等容量血液稀释对罗哌卡因犬药代动力学的影响

目的：探讨等容血液稀释对罗哌卡因阻滞犬坐骨神经时药代动力学的影响。方法：健康杂种犬12只，体重13．5～15．8kg，年龄6～8月龄，随机分为两纽（n=6）：A组为等容血液稀释组，B组为对照组。肌肉注射3％戊巴比妥钠30mg／kg麻醉后，解剖坐骨神经，鞘内置管，恢复48h。股静脉与股动脉穿刺。等容量血液稀释组由股动脉放血，同时经股静脉1：1快速输入6％羟乙基淀粉，直至红细胞压积达25％。两组分别采用0．5％罗哌卡因10mg／kg行单次坐骨神经阻滞，分别于罗哌卡因给药前、给药后10、20、30、40、60、90、120、150、180、240、360、720min抽取股动脉血5mL，反相高效液相色谱法测定血浆罗哌卡因浓度，监测心电图（ECG）、血压（BP）、心率（HR），记录不良反应。结果：两组未见中枢神经系统毒性反应和其他局麻药中毒症状，各时点HR、收缩压（SBP）、舒张压（DBP）、平均动脉压（MAP）差异无统计学意义（P〉0．05）。血液稀释组分布半衰期（t1/2α）、峰值浓度（Cmax）、曲线下面积（AUC）、一阶矩曲线下面积（AUMC）降低，消除半衰期（t1/2β）、达峰时间（tmax）延长（P〈0．01）。结论：等容血液稀释对罗哌卡因的药代动力学产生影响，降低了血药峰值浓度（Cmax）。

Effect of isovolemic hemodilution on pharmacokinetics of ropivacaine for sciatic nerve block in dogs

AIM. To investigate the effect of isovolemic hemodilution on pharmacokinetics of ropivacaine for sciatic nerve block in dogs. METHODS- Twelve healthy adult mongrel dogs （6 male, 6 {emale） weighing 13.5--15.8 kg were divided into 2 groups （n = 6 each）, isov- olemic hemodilution group and control group. The animals were anesthetized with intramuscu- lar 3% pentobarbital 30 mg/kg. A polyethylene catheter was surgically inserted into the sheath of sciatic nerve for nerve block with ropivacaine. Femoral artery and vein was cannulated respec- tively. Isovolemie hemodilution group was con- ducted by removing blood from femoral artery and replacing it with 6% hydroxyethyl starch （HES） until hematocrit（Hct） was reduced to 25%. Ropivacaine 10 mg/kg was injected into the sheath of sciatic nerve through the catheter at 48 hours after cannulation. Arterial blood samples （5 mL）were taken for determination of plasma ropivacaine concentration （using HPLC） before and at 10, 20, 30, 60, 90, 120, 150,180, 240, 360 and 720 min after ropivacaine in- jection. The pharmacokinetic parameters were determined from concentration-time data using DAS 1. 0 software package. Electrocardiogram （ECG） ,blood pressure（BP）, heart rate（ HR） and heart rate（HR） were continuously monitored be- fore and after ropivacaine injection. RESULTS： No signs of cardiovascular or central nervous system（CNS） toxicity were observed after sciatic nerve block with ropivacaine in the two groups. The pharmacokinetic parameters of t1/2β, C AUC, AUMC were decreased in the isovolemic hemodilution group, but t1/2β, t were in- creased. CONCLUSION- Normovolemic hemodi- lution leads to lower plasma ropivacaine concen- trations after epidural anesthesia, probably due to an increased volume of distribution.