Baker Max T, Gregerson Marc S, Martin Sean M, Buettner Garry R
Department of Anesthesia, University of Iowa, Iowa City, USA.
Crit Care Med. 2003 Mar;31(3):787-92. doi: 10.1097/01.CCM.0000053560.05156.73.
Some propofol emulsion formulations contain EDTA or sodium metabisulfite to inhibit microbe growth on extrinsic contamination. EDTA is not known to react with propofol formulation components; however, sulfite has been shown to support some oxidation processes and may react with propofol. This study compared the oxidation of propofol and the formation of free radicals by electron paramagnetic resonance analysis in EDTA and sulfite propofol emulsions during a simulated intensive care unit 12-hr intravenous infusion.
Controlled laboratory study.
University laboratory.
Propofol emulsions (3.5 mL) were dripped from spiked 50-mL vials at each hour for 12 hrs. Two propofol oxidation products, identified as propofol dimer and propofol dimer quinone, were detected in sulfite and EDTA propofol emulsions; however, sulfite propofol emulsion contained higher quantities of both compounds. After initiation of the simulated infusion, the quantities of propofol dimer and propofol dimer quinone increased in the sulfite propofol emulsion, but the lower levels in the EDTA propofol emulsion remained constant. Sulfite propofol emulsion began to visibly yellow at about 6-7 hrs. The EDTA propofol emulsion remained white at all times. The absorbance spectra of the propofol dimer and propofol dimer quinone extracted from sulfite propofol emulsion showed that propofol dimer did not absorb in the visible spectrum, but the propofol dimer quinone had an absorbance peak at 421 nm, causing it to appear yellow. Electron paramagnetic resonance analysis of the propofol emulsion containing metabisulfite revealed that the sulfite propofol emulsion yielded a strong free radical signal consistent with the formation of the sulfite anion radical (SO3*-). The EDTA propofol emulsion yielded no free radical signal above background.
Sulfite from the metabisulfite additive in propofol emulsion creates an oxidative environment when these emulsions are exposed to air during a simulated intravenous infusion. This oxidation results in propofol dimerization and emulsion yellowing, the latter of which is caused by the formation of propofol dimer quinone. These processes can be attributed to the rapid formation of the reactive sulfite free radical.
一些丙泊酚乳剂配方含有乙二胺四乙酸（EDTA）或焦亚硫酸钠以抑制外部污染时的微生物生长。已知EDTA不会与丙泊酚配方成分发生反应；然而，亚硫酸盐已被证明会促进某些氧化过程，并且可能与丙泊酚发生反应。本研究通过电子顺磁共振分析比较了在模拟重症监护病房12小时静脉输注期间，EDTA和亚硫酸盐丙泊酚乳剂中丙泊酚的氧化及自由基的形成情况。
对照实验室研究。
大学实验室。
丙泊酚乳剂（3.5 mL）在12小时内每小时从加样的50 mL小瓶中滴出。在亚硫酸盐和EDTA丙泊酚乳剂中检测到两种丙泊酚氧化产物，分别鉴定为丙泊酚二聚体和丙泊酚二聚体醌；然而，亚硫酸盐丙泊酚乳剂中这两种化合物的含量更高。在模拟输注开始后，亚硫酸盐丙泊酚乳剂中丙泊酚二聚体和丙泊酚二聚体醌的含量增加，但EDTA丙泊酚乳剂中较低的含量保持恒定。亚硫酸盐丙泊酚乳剂在大约6 - 7小时开始明显变黄。EDTA丙泊酚乳剂始终保持白色。从亚硫酸盐丙泊酚乳剂中提取的丙泊酚二聚体和丙泊酚二聚体醌的吸收光谱表明，丙泊酚二聚体在可见光谱中不吸收，但丙泊酚二聚体醌在421 nm处有一个吸收峰，使其呈现黄色。对含有焦亚硫酸钠的丙泊酚乳剂进行电子顺磁共振分析发现，亚硫酸盐丙泊酚乳剂产生了与亚硫酸根阴离子自由基（SO3*-）形成一致的强自由基信号。EDTA丙泊酚乳剂产生的自由基信号不高于背景值。
丙泊酚乳剂中焦亚硫酸钠添加剂中的亚硫酸盐在模拟静脉输注过程中使这些乳剂暴露于空气时会产生氧化环境。这种氧化导致丙泊酚二聚化和乳剂变黄，后者是由丙泊酚二聚体醌的形成引起的。这些过程可归因于活性亚硫酸自由基的快速形成。
