年龄因素对患者硬膜外注射左旋布比卡因药效学和药代动力学的影响

目的 探讨年龄因素对患者硬膜外注射左旋布比卡因药效学和药代动力学的影响.方法 择期拟行下肢手术患者45例,年龄30～72岁,体重52～83 ks,ASA Ⅰ或Ⅱ级,按不同年龄分为3组:Ⅰ组(≤45岁)、Ⅱ组(46～64岁)和Ⅲ组(>64岁),每组15例,均采用腰段硬膜外麻醉,左旋布比卡因(7.5 mg/ml)用量1.8 mg/kg(含肾上腺素5 μg/ml).经L1,2硬膜外穿刺成功后,注射试验量0.5%左旋布比卡因3 ml,3 min后注射剩余量0.75%左旋布比卡因.硬膜外注药后记录感觉和运动阻滞效果及不良反应的发生情况;每组随机选择9例,于注药后即刻、注药后10、20、30、45、60、90、120、180、240、360、480、840、和1 440 min时采用高效液相色谱法测定血浆左旋布比卡因浓度,绘制血浆左旋布比卡因浓度-时间曲线,计算3组药代动力学参数.结果 与Ⅰ组比较,Ⅲ组最高感觉阻滞平面高,感觉和运动阻滞维持时间长,(P<0.05);各组麻醉效果优良率均达100%;各组左旋布比卡因的血浆药物浓度-时间曲线均符合二房室开放模型;硬膜外注药后1 440 min时Ⅱ组和Ⅲ组左旋布比卡因血药浓度高于Ⅰ组(P<0.05);Ⅱ组和Ⅲ组左旋布比卡因消除半衰期明显长于Ⅰ组,Ⅲ组明显长于Ⅱ组(P<0.05).结论 不同年龄患者硬膜外注射0.75%左旋布比卡因1.8 mg/kg安全有效;随年龄增加,感觉阻滞平面升高、感觉和运动阻滞恢复时间延长,药物代谢明显减慢.

Effects of age on pharmacodynamics and pahrmacokinetics of levobupivacaine after epidural administration

Objective To investigate the effects of age on the pharmacokineties and pharmacodynamics of levobupivacaine after epidural administrstion.Methods Forty-five ASA Ⅰ or Ⅱ patients of both sexes (26 male, 19 female) aged 30-72 yr, weighing 52-83 kg scheduled for elective lower extremity surgery under epidural anesthesia, were divided into 3 age groups ( n = 15 each) : group Ⅰ≤45 yr; group Ⅱ 46-64 yr and group Ⅲ > 64 yr. Epidural anesthesia was performed at the L1,2 interspace. All of the patients received levobupivacaine 1.8 mg/kg with epinephrine 5 μg/ml given epidurally over 1.5 min. Assessment of sensory block (onset time, peak effect time, upper spread of sensory block, duration of anesthesia) and degree of motor block (using modified Bromage scale) were made. Blood samples were taken from central vein at 0, 10, 20, 30, 45, 60 90, 120, 240, 360, 480, 840 and 1 440 min after epidural administration for determination of plasma concentration of levobupivacaine by high-performance liquid chromatography (HPLG) in nine patients in each group. The pharmacokinetic parameters were calculated from plasma concentration-time data with 3P97 software package. Results The cephalad spread of sensory block was significantly higher in group Ⅲ than in group Ⅰ . The duration of sensory and motor block was significantly longer in group Ⅲ than in group Ⅰ . The plasma concentration-time curves of levobupivacaine were fitted to a two-compartment open model in the 3 groups. The plasma concentrations of levobupivacaine were significantly higher at 1 440 min after epidural administration in group Ⅲ and Ⅱ than in group Ⅰ. The t1/2β was significantly different among the 3 groups. Conclusion 0.75% levobupivacaine is safe and effective for epidural anesthesia. Age affects the pharmacokinetics (t1/2β in particular) and pharmacodynamics of levobupivacaine administered epidurally.