Development of a Pharmacodynamic Model for Propofol in Older Adults

NCT05790720 | Recruiting

• 1 other identifier: 230125002
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Aged

Keywords

Propofol; TCI; TIVA

Outcome Measures

Primary Outcomes (1)

• Performance Error (PE)

  Difference between the measured (according to Eleveld) and predicted concentrations, divided by the predicted concentration. Multiplied by 100. Unit of measure: percentage (%).

  Intravenous infusion start to one minute after start of burst suppression in EEG

Secondary Outcomes (5)

• Median Absolute Performance Error (MDAPE)

  Intravenous infusion start to one minute after start of burst suppression in EEG

• Median Prediction Error (MDPE)

  Intravenous infusion start to one minute after start of burst suppression in EEG

• Time of Loss of response (LOR)

  Intravenous infusion start to one minute after start of burst suppression in EEG

• Time of Burst-suppression (BS)

  Intravenous infusion start to one minute after start of burst suppression in EEG

• Time of Return of response (ROR).

  Intravenous infusion start to one minute after start of burst suppression in EEG

Study Arms (1)

Intervention

EXPERIMENTAL

Patients older than 65 years of age will receive an intravenous infusion of Propofol with prespecified plasma targets. During its administration, registration of BIS values, frontal electroencephalography, and clinical signs of consciousness will be performed. Two models will be created and compared retrospectively: BIS (Eleveld Validation) and EEG Frontal Marker (New model).

Drug: Propofol

Interventions

Propofol DRUG

Patients older than 65 years of age will receive an intravenous infusion of Propofol with prespecified plasma targets. During its administration, registration of BIS values, frontal electroencephalography, and clinical signs of consciousness will be performed.

Intervention

Eligibility Criteria

• Age: 65 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Patients undergoing non-cardiac elective surgery requiring general anesthesia
• American Society of Anesthesiologists Physical Status I to III

You may not qualify if:

• Patients undergoing emergency surgery
• Neurosurgical patients
• History of alcohol abuse or recreational drug use
• Known allergie to Propofol
• Body mass index ≥ 35 Kg m-2
• Unstable heart failure

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (1)

Pontificia Universidad Católica de Chile

Santiago, Santiago Metropolitan, 8330024, Chile

RECRUITING

Related Publications (15)

• 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.

  PMID: 10360845 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.

  PMID: 31337479 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.

  PMID: 12817915 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.

  PMID: 10935002 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.

  PMID: 9706888 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.

  PMID: 29661412 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.

  PMID: 21190458 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.

  PMID: 26275092 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.

  PMID: 33456946 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.

  PMID: 23487781 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.

  PMID: 26174300 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.

  PMID: 28533746 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.

  PMID: 33328973 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.

  PMID: 32747077 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.

  PMID: 33079876 BACKGROUND

MeSH Terms

Interventions

Propofol

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Central Study Contacts

Juan C. Pedemonte, MD

CONTACT

+ 56 22 3543270; jcpedemo@gmail.com

Luis I. Cortinez, MD

CONTACT

+ 56 22 3543270; icortinez@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pharmacokinetic-pharmacodynamic model that uses the pharmacokinetic parameters of the Eleveld model and new pharmacodynamic parameters derived from frontal EEG in a population older than 65 years.

Study Record Dates

• First Submitted: March 2, 2023
• First Posted: March 30, 2023
• Study Start: June 1, 2024
• Primary Completion: July 1, 2025
• Study Completion: August 1, 2025
• Last Updated: May 31, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CL (1)