Journal Article

Do epoch lengths of hypnotic depth indicators affect estimated of blood-brain equilibration rate constants of propofol?

Byung-Moon, Choi, Ji-Yeon, Bang, Park Sookyung, Gyu-Jeong, Noh, Kim Kyung Mi, Kang, Bong Jin

2021

Overview

This study aimed to investigate the effect of epoch length of hypnotic depth indicators on the blood–brain equilibration rate constant (ke0) estimates of propofol. Propofol was administered by zero-order infusion (1.5, 3.0, 6, and 12 mg·kg−1·h−1) for one hour in 63 healthy volunteers. The ke0 of propofol was estimated using an effect-compartment model linking pharmacokinetics and pharmacodynamics, in which response variables were electroencephalographic approximate entropy (ApEn) or bispectral index (BIS) (n = 32 each for propofol infusion rates of 6 and 12 mg·kg−1·h−1). Epoch lengths of ApEn were 2, 10, 30, and 60 seconds (s). The correlations between plasma propofol concentrations (Cp) and BIS and ApEn 2, 10, 30, and 60 s were determined, as was the Ce associated with 50% probability of unconsciousness (Ce50,LOC). The pharmacokinetics of propofol were well described by a three-compartment model. The correlation coefficient between Cp and ApEn 2, 10, 30, and 60 s were −0.64, −0.54, −0.39, and −0.26, respectively, whereas correlation coefficient between Cp and BIS was −0.74. The blood-brain equilibration half-life based on the ke0 estimates for ApEn at 2, 10, 30, 60 s and BIS were 4.31, 3.96, 5.78. 6.54, 5.09 min, respectively, whereas the Ce50,LOC for ApEn at 2, 10, 30, 60 s and BIS were 1.55, 1.47, 1.28, 1.04, and 1.55 μg·ml−1, respectively. Since ke0, which determines the onset of drug action, varies according to the epoch length, it is necessary to consider the epoch length together when estimating ke0.

• Publisher: Springer Nature B.V
• Subject: Blood / EEG / Entropy / Pharmacodynamics / Pharmacokinetics / Propofol