title: Combined Use of Etomidate and Dexmedetomidine Produces an Additive Effect in Inhibiting the Secretion of Human Adrenocortical Hormones.
abstract: BACKGROUND The direct effects of etomidate were investigated on the secretion of cortisol and its precursors by dispersed cells from the adrenal cortex of human of animals. Dexmedetomidine (DEX) is an anesthetic agent that may interfere with cortisol secretion via an unknown mechanism, such as involving inhibition of 11b-hydroxylase and the cholesterol side-chain cleavage enzyme system. The aim of this study was to determine whether dexmedetomidine (DEX) has a similar inhibitory effect on adrenocortical function, and whether combined use of etomidate (ETO) and DEX could produce a synergistic action in inhibiting the secretion of human adrenocortical hormones. MATERIAL AND METHODS Human adrenocortical cells were exposed to different concentrations of ETO and DEX. The dose-effect model between the ETO concentration and the mean secretion of cortisone (CORT) and aldosterone (ALDO) per hour was estimated. RESULTS Hill's equation well-described the dose-effect correlation between the ETO concentration and the amount of ALDO and CORT secretion. When the DEX concentration was introduced into the model by using E0 (basal secretion) as the covariate, the goodness of fit of the ETO-CORT dose-effect model was improved significantly and the objective function value was reduced by 4.55 points (P<0.05). The parameters of the final ETO-ALDO pharmacodynamics model were EC50=9.74, Emax=1.20, E0=1.33, and γ=18.5; the parameters of the final ETO-CORT pharmacodynamics model were EC50=9.49, Emax=8.16, E0=8.57, and γ=37.0. In the presence of DEX, E0 was 8.57-0.0247×(CDEX-4.6), and the other parameters remained unchanged. All parameters but γ were natural logarithm conversion values. CONCLUSIONS Combined use of DEX and ETO reduced ETO's inhibitory E0 (basal secretion) of CORT from human adrenocortical cells in a dose-dependent manner, suggesting that combined use of ETO and DEX produced an additive effect in inhibiting the secretion of human adrenocortical hormones.
authors.affiliation: Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China (mainland).
authors.forename: Hongbin
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China (mainland).
authors.forename: Mazhong
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China (mainland).
authors.forename: Meihua
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China (mainland).
authors.forename: Jinfen
authors.initials: J
authors.lastname: Liu
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000378:metabolism / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D002478:Cells, Cultured; D020927:Dexmedetomidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005045:Etomidate / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism / Q000494:pharmacology; D008954:Models, Biological
chemical_list: D000305:Adrenal Cortex Hormones; D020927:Dexmedetomidine; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D005045:Etomidate