From the Departments of Anesthesia and Pain Management.
Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Anesth Analg. 2019 Apr;128(4):671-678. doi: 10.1213/ANE.0000000000002834.
Prolonged continuous oxytocin administration during labor may induce oxytocin receptor desensitization, which attenuates the response of the myometrium to further oxytocin, increasing the risk of postpartum hemorrhage. The literature comparing pulsatile (intermittent) versus continuous oxytocin administration for induction and augmentation of labor is inconsistent with regard to maternal outcomes. We aimed to determine the effect of intermittent versus continuous oxytocin preexposure on myometrial responsiveness to subsequent oxytocin. We hypothesized that intermittent oxytocin pretreatment would result in superior subsequent oxytocin-induced contractility than continuous oxytocin pretreatment.
This in vitro study was undertaken using myometrium obtained from women undergoing elective cesarean deliveries. Each myometrial strip was mounted in an individual organ bath with physiological salt solution under homeostatic conditions and allocated to one of 3 groups: (1) control (no pretreatment); (2) continuous (pretreatment with oxytocin 10(-5) M for 2 hours); or (3) intermittent (pretreatment with alternating oxytocin 10 M and physiological salt solution every 15 minutes, for 2 hours). After pretreatment, dose-response testing to oxytocin 10(-5) to 10(-5) M was performed and contractile parameters were measured. The primary outcome was motility index (MI, amplitude × frequency) of contractions.
Eighteen women were recruited, and 86 successful experiments were performed (control n = 29, continuous n = 28, intermittent n = 29). The means (standard errors) of MI (√g·contractions/10 min) in the control, continuous, and intermittent groups were 2.34 (0.09), 1.78 (0.09), and 2.13 (0.11), respectively. The MI was significantly reduced in the continuous group when compared to the control (estimated difference [95% confidence interval {CI}], -0.56 [-0.81 to -0.31]; P < .01) and intermittent group (estimated difference [95% CI], -0.35 [-0.62 to -0.08]; P = .01). There was no significant difference in MI between the intermittent and control group (estimated difference [95% CI], -0.21 [-0.51 to 0.09]; P = .17).
Human myometrium remains more responsive to subsequent oxytocin after intermittent compared to continuous exposure to oxytocin, most likely due to reduction in oxytocin receptor desensitization, or facilitation of receptor resensitization in the intermittent group. Hence, intermittent oxytocin administration during labor warrants further investigation as a technique to preserve uterine oxytocin responsiveness.
分娩过程中长时间持续给予催产素可能会导致催产素受体脱敏，从而减弱子宫肌对进一步催产素的反应，增加产后出血的风险。关于催产素诱导和加强分娩时脉冲式（间歇性）与持续给药的文献结果不一致，关于产妇结局的结果也不一致。我们旨在确定间歇与持续预先接触催产素对随后催产素诱导的子宫收缩反应的影响。我们假设，与持续催产素预处理相比，间歇催产素预处理会导致随后的催产素诱导收缩性更好。
本体外研究使用择期剖宫产妇女获得的子宫肌进行。每个子宫肌条在生理盐溶液中恒稳态条件下置于单独的器官浴中，并分配到 3 组之一：（1）对照组（无预处理）；（2）持续组（用 10-5M 催产素预处理 2 小时）；或（3）间歇组（每隔 15 分钟交替用 10M 催产素和生理盐水预处理，持续 2 小时）。预处理后，进行 10-5 至 10-5M 催产素的剂量反应测试，并测量收缩参数。主要结局是收缩的运动指数（MI，振幅×频率）。
共招募 18 名女性，成功进行了 86 项实验（对照组 n=29，持续组 n=28，间歇组 n=29）。对照组、持续组和间歇组的 MI（√g·收缩/10min）平均值（标准误差）分别为 2.34（0.09）、1.78（0.09）和 2.13（0.11）。与对照组相比，持续组的 MI 显著降低（估计差值[95%置信区间{CI}]，-0.56[-0.81 至-0.31]；P<.01）和间歇组（估计差值[95% CI]，-0.35[-0.62 至-0.08]；P=0.01）。间歇组和对照组之间的 MI 无显著差异（估计差值[95% CI]，-0.21[-0.51 至 0.09]；P=0.17）。
与持续接触催产素相比，间歇接触催产素后，人子宫肌对随后的催产素仍更敏感，这可能是由于催产素受体脱敏减少，或间歇组受体再敏化得到促进。因此，分娩时间歇给予催产素作为一种维持子宫催产素反应性的技术值得进一步研究。
