Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Int J Obstet Anesth. 2010 Jul;19(3):246-53. doi: 10.1016/j.ijoa.2009.09.005. Epub 2010 Feb 19.
The purpose of this two-part prospective observational and blinded trial was to determine whether the single nucleotide polymorphism of the mu-opioid receptor gene (OPRM1:c.304A>G) modifies (1) the duration of intrathecal fentanyl labor analgesia and (2) supplemental analgesic requirements after intrathecal morphine analgesia following cesarean delivery.
Labor analgesia was initiated with intrathecal fentanyl 25 microg. Patients undergoing primary cesarean delivery under spinal anesthesia received intrathecal morphine 150 microg. The primary outcome variables were duration of intrathecal fentanyl analgesia in the labor study and the requirement for supplemental systemic analgesia in the cesarean study. Outcomes were compared between 304A homozygotes (group A) and 304A>G heterozygotes and 304G homozygotes (group G).
The labor study included 190 participants and the post-cesarean study included 103 participants; 24% subjects carried the 304A>G allele. The median (95% CI) duration of intrathecal fentanyl analgesia was 70 min (62, 78) in group A and 63 min (50, 76) in group G (P = 0.54). There was no difference in the amount of supplemental oral morphine equivalents required to treat breakthrough pain within 72 h after intrathecal morphine between groups A and G (median [IQR] 68 mg (37, 97) and 75 mg (37, 90) respectively, P = 0.99) or in the duration of intrathecal morphine analgesia (P = 0.84). The incidence of pruritus was greater in group A.
Using the two outcome parameters duration of analgesia and treatment for breakthrough pain, we did not find a simple association between intrathecal opioid analgesia and OPRM1 304A/G polymorphism.
本项前瞻性观察性双盲试验的目的在于确定阿片受体 μ 型基因(OPRM1:c.304A>G)单核苷酸多态性是否会(1)改变椎管内芬太尼分娩镇痛的持续时间和(2)改变剖宫产术后鞘内吗啡镇痛后的补充镇痛需求。
分娩镇痛起始于鞘内注射 25μg 芬太尼。椎管内麻醉下施行初次剖宫产的患者接受鞘内注射 150μg 吗啡。主要结局变量是分娩研究中鞘内芬太尼镇痛的持续时间和剖宫产研究中补充全身镇痛的需求。比较 304A 纯合子(A 组)、304A>G 杂合子和 304G 纯合子(G 组)之间的结局。
分娩研究纳入 190 例患者,剖宫产研究纳入 103 例患者;24%的患者携带 304A>G 等位基因。A 组鞘内芬太尼镇痛的中位(95%CI)持续时间为 70 分钟(62,78),G 组为 63 分钟(50,76)(P=0.54)。鞘内吗啡后 72 小时内治疗突破性疼痛所需的口服吗啡等效物量在 A 组和 G 组之间无差异(中位数[IQR]分别为 68mg(37,97)和 75mg(37,90),P=0.99),鞘内吗啡镇痛的持续时间也无差异(P=0.84)。A 组瘙痒的发生率更高。
使用镇痛持续时间和突破性疼痛治疗这两个结局参数,我们未发现鞘内阿片类药物镇痛与 OPRM1 304A/G 多态性之间存在简单关联。