常见 OPRM1、COMT、SLC6A4、ABCB1 和 CYP2B6 多态性对甲状腺切除术患者围手术期镇痛和丙泊酚需求的影响。
Effect of common OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 polymorphisms on perioperative analgesic and propofol demands on patients subjected to thyroidectomy surgery.
机构信息
Department of Anesthesiology and Intensive Care Unit, School of Medicine, Faculty of Health Sciences, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
1st Laboratory of Pharmacology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
出版信息
Pharmacol Rep. 2023 Apr;75(2):386-396. doi: 10.1007/s43440-023-00455-7. Epub 2023 Feb 7.
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.
背景
围手术期的麻醉和/或镇痛需求存在相当大的差异，其中一部分差异似乎源于遗传。在这里，我们研究了 OPRM1、COMT、SLC6A4、ABCB1 和 CYP2B6 基因中的常见多态性对接受甲状腺切除术的患者术中瑞芬太尼和丙泊酚消耗以及术后镇痛需求的影响。
方法
我们进行了一项前瞻性队列研究，纳入 90 例拟行择期甲状腺切除术的患者，采用丙泊酚和瑞芬太尼靶控输注（TCI）实现全静脉麻醉。根据方案为患者提供术后镇痛，并根据个体需要按需提供。通过 PCR-RFLP 方法确定基因型。记录每位患者的基因型数据、术中血流动力学、瑞芬太尼和丙泊酚的总消耗量、术后镇痛需求和疼痛感知。
结果
与 C 携带者相比，ABCB1 3435TT 基因型的患者术后 1 小时内疼痛明显减轻[平均 VAS（SD）=0.86（1.22）vs. 2.42（1.75）；p=0.017]，这一发现仅限于寻求补救性镇痛治疗的患者。术中，OPRM1 A118G 和 CYP2B6 G516T 次要等位基因的纯合子患者似乎消耗较少的瑞芬太尼[平均（SD）=9.12（1.01）vs. 13.53（5.15），用于 OPRM1 118GG 和 A 携带者]和丙泊酚[中位数（范围）=14.95（11.53，1359.5）vs. 121.4（1.43，2349.4），用于 CYP2B6 516TT 和 G 携带者，分别]，但在我们的样本中差异无统计学意义。
结论
ABCB1 C3435T 多态性似乎影响了低疼痛阈值患者术后对手术疼痛的感知。OPRM1 A118G 和 CYP2B6 G516T 多态性的少数等位基因纯合子数量较少，无法根据本研究结果确定将后者纳入 TCI 编程算法的结论。
临床试验注册号
ACTRN12616001598471。
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