Gene Polymorphisms and Morphine Analgesic Consumption

Overview

Variation of morphine requirements are seen considerably. Studies showed that pharmacogenetics (PGx) could possibly be used to tailor pain medication according to an individual's genetic background. While prior studies demonstrated the association of genetic polymorphism with opioid requirements in various types of surgeries in Asian and European populations, there are no published data in Middle East populations especially Arabs. However, in our area we have a lot of theincity that may give us an answer for this research question. Objectives: The primary Objective of this study is to investigate whether the genetic polymorphism of human μ-opioid receptor gene (OPRM1), ATP binding cassette gene (ABCB1) and rs2952768 are contributing to the variation of morphine consumption in women undergoing laparoscopic cholecystectomy. The secondary objective is to assess the effect of these genetic polymorphisms on pain score, analgesic dosage requirements, and complications of morphine use in these patients within the first 24 hours.

Background: Variation of morphine requirements are seen considerably. Studies showed that pharmacogenetics (PGx) could possibly be used to tailor pain medication according to an individual's genetic background. While prior studies demonstrated the association of genetic polymorphism with opioid requirements in various types of surgeries in Asian and European populations, there are no published data in Middle East populations especially Arabs. Objectives: The primary Objective of this study is to investigate whether the genetic polymorphism of human μ-opioid receptor gene (OPRM1), ATP binding cassette gene (ABCB1) and rs2952768 are contributing to the variation of morphine consumption in women undergoing laparoscopic cholecystectomy. The secondary objective is to assess the effect of these genetic polymorphisms on pain score, analgesic dosage requirements, and complications of morphine use in these patients within the first 24 hours. Methods: This is a pilot prospective cohort study to be conducted at Al-Wakrah Hospital, HMC after receiving IRB approval from MRC. The aim is to recruit 100 adult female Arab patients with American Society of Anesthesiologists physical status of I or II in whom planned postoperative pain management by morphine will be requested after laparoscopic cholecyctectomy Baseline demographic information will be collected at baseline along with 4ml blood sample for genotyping. Morphine will be administered repeatedly for postoperative pain relief and the total dose administered within the first 24 hours will be collected. The analgesic effect will be evaluated using a visual analogue scale (VAS). Multiple linear regression will be used to evaluate the association of the genetic variant groups with the morphine dose and the pain score after adjusting for different confounders. Logistic regression will be used to evaluate the association of side effect of vomiting and respiratory depression with the genetic variants. Baseline characteristic values will be reported as mean ± SD for continuous variables or frequency and percentage for categorical variables. A priori P value of ≤ 0.05 will be considered significant. All analyses will be done using the Statistical version 25 of SPSS software.