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

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

Propofol infusion rate does not affect local pain on injection.

BACKGROUND: Local pain at the site of an i.v. injection of propofol is a well-known problem, particularly in infants. This randomised investigator-blinded crossover study was designed to assess the effect of the i.v. bolus infusion rate on propofol-induced pain at the site of injection. METHODS: Thirty unpremedicated patients scheduled for ear-nose-throat or plastic surgery at Malmö University Hospital, Sweden, were given two consecutive 2.0 ml injections of propofol 10 mg/ml (Diprivan, AstraZeneca, Sweden/UK), at different infusion rates (0.2 or 1.0 ml/s), immediately before induction of general anesthesia. Half of the patients (n=15) received the first bolus of propofol over 2 s and the second bolus over 10 s, and the other half (n=15) had their injections in reversed order. After each injection, the patient was asked by an investigator to indicate pain intensity on a visual analog scale (VAS) and to report the times of the appearance, maximum point and disappearance of pain. The injections were given approximately 2 min apart. The investigators scoring pain intensity, as indicated by the patients on a 10-point numerical rate scale, were blinded to the order in which the injections were given, as were the patients themselves. RESULTS: There were no statistically significant differences in the incidence (both 86%) of intensity (median; 25th; 75th percentiles, in VAS units: 3.1; 1.0; 5.3 and 3.3; 1.4; 5.0, respectively) or duration (66+/-31 and 73+/-26 s, respectively) of pain between the faster (1.0 ml/s) and slower (0.2 ml/s) bolus infusion rates of propofol studied. CONCLUSIONS: We conclude that the i.v. bolus infusion rate of propofol does not influence drug-induced local pain on injection, at least not within the infusion rate interval studied. Therefore, adjusting i.v. injection speed does not seem to be a clinically useful tool for reducing the intensity or duration of propofol-induced pain at the site of administration

Less local pain on intravenous infusion of a new propofol emulsion

Background: Local pain at the site of intravenous (iv) injection of propofol remains a considerable problem in clinical anaesthesiology, and particularly so in infants. The aim of the present study was to compare the influence of two different emulsions of propofol on local pain following iv administration. Methods: Eighty adult patients (ASA I-II) scheduled for ear-nose-throat or plastic surgery were randomly allocated into two study groups: A and B. A 1.0-mm teflon cannula (BD, Helsingborg, Sweden) was inserted into a dorsal vein on each hand. Each patient was given two 3.0-ml iv bolus injections of two different propofol emulsions of 10 mg ml(-1) over 2 s, one in each cannula, at 5-min intervals. The first study drug administered was Diprivan((R)) (AstraZeneca, Sodertalie, Sweden) in group A (n = 34) and Propofol-Lipuro (Braun, Melsungen, Germany) in group B (n = 39). Each patient was then asked by a blinded investigator to score maximal pain intensity on a visual analogue scale (VAS). Results: The maximal intensity of propofol-induced local pain was significantly (P < 0.0001) lower after Propofol-Lipuro than after Diprivan((R))- median 1 (25th percentile: 0; 75th percentile: 2) range 0-6 vs. 3 (0; 5) 0-9 VAS units. Conclusion: The considerably lower intensity of local pain found to be associated with iv administration of the new drug formula Propofol-Lipuro indicates that emulsions of propofol based on medium- and long-chain triglycerides have a clinical advantage over traditional ones for induction of anaesthesia

Sustained intravascular exposure to propofol does not prolong pain at the site of injection

Background Pain at the site of intravenous injection of propofol is a common clinical finding. This double-blind, randomized cross-over study was designed to evaluate whether venous occlusion applied during injection of a low dose of propofol reduces the intensity of pain at the site of injection compared with no occlusion. Methods Bilateral 0.5-ml injections of an emulsion containing 10 mg/ml of propofol were given over 30 s in 75 adult surgical patients. Each patient was given one injection with and one without 60-s occlusion of the cannulated vein with a 10-min interval, and asked to score the maximal pain intensity on a visual analogue scale (VAS). Results The maximal pain intensity [median (25th percentile; 75th percentile), range] at the site of injection was 0.5 (0; 3.5), 0-8.0 VAS units with venous occlusion and 0.5 (0; 1.4), 0-6.0 VAS units without occlusion (P = 0.042). Pain was first reported within 20 s regardless of the study regimen and was not prolonged by local venous occlusion. Conclusions Venous occlusion augments pain intensity at the site of propofol injection without prolonging pain, implying that propofol-induced pain is determined more by the blood concentration than by the duration of intravascular exposure. The low intensity of pain induced by low-dose propofol and the fading of pain despite sustained exposure suggest that initial low-dose administration of propofol should be evaluated for the attenuation of local pain induced by higher intravenous doses of propofol