Bilirubin potentiates etomidate-induced sedation by enhancing GABA-induced currents after bile duct ligation

BMC Pharmacology and Toxicology

Research Article

Wei-Feng Yu¹  Ying-Fu Jiao¹  Jian-Gang Song²  Jin-Chao Song³  Qian Zhao³  Hao Gao⁴  Guo-Xia Hu⁵ 

[1]Department of Anesthesiology, Renji Hospital Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai, China

[2]Department of Anesthesiology, Shanghai Shuguang Hospital, University of Traditional Chinese Medicine, Shanghai, China

[3]Department of Anesthesiology, Shidong Hospital of Shanghai, University of Shanghai for Science and Technology, Shanghai, China

[4]Department of Anesthesiology, Shidong Hospital of Shanghai, University of Shanghai for Science and Technology, Shanghai, China

[5]Department of Anesthesiology, Shanghai Shuguang Hospital, University of Traditional Chinese Medicine, Shanghai, China

[6]Department of Transfusion Medicine, Changhai Hospital, Naval Medical University, Shanghai, China

关键词: Bilirubin;    Etomidate;    Obstructive jaundice;    GABA receptors;   

DOI  :  10.1186/s40360-023-00675-w

 received in 2022-02-09, accepted in 2023-05-09,  发布年份 2023

来源: Springer

【 摘 要 】

ObjectivesOur previous clinical trial showed that etomidate requirements to reach an appropriate level of anesthesia in patients with obstructive jaundice were reduced, which means that these patients are more sensitive to etomidate. However, the mechanism is still not completely clear. The present study was aimed to investigate the mechanism by which bilirubin facilitates etomidate induced sedation.MethodsA bile duct ligation (BDL) rat model was used to simulate obstructive jaundice. Anesthesia sensitivity to etomidate was determined by the time to loss of righting reflex (LORR). Intrathecal injection of bilirubin was used to test the effects of bilirubin on etomidate induced sedation. The modulating effects of bilirubin on GABA responses were studied using the whole-cell patch clamp technique.ResultsThe time to LORR induced by etomidate was significantly decreased in the BDL groups (p < 0.05), and unconjugated bilirubin in serum and cerebrospinal fluid (CSF) were markedly increased (p < 0.05). The time to LORR induced by etomidate was decreased after intrathecal injection of bilirubin (p < 0.05). A bilirubin concentration of 1.0 μM increased the GABA-induced currents of rat cortical pyramidal neurons (p < 0.05). Furthermore, 1.0 μM bilirubin enhanced GABA-induced currents modulated by etomidate (p < 0.05).ConclusionsOur results demonstrated that pathologic bilirubin in CSF could enhance etomidate induced sedation. The mechanism may be that bilirubin increase the GABA-induced currents of rat pyramidal neurons.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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