Ashraf A Dahaba1, Zhaoyang Xiao2,3, Xiaoling Zhu4, Hailong Dong4, Lize Xiong4, Peter Rehak5, Sieglinde Zelzer6, Kun Wang7, Gilbert Reibnegger8. 1. Department of Anaesthesiology and Intensive Care Medicine, Suez Canal University, Ismailia, Egypt. 2. Department of Anesthesiology, Xijing Hospital of Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China. xiaozhaoy2012@163.com. 3. Department of Anesthesiology, Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Dalian, 116023, People's Republic of China. xiaozhaoy2012@163.com. 4. Department of Anesthesiology, Xijing Hospital of Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China. 5. Biomedical Engineering and Computing Unit of the Department of Surgery, Medical University of Graz, Graz, Austria. 6. Institute for Medical and Chemical Diagnostics, Medical University of Graz, Graz, Austria. 7. Laboratory of Pharmacometrics, Shanghai Qiangshi Information Technology Co. Ltd., Shanghai, People's Republic of China. 8. Institute of Physiological Chemistry, Medical University of Graz, Graz, Austria.
Abstract
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 (Cp) 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 (Emax). First-order rate constant Ke0 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 Cp 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 Cp of 3.5 μg mL-1 might not yield BIS value of 50 in elderly patients. Our simulations showed that the recommended regimen of Cp 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.
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 (Cp) 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 (Emax). First-order rate constant Ke0 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 Cp 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 Cp of 3.5 μg mL-1 might not yield BIS value of 50 in elderly patients. Our simulations showed that the recommended regimen of Cp 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.
Entities:
Keywords:
Age; Bispectral index; Diagnostic accuracy; Electroencephalography; Pharmacokinetic–pharmacodynamic; Statistical model
Authors: D A Chernik; D Gillings; H Laine; J Hendler; J M Silver; A B Davidson; E M Schwam; J L Siegel Journal: J Clin Psychopharmacol Date: 1990-08 Impact factor: 3.153
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