Effect on emergence from anesthesia following induction with diazepam and its association with CYP2C9, CYP2C19 and CYP3A4 gene polymorphisms

Abstract

Introduction & Objectives: Benzodiazepines are commonly used as adjuvants to IV anesthetic agents. Diazepam dosage varies widely depending on the desired endpoints. The rationale behind such inter-individual variability in drug responses has been attributed to genetically determined alterations in the enzyme activities. We assessed the emergence time in patients after induction of anesthesia with two different doses of diazepam and evaluated if any correlation exists between the emergence time and genetic polymorphism in drug metabolizers CYP2C19, CYP2C9, and CYP3A4 genes. Methodology: The study was conducted on randomly selected adult patients scheduled for elective surgery between 40-60 y of age with predefined inclusion and exclusion criteria. The patients were distributed into 2 groups, with group 1 receiving 0.2 mg/kg and group 2 given 0.3 mg/kg diazepam. Wake-up time after surgery was determined after a standardized verbal command played by a tape-recorder. Three ml blood in Ethylenediaminetetraacetic acid (EDTA) was collected before administering anesthesia. Results: Wake-up time between 8-18 min did not vary between the two groups. Comparatively persons having 2C19 2 took longer time to wake-up but this association was not statistically significant. However, CYP2C9 2 and 2 C9 3 and CYP3A4 genotypes had no influence on wake-up time. Conclusion: The pilot study suggests the emergence time from diazepam is longer in patients having 2C19 2 which confers slow-metabolizer phenotype. However, this study needs to be replicated in larger sample size to arrive at definitive conclusions before clinical applications. Abbreviations: BDZ- benzodiazepine; EDTA- Ethylenediaminetetraacetic acid; GA-General Anesthesia Key words: Diazepam; Emergence; Gene Polymorphism; Pharmacogenetics Citation: Mittal T, Badhe VK, Badhe DSD, Ahluwalia P, Mitta Bl, Mittal R. Effect on emergence from anesthesia following induction with diazepam and its association with CYP2C9, CYP2C19 and CYP3A4 gene polymorphisms.  Anaesth. pain intensive care 2024;28(1):126-138. DOI: 10.35975/apic.v28i1.2380 Received: July 20, 2023; Reviewed: December 07, 2023; Accepted: December 07, 2023