Genetic Factors Associated with Morphine Consumption in Women Undergoing Laparoscopic Cholecystectomy: A Prospective Cohort Study

Hamed M Elgendy; Sami M Ibrahim; Loulia Bader; Rudaina A Mohammad; Zainab O Ali; Mohamed Ben Allala Bejaoui; Mohamad Hilani; Hesham Ismail; Hazem F Elewa

doi:10.2147/JPR.S420447

Genetic Factors Associated with Morphine Consumption in Women Undergoing Laparoscopic Cholecystectomy: A Prospective Cohort Study

J Pain Res. 2023 Jul 15:16:2407-2417. doi: 10.2147/JPR.S420447. eCollection 2023.

Authors

Hamed M Elgendy^{1

2}, Sami M Ibrahim^{1

3}, Loulia Bader⁴, Rudaina A Mohammad⁵, Zainab O Ali⁵, Mohamed Ben Allala Bejaoui⁵, Mohamad Hilani¹, Hesham Ismail¹, Hazem F Elewa⁴

Affiliations

¹ Department of Anaesthesia, Hamad Medical Corporation, Doha, Qatar.
² Department of Anaesthesia, Assiut University Hospitals, Assiut, Egypt.
³ Department of Anaesthesia and ICU, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
⁴ College of Pharmacy, QU Health, Qatar University, Doha, Qatar.
⁵ Hamad Medical Corporation, Medical Research Center, Doha, Qatar.

Abstract

Introduction: Morphine has been a crucial analgesic agent used perioperatively in various surgical procedures. Genetic factors can lead to morphine dose requirement interpatient variability. Our objective was to determine the contribution of genetic polymorphisms in human μ-opioid receptor gene (OPRM1), ATP binding cassette gene (ABCB1) and rs2952768 to the variation of the perioperative morphine consumption in women undergoing laparoscopic cholecystectomy.

Methods: This is a prospective cohort study that included 102 adult Arab females undergoing laparoscopic cholecystectomy. The exposures were carrying the genetic variants of OPRM1, ABCB1 and rs2952768. Our primary outcome was total morphine or morphine equivalent dose required perioperatively. The secondary outcomes were pain score during the first 24 hours and adverse drug reactions. A standardized, general anaesthesia was used for all subjects. In addition to the genetic factors, we also investigated non-genetic factors influencing post-operative pain sensitivity and morphine consumption.

Results: Both (rs1799971, A>G) in OPRM1 and (rs2952768, T>C) showed statistically significant association with intra-operative total morphine dose requirements. Patients carrying the "G" allele in OPRM1 had a significantly higher total morphine mean rank dose compared to the AA genotype [62.9 vs 47.1, p=0.008]. Furthermore, patients homozygous for the rs2952768 (T>C) minor allele "CC" had a higher mean rank compared to the other genotypes [72.7 vs 50.1, p=0.046].

Conclusion: OPRM1 (rs1799971) and rs2952768 are associated with variation of intra-operative morphine consumption in laparoscopic cholecystectomy.

Clinical trial identifier: This study was registered at ClinicalTrials.gov, NCT04621864. https://clinicaltrials.gov/ct2/show/NCT04621864.

Keywords: ABCB1; Arabs; OPRM1; genetic polymorphisms; opioid; post-operative pain; women.

Associated data

ClinicalTrials.gov/NCT04621864

Grants and funding

The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: this research was funded by Hamad Medical Corporation, Doha, Qatar (grant number -MRC# 01-18-270). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.