Comparison of PIEB vs CEI for Labor Analgesia

Phase 4

Completed

Conditions: Labor Pain

Interventions: Other: Programmed Intermittent Epidural Bolus
Other: Continuous Epidural Infusion
Drug: Ropivacaine
Drug: Fentanyl

Registration Number: NCT02949271

Lead Sponsor: Duke University

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 179

Inclusion Criteria

American Society of Anesthesiology (ASA) class 2 and 3 women
Nulliparous
Age > 18 yrs
gestational age > 36 weeks
singleton pregnancies
vertex pregnancies
spontaneous labor or scheduled induction of labor
cervical dilatation 2-5 cm at time of epidural placement
Pain score > 5

Exclusion Criteria

BMI > 50 kg/m2
history of past or current intravenous drug or chronic opioid abuse
chronic analgesic use
allergy or contraindication to any study medications
any maternal or fetal condition requiring planned assisted stage 2 delivery

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Programmed Intermittent Epidural Bolus	Programmed Intermittent Epidural Bolus	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.
Continuous Epidural Infusion	Continuous Epidural Infusion	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.
Continuous Epidural Infusion	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.
Programmed Intermittent Epidural Bolus	Ropivacaine	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.
Programmed Intermittent Epidural Bolus	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 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.
Continuous Epidural Infusion	Ropivacaine	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.

Primary Outcome Measures

Name	Time	Method
Volume of Local Anesthetic Received Through Patient Controlled Epidural Analgesia (PCEA) Per Hour	duration of labor, up to 24hrs	The volume of local anesthetic that the patient received through activation of the patient-controlled epidural analgesia system per hour.

Secondary Outcome Measures

Name	Time	Method
Time to First Patient Controlled Epidural Analgesia (PCEA) Bolus	duration of labor, up to 24hrs
Degree of Motor Blockade Measured as Lowest Recorded Modified Bromage Score	duration of labor, up to 24hrs	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.
Total Number of Subjects Experiencing Each Mode of Delivery	duration of labor, up to 24hrs	Modes of delivery: spontaneous vaginal delivery (SVD), assisted vaginal delivery (AVD), and caesarean delivery (CD)
Number of Patient Controlled Epidural Analgesia (PCEA) Attempts	duration of labor, up to 24hrs	Determined by the number of times subject activates the PCEA pump
Volume of Local Anesthetic Required Per Hour	duration of labor, up to 24hrs	The total volume of local anesthetic that the patient received from the CAPP pump per hour.
Number of Subjects Who Were Satisfied With Procedure	duration of labor, up to 24hrs	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.
Ratio of Patient Controlled Epidural Analgesia (PCEA) Successful Attempts to Unsuccessful Attempts	duration of labor, up to 24hrs	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.
Maximum Reported Labor Pain Score	duration of labor, up to 24hrs	Measured using a verbal analog pain scale of 1-10, where 0=no pain and 10=worst possible pain.
Number of Subjects Experiencing Hypotension Requiring Vasopressor Treatment	duration of labor, up to 24 hrs	Number of patients who needed a vasopressor medication to treat a drop in blood pressure
Duration of Second Stage of Labor	duration of labor, up to 24hrs