序贯法测定甲氧明持续泵注预防剖宫产术腰硬联合麻醉后低血压的半数有效量

Determination of the 50% effective dose of sequential method for determining methoxamine with continued pumping and infusion to prevent hypotension during combined spinal epidural anesthesia

摘要:

目的：用序贯法确定甲氧明恒速静脉泵注预防剖宫产腰硬联合麻醉后低血压的半数有效量。方法：该试验是一个前瞻、双盲研究，44例单胎足月孕拟实施择期剖宫产产妇，于腰3/4（L3～4）间隙行腰硬联合麻醉，麻醉完成时以100 mL/h静脉泵注相应浓度的甲氧明，胎儿取出时停止输注。麻醉期间持续观察并记录血压、心率、产妇不良反应及胎儿脐动脉血气分析结果和新生儿1 min、5 min的Apgar评分。甲氧明初始浓度为70 μg/mL，固定输注速度为100 mL/h，目标血压收缩压维持在基础值水平，用序贯法决定下一产妇的药物浓度，浓度梯度为1 μg/mL。药物输注的观察期间收缩压低于基础收缩压，视为该试验浓度无效；若能维持收缩压等于或高于基础收缩压，则视为该试验浓度有效。采用Probit回归分析甲氧明半数有效量（50% effective dose，ED50）及95%可信区间。根据计算的甲氧明半数ED50收集20例产妇，验证该方法计算的甲氧明ED50的有效性。结果：100 mL/h持续静脉输注甲氧明在预防剖宫产腰硬联合麻醉后低血压的半数有效量ED50为79.38 μg/mL（95%CI=76.59~112.48）。该试验方法计算的甲氧明ED50有效性为80%。胎儿的脐动脉血pH均大于7.2，新生儿1 min、5 min的Apgar评分均大于7分。试验中在有效浓度下未观察到母体副作用，如恶心、呕吐、寒战、心动过缓等。结论：以100 mL/h持续静脉泵注，维持产妇腰硬联合麻醉后血压基础水平所需要的甲氧明半数有效量ED50为79.38 μg/mL（95%CI=76.59~112.48）。

Abstract:

Objective：To determine the 50% effective dose（ED50） of methoxamine to prevent spinal-induced hypotension at elective cesarean delivery with constant-speed infusion. Methods：This was a prospective and double-blinded study. Forty-four pregnant women，with single fetus and full term，who were going to have cesarean delivery were included. The combined spinal epidural anesthesia was performed in the interspace of lumbus 3/4（L3～4）. When the spinal epidural anesthesia was completed，the methoxamine was infused at a rate of 100 mL/h，and the infusion was stopped after the baby was delivered. The initial concentration of methoxamine was 70 μg/mL and the constant speed was 100 mL/h. The targeted contractive blood pressure was maintained at the basic level and the sequential method was used to determine the drug concentration of next women，with concentration gradient of 1 μg/mL. Systolic blood pressure was lower than the base value was defined as ineffective concentration；systolic blood pressure was maintained the base value was defined as effective concentration. Probit regression was used to analyze the ED50 of methoxamine and 95% confidence index（CI）. Twenty pregnant women were collected in accordance with ED50，and the effective value of ED50 was calculated. Results：The ED50 of 100 mL/h methoxamine was 79.38 μg/mL（95%CI=76.59-112.48） and the effective value was 80%. The neonatal umbilical blood pH values were greater than 7.2. All neonatal Apgar scores at 1 min and 5 min were greater than 7. There was no side effects（nausea，vomiting，shivering，bradycardia and so on） in patients with effective blood pressure control. Conclusion：The ED50 of 100 mL/h methox－amine to prevent hypotension under spinal anesthesia during caesarean section is 79.38 μg/mL（95%CI=76.59-112.48）.