Two Different Sized Spinal Needles DPE vs Conventional Epidural Technique

Overview

DPEA (Dural Puncture Epidural Analgesia) is an alternative to the conventional epidural analgesia and technically a Combined Spinal Epidural (CSE) with omission of intrathecal drugs administration. To date, literature has proved several advantages of the DPEA techniquecompared to conventional epidural. However, these advantages are supposed to be limited to the use of 25 Gauge spinal needles. The aim of this project is to compare the quality of analgesia achieved after a DPEA technique performed with a 25 Gauge spinal needle versus a 27 Gauge spinal needle versus a conventional epidural, with a PIEB pump installed for analgesia maintenance. The Primary outcome will be the quality of analgesia, defined as the area under the curve (AUC) of the Numeric Pain Rating Scale (NPRS 100-0) ≤ 30 measured throughout labor and divided by labor duration (TWA-NPRS). 240 nulliparous women between the 36th and 42nd gestational week in active labor and with a cervical dilation ≤ 5 cm will be randomized according to a computer-generated random number sequence to receive a DPEA with a 25 Gauge spinal needle, a DPEA with a 27 Gauge spinal needle, or a conventional epidural.

DPEA (Dural Puncture Epidural Analgesia) is an alternative to the conventional epidural analgesia and technically a Combined Spinal Epidural (CSE) with omission of intrathecal drugs administration. Analgesia is achieved through the effect of epidural agents and their partial translocation into the intrathecal space. To date, literature has proved several advantages of the DPEA technique, such as confirmation of epidural needle placement and lower rates of malfunctioning epidural catheters with reduced need for their manipulation or resiting. Overall, DPEA seems to mitigate some limitations of the conventional epidural technique while reducing the side effects associated with the CSE technique (fetal bradycardia, uterine hypertonus and pruritus). However, these advantages are supposed to be limited to the use of atraumatic 25 Gauge spinal needles, and evidence mostly come from studies that compared the DPEA performed with 25 Gauge or 27 Gauge spinal needles with the conventional epidural or with the CSE. The only direct comparison between two spinal needles of different sizes as part of a DPEA technique (25 vs 27 Gauge) was published by Contreras et al in 2019, who evaluated the onset time of the analgesic effect. The aim of this project is to compare the quality of analgesia achieved after a DPEA technique performed with a 25 Gauge spinal needle versus a 27 Gauge spinal needle versus a conventional epidural, with a PIEB pump installed for analgesia maintenance. The Primary outcome will be the quality of analgesia, defined as the area under the curve (AUC) of the Numeric Pain Rating Scale (NPRS 100-0) ≤ 30 measured throughout labor and divided by labor duration (TWA-NPRS). Secondary outcomes will be a composite outcome of patient satisfaction (consisting of 5 points - comfort in the first 30 minutes, comfort throughout labor, presence of asymmetric block, manipulation/resiting of the epidural catheter, total anesthetic volume, analgesia onset time, NPRS and level of sensory block. Exploratory oytcomes will be the number of episodes of breakthrough pain, the nincidence of motor block, the incidence of instrumental vaginal delivery and cesarean section, the maternal hemodynamic changes, the incidence of uterine hypertonicity and fetal cardiotocographic abnormalities, the presence of nausea/vomiting and pruritus, the incidence of dural puncture headache, the fetal well-being. The hypothesys is that the quality of analgesia is superior with the DPEA technique performed with a 25 Gauge spinal needle. Recently published RCTs proved several benefits of the DPEA technique performed with both 25 and 27 Gauge spinal needles, such as no significant differences in the quality of labor analgesia following initiation of a CSE compared with a 25 Gauge DPEA, faster onset of labor analgesia with good sacral coverage of a double 25 Gauge DPEA compared with the conventional epidural and faster sacral blockade of a 27 Gauge DPEA compared with the conventional epidural. Moreover a 35% reduction in the bupivacaine dose to achieve initial ED90 analgesia has been found in a group of parturients randomized to receive a 25 Gauge DPEA compared to those who receive a conventional epidural. All these findings indicate that the flow rate of anesthetic through the dura and the consequent analgesic effect resulting from a 25 Gauge DPEA is effective, but direct comparisons of 25 and 27 Gauge spinal needles as part of a DPEA technique are scarce as the only evidence reported to date is that labor analgesia onset time is 1,6 minutes shorter after a 25 Gauge DPEA compared with a 27 Gauge DPEA, which may not be clinically relevant. After obtaining informed consent, nulliparous women between the 36th and 42nd gestational week in active labor and with a cervical dilation ≤ 5 cm will be randomized according to a computer-generated random number sequence to receive a DPEA with a 25 Gauge spinal needle, a DPEA with a 27 Gauge spinal needle, or a conventional epidural. Exclusion criteria will be: age \< 18 years, ASA status \> 2, patient's refusal, known fetal pathologies, contraindications to neuraxial techniques, uterine anomalies or previous uterine surgery, BMI ≥ 35, twinning and fetal malpresentation (non cephalic). With the patient in the sitting position, the epidural space will be identified using a 18 Gauge Tuohy needle with a loss-of-resistance to saline technique, as per standard clinical practice. Patients in the DPEA groups will also receive an intentional dural puncture with a 25 Gauge or 27 Gauge Whitacre spinal needle, depending on randomization, using the needle-through-needle technique. In all patients, a 20 Gauge multi-port epidural catheter will be inserted 5 cm into the epidural space and adequately secured as per standard clinical practice. After a negative aspiration test for blood and cerebrospinal fluid, all patients will receive a mixture of 15 ml of 0,1% ropivacaine plus 0,5 mcg/ml sufentanil in the epidural catheter. Analgesia will be maintained in all groups with a PIEB pump (CADD®-Solis 2110 Infusion System, Smith Medical, USA) providing boluses of 10 ml of ropivacaine 0,1% + sufentanil 0,5 mcg/ml hourly at a flow rate of 250 mL/h . In case of breakthrough pain (NPRS ≥ 30), a manual top up of ropivacaine 0,13% 10 ml will be administered. A dose of ropivacaine 0,15% 10 ml will instead be used to treat breakthrough pain at full cervical dilation. In case of unilateral block (difference of \> 2 dermatomal levels between the two sides), the patient will be positioned in the lateral decubitus on the side with discomfort and a rescue dose will be provided. If the block persists after 10 minutes, the epidural catheter will be withdrawn 1 cm and a further rescue dose will be administered. If this fails, the epidural catheter will be repositioned. Pain will be reported in a data collection form using the NPRS scale (from 100 to 0 mm) starting from the end of the administration of the first epidural dose at the following intervals: 5, 10, 15, 20, 25, 30, 60 minutes and then every hour. A further pain assessment will be performed 15 minutes after each rescue dose. Data that constitute secondary outcomes will be collected starting from 30 minutes after the first epidural dose administration and every hour thereafter. At the beginning of the second stage the sensory block level will be checked using a pinprick test. Fetal well-being (Apgar Score) and maternal satisfaction will be recorded after delivery, while the presence of dural puncture headache will be checked 24 and 48 hours after delivery. The quality of analgesia will be defined as the weighted average of the NPRS over time, which is equivalent to the area under the curve of the NPRS divided by the duration of labor. Based on a previous study, a 35% reduction in the DPEA 25 Gauge group at 1.5 has been hypothesized. Power analysis comparing the means of three groups with one-way ANOVA (alpha 0.05, power 80%) showed that a minimum of 68 patients per group is required. Considering a possible dropout rate of 15%, this number was increased to 80. The analysis will be conducted according to an intention-to-treat (ITT) principle. To evaluate the primary outcome and the time-to-event variables, Kaplan-Meier curves and the two-sample log-rank test will be used, according to the Peto method (equivalent to the modification of the Gehan-Breslow-Wilcoxon test) for the primary outcome. Events occurring at the same time interval will be compared using the Efron method. The assumption of proportionality of risks will be verified graphically and based on the partial residuals of Schoenfeld, while the identification of outliers will be based on the residuals of deviation. The sample will be described with regard to its clinical and demographic characteristics using descriptive statistics techniques. Continuous quantitative variables with a normal distribution will be reported as mean and standard deviation or as median, and non-normal variables will be reported as the 25th or 75th percentile. The Mann-Whitney test will be used to compare the distributions of continuous quantitative variables. Missing data will be presented as absolute values and percentages, n (%). For comparisons between categorical data, results will be reported as RRs, 95% confidence intervals, and P-values based on the Pearson chi-square test or Fisher exact test, as appropriate. A P-value \<0.05 will be considered significant. All analyses will be performed with the R statistical software (version 3.6.2) (R-project.org/foundation).