To examine the physicochemical stability of combinations of propofol-lidocaine mixtures frequently used in clinical practice, we added lidocaine 5, 10, 20, or 40 mg to commercially available 1% propofol 20 mL. To assess chemical stability, propofol concentrations were determined by gas chromatography assay for 24 h after preparation of the mixture. In addition, scanning electron microscopy was used to determine the maximum detectable droplet size in randomly selected fields. Macroscopically, separate, colorless layers were first seen at 3 and 24 h after the addition of 40 and 20 mg of lidocaine to propofol, respectively, whereas the mixture with 5 or 10 mg of lidocaine was macroscopically stable. Propofol concentrations in the mixture with 40 mg of lidocaine decreased linearly and significantly from 4 to 24 h after preparation, whereas those combined with other lidocaine doses were unchanged compared with baseline concentrations. Scanning electron microscopy showed that droplets with diameters >or=5 microm first appeared 30 min after the addition of 40 mg of lidocaine to propofol, and the emulsion droplets were enlarged in a time- and dose-dependent fashion. Our results indicate that the addition of lidocaine to propofol results in a coalescence of oil droplets, which finally proceeds to a visible separate layer. Depending on the dose of lidocaine and the duration between its preparation and administration, this combination may pose the risk of pulmonary embolism. IMPLICATIONS: The addition of lidocaine to propofol results in time- and dose-dependent increases in oil droplet diameters in emulsion. This mixture is physicochemically unstable over time and may cause pulmonary embolism, depending on the dose of lidocaine.
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