大鼠单次静脉注射异丙酚-异氟醚乳化合剂的ED₅₀和LD₅₀测定

【作者】 陈晔凌；

【导师】 刘进；

【作者基本信息】 四川大学 ， 麻醉学， 2004， 硕士

【摘要】 关于吸入麻醉药经静脉给药的研究已有数十年历史。近年来本实验室将异氟醚溶解到30%的脂肪乳中制成乳化剂用于静脉注射,在动物身上取得了满意的麻醉效果,且安全性较好。目前临床上异丙酚与异氟醚联合进行静脉-吸入复合全麻得到了广泛的应用,而异丙酚也是10%的脂肪乳剂,故本实验将异丙酚和异氟醚共同溶解到脂肪乳中制成静脉合剂,并通过测定其半数有效量(ED₅₀)和半数致死量(LD₅₀),计算其治疗指数(TI=LD₅₀/ED₅₀),来对其有效性和安全性进行初步评价。 方法:采用序贯法分别测定10mg/ml异丙酚,120mg/ml乳化异氟醚,10mg/ml异丙酚与40mg/（50）ml异氟醚合剂,5mg/ml异丙酚与40mg/ml异氟醚合剂对SD大鼠单次静脉注射时的ED₅₀和LD₅₀。测定ED₅₀时,以大鼠前爪翻正反射消失作为麻醉有效的指标,记录翻正反射消失,恢复的时间;测定LD₅₀时,以心电图持续显示一条直线为大鼠死亡的指标,记录翻正反射消失,恢复和大鼠死亡的时间,并记录呼吸,心率的变化情况。 结果:四个药物组大鼠的体重在统计学上没有显著差异。10mg/ml更多还原

【Abstract】 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.更多还原