Population pharmacokinetic-pharmacodynamic model of dexmedetomidine in elderly patients undergoing sedation after abdominal aortic surgery

Justyna Alicja Ber; Agnieszka Bienert; Paweł Sobczyński; Małgorzata Nowicka; Łukasz Żurański; Marcin Hołysz; Edmund Grześkowiak; Paweł Wiczling

doi:10.20883/medical.e770

Authors

Justyna Alicja Ber Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poland https://orcid.org/0000-0003-2270-4386
Agnieszka Bienert Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poland https://orcid.org/0000-0001-7272-5738
Paweł Sobczyński Department of Anaesthetics and Intensive Therapy, The Lord’s Transfiguration University Hospital, Poznan University of Medical Sciences, Poland https://orcid.org/0000-0002-6447-8615
Małgorzata Nowicka Department of Anaesthetics and Intensive Therapy, The Lord’s Transfiguration University Hospital, Poznan University of Medical Sciences, Poland
Łukasz Żurański Department of Anaesthetics and Intensive Therapy, The Lord’s Transfiguration University Hospital, Poznan University of Medical Sciences, Poland https://orcid.org/0000-0003-3343-8765
Marcin Hołysz Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poland https://orcid.org/0000-0003-2505-3582
Edmund Grześkowiak Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poland https://orcid.org/0000-0002-9938-6729
Paweł Wiczling Department of Biopharmacy and Pharmacodynamics, Medical University of Gdańsk, Poland https://orcid.org/0000-0002-2878-3161

DOI:

https://doi.org/10.20883/medical.e770

Keywords:

pharmacodynamics, dexmedetomidine, intensive care units, geriatrics, analgosedation

Abstract

Background. Dexmedetomidine (DEX) is a widely used sedative agent for treating post-surgery patients. It also acts on hemodynamic parameters like heart rate or cardiac output. This study aimed to develop a pharmacokinetic-pharmacodynamic (PK/PD) model of DEX using bispectral index (BIS) and cardiac output (CO) as a response.

Methodology and results. 21 mechanically ventilated elderly cardiac patients undergoing abdominal aortic surgery were enrolled in the study. DEX was given to maintain moderate or deep sedation. Genotypes of ADR2A*55 were identified using real-time PCR-HRM. Data were analyzed using nonlinear mixed-effect modelling. A two-compartment model described DEX pharmacokinetics. The sigmoid E_max and linear models were used to describe BIS and CO measurements. The typical value of EC₅₀for DEX effects on BIS was 3.62 ng/ml, and the slope between CO and DEX concentrations was 0.819 (L/min)/(ng/ml). We were unable to show the effects of considered covariates on DEX pharmacodynamics.

Conclusions. WE proposed the PK/PD model of DEX to understand better the BIS and CO changes observed after surgery. The measured CI values were in the reference range showing that the used doses of DEX ensured stable cardiac function in the studied patients.