Gene Polymorphisms and Morphine Analgesic Consumption
Condition: Gene; Polymorphosis
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        After the approval of the our institutional review board committee IRB at HAMAD MEDICAL
        CORPORATION (HMC), Doha, Qatar, and written, informed consent, 100 adult female 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
        cholecystectomy can will be included in this study; at the Wakrah Hospital, HMC. We planned
        to study 300 patients. If a genetic abnormality was found in 15% of patients and the
        average total morphine use in this subgroup was 40% lower than in the remainder of the
        patients, then there was 80% chance that a t test comparing average log-total morphine
        would be significant at P ≤ 0.05.
      
Biospecimen description: 
      Withdraw a 5 ml blood sample just after induction anesthesia. This sample will be stored at
      the refrigerator at 4 °C till handled to one of our research coordinator at faculty of
      pharmacy at QU.
    
Keywords: Gene; Polymorphisms;morphine;analgesia;laparoscopic