{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:25:01Z","timestamp":1776990301244,"version":"3.51.4"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,12,10]],"date-time":"2008-12-10T00:00:00Z","timestamp":1228867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:sec><jats:label\/><jats:p> <jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold> <\/jats:p><jats:p>\u2022\u2003Aqueous free propofol in lipid emulsion elicits pain.<\/jats:p><jats:p>\u2022\u2003No data on the incidence and severity of injection pain for Aquafol\u2122 (Daewon Pharmaceutical Co., Ltd, Seoul, Korea), a lipid\u2010free microemulsion propofol, are available.<\/jats:p><jats:p>\u2022\u2003Two hypotheses involving plasma bradykinin generation have been proposed to explain propofol\u2010induced pain; one implicates aqueous free propofol, the other implicates the lipid solvent.<\/jats:p><jats:p> <jats:bold>WHAT THIS STUDY ADDS<\/jats:bold> <\/jats:p><jats:p>\u2022\u2003Microemulsion propofol produces more frequent and severe pain on injection, an effect that may be attributable to the high concentration of aqueous free propofol.<\/jats:p><jats:p>\u2022\u2003There was no evidence that plasma bradykinin generation caused propofol\u2010induced pain.<\/jats:p><jats:p>\u2022\u2003In addition, agents known to prevent propofol\u2010induced pain did not decrease aqueous free propofol concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>AIMS<\/jats:title><jats:p>To evaluate the incidence and severity of injection pain caused by microemulsion propofol and lipid emulsion propofol in relation to plasma bradykinin generation and aqueous free propofol concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Injection pain was evaluated in 147 patients. Aqueous free propofol concentrations in each formulation, and in formulation mixtures containing agents that reduce propofol\u2010induced pain, were measured by high\u2010performance liquid chromatography. Plasma bradykinin concentrations in both formulations and in their components mixed with blood sampled from six volunteers were measured by radioimmunoassays. Injection pain caused by 8% polyethylene glycol 660 hydroxystearate (PEG660 HS) was evaluated in another 10 volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The incidence of injection pain [visual analogue scale (VAS) &gt;30\u2003mm] caused by microemulsion and lipid emulsion propofol was 69.7 and 42.3% (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001), respectively. The median VAS scores for microemulsion and lipid emulsion propofol were 59 and 24\u2003mm, respectively (95% confidence interval for the difference 12.5, 40.0). The aqueous free propofol concentration of microemulsion propofol was seven times higher than that of lipid emulsion propofol. Agents that reduce injection pain did not affect aqueous free propofol concentrations. Microemulsion propofol and 8% PEG660 HS enhanced plasma bradykinin generation, whereas lipid emulsion propofol and lipid solvent did not. PEG660 HS did not cause injection pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Higher aqueous free propofol concentrations of microemulsion propofol produce more frequent and severe pain. The plasma kallikrein\u2013kinin system may not be involved, and the agents that reduce injection pain may not act by decreasing aqueous free propofol concentrations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2008.03358.x","type":"journal-article","created":{"date-parts":[[2008,12,11]],"date-time":"2008-12-11T01:11:30Z","timestamp":1228957890000},"page":"316-325","source":"Crossref","is-referenced-by-count":63,"title":["Pain on injection with microemulsion 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