Department of Laboratory Medicine, University of California-San Francisco, San Francisco, California 94107, USA.
Anesthesiology. 2012 Feb;116(2):334-9. doi: 10.1097/ALN.0b013e318242a5f1.
Lipid emulsion infusion reverses cardiac toxicity of local anesthetics. The predominant effect is likely creation of a "lipid sink." This in vitro study determined the extent to which Intralipid® (Fresenius Kabi, Uppsala, Sweden) and Lipofundin® (B. Braun Melsungen AG, Melsungen, Germany) sequester anesthetics from serum, and whether it varies with pH.
Bupivacaine, ropivacaine, and mepivacaine were added to human drug-free serum (pH 7.4) at 10 μg/ml. The lipid emulsions were added, and the mixture shaken and incubated at 37°C. Lipid was removed by ultracentrifugation and drug remaining in the serum measured. Additional experiments were performed using 100 μg/ml bupivacaine and at pH 6.9.
Lipofundin® extracted all three anesthetics to a greater extent than Intralipid® (34.7% vs..22.3% for bupivacaine, 25.8% vs..16.5% for ropivacaine, and 7.3% vs..4.7% for mepivacaine). By increasing either concentration of bupivacaine or lipid, there was an increase in drug extraction from serum. Adjusting the pH to 6.9 had no statistically significant effect on the percentage of bupivacaine sequestered.
Bupivacaine, ropivacaine, and mepivacaine were sequestered to an extent consistent with their octanol:water partition constants (logP). In contrast with previous studies of extraction of lipids from buffer solutions, an emulsion containing 50% each of medium- and long-chain triglycerides extracted local anesthetics to a greater extent from human serum than one containing exclusively long-chain triglycerides, calling into question recent advanced cardiac life support guidelines for resuscitation from anesthetic toxicity that specify use of a long-chain triglyceride. The current data also do not support recent recommendations to delay administration until pH is normalized.
脂质乳剂输注可逆转局部麻醉剂的心脏毒性。主要作用可能是创建“脂质汇”。本体外研究旨在确定 Intralipid®（Fresenius Kabi，Uppsala，瑞典）和 Lipofundin®（B. Braun Melsungen AG，Melsungen，德国）从血清中隔离麻醉剂的程度，以及其是否随 pH 值而变化。
将布比卡因、罗哌卡因和甲哌卡因以 10 μg/ml 的浓度加入人无药物血清（pH 7.4）中。加入脂质乳剂，混合并在 37°C 下孵育。通过超速离心去除脂质，并测量血清中残留的药物。使用 100 μg/ml 布比卡因和 pH 6.9 进行了额外的实验。
与 Intralipid®相比，Lipofundin®提取了所有三种麻醉剂（布比卡因分别为 34.7%和 22.3%，罗哌卡因分别为 25.8%和 16.5%，甲哌卡因分别为 7.3%和 4.7%）。通过增加布比卡因或脂质的浓度，从血清中提取药物的量增加。将 pH 调整至 6.9 对布比卡因的结合百分比没有统计学意义的影响。
布比卡因、罗哌卡因和甲哌卡因的结合程度与其辛醇：水分配系数（logP）一致。与先前从缓冲液中提取脂质的研究不同，含有 50%中链和长链甘油三酯的乳剂从人血清中提取局部麻醉剂的程度大于仅含有长链甘油三酯的乳剂，这对最近关于使用长链甘油三酯复苏麻醉毒性的高级心脏生命支持指南提出了质疑。目前的数据也不支持最近的建议，即在 pH 值正常化之前延迟给药。
