Impact of Prophylactic Ephedrine on Fetal Heart Tracing and Uterine Tetanic Contraction After CSE

Study Overview
=================
Brief Summary
-----------------
Labor analgesia is an important component of the care of laboring patients. A known side effect of combined spinal and epidural anesthesia (a type of labor analgesia) is an increased incidence of category II fetal heart rate tracing (defined below) and low blood pressure. The study team aims to study if a prophylactic dose of ephedrine will decrease the occurrence of this type of tracing after combined spinal epidural (CSE) anesthesia placement. Ephedrine is not currently routinely used as prevention for category II tracings or low blood pressure. The use of Ephedrine in this study is investigational (this is the first time that the drug has been studied for its effect on these conditions). Fetal heart rate (FHR) tracings are classified into three categories. In clinical practice, FHR tracing categories are used as a guide to obstetric management and suggest the following approach: Category I tracing is reactive and reassuring → may continue labor Category II tracing is neither category I nor category III. For obvious reasons, category II is the broadest and largest category, consisting of various FHR tracing patterns that do not fit into either category I or category III. Category III tracing is non-reassuring → expedited vaginal or cesarean delivery recommended. A Category II tracing is not diagnostic. Most pregnancies have at least one Category II tracing. There is not always an identifiable reason for a Category II tracing. Ephedrine is a medication that causes an increase in heart rate and blood pressure while also causing some degree of relaxation of the uterus therefore improving uterine blood flow. It has been used in the obstetric population for over 50 years without issues. The dose that the research team will administer, 7.5 mg, is below the dose the research team will often administer to treat hypotension (low blood pressure).

Official Title
-----------------
Impact of Prophylactic Ephedrine on Fetal Heart Tracing and Uterine Tetanic Contraction After Combined Spinal Epidural on Laboring Parturients

Conditions
-----------------
Labor

Intervention / Treatment
-----------------
* Drug: Ephedrine
* Drug: Normal Saline Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women aged 18-55 years Requesting labor analgesia Able to provide informed written consent Category 1 fetal tracing prior to placement of neuraxial anesthesia Exclusion Criteria: Refusal of neuraxial anesthesia History of hypertension Suspected pre-eclampsia Category 2 or 3 fetal tracing prior to placement of neuraxial anesthesia

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ephedrine<br>3 minutes after the placement of a combined spinal epidural with 25 mcg fentanyl, 7.5 mg ephedrine IV will be administered to the patient, 12 minutes later, a second dose of 7.5mg will be administered to the patient as long as the patient is not hypertensive (BP no greater than 140/90) | Drug: Ephedrine<br>* The intervention will be up to two 7.5 mg doses of ephedrine given after the placement of a combined spinal epidural with 25 mcg intrathecal fentanyl timed 3 and 15 minutes after intrathecal opiate administration.<br>|
| Placebo Comparator: Placebo<br>3 minutes after the placement of a combined spinal epidural with 25 mcg fentanyl, 2.5cc 0.9% NS IV will be administered to the patient, 12 minutes later, a second dose of , 2.5cc 0.9% NS will be administered to the patient. | Drug: Normal Saline Placebo<br>* Placebo will be administered at matching rate.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of category II fetal heart rate tracing | Incidence of category II fetal heart rate tracing up to 30 minutes after administration of intrathecal opiate | day 1, 30 minutes after administration of intrathecal opiate | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of uterine tetanic contractions | Incidence of uterine tetanic contractions after combined spinal epidural placement | day 1, 30 minutes after administration of intrathecal opiate | 
| Incidence of uterine hypertorus | Incidence of uterine hypertorus up to 30 minutes after administration of intrathecal opiate | day 1, 30 minutes after administration of intrathecal opiate | 
| Incidence of fetal bradycardia | Incidence of fetal bradycardia up to 30 minutes after administration of intrathecal opiate | day 1, 30 minutes after administration of intrathecal opiate | 
| Incidence of rescue administration of ephedrine, terbutaline, or nitroglycerin | Incidence of rescue administration of ephedrine, terbutaline, or nitroglycerin up to 30 minutes after administration of intrathecal opiate | day 1, 30 minutes after administration of intrathecal opiate | 
| Incidence of antihypertensive treatment after ephedrine administration | Incidence of antihypertensive treatment after ephedrine administration | day 1, 30 minutes after administration of intrathecal opiate | 
| Incidence of urgent/emergent cesarean delivery | Incidence of urgent/emergent cesarean delivery within 30 minutes of intrathecal opiate administration | day 1, 30 minutes after administration of intrathecal opiate | 
| Incidence of hypotension | Incidence of hypotension as defined as systolic blood pressure decrease of 20% versus baseline, systolic blood pressure under 90 mmHG, or symptoms of hypotension such as light headedness | day 1, 30 minutes after administration of intrathecal opiate | 
| Average HR changes | Average HR changes 30 minutes after intrathecal opiate administration | day 1, 30 minutes after administration of intrathecal opiate | 
| Average blood pressure changes | Average blood pressure changes 30 minutes after intrathecal opiate administration of systolic and diastolic blood pressure | day 1, 30 minutes after administration of intrathecal opiate | 
| Number of patients with systolic blood pressure under 90 mmHG | Systolic blood pressure under 90 mmHG, or symptoms of hypotension such as light headedness | End of study, at 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Randomized Control Trial, Prophylactic Ephedrine, Fetal Heart Rate Tracing, Combined Spinal Epidural, Labor analgesia