This article reviews the chemical properties and preparations of propofol, the postulated mechanisms for causing injection pain and methods that have been investigated to minimise the incidence of pain.

Chemical properties and preparation of propofol

Propofol is a hindered phenol that is chemically dissimilar to any other compounds used in anaesthesia. It has a molecular weight of 178 Da and is a colourless liquid at room temperature. The compound absorbs light in the ultraviolet range of the electromagnetic spectrum (lmax ˆ 275 nm) and fluoresces at 310 nm with an excitation wavelength of 276 nm.

Fluorescence detection with high-performance liquid chromatography forms the basis of the blood concentration assay technique. Propofol was initially formulated as a 2% solution in 16% polyethylated castor oil (Cremophor EL) and 8% ethanol because of its low aqueous solubility and then as a 1% solution in 16% Cremophor EL. However, it was reformulated in a soyabean emulsion because of concerns over the high incidence of injection pain with this preparation and in order to avoid Cremophor-related reactions [14]. The currently available preparation is a 1% w/v aqueous emulsion containing 10% w/v soya bean oil (as a solubilising agent), 1.2% w/v egg phosphatide (as an emulsifying agent) and 2.25% w/v glycerol (to make the preparation isotonic), sealed under nitrogen. The pH is 6–8.5 and the pKa of the drug in water is 11.

The preparation is compatible with injection into fast running infusions of 5% dextrose, 4% dextrose/0.18% sodium chloride and 0.9% sodium chloride. It should be stored below 25 8C to prevent degradation. Mechanisms of pain on injection of propofol Many factors appear to affect the incidence of pain on propofol injection. These include the site of injection, size of vein, speed of injection, propofol concentration in the aqueous phase and the buffering effect of blood. These factors will be discussed in this section.