Pharmacogenetics in obstetric anesthesia

Landau, Ruth; Smiley, Richard M.

doi:10.1016/j.bpa.2017.01.004

Cited by 9 publications

(3 citation statements)

References 69 publications

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“…Our findings with respect to the effect of the five gene polymorphisms on the intra-operative remifentanil and propofol consumption were less promising, even though it is perhaps worth mentioning that all four carriers of the OPRM1 118GG genotype consumed low amounts of remifentanil, and so did five out of six patients with the CYP2B6 516TT genotype with respect to propofol. A small number of studies have examined the association of the same OPRM1 polymorphism with intra-operative opioid (fentanyl, sulfentanil, or morphine) requirements, all of them involving obstetrics analgesia [reviewed in [ 31 ], and in [ 32 ], with inconclusive results, even though carriage of the G allele appeared to somewhat increase opioid efficacy, which is not contradictory to our findings. According to our literature search, no study has examined the effect of OPRM1 A118G on remifentanil requirements thus far, with the exception of a single report highlighting a protective effect of the maternal G allele on neonates whose mothers had received remifentanil in the context of labor anesthesia [ 15 ].…”

Section: Discussioncontrasting

confidence: 43%

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

et al. 2023

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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.

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Section: Discussioncontrasting

confidence: 43%

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

et al. 2023

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“…A genetic basis for propensity to hypotension has also been proposed. [ 5 ] Recently, ondansetron has been shown to minimise the incidence of hypotension and bradycardia by inhibiting the Bezold--Jarisch reflex. The effect was only moderate (NNT of 5.3 and 7.6 for preventing hypotension and bradycardia).…”

Section: Discussionmentioning

confidence: 99%

Effect of prophylactic combination of glycopyrrolate, ondansetron, and ephedrine upon hypotension during obstetric spinal anaesthesia–A randomised controlled trial

Vadhanan¹,

Kalyanasundaram²,

Sundaram³

et al. 2021

Indian J Anaesth

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Background and Aims: Various pharmacological and non-pharmacological strategies have been employed to minimise hypotension during obstetric spinal anaesthesia. We compared a prophylactic combination of glycopyrrolate, ondansetron, and ephedrine in terms of total vasopressor consumption, with standard treatment in this randomised controlled trial. Methods: One hundred patients undergoing elective caeserean sections were randomly divided into two groups of 50 each, the study group received prophylactic ondansetron and glycopyrrolate boluses followed by an infusion of ephedrine, while the control group received ephedrine boluses as required. The total ephedrine consumption (primary objective), incidence and degree of hypotension, heart rate variations, and neonatal APGAR scores (secondary objectives) were analysed. Results: The median ephedrine requirement was lesser in the study group compared to the control group [13.2 mg (10--15.75) vs. 27.7 mg (12--24)], with a P value of 0.02. Fewer participants experienced hypotension in the study group before baby delivery compared to the control group (12 vs. 36, P = 0.004). Heart rate was higher in the study group. No significant differences were observed in neonatal APGAR scores and incidence of adverse events. Conclusion: A combination of glycopyrrolate, ondansetron, and ephedrine might offer better haemodynamic stability and reduce vasopressor consumption in obstetric patients undergoing spinal anaesthesia as opposed to standard treatment.

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“…16 Candidate gene studies focusing on labor pain have been undertaken with associative findings in ADRB2 (β2-andrenergic receptor), OPRM1 (µ-opioid receptor), and GCH1 (guanosine triphosphate cyclohydrolase). 17…”

Section: Introductionmentioning

confidence: 99%

Genetic associations of perinatal pain and depression

et al. 2019

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Underlying genetic influences may affect perinatal pain, depression, or both. We investigated the role of 59 single-nucleotide polymorphisms on 20 quantitative traits measured in perinatal women. Moreover, 183 pregnant women (28–37 weeks’ gestation) were prospectively genotyped for single-nucleotide polymorphisms with known prior associations with either pain or depression in nonpregnant populations. Prenatal saliva samples were collected. Phenotypic data were gathered during prenatal, labor and delivery, and postpartum (six weeks and three months) periods, capturing labor pain, Edinburgh Postnatal Depression Score, and Brief Pain Inventories. Following quality control, genotypes were used as predictors and phenotypes as dependent variables in multiple linear regression analyses to detect associations. Three statistical models were tested: additive allele effects, deviation from dominant allele effects, and the joint test of both. rs4633 (a synonymous single-nucleotide polymorphism in COMT) associated with “pain right now” scores at six weeks postpartum. Single-nucleotide polymorphisms rs1135349 (a single-nucleotide polymorphism within a small noncoding RNA that has many prior associations for depression) and rs7548151 (intronic in ASTN1) were associated with the maximum pain unpleasantness score experienced during labor (a measure of the emotional valence of labor pain), controlling for the Holm–Bonferroni family-wise error rate. Sensory dimensions of labor pain (i.e., pain intensity) and postpartum depression scores were not associated with genotyped single-nucleotide polymorphisms. Identifying genomic components of these perinatal complex disorders may produce insights into relevant pathways or novel treatment options.

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Pharmacogenetics in obstetric anesthesia

Cited by 9 publications

References 69 publications

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

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

Effect of prophylactic combination of glycopyrrolate, ondansetron, and ephedrine upon hypotension during obstetric spinal anaesthesia–A randomised controlled trial

Genetic associations of perinatal pain and depression

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