The Pharmacodynamic Action of Propofol in Elderly Patients during Propofol Induced Sedation<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

李　民 Min Li 医学博士
蒋建渝 Jianyu Jiang 教授
北京大学第三医院麻醉科，北京 100083
Department of Anesthiology, Peking University Third Hospital, Beijing 100083

ABSTRACT

Objective：To study the pharmacodynamic action of propofol in elderly patients during propofol induced sedation.
Methods：20 male patients of Group Old (aged 60-80 yr) and 20 male patients of Group Young (aged 20-45) were studied. The levels of sedation were assessed by modified OAA/S method. Patients were titrated propofol at the rate which was increased every 15min. Plasma propofol concentrations were analyzed by HPLC.
Results：The comsumption of propofol at the time of unconsciousness in Group Old was much less than that in Group Young. At each sedation level, propofol plasma concentrations of Group Old was significantly lower than that of Group Young. The Cp₅₀ and Cp₉₅ of the Group Old were significantly lower than Group Young.
Conclusion：Aging is a important factor which influence the pharmacodymamic effect of propofol. The Cp₅₀ and Cp₉₅ of the elderly were lower than that of the young, suggesting that the central nerve system of the elderly might be more sensitive to propofol than that of the young.
Key Words: Propofol; Elderly; Pharmacodynamic

　　麻醉中老年人对镇静催眠及镇痛药物的需求均小于年轻人，年龄引起的对药物需要量的减少可能是药代动力学或药效学或两方面的改变所引起的。本研究设计的给药方案旨在提供稳态的异丙酚血药浓度和效应室浓度，以研究老年人对异丙酚的药理效应，及药理效应与血药浓度的关系。

资料与方法<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

　　本研究对象为ASA I或II级、行下肢或下腹部手术的男性病人，年轻组20-45岁，老年组60-80岁，每组20人。不用术前药。采用HP Viridia 24C多功能监测仪持续监测BP、ECG、SpO₂。行硬膜外腔穿刺置管，使麻醉平面维持在T4以下。行桡动脉穿刺连接动脉测压装置，用于直接测压及采血。患者通过Ohmeda Excel 210SE型麻醉机，面罩吸入100%氧气，氧流量4L/min。
　　实验过程中采用Grasby 3500输液泵维持静脉异丙酚输注。以50ml/min的速度单次注射异丙酚05mg/kg后，静注异丙酚2.5mg/kg•h，维持15min。以后逐渐增加异丙酚静注速度，每次增加0.5mg/kg•h，每个速度维持15min，每次提高速度前以50ml/min的速度注射0.3mg/kg。每个恒定速度静注末大声呼唤病人睁眼，如病人无反应，则推动或摇动病人并呼其睁眼。按照以下方法评定镇静程度(改良的OAA/S评分)：5分-对呼唤反应迅速；4分-瞌睡，对呼唤反应迟钝；3分-对单纯呼唤反应消失，对推动或摇动并反复呼唤有反应；2分-不能被推动或摇动并反复呼唤唤醒。1分-不能被置于左上臂的25Hz，15mA低电流刺激唤醒。镇静评分达到1分后停止输注异丙酚。
　　镇静加深阶段每个恒定速度静注异丙酚的第15min取动脉血。每次取动脉血3ml，肝素抗凝。抗凝血以3000rbp离心10min2次后取血浆，-20℃保存，于一周内采用高效液相色谱法进行异丙酚血药浓度测定。
　　所得数据以均值±标准差表示，两组病人计量资料的相互比较采用t-test，计数资料的比较采用X²检验。将镇静评分小于或等于2作为评定意识消失的指标，采用Logsitic regression(对数优势线性回归）对两组病人异丙酚血药浓度与意识(均表示为indicator）的关系进行分析^[1]。根据Smith等的方法^[2]，以预测概率(prediction probability, PK）评价异丙酚血药浓度预测意识水平的能力。Pk=0.5表示某指标能正确预测的机率只有50%，即仅为50%对50%的猜测。Pk=1表示这一指标能100%地正确预测。

结　果

　　一、两组病人一般情况(见表1）。
　　两组病人身高、体重及硬膜外麻醉阻滞平面无明显差别。老年组镇静总时间及意识消失所需时间明显小于年轻组(P＜0.01）。老年组意识恢复所需时间明显长于年轻组(P＜0.01）。老年组意识消失时的累积异丙酚用量及静滴异丙酚总量比年轻组明显减少(P＜0.01）。
　　二、两组血药浓度的比较
　　每一静滴阶段的第10和第15min测定的血药浓度的范围，老年组为-0.28ug/ml～+0.23ug/ml，年轻组为-0.34ug/ml～+0.35ug/ml；每一静滴阶段两个血药浓度的变化程度可以用相应第10和第15min测定的血药浓度差值与其平均值之比表示，老年组为-21.0%～+23.7%，年轻组为-34.7%～+32.9%。
两组在第一静滴阶段的血药浓度(见表2）。在第1至第6阶段，年轻组血药浓度均低于老年组。因第5阶段之后老年组达镇静评分1分并停止静滴异丙酚的患者数目逐渐增加，故第7阶段至第9阶段老年组采集的血样数目较少，影响相同静滴阶段两组血药浓度比较的统计结果。在4-1分相同镇静评分下，老年组异丙酚血药浓度均低于年轻组(P＜0.01），两组在各镇静评分下的血药浓度(见表3）。

　　在另一方面，由于异丙酚具有很高的蛋白结合力，体内血浆蛋白的高低将影响游离异丙酚的浓度。本研究中没有直接测定游离异丙酚的浓度，虽然两组患者血浆总蛋白及白蛋白、血红蛋白浓度无明显差别，但亦不能排除在相同镇静状态下血浆游离异丙酚浓度老年人与年轻人相近的可能。年龄增长是否引起大脑对异丙酚敏感性增加的问题还有待进一步研究。<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

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　　蒋建渝　1941年生　北京大学麻醉学教授、主任医师、硕士导师、博士副导师、国务院特殊津帖获得者、国家自然科学基金评审专家。现任北京大学第三医院麻醉科主任、麻醉学会北京市委员、中国微创外科杂志编委、本刊常务编委。