplant surgery. The kidneys account for roughly 30% of total body clearance. The lungs have also been implicated in propofol metabolism and are responsible for 30% uptake and first-pass metabolism after bolus dose. Propofol exhibits concentration-dependent inhibition of cytochrome P450, specifically CYP 3A4. It may alter metabolism of other drugs that are metabolized by this system, such as opiates and midazolam, which are both often coadministered during induction.

TABLE 53-1Pharmacokinetic Profile for Propofol

Fospropofol (phosphono-O-methyl 0-2, 6-diisopropylphenol) is a prodrug of propofol with a slightly longer time to peak effect and a prolonged effect. Fospropofol undergoes hydrolysis by endothelial cell ...

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