Obstetric Pain
Conditions
Keywords
Epidural, analgesia, labor, cytokines
Brief summary
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.
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.
Interventions
PROCEDUREPreemptive 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.
DRUGStandard of care
Epidural analgesia with parturients with cervical dilatation and painful labor (VAS \>5)
Sponsors
Rabin Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maternal Cytokine IL-10 Levels of pg/ml Upon Enrollment | Right after enrollment | Maternal serum cytokine IL-10 levels of pg/ml measured upon enrollment |
| Maternal Cytokine of pg/ml IL-10 Levels 24 Hours After Delivery | 24 hours after delivery | Maternal serum cytokine levels of pg/ml IL-10 as measured 24 hours after delivery |
| Umbilical Cord Cytokine of pg/ml IL-10 Levels at Birth | At birth of parturients | Umbilical cord cytokine IL-10 levels pg/ml as measured at delivery |
Countries
Israel
Participant flow
Recruitment details
Women in labor were recruited for the study at entry to the triage area of the delivery room of a major tertiary medical center from January to May 2006.
Participants by arm
| Arm | Count |
|---|---|
| Randomized to Early Epidural Analgesia Parturients were allocated to receive epidural analgesia immediately on admission, before the onset of painful contractions | 20 |
| Randomized to Epidural Analgesia Upon Request Parturient's pain was monitored every 15 min until it reached a level of \>50 on the VAS and then epidural analgesia was initiated. | 21 |
| Total | 41 |
Baseline characteristics
| Characteristic | Randomized to Early Epidural Analgesia | Randomized to Epidural Analgesia Upon Request | Total |
|---|---|---|---|
| Age, Continuous | 30.5 years STANDARD_DEVIATION 3.6 | 29.1 years STANDARD_DEVIATION 4.9 | 30.5 years STANDARD_DEVIATION 4.9 |
| Region of Enrollment Israel | 20 Participants | 21 Participants | 41 Participants |
| Sex: Female, Male Female | 20 Participants | 21 Participants | 41 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 20 | 0 / 21 |
| serious Total, serious adverse events | 0 / 20 | 0 / 21 |
Outcome results
Primary
Maternal Cytokine IL-10 Levels of pg/ml Upon Enrollment
Maternal serum cytokine IL-10 levels of pg/ml measured upon enrollment
Time frame: Right after enrollment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized to Early Epidural Analgesia | Maternal Cytokine IL-10 Levels of pg/ml Upon Enrollment | 12.7 pg/ml | Standard Deviation 4.5 |
| Randomized to Epidural Analgesia Upon Request | Maternal Cytokine IL-10 Levels of pg/ml Upon Enrollment | 14.2 pg/ml | Standard Deviation 7 |
Primary
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
Time frame: 24 hours after delivery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized to Early Epidural Analgesia | Maternal Cytokine of pg/ml IL-10 Levels 24 Hours After Delivery | 15.22 pg/ml | Standard Deviation 5.6 |
| Randomized to Epidural Analgesia Upon Request | Maternal Cytokine of pg/ml IL-10 Levels 24 Hours After Delivery | 16.77 pg/ml | Standard Deviation 0 |
Primary
Umbilical Cord Cytokine of pg/ml IL-10 Levels at Birth
Umbilical cord cytokine IL-10 levels pg/ml as measured at delivery
Time frame: At birth of parturients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized to Early Epidural Analgesia | Umbilical Cord Cytokine of pg/ml IL-10 Levels at Birth | 1 pg/ml | Standard Deviation 0.6 |
| Randomized to Epidural Analgesia Upon Request | Umbilical Cord Cytokine of pg/ml IL-10 Levels at Birth | 1.5 pg/ml | Standard Deviation 1.3 |