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Influence of Potential Gene Polymorphisms on Propofol Dosage Regimen in Patients Undergoing Abdominal Hysterectomy.

ABSTRACT: Propofol (2,6-diisopropylphenol) is the most common intravenous anesthetic used in modern medicine. It is postulated that individual differences in genetic factors [polymorphism of single nucleotide polymorphisms (SNPs)] in the genes encoding metabolic enzymes, molecular targets and molecular binding sites of propofol can be responsible for susceptibility to propofol effects. The aim of our study was to investigate the influence of the cytochrome P450 2B6 isozyme CYP2B6 (rs3745274), γ-aminobutyric acid type A (GABAA) receptor α1 subunit GABRA1 (rs2279020) and ATP-binding cassette subfamily B member 1 ABCB1 (rs1045642) gene polymorphisms on propofol therapeutic outcomes in the patients undergoing abdominal hysterectomy. Ninety patients aged 29-74 years, with different ethnicities were included in this study. The presence of polymorphisms was analyzed using TaqMan SNP genotype analysis on Stratagene MxPro 3005P real-time polymerase chain reaction (qPCR). The distribution of all three genetic variants was within the Hardy-Weinberg equilibrium. There was no significant difference (p >0.05) in the allelic frequencies of polymorphic variants and genotype distributions between adult and older patients and between patients of different ethnicities. Our study did not detect a statistically significant influence of the CYP2B6 (c.516G>A), GABRA1 (c.1059+15G>A) and ABCB1 (c.3435T>C) variants on the variability of clinical parameters (doses for induction in anesthesia, additional doses, induction time and wake time after anesthesia and side effects of propofol). However, the observed trend on the possible influence of the CYP2B6 (c.516G>A) and GABRA1 (c.1059+15G>A) variants warrant an extension of these studies on a larger number of patients.

SUBMITTER: Ivanov E

PROVIDER: S-EPMC8009561 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The aim of the present study was to elucidate the influence of the anesthetics propofol and sevoflurane on gene expression in patients undergoing coronary artery bypass graft surgery (CABG) and to provide a basis for the selection of the appropriate anesthetic. The gene expression profiles of patients receiving one of the two anesthetics were analyzed prior to and following the induction of anesthesia. GSE4386 microarray data obtained from the Gene Expression Omnibus database was used to identify the differentially expressed genes (DEGs) by significance analysis of the microarray. The data set contained data regarding atrial tissue samples from 40 patients that underwent CABG, and that received either propofol (n=10) or sevoflurane (n=10) or were control subjects (n=20). The 20 control samples comprised the same patients prior to undergoing CABG. The Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO) Enrichment Analysis was applied to the DEGs using the Database for Annotation, Visualization and Integration Discovery functional annotation bioinformatics microarray tool. A total of 242 and 560 DEGs were identified in the human atrial samples treated with propofol and sevoflurane, respectively. Among these, 116 upregulated DEGs and no downregulated DEGs were found to be unique to sevoflurane, while 10 upregulated and 212 downregulated DEGs were unique to propofol. The majority of the pathways that were significantly over-represented among the upregulated DEGs were associated with the immune response, such as Toll- and NOD-like receptors and Jak-STAT signaling pathways. GO enrichment analysis revealed that the downregulated DEGs unique to sevoflurane treatment were involved in the immune response and glucose metabolism, while the upregulated DEGs were associated with cellular ion homeostasis and epithelial cell development. Compared with propofol, sevoflurane appeared to exert a more marked effect on biological pathways, such as drug metabolism, glycolysis, cellular ion homeostasis and epithelial cell development.

Project description:Target-controlled infusion (TCI) provides precise pharmacokinetic control of propofol concentration in the effect-site (Ce), eg. brain. This pilot study aims to evaluate the feasibility and optimal TCI regimen for flexible bronchoscopy (FB) sedation.After alfentanil bolus, initial induction Ce of propofol was targeted at 2 ?g/ml. Patients were randomized into three titration groups (i.e., by 0.5, 0.2 and 0.1 ?g/ml, respectively) to maintain stable sedation levels and vital signs. Adverse events, frequency of adjustments, drug doses, and induction and recovery times were recorded.The study was closed early due to significantly severe hypoxemia events (oxyhemoglobin saturation <70%) in the group titrated at 0.5 ?g/ml. Forty-nine, 49 and 46 patients were enrolled into the 3 respective groups before study closure. The proportion of patients with hypoxemia events differed significantly between groups (67.3 vs. 46.9 vs. 41.3%, p?=?0.027). Hypotension events, induction and recovery time and propofol doses were not different. The Ce of induction differed significantly between groups (2.4±0.5 vs. 2.1±0.4 vs. 2.1±0.3 ?g/ml, p?=?0.005) and the Ce of procedures was higher at 0.5 ?g/ml titration (2.4±0.5 vs. 2.1±0.4 vs. 2.2±0.3 ?g/ml, p?=?0.006). The adjustment frequency tended to be higher for titration at 0.1 ?g/ml but was not statistically significant (2 (0?6) vs. 3 (0?6) vs. 3 (0?11)). Subgroup analysis revealed 14% of all patients required no further adjustment during the whole sedation. Comparing patients requiring at least one adjustment with those who did not, they were observed to have a shorter induction time (87.6±34.9 vs. 226.9±147.9 sec, p<0.001), a smaller induction dose and Ce (32.5±4.1 vs. 56.8±22.7 mg, p<0.001; 1.76±0.17 vs. 2.28 ±0.41, p<0.001, respectively), and less hypoxemia and hypotension (15.8 vs.56.9%, p?=?0.001; 0 vs. 24.1%, p?=?0.008, respectively).Titration at 0.5 ?g/ml is risky for FB sedation. A subgroup of patients required no more TCI adjustment with fewer complications. Further studies are warranted to determine the optimal regimen of TCI for FB sedation.ClinicalTrials.gov NCT01101477.

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Influence of Potential Gene Polymorphisms on Propofol Dosage Regimen in Patients Undergoing Abdominal Hysterectomy.

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