Fluoropolymer-Based Emulsions for the Intravenous Delivery of Sevoflurane
Autor: | Fast, Jonathan P., Perkins, Mark G., Pearce, Robert A., Waters, Ralph M., Mecozzi, Sandro |
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Jazyk: | angličtina |
Rok vydání: | 2008 |
Předmět: |
Male
Methyl Ethers Fat Emulsions Intravenous Fat emulsion Median lethal dose Sevoflurane Article Lethal Dose 50 Rats Sprague-Dawley Route of administration chemistry.chemical_compound Medicine Animals Fluorocarbons business.industry Volatile anesthetic Rats Sprague dawley Anesthesiology and Pain Medicine chemistry Anesthesia Emulsion Injections Intravenous Fluoropolymer Emulsions business Anesthetics Intravenous medicine.drug |
Popis: | Background The intravenous delivery of halogenated volatile anesthetics has been previously achieved using phospholipid-stabilized emulsions, e.g., Intralipid. However, fluorinated volatile anesthetics, such as sevoflurane, are partially fluorophilic and do not mix well with classic nonfluorinated lipids. This effect limits the maximum amount of sevoflurane that can be stably emulsified in Intralipid to 3.5% vol/vol. This is a significant limitation to the potential clinical use of Intralipid-based emulsions. Methods The authors prepared a 20% vol/vol sevoflurane emulsion using a novel fluorinated surfactant and tested its effectiveness and therapeutic index by administering it to male Sprague-Dawley rats via intravenous injection into the jugular vein. The median effective dose to induce anesthesia (ED50), the median lethal dose (LD50), and the therapeutic index (LD50/ED50) were determined. Anesthesia was measured by loss of the forepaw righting reflex. Results The ED50 and LD50 values were found to be 0.41 and 1.05 ml emulsion/kg body weight, respectively. These lead to a therapeutic index of 2.6, which compares favorably with previously determined values of emulsified isoflurane, as well as values for propofol and thiopental. Conclusions A novel semifluorinated surfactant was able to considerably increase the maximum amount of stably emulsified sevoflurane compared with Intralipid. These formulations can be used to rapidly induce anesthesia with bolus dosing from which recovery is smooth and rapid. |
Databáze: | OpenAIRE |
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