Bekkenes Maria, Jørgensen Marte Morin, Flem Jacobsen Anne, Wang Fagerland Morten, Rakstad-Larsen Helene, Solberg Ole Geir, Aaberge Lars, Klingenberg Olav, Steinsvik Trude, Rosseland Leiv Arne
Department of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
F1000Res. 2021 Sep 27;10:973. doi: 10.12688/f1000research.73112.2. eCollection 2021.
: Both oxytocin and carbetocin are used to prevent uterine atony and post-partum haemorrhage after caesarean delivery in many countries, including Norway. Oxytocin causes dose-dependent ST-depression, troponin release, prolongation of QT-time and arrythmia, but little is known about myocardial effects of carbetocin. We have previously demonstrated comparable vasodilatory effects of oxytocin and carbetocin and are now undertaking a Phase 4 trial to investigate whether carbetocin causes similar changes to myocardial markers compared with oxytocin. Our randomized controlled trial will be conducted at three obstetrics units at Oslo University Hospital and Akershus University Hospital, Norway. Planned enrolment will be of 240 healthy, singleton pregnant women aged 18 to 50 years undergoing planned caesarean delivery. Based on pilot study data, each participant will receive a one-minute intravenous injection of either oxytocin 2.5 IU or carbetocin 100 µg during caesarean delivery. The prespecified primary outcome is the change from baseline in high-sensitive troponin I plasma concentrations at 6-10 hours after study drug administration. Secondary outcomes include uterine tone grade at 2.5 and five minutes after study drug administration, adverse events for up to 48 hours after study drug administration, estimated blood loss within eight hours of delivery, need for rescue treatment and direct/indirect costs. Enrolment and primary analysis are expected to be completed by the end of 2021. Women undergoing caesarean delivery should be assessed for cardiovascular risk particularly as women with an obstetric history of pregnancy induced hypertension, gestational diabetes mellitus, preterm birth, placental abruption, and stillbirth are at increased risk of future cardiovascular disease. Any additional ischaemic myocardial risk from uterotonic agents will need to be balanced with the benefit of reducing the risk of postpartum haemorrhage. Any potential cardiotoxicity difference between oxytocin and carbetocin will help inform treatment decisions for pregnant women. Clinicaltrials.gov NCT03899961 (02/04/2019).
在包括挪威在内的许多国家，催产素和卡贝缩宫素都被用于预防剖宫产术后的子宫收缩乏力和产后出血。催产素会引起剂量依赖性的ST段压低、肌钙蛋白释放、QT间期延长和心律失常，但关于卡贝缩宫素对心肌的影响知之甚少。我们之前已经证明了催产素和卡贝缩宫素具有相似的血管舒张作用，现在正在进行一项4期试验，以研究与催产素相比，卡贝缩宫素是否会引起类似的心肌标志物变化。我们的随机对照试验将在挪威奥斯陆大学医院和阿克什胡斯大学医院的三个产科单位进行。计划招募240名年龄在18至50岁之间、计划进行剖宫产的健康单胎孕妇。根据前期研究数据，每位参与者在剖宫产期间将接受1分钟的静脉注射，注射药物为2.5 IU催产素或100 μg卡贝缩宫素。预先设定的主要结局是研究药物给药后6至10小时高敏肌钙蛋白I血浆浓度相对于基线的变化。次要结局包括研究药物给药后2.5分钟和5分钟时的子宫张力分级、研究药物给药后长达48小时的不良事件、分娩后8小时内的估计失血量、抢救治疗的需求以及直接/间接费用。预计招募和初步分析将于2021年底完成。接受剖宫产的女性应评估心血管风险，特别是有妊娠高血压、妊娠期糖尿病、早产、胎盘早剥和死产产科病史的女性未来患心血管疾病的风险会增加。宫缩剂带来的任何额外缺血性心肌风险都需要与降低产后出血风险的益处相权衡。催产素和卡贝缩宫素之间任何潜在的心脏毒性差异将有助于为孕妇的治疗决策提供依据。Clinicaltrials.gov NCT03899961（2019年4月2日）
