Department of Anaesthesiology and Intensive Care Medicine, Suez Canal University, Ismailia, Egypt.
Department of Anesthesiology, Xijing Hospital of Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
J Pharmacokinet Pharmacodyn. 2020 Apr;47(2):145-161. doi: 10.1007/s10928-020-09678-0. Epub 2020 Feb 25.
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.
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) to gradually reach 3.5 μg mL over 3.5-min. In each patient, we constructed a PK/PD model and conducted a population PK/PD (PopPK-PD) covariate analysis.
Age was significant covariate for baseline BIS effect (E), inhibitory propofol concentration at 50% BIS decline (IC) and maximum BIS decline (E). First-order rate constant K of 0.47 min in vicenarians (20-29 year) gradually increased with age-progression to 1.85 min in nonagenarians (90-99 year). Simulation modelling showed that clinically recommended C of 3.5 μg mL 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.
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 of 3.5 μg mL might not yield BIS value of 50 in elderly patients. Our simulations showed that the recommended regimen of C 3.5 μg mL for 20-29 year should be gradually decreased to 2.0 μg mL for 80-89 year.
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.
药代动力学/药效动力学（PK/PD）模型在静脉麻醉中做出了巨大贡献。由于老年人在生理、药理和病理方面的改变，精确滴定全身麻醉是一项具有挑战性的任务。
连续纳入 80 名患者，按年龄分为 8 组，从百岁老人（20-29 岁）到 90-99 岁的非百岁老人。我们使用靶控输注（TCI）和脑电双频指数（BIS），使丙泊酚的血浆浓度（C）逐渐在 3.5 分钟内达到 3.5μg/ml。在每个患者中，我们构建了 PK/PD 模型并进行了群体 PK/PD（PopPK-PD）协变量分析。
年龄是基线 BIS 效应（E）、抑制丙泊酚浓度 50% BIS 下降（IC）和最大 BIS 下降（E）的显著协变量。20-29 岁的百岁老人（20-29 岁）的一阶速率常数 K 为 0.47 min，逐渐随年龄增加到 90-99 岁的非百岁老人（90-99 岁）的 1.85 min。模拟模型表明，对于 20-29 岁 BIS 50 的推荐浓度 3.5μg/ml，应分别降低到 30-49 岁的 3.0μg/ml、50-69 岁的 2.5μg/ml和 80-89 岁的 2.0μg/ml。
我们对按十年为单位划分的不同年龄组进行了 EEG-BIS 年龄进展的量化和分级。我们证明了随着年龄的增长，BIS 值会更深。我们的数据对丙泊酚给药具有重要意义。对于老年患者，使用丙泊酚 C 3.5μg/ml 可能无法达到 BIS 值 50 的实际意义。我们的模拟结果表明，对于 20-29 岁的患者，推荐的 C 3.5μg/ml 方案应逐渐降低至 80-89 岁的 2.0μg/ml。
欧洲共同体临床试验数据库 EudraCT（http://eudract.emea.eu）初始试验注册编号：2011-002847-81，随后在 www.clinicaltrials.gov 注册；试验注册号：NCT02585284. 第四军医大学西京医院伦理委员会批准文号 20110707-4.
