Effect of common OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 polymorphisms on perioperative analgesic and propofol demands on patients subjected to thyroidectomy surgery.
Humans
Propofol
/ therapeutic use
Remifentanil
/ therapeutic use
Cytochrome P-450 CYP2B6
/ genetics
Prospective Studies
Thyroidectomy
Polymorphism, Single Nucleotide
Pain
/ drug therapy
Analgesics, Opioid
/ therapeutic use
Analgesics
/ therapeutic use
Pain, Postoperative
/ drug therapy
Anesthetics, Intravenous
/ therapeutic use
Receptors, Opioid, mu
/ genetics
ABCB1
COMT
CYP2B6
OPRM1
Propofol
Remifentanil
SLC6A4
Journal
Pharmacological reports : PR
ISSN: 2299-5684
Titre abrégé: Pharmacol Rep
Pays: Switzerland
ID NLM: 101234999
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
received:
02
11
2022
accepted:
27
01
2023
revised:
26
01
2023
medline:
31
3
2023
pubmed:
8
2
2023
entrez:
7
2
2023
Statut:
ppublish
Résumé
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. 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. 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. 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. ACTRN12616001598471.
Sections du résumé
BACKGROUND
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
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
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
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
BACKGROUND
ACTRN12616001598471.
Identifiants
pubmed: 36749481
doi: 10.1007/s43440-023-00455-7
pii: 10.1007/s43440-023-00455-7
pmc: PMC10060341
doi:
Substances chimiques
Propofol
YI7VU623SF
Remifentanil
P10582JYYK
Cytochrome P-450 CYP2B6
EC 1.14.14.1
Analgesics, Opioid
0
Analgesics
0
Anesthetics, Intravenous
0
CYP2B6 protein, human
EC 1.14.14.1
OPRM1 protein, human
0
Receptors, Opioid, mu
0
SLC6A4 protein, human
0
ABCB1 protein, human
0
COMT protein, human
EC 2.1.1.6
Banques de données
ANZCTR
['ACTRN12616001598471']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
386-396Informations de copyright
© 2023. The Author(s).
Références
PLoS One. 2009 Jun 23;4(6):e6016
pubmed: 19547755
Neurosci Lett. 2012 Jan 11;506(2):214-9
pubmed: 22101356
Neurosci Lett. 1997 Jan 17;221(2-3):202-4
pubmed: 9121699
Eur J Clin Pharmacol. 2012 Apr;68(4):397-406
pubmed: 22006347
Best Pract Res Clin Anaesthesiol. 2017 Mar;31(1):23-34
pubmed: 28625302
Mol Pain. 2009 Jul 01;5:37
pubmed: 19570226
Anesthesiology. 2004 Jun;100(6):1373-81
pubmed: 15166554
Emerg Med J. 2012 Jan;29(1):37-9
pubmed: 21362724
Annu Rev Neurosci. 2018 Jul 8;41:453-473
pubmed: 29852083
Anesth Analg. 2021 Oct 1;133(4):1028-1035
pubmed: 34153010
J Pain Res. 2017 May 09;10:1071-1078
pubmed: 28533695
Biol Res Nurs. 2017 Mar;19(2):170-179
pubmed: 27903758
Curr Neuropharmacol. 2017 Nov 14;15(8):1156-1173
pubmed: 28474563
Drugs R D. 2020 Sep;20(3):225-236
pubmed: 32409981
Clin Perinatol. 2013 Sep;40(3):575-87
pubmed: 23972758
Pharmacogenomics J. 2020 Jun;20(3):471-481
pubmed: 31806881
Clin J Pain. 2017 Dec;33(12):1117-1130
pubmed: 28379874
Pharmacogenetics. 2001 Jul;11(5):399-415
pubmed: 11470993
Eur J Clin Pharmacol. 2013 Sep;69(9):1651-8
pubmed: 23686330
Clin Pharmacol Ther. 2021 Jul;110(1):82-97
pubmed: 33448339
J Headache Pain. 2014 Jun 20;15:42
pubmed: 24950698
Ther Drug Monit. 2016 Aug;38(4):525-33
pubmed: 27027462
Med Sci Monit. 2019 Jul 15;25:5258-5262
pubmed: 31346154
Mol Pharmacol. 2013 Nov;84(5):774-86
pubmed: 24019224
Peptides. 2001 Dec;22(12):2015-20
pubmed: 11786185
Handb Clin Neurol. 2012;106:227-37
pubmed: 22608624
Anesth Analg. 1998 May;86(5):1045-50
pubmed: 9585294
Clin Pharmacokinet. 2018 Dec;57(12):1539-1558
pubmed: 30019172
Anaesthesia. 2010 Feb;65(2):130-5
pubmed: 20003118
Anesth Analg. 2016 Jan;122(1):56-69
pubmed: 26516804
Drug Metab Pharmacokinet. 2014;29(2):215-8
pubmed: 24153159
Int J Emerg Med. 2014 Jan 03;7(1):2
pubmed: 24386899
Physiol Res. 2015;64(Suppl 4):S529-38
pubmed: 26681083
Eur J Drug Metab Pharmacokinet. 2016 Oct;41(5):511-5
pubmed: 26141406
J Headache Pain. 2014 Jul 21;15:46
pubmed: 25043824
Pharmacogenomics. 2021 Jun;22(9):573-586
pubmed: 34013775
Br J Anaesth. 2020 Oct;125(4):483-491
pubmed: 32654750
Ann Pharmacother. 2021 Dec;55(12):1486-1501
pubmed: 33771051
Front Genet. 2013 Mar 05;4:24
pubmed: 23467454
J Clin Anesth. 1996 Dec;8(8):679-82
pubmed: 8982900
Pharmacol Rep. 2016 Apr;68(2):476-82
pubmed: 26922556