Single Intravenous Injection Of Propofol - Isoflurane Ether Emulsified Mixture Of Ed In Rats <sub> 50 </ Sub> And Ld <sub> 50 </ Sub> Determination

Background: It has been several decades since the first trial on intravenous administration of volatile anesthetics emulsified in lipid was reported by Krantz et al in 1962. Recently, we established the method of preparing emulsified isoflurane of proper concentration in 30% intralipid. The efficacy and safety of this formulation has been proved in animals (rats, dogs, et al.). Moreover, this formulation was found to have a short time for both induction and recovery when compared with propofol. In the present study, we tried to emulsify isoflurane and propofol together in intralipid for intravenous injection. We assumed such a blend might provide a faster induction and recovery profile than propofol alone and might have some potential advantages in anesthesia. The ED₅₀ (half effective dosage) and LD₅₀ (half lethal dosage) of the blends were determined in SD rats by a single intravenous bolus injection to evaluate grossly the efficacy and safety of this formulation and provide some clues for further researches. Materials and Methods: Two blends were used in this study. One contains propofol 10mg/ml and isoflurane 40mg/ml; the other contains propofol 5mg/ml and isoflurane 40mg/ml. Both were prepared in 10% intralipid. The ED₅₀ and LD₅₀ of propofol (10mg/ml), emulsified isoflurane (120mg/ml) and the two blends were determined with Dixon's up-and-down method in SD rats by a bolus intravenous injection through their tail vein. The loss of forepaw righting reflex was defined as criterion of anesthesia and the disappearance of ECG waveform as the criterion of death. Results: Average weights of ratswere similar in all groups. The ED50 was 0.63ml/kg for propofol alone, 0.62ml/kg for emulsified isoflurane alone, 0.54ml/kg for the blend containing propofol lOmg/ml and isoflurane 40mg/ml, 0.91ml/kg for the blend containing propofol 5mg/ml and isoflurane 40mg/ml, respectively. The LD5o was 2.90ml/kg for propofol alone, 1.63ml/kg for emulsified isoflurane alone, 1.88ml/kg for the blend containing propofol lOmg/ml and isoflurane 40mg/ml, 2.68ml/kg for the blend containing propofol 5mg/ml and isoflurane 40mg/ml, respectively. And the therapeutic index (TI=LDso/ED5o) was.4.62, 2.62, 3.48 and 2.94 for the above four medicines respectively. The cause of death might mainly be the severe respiratory depression. Conclusions: The blends of propofol and isoflurane emulsified in intralipid could provide effective and safe anesthesia in rats for intravenous injection. The therapeutic indexes of the blends are just between those of propofol and emulsified isoflurane.