Pain induced by propofol - clinical studies on drug composition and adminstration

Abstract: Over the last 25 years a number of new anaesthetic drugs have been introduced on the market to allow for better patient satisfaction and faster recovery after anaesthesia and sedation. Propofol (2,6-di-isopropylphenol), one of our most common iv anaesthetics, is associated with pleasant sleep and rapid recovery with little postoperative nausea. When used for anaesthetic induction propofol causes severe or even intolerable pain or discomfort on injection in up to 90 % of patients. Pain on injection of propofol is even ranked by anaesthesiologists as the seventh most important clinical problem in modern anaesthesia. The concentration of free propofol within the aqueous phase of the drug formula is believed to be particularly associated with injection pain. The general aim of these studies was to investigate if we could reduce the local pain induced by iv propofol by various clinical measures. Traditional long-chain triglyceride (LCT) emulsions of propofol were used in studies I-III, while a new medium- and long-chain triglyceride (MCT/LCT) formula was used in studies III-V. Both formulas were used and compared in study III. In study I the influence of a carrier fluid was evaluated. Simultaneous iv infusion of carrier fluid was found not to influence pain intensity but to decrease the duration of pain at the site of propofol injection. In study II we investigated the effect of various bolus rates of propofol on pain at site of injection. There were no differences in the incidence, intensity or duration of pain between the faster and slower rates compared. In study III we compared the influence of two different formulas of propofol on local pain at the site of administration. Propofol emulsions based on MCT/LCT were associated with lower pain intensity than those based on LCT only. Study IV was designed to examine if local venous occlusion applied during and immediately after injection of propofol reduces the intensity of pain at the site of injection. Venous occlusion was found to increase the intensity but not the duration of pain at the site of propofol injection, indicating that the pain response to propofol fades during prolonged intravascular exposure. Study V was carried out to examine if pain on injection of propofol can be reduced by previous low-dose administration of propofol by the same iv route. A lower incidence of moderate or severe local pain was induced by propofol after the low dose of propofol had been administered. Our most important results show that formulas of propofol based on MCT/LCT are associated with less pain at the site of iv injection than are traditional LCT formulas. Furthermore the incidence of moderate to severe propofol-induced pain can be reduced by previous injection of a low dose of propofol by the same iv route. These measures can easily be taken by any anaesthetist in virtually any clinical situation not calling for rapid induction of anaesthesia.