Effect of common OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 polymorphisms on perioperative analgesic and propofol demands on patients subjected to thyroidectomy surgery

Pharmacol Rep. 2023 Apr;75(2):386-396. doi: 10.1007/s43440-023-00455-7. Epub 2023 Feb 7.

Abstract

Background: Perioperative anesthetic and/or analgesic demand present considerable variation, and part of that variation appears to be genetic in origin. Here we investigate the impact of common polymorphisms in OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 genes, on the intra-operative consumption of remifentanil and propofol, as well as the postoperative analgesic needs, in patients subjected to thyroidectomy surgery.

Methods: We conducted a prospective cohort study with 90 patients scheduled to undergo elective thyroidectomy, under total intravenous anesthesia achieved by target control infusion (TCI) of propofol and remifentanil. Postoperative analgesics were administered by protocol and on-demand by the individual patient. Genotyping was established by PCR-RFLP methods. Genotyping data, intra-operative hemodynamics, and total consumption of remifentanil and propofol, as well as postoperative analgesic needs and pain perception, were recorded for each individual.

Results: Patients with the ABCB1 3435TT genotype appeared to experience significantly less pain within one hour post-operatively, compared to C carriers [mean VAS (SD) = 0.86 (1.22) vs. 2.42 (1.75); p = 0.017], a finding limited to those seeking rescue analgesic treatment. Intra-operatively, homozygotes patients for the minor allele of OPRM1 A118G and CYP2B6 G516T appeared to consume less remifentanil [mean (SD) = 9.12 (1.01) vs. 13.53 (5.15), for OPRM1 118GG and A carriers] and propofol [median (range) = 14.95 (11.53, 1359.5) vs. 121.4 (1.43, 2349.4), for CYP2B6 516TT and G carriers, respectively] but the difference was not statistically significant in our sample.

Conclusions: The ABCB1 C3435T polymorphism appears to affect the postoperative perception of surgical pain among patients with low pain threshold. The small number of minor allele homozygotes for the OPRM1 A118G and CYP2B6 G516T polymorphisms precludes a definitive conclusion regarding the inclusion of the latter in a TCI-programming algorithm, based on the results of this study.

Clinical trial registration number: ACTRN12616001598471.

Keywords: ABCB1; COMT; CYP2B6; OPRM1; Propofol; Remifentanil; SLC6A4.

MeSH terms

  • Analgesics / therapeutic use
  • Analgesics, Opioid / therapeutic use
  • Anesthetics, Intravenous / therapeutic use
  • Cytochrome P-450 CYP2B6 / genetics
  • Humans
  • Pain / drug therapy
  • Pain, Postoperative / drug therapy
  • Pain, Postoperative / genetics
  • Polymorphism, Single Nucleotide
  • Propofol* / therapeutic use
  • Prospective Studies
  • Receptors, Opioid, mu / genetics
  • Remifentanil / therapeutic use
  • Thyroidectomy

Substances

  • Propofol
  • Remifentanil
  • Cytochrome P-450 CYP2B6
  • Analgesics, Opioid
  • Analgesics
  • Anesthetics, Intravenous
  • CYP2B6 protein, human
  • OPRM1 protein, human
  • Receptors, Opioid, mu
  • SLC6A4 protein, human
  • ABCB1 protein, human
  • COMT protein, human

Associated data

  • ANZCTR/ACTRN12616001598471