Clinical trial NCT05068661
Conditions: Labor Pain
Keywords: labor analgesia neuraxial technique combined spinal epidural dural puncture epidural
Sponsor: Duke University
Start date: 2021-11-21; Completion date: 2023-12-07
Enrollment: 101 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The primary purpose of this study is to determine if there are differences in block quality between the CSE and DPE techniques for labor analgesia in parturients in active labor. We hypothesize that when compared to the CSE technique, the DPE technique will significantly improve block quality in this population and require fewer "top-ups" and catheter replacements.

Detailed description:
This will be a prospective, double-blinded, randomized trial.

Subject identification and recruitment:

Women admitted to the Duke Birthing Center for spontaneous or induced labor will be screened. After usual consultation with the anesthesia team is completed and consent for anesthesia services are obtained, eligible patients will be approached to by a member of the study team. As indicated below, we will plan to enroll up to 120 patients to have 100 patients with complete data (50 for the CSE group and 50 for the DPE group).

Assignment of Study Cohorts:

Study participants will be randomized by computer-generated sequence to CSE or DPE arms, stratified by parity (nulliparous versus multiparous). After the consented and enrolled participant requests labor epidural, a study member will give the anesthesia provider a sealed envelope with study assignment for either standard CSE or DPE technique.

Epidural technique:

Once the patient requests labor analgesia, the usual standard of care for epidural placement will be initiated. The patient will receive 500-1000 mL fluid preload. Vitals will be monitored by the labor nurse, including continuous pulse oximetry, non-invasive blood-pressure monitoring, and external tocodynamometry. Anesthesia time-out will be performed by the anesthesia provider with participation from the nurse and the patient.

All patients will receive a neuraxial technique in the sitting position at L3/4 or L4/5 using loss of resistance to saline. In both the CSE and DPE groups, a 25-G Whitacre needle will be used to puncture the dura. In the CSE group, 10 mcg of preservative-free fentanyl and 2 mg of preservative-free isobaric 0.25% bupivacaine will be administered into the intrathecal space. In both groups, the epidural catheter will be threaded 5 cm into the epidural space. In the DPE group, an initiation dose of 20 mL of ropivacaine 0.1% with fentanyl (2 mcg/mL) over 6 minutes. This would not be administered in the CSE group. Labor analgesia will be maintained by programmed intermittent bolus with 8 mL of the same solution every 45 minutes starting 30 minutes after the initial dose. Patients will have patient-controlled epidural analgesia (PCEA) available with an 10 mL dose per demand, every 10 minutes, for a maximum dose of 50 mL for every hour.

Data Collection:

After the block is placed, a blinded provider will enter the room to collect data. Data will be collected every 3 minutes for the first 30 minutes or until pain score is 1 or 0 with uterine contractions. Subsequent assessments will be every 2 hours until delivery.

Management of breakthrough pain will be standardized.

Arms: arm 1: 10 mcg of preservative-free fentanyl and 2 mg of preservative-free isobaric 0.25% bupivacaine will be administered into the intrathecal space to initiate analgesia. Labor analgesia will be maintained by programmed intermittent bolus with patient-controlled epidural analgesia (PCEA) as per standard of care. arm 2: A 25-G Whitacre needle will be used to puncture the dura. An initiation dose of 20 mL of ropivacaine 0.1% with fentanyl (2 mcg/mL) will be administered. Labor analgesia will be maintained by programmed intermittent bolus with patient-controlled epidural analgesia (PCEA) as per standard of care.
Interventions: intervention 1: Ropivacaine 0.1% Injectable Solution intervention 2: Bupivacaine 0.25% Injectable Solution
Intervention descriptions: intervention 1: DPE intervention 2: CSE

Protocol documents:
Prot_SAP_000.pdf: 
Comparing Effectiveness of CSE Versus DPE for Labor Analgesia 
NCT05068661 
3/22/2024


After obtaining written informed consent, parturients are randomised in a 1:1 ratio by computer-
generated random sequence to CSE or DPE arms, stratified by parity (nulliparous versus 
multiparous) and class of obesity (BMI <40 vs. 40-50 kg.m-2). Allocation is concealed in sequentially 
numbered opaque envelopes. Patients, obstetricians, nurses, and anesthesia providers involved in 
follow-up of labour analgesia and data collection are blinded to group allocation. The anesthesia 
provider placing the neuraxial block and the supervising attending anesthesiologist are not involved 
in data collection or in follow up of labour analgesia.  
 
Before neuraxial placement, all patients have an intravenous catheter placed with automated non-
invasive blood pressure, pulse oximetry, and external tocodynamometry monitors applied. All 
women receive a 500 ml intravenous bolus of crystalloid solution immediately before the initiation 
of neuraxial analgesia. The epidural space is identified using a 17-gauge Tuohy needle with the 
patients in the seated position at the estimated L3-4 or L4-5 interspace, via a midline approach 
using a loss of resistance to saline technique. After identification of the epidural space, a needle-
through-needle technique is performed using a 25-G Whitacre needle, placed into the shaft of the 
previously sited epidural needle to create a single dural puncture. After confirmation of free flow of 
CSF, initial dosing consists of intrathecal 0.25% bupivacaine 2 mg (0.8 ml) and 10 μg (0.2 ml) 
fentanyl in the CSE group. Subsequently, the spinal needle is removed and the epidural catheter 
(19-gauge Duraflex wire-reinforced multiport catheter (Smith Medical, USA)) is advanced 5 cm into 
the epidural space and secured with the patient in the sitting upright position, using Tegaderm 
clear occlusive dressing (3M, USA). In the DPE group, after confirmation of free flow of CSF, the 
spinal needle is withdrawn and the epidural catheter advanced 5 cm into the epidural space. After 
negative aspiration for blood and CSF, initial dosing consists of 20 ml of 0.1% ropivacaine plus 
fentanyl 2 μg.ml-1 (premixed) administered in divided doses of 5 ml every 2 min. In both groups, 
analgesia is maintained using programmed intermittent epidural boluses of 8 ml of ropivacaine 
0.1% with fentanyl 2 μg.ml-1 every 45 min starting 30 min after the initial spinal or epidural loading 
dose, with patient-controlled epidural analgesia (PCEA) of 10 ml, a lockout of 10 min and maximum 
dose of 50 ml per hour. 
 
If analgesia is inadequate (defined as a patient request for supplemental analgesia beyond self-
administered PCEA boluses), an anesthesia provider blinded to group assignment assesses and, if 
warranted, administers top-up doses according to a predefined algorithm.  


 
The end time of administration of the loading dose (end of spinal dose injection in the CSE group or 
epidural medication administration in the DPE group) is designated time 0 (t = 0). A blinded 
investigator collects data at 15 and 30 min and subsequently at 2-h intervals from time zero until 
delivery. Analgesia is evaluated at all time points using the verbal numeric pain rating scale (NPRS) 
for the last contraction (0=no pain, 10=worst possible pain). The upper and lower sensory levels are 
evaluated at 15 and 30 min using temperature discrimination to ice. Motor blockade is assessed at 
all time points using the modified Bromage score. 
 
The following additional data are recorded every 2 h until delivery: presence of pruritus; nausea; 
hypotension (defined as systolic blood pressure ≤ 20% from the patient’s admission blood 
pressure); need for physician top-up; catheter adjustment and catheter replacement. We also 
assess for the presence of asymmetric blockade, defined as a difference > 2 dermatomal sensory 
levels between the left and right side as assessed at 15 and 30 min or at any time that sensory 
levels are checked because of complaints of pain. An obstetrician blinded to group assignments 
accesses the electronic medical record to review tocometry and continuous fetal monitoring strips 
and extract uterine contraction and fetal heart rate monitoring patterns in 10-min epochs, for 1 h 
before and 1 h after the initial spinal (CSE group) or epidural (DPE group) dosing. On the ﬁrst 
postpartum day, we assessed for postdural puncture headache and satisfaction with labour 
analgesia (0-10, 0= very dissatisﬁed, 10=very satisﬁed) 
 
The primary outcome of the study is the quality of labour analgesia, which is defined by a 
composite of five components: asymmetric block after 30 min of initiation (difference in sensory 
level of more than two dermatomes); epidural top-up interventions; catheter adjustment; catheter 
replacement; failed conversion to neuraxial anesthesia for cesarean delivery, requiring general 
anesthesia or replacement of the neuraxial block.  
 
Secondary outcomes include: pain scores; Bromage scores; sensory levels at 15 and 30 min; 
adverse events (hypotension, nausea, pruritus, postdural puncture headache, fetal heart rate 
changes); duration of second stage of labor; mode of delivery; total anesthetic dose; PCEA use; and 
overall satisfaction with analgesia.  
 


Based on the study by Chau et al a sample size of 50 patients per group had an 80% power at alpha 
0.05 to detect a reduction in the composite primary outcome from 50% in the CSE group to 22.5 % 
in the DPE group. To account for dropouts, we aim to enrol up to 60 patients per group to have 
complete data on 100 subjects.  
 
Descriptive statistics for patient characteristics and outcomes are calculated and reported as 
median (IQR [range]) or number (proportion) as appropriate. The primary composite outcome is 
compared between exposure groups using a chi-squared test and an ekect size is reported as a 
risk ratio. Secondary outcomes are assessed using chi-squared or Fisher exact tests as 
appropriate, with associated risk ratios for categorical measures and univariate log-linear 
regression with mean ratios for continuous measures. All p values for the secondary outcomes are 
adjusted for multiple comparisons using the Bonferroni-Holm method to control family-wise error 
rate and adjusted p values are reported. Only p values and adjusted p values < 0.05 are considered 
statistically signiﬁcant. Analysis is performed using R version 4.3.1, with the power calculation 
performed using NQuery.