Development of a closed loop control system for total intravenous anesthesia

本研究的目的是开发一套全静脉麻醉的闭环控制系统。该系统分为四个子系统：(1)麻醉深度量化子系统为量化麻醉深度，研制了实时心率变异性频谱分析仪和脑电图仪功率谱分析程序。研究了呼气二氧化碳分压的精确测量方法。(2)短时间内血液中麻醉剂浓度的估算系统采用高效液相色谱法测定咪达唑仑、硫喷妥钠、五唑卡因和维库溴铵的浓度。(3)麻醉剂血药浓度模拟子系统研究了麻醉剂在血液和效应点的计算机模拟程序。用欧拉法或Runge-Kutta-Gill法计算浓度。研究了老化对咪达唑仑药代动力学和药效学的影响，以提高模拟的精度。(4)注射泵计算机控制系统研究了一种同时控制三个注射泵的计算机程序。该系统能够估计达到血液中药物预设浓度所需的时间。肌肉松弛药可以通过使用神经肌肉连接监测器的闭环控制方法进行注射。由于镇痛剂和催眠药效果的评估方法尚未完成，因此不可能使用闭环控制方法来注入这些药物。镇痛剂和催眠药根据模拟药物的浓度采用开环控制方法输注。实际浓度和模拟浓度之间的差异通过血液中的测量值进行了修正。

The purpose of this study was to develop a closed loop control system for total intravenous anesthesia. This system was divided into four subsystems as follows ;(1) Subsystem to quantify anesthesia depthTo quantify anesthesia depth, a real time spectral analyzer of the heart rate variability and a computer program to analyze power spectra of electroencephalograph were developed. A precise method for carbon dioxide tension measurement in expiratory gas was also studied.(2) Subsystem to estimate concentrations of anesthetic agents in blood within brief durationConcentrations of anesthetic agents ; midazolam, thiopental, pentazocine and vecuronium, were estimated using high performace liquid chromatography. An interval between blood sampling and estimation of blood concentration was less than twenty minutes.(3) Subsystem to simulate concentrations of anesthetic agents in blood and effect sitesA computer program to simulate anesthetic agents in blood and effect sites was studied. To calculate the concentrations, the Euler method or the Runge-Kutta-Gill method was applied. Influences of aging on pharmacokinetics and pharmacodynamics of midazolam were studied to improve the precision of the simulation.(4) Subsystem to control syringe pumps using a computerA computer program to simultaneously control three syringe pumps was studied. This system enabled estimation of the time required for reaching the presetting concentrations of the agents in blood.Muscle relaxants were able to be infused by a closed loop control method using a neuromuscular junction monitor. Since methods for estimation of effects of analgesics and hypnotics have not been completed, it is impossible to infuse those agents using a closed loop control method. Analgesics and hypnotics were infused by an open loop control method according to values of concentrations of the agents simulated. The differences between actual and simulated concentrations were corrected by the values measured in blood.