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Polymorphism of the μ-Opioid Receptor Gene (OPRM1 118A>G) Affects Fentanyl-Induced Analgesia During Anesthesia and Recovery

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Abstract

Background: There is much variation in the response of both individuals and different ethnic populations to opioids, with genetic differences being responsible for interindividual variation. The m-opioid receptor single nucleotide polymorphism (rs number 1799971) at nucleotide position 118 (OPRM1 118A>G) affects the analgesic response to opioids.

Objective: This study aimed to investigate the association between the OPRM1 118A>G polymorphism and the effects of fentanyl-induced analgesia, respiratory depression, and anesthetic recovery responses in a population of Han Chinese patients.

Study Design: The study was a case series in a hospital setting, with 1 year of study and 1 year of follow-up. A total of 189 patients (92 males and 97 females; American Society of Anesthesiologists Physical Status I or II, Glasgow Coma Scale = 15) who were scheduled for laparoscopic abdominal surgery received intravenous midazolam (Versed®) 0.08-0.01 mg/kg and fentanyl (Duragesic®) 5.0 μg/kg. The main outcome measure was the degree of postoperative pain, as assessed using the Visual Analog Scale (VAS). VAS scores were recorded 5, 15, 30, 45, and 60 minutes after a fentanyl bolus injection in the post-anesthesia care unit (PACU). The minute expiratory volume, end-tidal carbon dioxide concentration (EtCO2) and respiratory rate (RR) were measured continuously. The incidence of fentanyl-induced respiratory depression (RR <8/min and EtCO2 >45 mmHg) was recorded at its appearance and treated with respiratory assistance. Blood gas analysis was done 15, 30, 45, and 60 minutes after extubation. These parameters were correlated with genotyping results of genomic DNA extracted from whole blood.

Results: Patients with the OPRM1 118 AG or GG genotypes had significantly higher VAS pain scores 15 and 30 minutes after a fentanyl bolus injection in the PACU than AA genotype patients (p <0.05). A small but statistically significant difference was observed between the 118 AA and 118 AG/GG genotypes with regard to the carbon dioxide arterial pressure (PaCO2) at 15 and 30 minutes from the fentanyl bolus injection after extubation (p < 0.05); however, no clinically significant difference in the frequency of respiratory depression was seen. Homozygous 118 GG genotype patients had a significantly shorter time to awakening (p = 0.018) and extubation (p = 0.024) than patients with the 118 AA genotype. When the 118 GG and 118 AG genotypes were combined for analysis, a significantly shorter time to awakening (p = 0.011) and extubation (p = 0.010), compared with the 118 AA genotype, was also seen.

Conclusion: The OPRM1 118A>G polymorphism lessens the analgesic response to fentanyl and the time to awakening and extubation but has no clinically significant effect on the incidence of respiratory depression.

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Acknowledgments

W.D. Wu carried out the clinical studies, participated in the sequence alignment, and performed the statistical analysis. Y. Wang participated in the design of the study and drafted the manuscript. Y.M. Fang participated in the sequence alignment. H.Y. Zhou conceived the study, participated in its design and coordination, and helped to draft the manuscript. All authors read and approved the final manuscript.

No sources of funding were used to assist in the preparation of this study. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Department of Anesthesiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Jiefang Road 88, Hangzhou, 310009, China

    Wei Dong Wu,  Yi Wang & Hai Yan Zhou

  2. Cancer Institute, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

    Yong Ming Fang

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  1. Wei Dong Wu
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  2. Yi Wang
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Correspondence to Yi Wang.

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Dong Wu, W., Wang, Y., Ming Fang, Y. et al. Polymorphism of the μ-Opioid Receptor Gene (OPRM1 118A>G) Affects Fentanyl-Induced Analgesia During Anesthesia and Recovery. Mol Diag Ther 13, 331–337 (2009). https://doi.org/10.1007/BF03256337

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