Key result
Dexmedetomidine modeling in elderly patients estimates a cardiac output slope of ~0.82 L/min per ng/ml.
Why the study?
Dexmedetomidine is widely used for post-surgery sedation and affects hemodynamic parameters, motivating the development of a pharmacokinetic-pharmacodynamic model using bispectral index and cardiac output as responses.
Observational (n=21)
No
A pharmacokinetic-pharmacodynamic model of dexmedetomidine in elderly patients after abdominal aortic surgery demonstrates that standard sedative doses maintain stable cardiac output.
Model suggests stable cardiac output with standard dexmedetomidine dosing in elderly surgical patients; hypothesis-generating and requires prospective validation.
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 Emax and linear models were used to describe BIS and CO measurements. The typical value of EC50 for 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.
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Ber et al. (2023) conducted an observational in Sedation after abdominal aortic surgery (n=21). Dexmedetomidine was evaluated on Pharmacodynamic response (Bispectral index and Cardiac output). A pharmacokinetic-pharmacodynamic model of dexmedetomidine in elderly patients estimated the typical EC50 for bispectral index at 3.62 ng/ml and the slope for cardiac output at 0.819 (L/min)/(ng/ml).
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