Development of a Pharmacodynamic Model for Propofol in Older Adults

Summary

The goal of this pharmacodynamic study is to develop a model for Propofol administration for older adults (\>65 years). The main objective is to create a model based on a new pharmacodynamic parameter, derived from frontal electroencephalogram (EEG), to admininster Propofol in older adults. With this new model, the investigators aim to: * Evaluate the relationship between the plasmatic concentration, described by the Eleveld pharmacokinetic model, versus the effect of the drug represented with a new parameter derived from the intraoperative frontal EEG. * To validate the predictive ability of Eleveld's pharmacokinetic-pharmacodynamic model, based on the bispectral index (BIS), compared to the new model based on a parameter derived from intraoperative frontal EEG. Participants will be asked to answer preoperative questionnaires, receive a Propofol intravenous infusion concomitantly with continuous BIS and EEG monitoring, and to be evaluated for clinical sings of loss and return of consciousness.

Timeline

Start

2024-06-01

Primary completion

2026-07-01

Completion

2026-08-01

Publications

• Background Schnider TW, Minto CF, Shafer SL, Gambus PL, Andresen C, Goodale DB, Youngs EJ. The influence of age on propofol pharmacodynamics. Anesthesiology. 1999 Jun;90(6):1502-16. doi: 10.1097/00000542-199906000-00003.
• Background Andres TM, McGrane T, McEvoy MD, Allen BFS. Geriatric Pharmacology: An Update. Anesthesiol Clin. 2019 Sep;37(3):475-492. doi: 10.1016/j.anclin.2019.04.007. Epub 2019 Jun 19.
• Background Vuyk J. Pharmacodynamics in the elderly. Best Pract Res Clin Anaesthesiol. 2003 Jun;17(2):207-18. doi: 10.1016/s1521-6896(03)00008-9.
• Background Roy RC. Choosing general versus regional anesthesia for the elderly. Anesthesiol Clin North Am. 2000 Mar;18(1):91-104, vii. doi: 10.1016/s0889-8537(05)70151-6.
• Background Warner MA, Saletel RA, Schroeder DR, Warner DO, Offord KP, Gray DT. Outcomes of anesthesia and surgery in people 100 years of age and older. J Am Geriatr Soc. 1998 Aug;46(8):988-93. doi: 10.1111/j.1532-5415.1998.tb02754.x.
• Background Eleveld DJ, Colin P, Absalom AR, Struys MMRF. Pharmacokinetic-pharmacodynamic model for propofol for broad application in anaesthesia and sedation. Br J Anaesth. 2018 May;120(5):942-959. doi: 10.1016/j.bja.2018.01.018. Epub 2018 Mar 12.
• Background Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and coma. N Engl J Med. 2010 Dec 30;363(27):2638-50. doi: 10.1056/NEJMra0808281. No abstract available.
• Background Purdon PL, Sampson A, Pavone KJ, Brown EN. Clinical Electroencephalography for Anesthesiologists: Part I: Background and Basic Signatures. Anesthesiology. 2015 Oct;123(4):937-60. doi: 10.1097/ALN.0000000000000841.
• Background Kim MC, Fricchione GL, Brown EN, Akeju O. Role of electroencephalogram oscillations and the spectrogram in monitoring anaesthesia. BJA Educ. 2020 May;20(5):166-172. doi: 10.1016/j.bjae.2020.01.004. Epub 2020 Feb 20. No abstract available.
• Background Purdon PL, Pierce ET, Mukamel EA, Prerau MJ, Walsh JL, Wong KF, Salazar-Gomez AF, Harrell PG, Sampson AL, Cimenser A, Ching S, Kopell NJ, Tavares-Stoeckel C, Habeeb K, Merhar R, Brown EN. Electroencephalogram signatures of loss and recovery of consciousness from propofol. Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):E1142-51. doi: 10.1073/pnas.1221180110. Epub 2013 Mar 4.
• Background Purdon PL, Pavone KJ, Akeju O, Smith AC, Sampson AL, Lee J, Zhou DW, Solt K, Brown EN. The Ageing Brain: Age-dependent changes in the electroencephalogram during propofol and sevoflurane general anaesthesia. Br J Anaesth. 2015 Jul;115 Suppl 1(Suppl 1):i46-i57. doi: 10.1093/bja/aev213.
• Background Giattino CM, Gardner JE, Sbahi FM, Roberts KC, Cooter M, Moretti E, Browndyke JN, Mathew JP, Woldorff MG, Berger M; MADCO-PC Investigators. Intraoperative Frontal Alpha-Band Power Correlates with Preoperative Neurocognitive Function in Older Adults. Front Syst Neurosci. 2017 May 8;11:24. doi: 10.3389/fnsys.2017.00024. eCollection 2017.
• Background Touchard C, Cartailler J, Leve C, Serrano J, Sabbagh D, Manquat E, Joachim J, Mateo J, Gayat E, Engemann D, Vallee F. Propofol Requirement and EEG Alpha Band Power During General Anesthesia Provide Complementary Views on Preoperative Cognitive Decline. Front Aging Neurosci. 2020 Nov 27;12:593320. doi: 10.3389/fnagi.2020.593320. eCollection 2020.
• Background Kaiser HA, Hirschi T, Sleigh C, Reineke D, Hartwich V, Stucki M, Rummel C, Sleigh J, Hight D. Comorbidity-dependent changes in alpha and broadband electroencephalogram power during general anaesthesia for cardiac surgery. Br J Anaesth. 2020 Oct;125(4):456-465. doi: 10.1016/j.bja.2020.06.054. Epub 2020 Jul 31.
• Background Shao YR, Kahali P, Houle TT, Deng H, Colvin C, Dickerson BC, Brown EN, Purdon PL. Low Frontal Alpha Power Is Associated With the Propensity for Burst Suppression: An Electroencephalogram Phenotype for a "Vulnerable Brain". Anesth Analg. 2020 Nov;131(5):1529-1539. doi: 10.1213/ANE.0000000000004781.

Drugs

Indications

No indication recorded.