OBSTETRIC ANESTHESIA: TOCOLYSIS AND HEMORRHAGE

产科麻醉：安胎和出血

• 批准号: 3467320
• 负责人: DAVID H CHESTNUT
• 金额: $ 8.93万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3467320
• 关键词: beta adrenergic agent; beta adrenergic receptor; dosage; eicosanoid metabolism; embryo /fetus drug adverse effect; embryo /fetus pharmacology; ephedrine; epidural anesthesia; hemorrhage; indomethacin; inhibitor /antagonist; labor complications; magnesium; muscle contraction; muscle relaxants; obstetric anesthesia; phenylephrine; pregnancy circulation; sheep; sulfates; tissue /cell culture

Preterm delivery is the leading cause of perinatal morbidity and mortality in the United States. Obstetricians often give beta- sympathomimetic agents (e.g. ritodrine) to treat preterm labor, a therapy called tocolysis. Although ritodrine is relatively selective for the beta 2 receptor (e.g., uterine smooth muscle), beta 1-receptor stimulation also occurs, resulting in increased maternal heart rate and systemic vasodilation. Magnesium sulfate (MgSO4) is often given as an alternate tocolytic drug; many clinicians believe that it incurs less risk of cardiovascular side effects. Obstetrician usually avoid ritodrine in patients at risk for hemorrhage, for fear of severe hypotension. Anesthesiologists often avoid regional anesthesia in patients recently subjected to infusion of either ritodrine or MgSO4. There are few data regarding interactions between tocolysis, hemorrhage, and anesthesia. A recent study from this laboratory showed that MgSO4 significantly worsened the maternal hypotensive response to hemorrhage in gravid ewes. The specific aims of this proposal are: 1) To hemorrhage; 2) To determine whether the tachycardia response to ritodrine alters maternal and fetal hemodynamic responses to hemorrhage; 3) To study whether, and if so why, ritodrine increases the risk of hypotension with epidural anesthesia; and 4) To study whether MgSO4 increases the risk of hypotension with epidural anesthesia. Methods. In vitro studies will use the suspended isometric vascular ring model. The contractile responses of uterine and mesenteric arterial smooth muscle to various agonists, with and without MgSO4, endothelium, and indomethacin, will be examined. In vivo studies will use chronically instrumented gravid ewes. Maternal and fetal arterial catheters will permit continuous measurement of maternal and fetal systemic arterial pressures, and intermittent measurement of maternal cardiac output. An electromagnetic flow probe will allow measurement of uterine blood flow. A lumbar epidural catheter will facilitate induction of epidural anesthesia. The long-term objectives of this proposal are: 1) To elucidate mechanisms of interaction between tocolytic drugs, hemorrhage, and anesthesia; and 1) To provide an objective basis for the choice and management of tocolytic therapy in patients at risk for hemorrhage, as well as for the choice and management of anesthesia after failed tocolysis.

早产是围产期发病率的主要原因， 死亡率在美国。 产科医生经常给β- 拟交感神经药（如利托君）治疗早产， 叫做安胎。 虽然利托君对肿瘤的选择性相对较强， β 2受体（例如，子宫平滑肌），β 1受体 刺激也会发生，导致母体心率增加， 全身血管舒张。 硫酸镁（MgSO 4）通常作为一种 替代保胎药物;许多临床医生认为，它引起的 心血管副作用的风险。 产科医生通常避免 利托君在有出血风险的患者中， 低血压 麻醉师通常避免局部麻醉， 最近接受利托君或MgSO 4输注的患者。 关于安胎，出血， 和麻醉。 该实验室最近的一项研究表明，MgSO 4 显著恶化了母亲对出血的反应， 怀孕的母羊 这个建议的具体目的是：1）出血; 2)为了确定利托君引起的心动过速反应是否会改变 母体和胎儿对出血的血流动力学反应; 3）研究 利托君是否会增加低血压的风险，如果是，为什么？ 硬膜外麻醉; 4）研究MgSO 4是否会增加 低血压伴硬膜外麻醉。 方法. 体外研究将使用悬挂的等长血管环 模型 子宫动脉和肠系膜动脉的收缩反应 平滑肌对各种激动剂，有和没有MgSO 4，内皮， 和吲哚美辛，将进行检查。 体内研究将长期使用 仪器化的妊娠母羊。 母体和胎儿动脉导管将 允许连续测量母体和胎儿体动脉 压力和间歇性测量母体心输出量。 一个 电磁流量探头将允许测量子宫血流。 腰椎硬膜外导管将有助于硬膜外诱导 麻醉 这项建议的长远目标是：1）阐明 宫缩抑制药物、出血和 麻醉; 1）为选择提供客观依据， 在有出血风险的患者中进行保胎治疗， 以及麻醉失败后的选择和处理 安胎