A Phase 4 interventional study of Programmed Intermittent Epidural Bolus and Continuous Epidural Infusion in Labor Pain, sponsored by Duke University. Completed at 1 site in United States. Open to female participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-01-11.
Sponsored by Duke University · Phase 4, Interventional, and Supportive care
The aim of this prospective, doubled-blinded randomized study is to compare two modes of epidural analgesia delivery, programmed intermittent epidural boluses (PIEB) versus continuous epidural infusion (CEI) with patient controlled epidural analgesia (PCEA) dosing, for providing labor epidural analgesia. The primary outcome will be the volume of local anesthetic received through PCEA. Secondary outcomes will measure time to first PCEA bolus, labor pain scores, degree of motor blockade, mode of delivery, PCEA attempts and ratio of successful to unsuccessful attempts, frequency of hypotension, duration of first and second stages of labor and level of patient satisfaction. The investigator plans to enroll 120 nulliparous participants at 2-5 com cervical dilation, with 60 patients to each arm. The subject will be assigned to receive either delivery of epidural medication ropivacaine 0.1% with fentanyl 2mcg/mL with PIEB + PCEA dosing method or CEI + PCEA. Continuous data will be analyzed using the Kruskal-Wallis test or t-test as appropriate. Categorical data will be analyzed using Chi-square test or Fisher's exact test as appropriate.
Labor pain during childbirth is regarded as one of the most painful experiences in a woman's life with the potential to cause lasting emotional and psychological effects. Childbirth has also been associated with the development of chronic pain with the prevalence of between 4-10% after cesarean section and 6-18% after vaginal delivery. Hence, effective management of labor pain is instrumental in preventing the development of life altering chronic pain in women of childbearing age. Maintaining epidural analgesia with combined local anesthetic and an opioid is considered extremely safe and leads to superior neonatal and maternal short and long-term outcomes. Historically, maintenance of epidural analgesia involved intermittent provider-administered bolus injections, patient controlled epidural analgesia (PCEA) and continuous epidural infusions (CEI) with or without PCEA for breakthrough pain or discomfort. CEI has been shown to provide consistent analgesia in addition to improved patient satisfaction and reduced workload for the anesthesia providers. However, CEI is associated with greater local anesthetic consumption and increased maternal motor blockade. Increased motor block is associated with reduced mobility, decreased pelvic muscle tone and impaired ability for the parturient to adequately Valsalva during the second stage of labor. Motor blockade is also associated with increased incidence of shoulder dystocia and instrumental deliveries, which precipitate birth trauma to the fetus and the mother. Achieving adequate analgesia during labor, without compromising motor function is critical for optimizing both short-term and long-term outcomes for the mother and the neonate.
A more novel approach to labor analgesia involves the administration of small, programmed intermittent epidural boluses (PIEB) with PCEA dosing for breakthrough pain. Preliminary studies have indicated that PIEB could be a superior method of labor analgesia compared to current standard of care, CEI. A randomized double-blind study by Wong et al. compared CEI and PIEB incorporating the use of PCEA for breakthrough pain in healthy parturients with singleton pregnancies. Results suggested that the cohort receiving PIEB required less local anesthetic use, had similar analgesia and improved patient satisfaction when compared with CEI. Additionally, a subsequent study by Wong et al found that in healthy, term, nulliparous women in spontaneous labor, extending the PIEB interval and increasing volume decreased local anesthetic consumption, PCEA requests or rescue analgesia requirements without increasing patient discomfort or compromising satisfaction. Two subsequent studies allocating women to receive either PIEB or CEI in nulliparous parturients and women terminating pregnancy suggested PIEB recipients experienced less motor blockade when compared to those receiving CEI.
The investigator has recently performed a systematic review and meta-analysis of studies comparing the effects of labor analgesia with either PIEB or CEI with or without PCEA in laboring women. The meta-analysis included 9 studies and evaluated various primary outcomes including: patient satisfaction, required manual anesthesia interventions, labor progression and mode of delivery (vaginal, instrumental or cesarean delivery). Secondary outcomes included: degree of motor blockade, degree of sensory blockade, time to first anesthetic intervention, local anesthetic dose delivered per hour, pruritus, shivering, maternal fever, nausea and vomiting, neonatal Apgar scores at 1 minute and 5 minutes, and umbilical artery and vein pH. PIEB dosing of local anesthetic was associated with reduced local anesthetic consumption, decreased required anesthetic interventions, and an improvement in maternal satisfaction in comparison to laboring women receiving CEI. Pooled results indicated that PIEB and CEI were comparable with regard to the duration of first stage labor, but there was a statistically significant 22 min reduction in the length of stage two of labor with PIEB. Similarly, this review did not suggest statistically significant differences in cesarean delivery rate or required anesthetic intervention between CEI and PIEB. There were several limitations to these preliminarily studies. While, each of the 9 studies reported at least one primary outcome listed in the systematic review, none of the studies included all primary outcomes. Additionally, most studies only involved nulliparous women, which may limit the ability to apply results to multiparous women. Furthermore, many of these studies involved the use of two pumps, one to deliver CEI or PEIB and another to deliver PCEA in a research setting, or involved the use of non-commercially available research pumps.
Currently the CADD solis v 3.0 pump system has been upgraded to allow the co-administration of epidural anesthesia with PIEB or CEI and PCEA. This new technology has been available on the labor and delivery unit of Duke University Medical Center as the standard of care since March 2015. This new pump differs from those used in the preliminary studies, which utilized a two-pump approach to administer PIEB or CEI and PCEA for labor pain relief. Preliminary studies have not identified optimal PIEB settings, bolus volumes, lock out intervals, or drug concentrations, which represents a gap in literature at the present time. The investigator performed a retrospective study to explore whether PIEB was associated with reduced LA use, PCEA use and rescue analgesia in comparison to CEI in laboring women. The investigator also assessed whether PIEB decreased the number of instrumental deliveries and reduced motor blockade, which serves as an impediment to the progression of labor. The study divided patients into three groups. The first received CEI 5mL/hour, the second received PIEB 5mL every 60 min, the third used PIEB of 3mL every 30 min. Each group had access to PCEA set to 5 mL boluses with an 8-minute lockout period and maximum of 35mL per hour. The results of the study did not suggest what was expected as the study revealed no statistically significant difference between the LA consumption, amount of motor blockade or mode of delivery for patients receiving CEI or PEIB when using the single pump system instead of two-pump system employed by prior studies. However, this study did suggest patients who received PIEB regimen of 3mL every 30 minutes used a lower PCEA volume than patients receiving CEI. Patients receiving PEIB regimens had more attempts/PCEA given than the CEI patients and the PIEB 3ml/30 minute group had more unsuccessful PCEA attempts/hour than CEI recipients.
This study, unlike prior studies comparing PIEB vs. CEI with PCEA, used more concentrated solutions consisting of double the concentration and half the volume of bupivacaine. One of the investigators speculations is that larger boluses of a more dilute LA may have improved dissemination in the epidural space and thus improved analgesia. This study interpreted PCEA attempts/given and the number of unsuccessful PCEA attempts/hour as reflections of patient pain or discomfort, as an attempt is interpreted as an effort to achieve better pain relief. Another way to interpret the aforementioned PCEA attempts is as representation of the amount of time a patient "locked out" or prevented from receiving additional boluses of PCEA. Hence, a limitation of this study is the fact that patient satisfaction scores were not collected as they could help distinguish whether attempts reflect the lockout period or inadequate analgesia. Other limitations of this retrospective study include the fact that explicit instructions about how to properly use the PCEA was not standardized, and the fact that patient satisfaction or pain scores were not garnered due to the study's retrospective nature. Probably one of the most significant limitations of this study was the fact that patients were not randomized to treatment groups. Hence, the providers chose the analgesia received. On the other hand, another retrospective study utilizing a more dilute concentration of local anesthetic reported reduced need for physician interventions with PIEB compared to CEI. The investigators have recently switched the local anesthetic in our practice from bupivacaine 0.125 % to a more dilute concentration of ropivacaine 0.1% mixed with fentanyl 2 mcg/ml. The investigator therefore aims to prospectively study if the use of PIEB with the new epidural solution would be associated with improved analgesia compared to a regimen using CEI.
396 studies on the registry are indexed under Labor Pain; 66 are open to participants now.
This study's enrollment of 179 is above the median of 100 across 326 interventional studies indexed under Labor Pain.
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Epidural catheters will be placed at the L3/4 or L4/5 interspace with 4 cm of catheter being left in the epidural space. Epidural analgesia will be initiated and maintained with a solution of ropivacaine 0.1% with fentanyl 2 mcg/ml. After the initial epidural loading dose of 20 mL is administered in incremental fashion, patients will receive either 6 mL every 45 minutes in the PIEB arm (first bolus 30 minutes after epidural initiation). All study participants will be provided with PCEA set to 8mL boluses with a 10-minute lockout period. The maximum amount of PCEA analgesia will be set to a 1-hour maximum of 45mL.
Other: Programmed Intermittent Epidural Bolus · Drug: Ropivacaine · Drug: Fentanyl
Epidural catheters will be placed at the L3/4 or L4/5 interspace with 4 cm of catheter being left in the epidural space. Epidural analgesia will be initiated and maintained with a solution of ropivacaine 0.1% with fentanyl 2 mcg/ml. After the initial epidural loading dose of 20 mL is administered in incremental fashion, patients will receive 8mL/hr of continuous infusion beginning immediately after the loading dose for the maintenance of analgesia in the CEI arm. All study participants will be provided with PCEA set to 8mL boluses with a10-minute lockout period. The maximum amount of PCEA analgesia will be set to a 1-hour maximum of 45mL.
Other: Continuous Epidural Infusion · Drug: Ropivacaine · Drug: Fentanyl
Volume of Local Anesthetic Received Through Patient Controlled Epidural Analgesia (PCEA) Per Hour
The volume of local anesthetic that the patient received through activation of the patient-controlled epidural analgesia system per hour.
Time frame: duration of labor, up to 24hrs
Volume of Local Anesthetic Required Per Hour
The total volume of local anesthetic that the patient received from the CAPP pump per hour.
Time frame: duration of labor, up to 24hrs
Time to First Patient Controlled Epidural Analgesia (PCEA) Bolus
Time frame: duration of labor, up to 24hrs
Maximum Reported Labor Pain Score
Measured using a verbal analog pain scale of 1-10, where 0=no pain and 10=worst possible pain.
Time frame: duration of labor, up to 24hrs
Degree of Motor Blockade Measured as Lowest Recorded Modified Bromage Score
The Modified Bromage Score ranges from 1-5. 1 = complete block, 2 = almost complete block, 3 = partial block, 4 = detectable weakness of hip flexion, and 5 = no detectable weakness of hip flexion while supine.
Time frame: duration of labor, up to 24hrs
Total Number of Subjects Experiencing Each Mode of Delivery
Modes of delivery: spontaneous vaginal delivery (SVD), assisted vaginal delivery (AVD), and caesarean delivery (CD)
Time frame: duration of labor, up to 24hrs
Number of Patient Controlled Epidural Analgesia (PCEA) Attempts
Determined by the number of times subject activates the PCEA pump
Time frame: duration of labor, up to 24hrs
Ratio of Patient Controlled Epidural Analgesia (PCEA) Successful Attempts to Unsuccessful Attempts
Ratio generated by the number of times subjects activates PCEA and receives additional anesthetic compared with times subject activates PCEA and does not receive additional anesthetic.
Time frame: duration of labor, up to 24hrs
Number of Subjects Experiencing Hypotension Requiring Vasopressor Treatment
Number of patients who needed a vasopressor medication to treat a drop in blood pressure
Time frame: duration of labor, up to 24 hrs
Duration of Second Stage of Labor
Time frame: duration of labor, up to 24hrs
Number of Subjects Who Were Satisfied With Procedure
Determined using a 5-point scale where 1=very dissatisfied, 2=dissatisfied, 3=neutral, 4=satisfied, 5=very satisfied. Subjects were considered "satisfied" if selected "very satisfied" or "satisfied" on the patient questionnaire.
Time frame: duration of labor, up to 24hrs
The study took place at Duke University Medical Center from November 2016-November 2017.
| Milestone | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion |
|---|---|---|
| Started | 90 | 89 |
| Completed | 61 | 59 |
| Not completed | 29 | 30 |
| Withdrew: Lack of efficacy | 5 | 4 |
| Withdrew: Lost to follow-up | 3 | 6 |
| Withdrew: Physician decision | 5 | 5 |
| Withdrew: Protocol violation | 6 | 3 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Withdrew: Delivered prior to intervention | 7 | 9 |
| Withdrew: Outside the window for cervical dilation | 2 | 3 |
The volume of local anesthetic that the patient received through activation of the patient-controlled epidural analgesia system per hour.
| milliliters per hour | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion |
|---|---|---|
| Volume of Local Anesthetic Received Through Patient Controlled Epidural Analgesia (PCEA) Per Hour | 4.03 (2.15 to 7.07) | 4.52 (2.99 to 8.63) |
The total volume of local anesthetic that the patient received from the CAPP pump per hour.
| milliliters per hour | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion |
|---|---|---|
| Volume of Local Anesthetic Required Per Hour | 11.49 (9.21 to 14.84) | 12.38 (10.45 to 17.03) |
No measurements were reported for this outcome.
Measured using a verbal analog pain scale of 1-10, where 0=no pain and 10=worst possible pain.
| score on a scale | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion |
|---|---|---|
| Maximum Reported Labor Pain Score | 3 (0 to 6) | 2 (0 to 4) |
The Modified Bromage Score ranges from 1-5. 1 = complete block, 2 = almost complete block, 3 = partial block, 4 = detectable weakness of hip flexion, and 5 = no detectable weakness of hip flexion while supine.
| Participants | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion |
|---|---|---|
| Score of 5 | 37 | 26 |
| Score of 4 | 9 | 20 |
| Score of 3 | 4 | 3 |
| Score of 2 | 1 | 2 |
| Score of 1 | 0 | 1 |
Modes of delivery: spontaneous vaginal delivery (SVD), assisted vaginal delivery (AVD), and caesarean delivery (CD)
| Participants | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion |
|---|---|---|
| SVD | 41 | 37 |
| AVD | 5 | 5 |
| CD | 15 | 17 |
Determined by the number of times subject activates the PCEA pump
| attempts | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion |
|---|---|---|
| Number of Patient Controlled Epidural Analgesia (PCEA) Attempts | 0.75 (0.33 to 1.84) | 0.63 (0.42 to 1.35) |
Ratio generated by the number of times subjects activates PCEA and receives additional anesthetic compared with times subject activates PCEA and does not receive additional anesthetic.
| ratio of attempts | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion |
|---|---|---|
| Ratio of Patient Controlled Epidural Analgesia (PCEA) Successful Attempts to Unsuccessful Attempts | 0.17 (0.10 to 0.30) | 0.12 (0.08 to 0.18) |
Number of patients who needed a vasopressor medication to treat a drop in blood pressure
| Participants | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion |
|---|---|---|
| Number of Subjects Experiencing Hypotension Requiring Vasopressor Treatment | 8 | 3 |
| minutes | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion |
|---|---|---|
| Duration of Second Stage of Labor | 44 (15 to 119) | 63 (27 to 130) |
Determined using a 5-point scale where 1=very dissatisfied, 2=dissatisfied, 3=neutral, 4=satisfied, 5=very satisfied. Subjects were considered "satisfied" if selected "very satisfied" or "satisfied" on the patient questionnaire.
| Participants | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion |
|---|---|---|
| Very satisfied | 35 | 39 |
| Satisfied | 9 | 3 |
Collected over Duration of labor, up to 24hrs. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Programmed Intermittent Epidural Bolus | 0/61 (0%) | 0/61 (0%) | 8/61 (13.1%) |
| Continuous Epidural Infusion | 0/59 (0%) | 0/59 (0%) | 3/59 (5.1%) |
| Event | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion |
|---|---|---|
| HypotensionCardiac disorders | 8/61 | 3/59 |
Participants who completed the study
| Age, Continuous(years) | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion | Total |
|---|---|---|---|
| Mean | 28.5 ± 5.0 | 29.8 ± 5.3 | 29.2 ± 5.2 |
| Sex: Female, Male(Participants) | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion | Total |
|---|---|---|---|
| Female | 61 | 59 | 120 |
| Male | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 4 | 5 |
| Not Hispanic or Latino | 60 | 55 | 115 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 6 | 1 | 7 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 18 | 20 | 38 |
| White | 37 | 38 | 75 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(Participants) | Programmed Intermittent Epidural Bolus | Continuous Epidural Infusion | Total |
|---|---|---|---|
| United States | 61 | 59 | 120 |
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