Effect of Preemptive Epidural Analgesia in Labor on Cytokine Production

Effect of Preemptive Epidural Analgesia in Labor on Pro and Anti-inflammatory Cytokine Production in a Mother and a Newborn

During labor there is an increased production of inflammatory mediators called cytokines. Higher concentration of certain cytokines has been linked to adverse neonatal and maternal outcomes.

Epidural analgesia is commonly performed after the parturient feels labor pain.

We hypothesis that preemptive epidural analgesia (initiated before labor pain begins)can influence the production of cytokines.

Study Overview

• Status: Completed
• Conditions: Obstetric Pain
• Intervention / Treatment: Procedure: Preemptive epidural analgesia; Drug: Standard of care

Detailed Description

The interrelationship between vaginal labor, cytokine production, and epidural analgesia is unknown. Vaginal delivery is thought to induce a maternal inflammatory response. Though epidural analgesia during labor was found to significantly influence peripartum maternal and newborn interleukin concentrations, these studies did not address at what stage epidural analgesia was performed. Preemptive analgesia has been found to be associated with attenuated proinflammatory cytokines, at least in the postoperative period.

Healthy ASA I term parturients (>37 weeks) being accepted into delivery ward and wanting epidural analgesia will be studied.

Parturients will be divided into two groups:

• Group I- those who have painless contractions awaiting augmentation of labor.
• Group II- parturients with cervical dilatation and painful labor (VAS >5).

Parturients in Group I will be given epidural analgesia immediately upon arrival in the labor ward before onset of painful contractions (VAS<3). Parturients in Group 2 will be given epidural analgesia as soon as possible.

Epidural analgesia protocol will be identical for both groups: graduated doses of bupivicaine 0.1% 15cc and 100 mcg fentanyl followed by patient controlled analgesia at a concentration of bupivicaine 0.1% and fentanyl 2 mcg/cc delivered at 10cc per hour with possible boluses of 5 cc every ten minutes.

Maternal serum will be drawn before epidural insertion and 18-24 hours after delivery. Placental blood will be drawn after delivery.

These blood sample will be assessed for IL-1Beta, TNF alpha, IL-1ra, IL-2, Il-6, IL-8, IL-10, IL-18.

The patient's chart will be prospectively analyzed for demographic information about parturient and complications and progress of labor.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center/Beilinson Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Age>18
2. Singleton pregnancy with no known fetal malformations
3. Above or equal to 38 weeks of pregnancy

Exclusion Criteria:

1. Systemic medical illnesses
2. Chronic medications except for iron and vitamins
3. Women developing fever > 380C
4. Women with history of delivery of children with cerebral palsy
5. History of infertility
6. Premature contractions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Preemptive epidural analgesia; Parturients will receive epidural analgesia immediately upon arrival in the labor ward before onset of painful contractions (VAS<3).	Procedure: Preemptive epidural analgesia; Parturients will receive early epidural analgesia before onset of painful contractions as oppose to standard of care in which parturients receive epidural analgesia with onset of painful contractions.
Active Comparator: Standard of care; Parturients with cervical dilatation and painful labor (VAS >5) will receive epidural analgesia as soon as possible	Drug: Standard of care; Epidural analgesia with parturients with cervical dilatation and painful labor (VAS >5)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal Cytokine IL-10 Levels of pg/ml Upon Enrollment	Maternal serum cytokine IL-10 levels of pg/ml measured upon enrollment	Right after enrollment
Maternal Cytokine of pg/ml IL-10 Levels 24 Hours After Delivery	Maternal serum cytokine levels of pg/ml IL-10 as measured 24 hours after delivery	24 hours after delivery
Umbilical Cord Cytokine of pg/ml IL-10 Levels at Birth	Umbilical cord cytokine IL-10 levels pg/ml as measured at delivery	At birth of parturients

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Investigators: Study Director: Sharon Orbach-Zinger, M.D., Department of Anesthesiology, Rabin Medical Center/Beilinson Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): July 1, 2006
• Study Completion (Actual): July 1, 2006

Study Registration Dates

• First Submitted: August 6, 2006
• First Submitted That Met QC Criteria: August 6, 2006
• First Posted (Estimate): August 8, 2006

Study Record Updates

• Last Update Posted (Actual): April 9, 2018
• Last Update Submitted That Met QC Criteria: March 12, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Epidural; analgesia; cytokines; labor
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Labor Pain
• Other Study ID Numbers: 003692

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No