A Mixed (Long- and Medium-chain) Triglyceride Lipid Emulsion Extracts Local Anesthetic from Human Serum In Vitro More Effectively than a Long-chain Emulsion

• Published in: Anesthesiology (Philadelphia) 2012-02, Vol.116 (2), p.334-339
• Main Authors: WEIMING RUAN, FRENCH, Deborah, WONG, Alicia, DRASNER, Kenneth, WU, Alan H. B
• Format: Article
• Language: English
• Subjects: Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthetics, Local - administration & dosage; Anesthetics, Local - metabolism; Biological and medical sciences; Drug Combinations; Emulsions - administration & dosage; Fat Emulsions, Intravenous - administration & dosage; Fat Emulsions, Intravenous - metabolism; Humans; Medical sciences; Phospholipids - administration & dosage; Phospholipids - blood; Sorbitol - administration & dosage; Sorbitol - blood; Soybean Oil - administration & dosage; Soybean Oil - blood; Treatment Outcome; Triglycerides - administration & dosage; Triglycerides - blood
• ISSN: 0003-3022; 1528-1175
• 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.