Department of Anesthesiology and Pain Medicine, University of Washington, Medical Center, 1959 NE Pacific Street, Suite BB 1415B, Seattle, WA 98195, USA.
Anesth Analg. 2013 Feb;116(2):386-91. doi: 10.1213/ANE.0b013e318273f2c7. Epub 2013 Jan 9.
IV fentanyl is used as a labor analgesic; however, few studies have reported the effects of IV fentanyl for early labor analgesia. We evaluated the analgesic response to IV fentanyl according to the combined effect of the single-nucleotide polymorphisms rs1799971 (c.118A/G, p. 40Asn/Asp) of the µ-opioid receptor gene (OPRM1) and rs4680 (c.472G/A, p.158Val/Met) of the catechol-O-methyltransferase (COMT) gene in women requesting labor analgesia.
Labor analgesia was initiated with IV fentanyl 1.5 μg/kg. The primary outcome was analgesic success, defined as Numerical Verbal Pain Scale score≤10/100 15 minutes after the dose of fentanyl. Analgesic and side effect outcomes were compared according to OPRM1 and COMT genotypes.
One hundred six women were enrolled and received IV fentanyl. IV analgesic success was 6% in women with the combination Asn/Asn-Met/Met (n=17) versus 20% in all other women combined (not Asn/Asn-Met/Met; P=0.30; difference=14%; 95% confidence interval [CI], -10% to 26%). IV analgesic success was 20% in women 118A/A (Asn/Asn) versus 21% for A/G and G/G of OPRM1 (P=0.82; difference=2%; 95% CI, -17% to 19%), and 10% in women 472A (Met/Met) versus 22% for A/G (Met/Val) and G/G (Val/Val) of COMT (P=0.24; difference=12%; 95% CI, -6% to 26%). Met/Met158 (n=31) versus Met/Val or Val/Val of COMT was associated with a smaller decrease in Numerical Verbal Pain Scale (24±18 vs 37±23; P=0.005; mean difference=-13; 99% CI, -25 to -1).
This study was underpowered to draw firm conclusions on the influence of OPRM1 and COMT genotypes on labor analgesia with IV fentanyl. Further larger studies are needed to evaluate whether genotyping COMT alone or in combination with OPRM1 may have potentially useful clinical implications, such as not offering IV fentanyl in early labor to women who will most likely not benefit from it.
静脉注射芬太尼被用作分娩镇痛剂；然而，很少有研究报道静脉注射芬太尼用于早期分娩镇痛的效果。我们根据 μ-阿片受体基因（OPRM1）的单核苷酸多态性 rs1799971（c.118A/G，p.40Asn/Asp）和儿茶酚-O-甲基转移酶（COMT）基因的 rs4680（c.472G/A，p.158Val/Met）的联合作用，评估了接受分娩镇痛的女性对静脉注射芬太尼的镇痛反应。
分娩镇痛起始剂量为静脉注射芬太尼 1.5μg/kg。主要结局是镇痛成功，定义为芬太尼剂量后 15 分钟数字口述疼痛评分≤10/100。根据 OPRM1 和 COMT 基因型比较镇痛和副作用结局。
106 名女性入组并接受了静脉注射芬太尼。在阿片受体基因组合 Asn/Asn-Met/Met（n=17）的女性中，静脉镇痛成功率为 6%，而所有其他女性（非 Asn/Asn-Met/Met）的静脉镇痛成功率为 20%（P=0.30；差异=14%；95%置信区间[CI]，-10%至 26%）。在 OPRM1 中，118A/A（Asn/Asn）的女性中静脉镇痛成功率为 20%，A/G 和 G/G 的女性为 21%（P=0.82；差异=2%；95%CI，-17%至 19%），而 COMT 中 472A（Met/Met）的女性为 10%，A/G（Met/Val）和 G/G（Val/Val）的女性为 22%（P=0.24；差异=12%；95%CI，-6%至 26%）。COMT 的 Met/Met158（n=31）与 Met/Val 或 Val/Val 相比，数字口述疼痛评分下降幅度较小（24±18 与 37±23；P=0.005；平均差异=-13；99%CI，-25 至-1）。
本研究对 OPRM1 和 COMT 基因型对静脉注射芬太尼分娩镇痛的影响的研究力度不足。需要进一步的更大规模的研究来评估单独或联合检测 COMT 和 OPRM1 基因型是否具有潜在的临床意义，例如，对于不太可能从中受益的女性，不在早期分娩时给予静脉注射芬太尼。
