Background

Pharmacokinetic/pharmacodynamic (PK/PD) modeling has made an enormous contribution to intravenous anesthesia. Because of their altered physiological, pharmacological and pathological aspects, titrating general anesthesia in the elderly is a challenging task.

Methods

Eighty patients were consecutively enrolled divided by decades from vicenarians (20–29 year) to nonagenarians (90–99 year) into eight groups. Using target controlled infusion (TCI) and electroencephalographic (EEG)-derived bispectral index (BIS) we set propofol plasma concentration (C_p) to gradually reach 3.5 μg mL⁻¹ over 3.5-min. In each patient, we constructed a PK/PD model and conducted a population PK/PD (PopPK-PD) covariate analysis.

Results

Age was significant covariate for baseline BIS effect (E₀), inhibitory propofol concentration at 50% BIS decline (IC₅₀) and maximum BIS decline (E_max). First-order rate constant K_e0 of 0.47 min⁻¹ in vicenarians (20–29 year) gradually increased with age-progression to 1.85 min⁻¹ in nonagenarians (90–99 year). Simulation modelling showed that clinically recommended C_p of 3.5 μg mL⁻¹ for 20–29 year BIS 50 should be reduced to 3.0 for 30–49 year, 2.5 for 50–69 year and 2.0 for 80–89 year.

Conclusion

We quantified and graded EEG-BIS age-progression among different age groups divided by decades. We demonstrated deeper BIS values with decades’ age progression. Our data has important implications for propofol dosing. The practical information for physicians in their daily clinical practice is using propofol C_p of 3.5 μg mL⁻¹ might not yield BIS value of 50 in elderly patients. Our simulations showed that the recommended regimen of C_p 3.5 μg mL⁻¹ for 20–29 year should be gradually decreased to 2.0 μg mL⁻¹ for 80–89 year.

Clinical trial registry numbers

European Community Clinical Trials Database EudraCT (http://eudract.emea.eu) initial trial registration number: 2011-002847-81, and subsequently registered at www.clinicaltrials.gov; trial registration number: NCT02585284. Xijing Hospital of Fourth Military Medical University ethics committee approval number 20110707-4.

中文翻译：

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丙泊酚-双谱指数（BIS）脑电图的人群药代动力学/药效学（PopPk-PD）协变量分析中，年龄从虎鲸（20-29岁）到非鼠类（90-99岁）。

背景

药代动力学/药效学（PK / PD）模型为静脉麻醉做出了巨大贡献。由于其生理，药理和病理方面的改变，在老年人中全身麻醉进行滴定是一项艰巨的任务。

方法

连续招募了80名患者，按数十年的顺序将其从虎鲸（20-29岁）分为非鲸类（90-99岁）分成八组。使用目标控制输注（TCI）和脑电图（EEG）衍生的双光谱指数（BIS），我们将丙泊酚血浆浓度（C _p）设置为在3.5分钟内逐渐达到3.5μgmL ^-1。在每位患者中，我们构建了PK / PD模型并进行了PK / PD群体（PopPK-PD）协变量分析。

结果

年龄是基线BIS效应（E ₀），50％BIS下降（IC ₅₀）和最大BIS下降（E _max）时的异丙酚浓度的显着协变量。凡纳尔人（20-29岁）的一阶速率常数K _e0为0.47 min ^-1，随着年龄的增长逐渐增加，非纳那尔人（90-99岁）的1.85 min ^-1。仿真建模表明，临床推荐Ç _p的3.5微克毫升^-1为20-29年BIS 50应减少到3.0 30-49年，2.5 50-69年和2.0 80-89年。

结论

我们对不同年龄组的EEG-BIS年龄进展进行了量化和分级，除以数十年。随着数十年的发展，我们展示了更深的BIS值。我们的数据对丙泊酚剂量具有重要意义。医师在日常临床实践中的实用信息是使用丙泊酚C _p为3.5μgmL ^-1可能不会使老年患者的BIS值达到50。我们的模拟结果表明，建议的20–29年C _p 3.5μgmL ^-1方案应逐渐降低至80–89年2.0μgmL ^-1。

临床试验注册号

欧共体临床试验数据库EudraCT（http://eudract.emea.eu）的初始试验注册号：2011-002847-81，随后在www.clinicaltrials.gov上注册；试用注册号：NCT02585284。第四军医大学西京医院伦理委员会批准文号为20110707-4。