When providing labor epidural analgesia, an anesthesiologist must decide at what intervertebral level to place the catheter. This choice may be based on personal preference or on vertebral anatomy and body habitus. Anesthesiologists may also make their choice based on the neuroanatomy of labor pain,1 aiming higher to relieve the visceral pain of uterine contractions, or lower for the somatic perineal pain that passes through the pudendal nerve and the sacral nerve roots. Commonly, the anesthesiologist blindly chooses a mid-lumbar interspace, estimating the level based on anatomical landmarks. However, studies have shown that this estimation is frequently wrong, and the chosen level is often higher than intended.2 Currently, there is no evidence to guide the choice of epidural catheter placement level. In our institution, it is usually provider preference that guides this choice, and there are several anesthesiologists who prefer placing epidural catheters at higher intervertebral spaces. However, we (the authors) prefer placing catheters in lower intervertebral spaces, thinking that local analgesia introduced closer to the sacral nerve roots would more successfully block perineal labor pain. This pain is hard to block using lumbar epidural analgesia,3 likely because lumbar epidural catheters block lumbar and thoracic nerve roots more effectively than sacral nerve roots.4–6 Since we had no literature to help us with this dilemma, we devised this single blind randomized controlled trial to test the hypothesis that lower epidural catheters would require less rescue analgesia when used with a patient-controlled epidural analgesia (PCEA) infusion for labor pain.
Inclusion and Randomization
This randomized, single-blind, controlled trial was approved by the Mcgill University Health Center Office of Research Ethics and registered at www.clinicaltrials.gov under number NCT00954317 in August 2009 by Albert Moore. Written informed consent was obtained from all participants. The study took place between November 2009 and January 2016 on the labor floor of a university-affiliated tertiary care hospital. We included nulliparous women at less than 5 cm cervical dilation who were considering epidural analgesia and had been admitted on days when study personnel were available. Patients with known contraindications to epidural analgesia, a body mass index greater than 40 kg m−2, neurological illness, multiple gestations, fetal abnormalities, an American Society of Anesthesiologists physical status greater than 2, or patients requesting immediate epidural catheter placement were excluded from the study. A computer-generated randomization table assigned ascending study numbers to either the low epidural (L4-5) or the high epidural group (L1-2). These assignments were placed in sealed envelopes labeled with the study number. When enrolled patients who had not progressed past 5 cm dilation requested epidural analgesia, they were assigned sequential study numbers. Each envelope with the corresponding number was opened by the treating anesthesiologist, and the epidural catheter was placed in the interspace that corresponded to that group assignment.
The L4-L5 and L1-L2 vertebral interspaces were identified with the aid of a Logiq-e ultrasound system (GE Healthcare, Wauwatosa, WI) and a longitudinally oriented 5 MHz curved array ultrasound probe, following methods previously described.7 Briefly, the ultrasound probe was placed in the sagittal paramedian plane, the sacrum was identified, and, assuming there were 5 lumbar vertebrae, the vertebral interspaces were then counted cranially. Scanning was performed by authors (A.M., B.B., A.eB., I.K., and E.E.), all of whom had performed more than 20 previous scans. Perifix® FX custom continuous epidural kits (B. Braun Medical, Inc, Bethlehem, PA) were used for catheter placement. The epidural was placed by the staff, fellow, or resident anesthesiologist on duty on the labor floor. With patients in the sitting position and after skin sterilization, the epidural space was located with a loss of resistance to saline technique using a 16-gauge Touhy needle with a cranially directed bevel. A 20-gauge multi-orifice soft-tip catheter was then inserted 5 cm into the epidural space. After negative aspiration for blood or cerebrospinal fluid, epidural catheters were bolused with 3 mL of 0.125% bupivacaine. Five minutes later, they were bolused with 12 mL of 0.125% bupivacaine in 2 divided doses, separated by 5 minutes. Epidural catheters with evidence of intravascular placement were immediately replaced at the same level, and these patients remained in the analysis. Intrathecal catheter management was left to the discretion of the attending anesthesiologist, and these patients were excluded from further analysis. After placement, the catheter was fixed to the patient’s back with an occlusive dressing and opaque tape. The marks indicating the vertebral interspaces were wiped off the back, and a wide cotton girdle that held the fetal heart rate monitor was pulled over the epidural site to hide the lower back. The patient was not informed of where the catheter was placed, and study personnel who had not placed the epidural were responsible for assessing outcomes. Although we did not inform nursing staff and assessors of what level the catheter was placed, they could determine its position if they looked at the patient’s back. For this reason, we considered this study single blind.
Epidural Analgesia and Labor Management
Labor analgesia was managed as per institutional protocol. The epidural catheter was connected to a PCEA pump that was set to deliver 10 mL/hour of a solution containing 0.06% bupivacaine and 2 µg/mL of fentanyl, with a patient demand dose of 5 mL, a 10-minute lockout period, and no hourly maximum. Patients were nursed on their side with the head of the bed slightly elevated and were instructed to change the side they were laying on hourly. The function of the PCEA pump was described to the patients, and they were informed they could be given nurse-administered manual boluses of epidural medication if the PCEA did not provide adequate analgesia. On-duty labor floor nurses who were not involved in the study were responsible for providing rescue manual boluses of local anesthesia according to institutional protocol. If contraction pain using an 11-point verbal analogue scale (VAS; with 0 being no pain, and 10 being the worst pain possible) was greater than 4 and patients wished for more analgesia, it was provided with a bolus of 10 mL of 0.125% bupivacaine with 50 µg of fentanyl. Manual epidural boluses of 8 mL of 2% lidocaine were given if the bupivacaine bolus did not provide relief, or they could be used if second stage pain was greater than 4 on a VAS. Labor management was left to the discretion of the attending obstetrician. Oxytocin, when used, was started at a rate of 2 milliunits per minute and could be increased 2 milliunits per minute every 30 minutes. Cervical examinations were performed for obstetrical indications only.
We recorded patient demographic characteristics, including age, body mass index, total days of gestation, gravidity, baseline overall pain (via VAS), duration of epidural infusion, and whether labor was being induced. After delivery, we extracted information from the chart concerning the manual boluses given to each patient. Our primary outcome was the proportion of patients in each group who would require manual epidural boluses for analgesia. Secondarily, we were interested in determining group differences in the timing of manual boluses during early and late labor. In standardized partograms, fetal descent increases rapidly at 4 hours before delivery in the average patient, during the so-called “pelvic division” of labor.8,9 Since somatic perineal pain should worsen during this division of labor, we analyzed the timing of manual boluses given before (early labor) and after (late labor) this time point. We rated the pain patients felt in their abdomen (abdominal pain) and in their rectum or vagina (perineal pain) using a VAS at 30 and 60 minutes after the initial epidural bolus. The dermatome blockade was assessed at these same time points by placing ice at the L1 dermatome and then moving cranially or caudally until the patient noted a difference in cold sensation. The dermatome level was converted to an ordinal scale for analysis. The patients were visited as soon as possible (no later than 24 hours) after delivery, and those who had undergone a vaginal delivery were asked to rate the abdominal and perineal pain (via VAS) they felt during pushing.
The anesthesiologist was asked to rate the difficulty of the catheter placement using a 4-point scale of 1 = easy, 2 = mildly difficult, 3 = moderately difficult, or 4 = very difficult, and to record the duration of time between initial insertion of the Touhy needle and the placement of the catheter. The number of placement attempts, with an attempt being defined as a complete removal and redirection of the needle, was also recorded. At 30 and 60 minutes after initial epidural bolus, patient motor function was assessed using a Bromage scale.10 Data concerning the type of delivery, the duration of second-stage labor, the neonatal Apgar scores, and the umbilical cord pH were extracted from the chart. Patients were also asked at the postdelivery visit to rate their overall satisfaction with their pain management using an 11-point VAS, with 0 being not satisfied and 10 being completely satisfied.
It has been shown that nearly 50% of laboring patients with epidural analgesia will require manual epidural boluses.11 We hypothesized that a parturient with an epidural catheter placed in a low (caudad) lumbar space would require fewer manual bolus doses for breakthrough pain than a parturient with a catheter placed in a high (cephalad) lumber space. We predicted that 50% of patients with a high epidural would require a manual bolus and wished to determine whether that would reduce to 25% in the low epidural group. We wanted to have 80% power to find this difference. For our initial sample size calculation, we chose a single-sided α of 0.05, and using a χ2 squared statistic on a 2-way contingency table, we found that we needed 46 patients in each group. We planned on recruiting 100 patients. After 100 patients were recruited, we analyzed the primary and secondary outcomes and realized 2 things: (1) we had not accounted for the loss of patients to cesarean delivery who may not have entered into the pelvic division of labor; and (2) the use of a single-sided hypothesis test may not have been appropriate. We revised our sample size calculation to determine the same difference with 80% power and a double-sided α of 0.05 and found that we needed 58 patients in each group. To account for a 30% cesarean delivery rate, we increased this to 75 in each group. To account for the interim analysis, the O’Brian-Fleming type alpha spending function of Lan-DeMets12 was utilized, and a final P value of .038 was taken as the limit of significance.
For continuous data (age, body mass index, weeks of gestation, duration of epidural infusion, PCEA requirements, time for epidural placement, duration of second-stage labor, neonatal weight, and umbilical vein pH), the point estimates are presented as means with standard deviation (SD), and between-group comparisons were performed with t tests. For ordinal data (gravidity, cervical dilation, VAS, dermatome level, motor blockade, catheter placement difficulty level and attempts, patient satisfaction, and Apgar scores), the point estimates are presented as median with interquartile ranges and are compared with Mann-Whitney U tests. Categorical data are presented as proportions (percent) and are compared using Pearson χ2 tests when there are 2 possible outcomes (induction, oxytocin, overall proportion of patients who received manual boluses, comparison of all the boluses given in early versus late labor, intravascular catheter, unilateral blockade, and unilateral catheter) and nominal regression for more than 2 outcomes (delivery type).
Hypotheses generated before data collection included those for our primary outcome and the secondary outcomes related to manual bolus timing, pain scores, and dermatomal blockade. To limit the type I error to a familywise rate of 5% for these tests, we adjusted their P values using a sequential Bonferroni method.13 Observations of the collected data prompted a series of exploratory analyses, which included epidural placement time, epidural complications, delivery type, patient satisfaction, and neonatal outcomes. For these analyses we accepted an increased risk of type I error and did not adjust their P values. We used Stata 14 (StataCorp LP, College Station, TX) for the data analysis.
The Figure demonstrates the flow of patients through the study; we randomized 150 patients. One patient in the high group was found to have an intrathecal catheter immediately after placement, and 1 patient in the low group withdrew from the study. These patients were not included in the analysis. The groups were similar at baseline (Table 1).
Table 2 summarizes pain and analgesic requirements of the patients. Results in this table represent the hypotheses developed during study design, and P values are adjusted accordingly. For our primary hypothesis, we found no significant difference in the proportion of patients in the low and high groups requiring manual epidural boluses. We found there was a significant difference in the distribution of the manual boluses for the 56 patients in each group who delivered vaginally, with the low group receiving 13 more boluses than the high group in early labor and 16 fewer boluses in late labor (χ2 with 1 degree of freedom = 9.9314, adjusted P = .014). There were significantly higher abdominal pain scores and a more caudal thoracic and sacral dermatome blockade in the low group at both 30 and 60 minutes after catheter insertion. We found no significant difference in perineal pain scores at the 30-minute time point but a significantly lower score in the low group at 60 minutes. During pushing, there was no statistically significant difference in abdominal pain scores between groups, but the perineal pain scores were less in the low epidural group.
Further results presented are the hypotheses that were developed during data analysis, and the P values have not been adjusted for multiple comparisons. There were no differences noted in epidural complications, except for catheter dislodgement (Table 3). After request for additional analgesia and ice testing, 4 catheters were found to be dislodged and were replaced at the same level in the low epidural group. These patients remained in the analysis. There was no significant difference noted in the proportion of patients receiving manual boluses of only bupivacaine, only lidocaine, or both. There was no statistical difference found in rates of cesarean delivery in neonatal weight or neonatal outcomes between groups, but there was a trend toward increased rates of instrumental delivery in the low group (Table 4).
We performed this study to compare the labor analgesia requirements of epidural catheters placed in either high or low intervertebral spaces. We found that there was no statistical difference in the percentage of patients who require manual rescue analgesia boluses when comparing epidural catheters placed in the L1-2 to the L4-5 interspace. However, we did find that the timing of manual boluses did differ between groups. In early labor, significantly more boluses were given in the low epidural group, while in late labor, more were given to the high epidural group. It appears that low epidural catheters may be better at providing analgesia for late labor than for early labor, while high epidurals are better for early as opposed to late labor.
This is most likely because high catheters provide improved blockade of low thoracic nerve roots and their transmission of uterine distension pain, and low catheters provide improved blockade of sacral nerve roots and the transmitted perineal pain. This is supported by other findings of our study. In the first hour after placement, L1-2 catheters provided more relief of pain felt in the abdomen, while L4-5 catheters provided more relief of perineal pain. During pushing, when the perineal pain is at its greatest, patients with the L4-5 catheters had lower perineal pain scores than the high epidural group. In addition, the dermatome levels in each group reflected a difference in sacral and thoracic nerve root involvement; the lower catheters blocked more sacral dermatomes, and the high catheters provided a higher thoracic dermatome level.
Perineal labor pain is difficult to relieve with lumbar epidural analgesia, probably because lumbar nerve roots are larger and harder to block.3–6 The difficulty in providing perineal analgesia for labor with lumbar epidural catheters has led to the study of various methods to improve sacral blockade, which includes pudendal nerve blocks,14 caudal anesthesia,15 dural puncture epidural technique,16 and use of opioid medication. It is possible that placing epidurals in a low intervertebral space may also improve perineal analgesia. Although we demonstrated that this came at the cost of poorer relief of early labor pain, the 60-minute median pain scores differed by only 1 point, and the use of a higher volume of local anesthetic could possibly improve the onset of a blockade.
There is evidence supporting our findings. In a manuscript published in Chinese with an English abstract, the labor analgesia provided by a double-catheter technique, which combined a high and low epidural catheter, was compared to that that provided with a single catheter.17 No difference in analgesic requirements between groups was demonstrated, even though the double catheter group reported lower pain scores during the second stage of labor. It has been shown that better sacral blockade can be obtained when injecting medication through a caudally directed epidural catheter.18 This suggests measures that direct epidural medications closer to the sacral nerve roots will result in more sacral blockade.
There were 2 results from this study that were unexpected. We found there were more dislodged catheters and a trend for increased instrumental delivery in the low group. Since these were considered exploratory analyses, future trials are needed to formally test these possible associations.
There are limitations to this study. We did not have 24-hour availability of research personnel and relied on patient recall of pain during pushing. Although patients were instructed to remember their pushing pain levels, it is unclear how this delay in assessment would affect the recall of pain. Norvell demonstrated that patients tended to report higher pain scores during labor than 2 days after delivery,19 while Rofe demonstrated no difference between pain scores collected during labor and then 1–2 days after delivery.20 Either way, there is no reason to suspect that the level of epidural insertion should influence how women recall their pain, and any recall bias introduced should be nondifferential in nature. In addition, we were unable to assess the patient at multiple points during the labor, and we do not know how the groups’ pain scores and motor blockade differed during the middle of the labor. We selected nulliparous patients in early labor to study. Our results may not apply to other patients, notably the multiparous or those in advanced labor. In addition, because of the difficulties in masking a procedure such as this, this study should be taken as a single-blind study, with all its inherent biases.
To conclude, we compared the analgesic properties of epidural catheters placed at the L1-2 versus the L4-5 interspace in primiparous laboring women. We found that there was no between-group difference in the proportion of patients who received a manual rescue analgesia bolus, although more boluses were given in early labor to the low epidural group and in late labor to the high epidural group. We also found that patients with low catheters had greater abdominal pain and less perineal pain in the first hour and less perineal pain during pushing. A future trial is needed to test the hypothesis that low epidural catheter insertion increases risk for instrumental vaginal delivery.
Name: Albert Moore, MD.
Contribution: This author helped design the study, recruit patients, collect and analyze the data, and prepare the manuscript.
Name: Valerie Villeneuve, MD.
Contribution: This author helped design the study, collect the data, and prepare the manuscript.
Name: Bruno Bravim, MD.
Contribution: This author helped recruit patients, collect the data, and prepare the manuscript.
Name: Aly el-Bahrawy, MD.
Contribution: This author helped recruit patients, collect and analyze the data, and prepare the manuscript.
Name: Eva el-Mouallem, MD.
Contribution: This author helped recruit patients, collect and analyze the data, and prepare the manuscript.
Name: Ian Kaufman, MD.
Contribution: This author helped design the study, collect the data, and prepare the manuscript.
Name: Roupen Hatzakorzian, MD.
Contribution: This author helped design the study, analyze the data, and prepare the manuscript.
Name: William LiPiShan, MD.
Contribution: This author helped design the study and prepare the manuscript.
This manuscript was handled by: Jill M. Mhyre, MD.
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