Investigating the Novel Observation of Right-left Difference in Uterine Artery Vascular Resistance in Pre-eclampsia

Study Overview
=================
Brief Summary
-----------------
The investigators previously demonstrated that epidural ropivacaine reduces uterine artery vascular resistance in a dose dependent manner in pre-eclampsia. The investigators also noted a marked right-left difference in vascular resistance between paired uterine arteries, which was almost completely abolished following epidural ropivacaine. However, this novel observation was not a stated outcome variable before the study began. This study assesses right-left difference in vascular resistance between paired uterine arteries as a primary end-point, assesses the dose-response effect of epidural lidocaine and compares the effect observed in pre-eclampsia with that in two control populations (term normal pregnancy and non-pregnant controls).

Official Title
-----------------
Investigating the Novel Observation of Right-left Difference in Uterine Artery Vascular Resistance in Pre-eclampsia: A Double-blinded, Randomized, Placebo-controlled Study to Assess the Dose-dependent Effect of Epidural Lidocaine on Right-left Uterine Artery Blood Flow Differences in Pre-eclampsia, With Healthy Term Pregnant and Non-pregnant Controls

Conditions
-----------------
Pre-eclampsia

Intervention / Treatment
-----------------
* Drug: Epidural lidocaine
* Drug: Epidural lidocaine 2%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pre-eclampsia patients and normal pregnancy controls scheduled to receive epidural catheterization for induction of labor or Cesarean delivery. Non-pregnant controls receiving epidural catheterization for elective surgery. Pre-eclampsia group: gestational age between 35 to 40 completed weeks uterine artery notching OR evidence of reduced uterine artery blood flow resting systolic pressure > 140mmHg or diastolic pressure > 90mmHg measured twice at least 6 hours apart proteinuria (at least 0•1 g/l in two random samples at least 6 hours apart or at least 0•3g in a 24 hour collection). Normal pregnancy control group: gestational age between 35 to 40 completed weeks absence of other inclusion factors for the pre-eclampsia group. Non-pregnant control group: Non-pregnant women of reproductive age. Exclusion Criteria: Active labor, resting blood pressure ≥ 160/110 (recorded on at least two occasions 6 hours apart), coagulopathy or other contraindications for epidural catheterization, abnormal fetal heart tracing, known fetal anomaly, intrauterine infection, placental anomalies, twins, and refusal of consent.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Epidural lidocaine<br>30 women to receive 5 x 5mL boluses of epidural lidocaine 2%. 10 pre-eclampsia, 10 term pregnancy, 10 non-pregnant. | Drug: Epidural lidocaine<br>* Epidural 2% lidocaine, administered in 5mL incremental boluses. Looking at dose-response effect.<br>Drug: Epidural lidocaine 2%<br>* 5 x 5ml boluses of either epidural lidocaine 2% or epidural saline<br>|
| Placebo Comparator: Epidural saline<br>30 women to receive 5 x 5 mL boluses of epidural saline. 10 pre-eclamptics, 10 normal term pregnancy, 10 non-pregnant | Drug: Epidural lidocaine<br>* Epidural 2% lidocaine, administered in 5mL incremental boluses. Looking at dose-response effect.<br>Drug: Epidural lidocaine 2%<br>* 5 x 5ml boluses of either epidural lidocaine 2% or epidural saline<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uterine artery pulsatility index (by Doppler ultrasound). Specifically the right-left uterine artery difference. |  | 15min after each dose - on a dose--response curve | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uterine artery pulsatility index (worse vessel) |  | 15 min after dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pre-eclampsia, Pregnancy, Uteroplacental blood flow, Epidural, Anesthesia