Prophylactic Ephedrine to Reduce Fetal Bradycardia After Combined Spinal Epidural Labor Analgesia: a Randomized Double Blind Placebo-controlled Study

Background and explanation of rational:

Epidural analgesia (EA) has been used to provide labor pain relief for over 30 years. The technique has been refined over the past 20 years to provide laboring women with higher quality pain relief, less leg weakness and more control over the administration of the pain relief. Since the early 1990s a combined spinal-epidural (CSE) technique has become more popular because it provides more rapid onset pain relief (1). The Principal Investigator has performed a large randomized blinded study at Sharp Mary Birch Hospital for Women and Newborns to compare the effectiveness of CSE with a standard epidural technique and to describe the incidence of common side effects associated with each of them. These included itching, transient hypotension, motor block and transient fetal heart rate (FHR) abnormalities. It was found that the incidence of profound FHR deceleration was increased in the CSE group: 8.5% vs 4.5% for the standard epidural group, although no poor neonatal outcomes were seen in either group. The question was raised whether prophylactic ephedrine given concomitantly with CSE insertion would reduce the incidence of FHR deceleration, thus reducing a significant side effect associated with this otherwise superior pain relief modality for laboring patients. It is uncertain what causes fetal bradycardia after CSE but it is observed more frequently when high dose intraspinal opioids are used (2). Other potential causes include maternal hypotension associated with rapid onset sympathectomy, uterine tetanic contractions associated with sudden decrease in circulating maternal catecholamines, and rapid decent of the presenting part associated with pelvic floor relaxation. This study is not designed to determine the specific causal mechanism. Ephedrine remains one of the most extensively studied vasopressors used to treat hypotension in the obstetric population (3-5). It has both direct and indirect mechanisms of action, stimulating both alpha- and beta-receptors to increase cardiac output, heart rate and systolic and diastolic blood pressure. In the past both animal and laboratory data have demonstrated that ephedrine preserves uterine artery blood flow and fetal pH to a much better degree than other pressors. However, today it is controversial as to whether neosynephrine is a better option to treat hypotension associated with spinal anesthesia for cesarean delivery (6). Nevertheless, ephedrine has been used for decades for the treatment of maternal hypotension and fetal bradycardia associated with the use of epidural analgesia in laboring women.

Many anesthesiologists use prophylactic ephedrine 10mg intravenously to prevent an anticipated fall in maternal BP. As a consequence the risk of nausea and vomiting associated with hypotension is reduced. It is safe in the absence of maternal heart disease or hypertension.

Ephedrine 10 mg intravenously is used routinely in the labor unit and there is a standing order for the RN to use it to a maximum of 30mg when maternal systolic BP < 90mm Hg. Occasionally, ephedrine 10mg intravenously is used to treat fetal bradycardia in the absence of maternal hypotension.

Kreiser et al. studied 145 deliveries where epidural analgesia was administered (7). The patients were randomly allocated before administration of epidural analgesia to receive an intravenous infusion of 10 mg ephedrine, after epidural induction, followed by a continuous infusion for 60 minutes of 20 mg ephedrine (study group) or to receive no ephedrine (control group). The FHR tracing was evaluated for 20 minutes before and 40 minutes after initiating epidural analgesia. Demographic data and clinical and delivery outcome were assessed and compared between the 2 groups.