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Epidural Volume Extension During Combined Spinal-Epidural Labor Analgesia Does Not Increase Sensory Block

Zaphiratos, Valerie MD, MSc, FRCPC; George, Ronald B. MD, FRCPC; Macaulay, Bruce MD, FRCPC; Bolleddula, Prasad MD, FRCA; McKeen, Dolores M. MSc, MD, FRCPC

doi: 10.1213/ANE.0000000000001281
Obstetric Anesthesiology: Original Clinical Research Report

BACKGROUND: Combined spinal-epidural (CSE) analgesia is widely used for delivering labor analgesia. Epidural volume extension (EVE) involves the injection of fluid into the epidural space compressing the dural sac, causing cephalad shift of the cerebral spinal fluid. Our hypothesis was that EVE with 10 mL normal saline during CSE would increase the sensory block height at 15 minutes after intrathecal injection. We expected EVE to decrease pain scores, decrease analgesia onset time, and decrease motor block compared with performing CSE without EVE (NEVE).

METHODS: We randomly assigned 60 healthy term laboring nulliparous parturients with cervical dilation <5 cm to receive CSE either with EVE of 10 mL normal saline through the Tuohy needle before catheter insertion or CSE NEVE. Intrathecal analgesia consisted of 2 mg plain bupivacaine and 10 μg fentanyl (1 mL total). A blinded researcher assessed sensory dermatome level, analgesia, and motor blockade at regular intervals for 30 minutes. The primary outcome measure was the median peak sensory dermatome level at 15 minutes.

RESULTS: Fifty-four parturients were analyzed. There was no significant difference in peak sensory dermatome levels at 15 minutes (median difference, 1 dermatome level; 95% confidence interval of median difference, 0 to 2; P = 0.22) and 30 minutes (median difference, 0 dermatome level; 95% confidence interval, −2 to 2; P = 0.76). There was no difference in the time to peak dermatome, minimum pain score, or the time to minimum pain score between groups.

CONCLUSIONS: We found no significant difference between groups with regard to sensory dermatome level or pain scores when using EVE compared with NEVE. Our study demonstrates that addition of EVE does not offer superior analgesia when using a CSE technique for parturients requesting labor analgesia.

Published ahead of print April 15, 2016

From the IWK Health Centre, Department of Women’s and Obstetric Anesthesia, Dalhousie University, Halifax, Nova Scotia, Canada.

Valerie Zaphiratos, MD, MSc, FRCPC, is currently affiliated with Department of Anesthesia, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada.

Accepted for publication January 31, 2016.

Published ahead of print April 15, 2016

Funding: None.

The authors declare no conflicts of interest.

This report was previously presented, in part, at the Society for Obstetric Anesthesia and Perinatology Annual Meeting (2014), Canadian Anesthesiologists’ Society Annual Meeting (2014).

Reprints will not be available from the authors.

Address correspondence to Valerie Zaphiratos, MD, MSc, FRCPC, Department of Anesthesia, Maisonneuve-Rosemont Hospital, 5415 boul. de l’Assomption, H1T 2M4 Montreal, Quebec, Canada. Address e-mail to valerie@zaphiratos.ca.

Combined spinal-epidural (CSE) analgesia is widely used for delivering labor pain relief because of its rapid onset of profound analgesia, minimal motor blockade, and high patient satisfaction.1,2 In a recently published large randomized controlled trial, CSE provided faster and better first-stage analgesia and fewer epidural top-up boluses compared with traditional epidural labor analgesia.2 Intrathecal local anesthetics can spread cephalad with injection of volume into the epidural space.3–5 Deliberate injection of volume in the epidural space to increase the level of spinal anesthetic is termed epidural volume extension (EVE). The mechanism by which this occurs is not fully understood, but it has been postulated that the fluid in the epidural space causes a compression of the dural sac, resulting in a cephalad shift of local anesthetic within the cerebral spinal fluid6–8 (Figure 1).

Figure 1

Figure 1

Our study aimed to examine the effect of EVE on the intrathecal component of a CSE in laboring nulliparous parturients. Our hypothesis is that the epidural injection of 10 mL normal saline, while initiating CSE for labor analgesia, will increase the initial anesthetic sensory block height 15 minutes after intrathecal injection. In addition, we expect EVE to increase the sensory block height at 30 minutes, decrease pain scores, decrease analgesia onset time, and decrease motor block compared with performing CSE without EVE.

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METHODS

The study was registered before patient enrollment. Registry URL: https://clinicaltrials.gov/ct2/show/NCT01810406 Identifier: NCT01810406.

After receiving IWK Health Centre Research Ethics Board approval (REB1013037) and written informed patient consent, we recruited 60 laboring nulliparous parturients of ASA physical status I to II with singleton, vertex presentation fetuses at 37- to 42-week gestation in active labor with cervical dilation <5 cm, requesting neuraxial analgesia for the management of labor pain. Recruitment took place from January 2013 to August 2013 in this prospective, randomized, double-blinded study.

Exclusion criteria included age <18 years, inability to communicate in English, contraindication to neuraxial analgesia, conditions associated with abnormal spinal anatomy that can affect local anesthetic spread, conditions associated with an increased risk of a cesarean delivery, morbid obesity (body mass index ≥35 kg/m2), maternal comorbidity, such as pregnancy-induced hypertension or preeclampsia, severe maternal cardiac disease, known fetal anomalies/intrauterine fetal demise, enrollment in another study involving a study medication within 30 days, and any other physical or psychiatric condition that could impair their ability to cooperate with study data collection. Withdrawal criteria included failed subarachnoid injection, failure to insert epidural catheter, and intrathecal or intravascular epidural catheter placement.

After providing consent, the participants were randomly allocated by means of a computer-generated random number table into 1 of 2 groups. Preprinted allocation labels within sealed, opaque, numbered envelopes contained information on group allocation and were opened immediately before initiation of analgesia. An anesthesiologist aware of patient group allocation was responsible for performing the CSE. To ensure blinding of the procedure, an investigator unaware of patient group allocation was responsible for postprocedure data collection. All patients and their nurses were unaware of group allocation.

As per standard practice at the IWK, an IV catheter was in place before initiation of the technique. No specific amount of fluid is required at our institution before labor analgesia initiation; thus, no fluid bolus was administered. In the sitting position, the epidural space was identified with a 17-G or 18-G, 9-cm Tuohy epidural needle using a loss of resistance to air or saline (<1 mL) technique and a 25-G, 12-cm Whitacre spinal needle was placed through the shaft of the epidural needle. The presence of cerebral spinal fluid in the hub of the 25-G Whitacre needle confirmed dural puncture. Plain bupivacaine 0.25% 0.8 mL (2 mg) + fentanyl 10 μg (total 1 mL) was injected into the intrathecal space. Depending on group randomization, group with EVE (EVE) subjects received 10 mL normal saline for EVE via the Tuohy needle, and an epidural catheter was threaded 4 to 5 cm into the epidural space. Group without EVE (NEVE) subjects did not receive EVE, and an epidural catheter was threaded 4 to 5 cm into the epidural space.

After epidural catheter placement, an infusion of 1 mg/mL ropivacaine 0.1% + 2 μg/mL fentanyl at 6 mL/h was initiated, with the option of patient-controlled epidural analgesia (PCEA) boluses of 6 mL, a lockout interval of 8 or 10 minutes, and no hourly maximum, as needed by the patient. This is the standard, IWK Health Centre protocol for labor epidural infusions. If an intravascular or intrathecal catheter placement was confirmed by aspiration testing, these patients were withdrawn from the study. As per standard protocol, fetal heart rate was monitored immediately after the procedure, and blood pressure was taken immediately and every 5 minutes for 30 minutes after the procedure.

Immediately after the procedure, patients were repositioned to the left lateral position (standard in our institute). A blinded researcher then entered the room and assessed sensory dermatome level by a nontraumatic pinprick test that started at the S2 dermatome and moved cephalad. The nontraumatic pinprick test was performed with a blunt needle (18-G 1½″ blunt fill needle; BD Medical, Franklin Lakes, NJ), used for piercing and aspirating vials of medication, and capable of eliciting a nontraumatic pinprick. The sensation was first tested on the hand or forearm to establish a baseline, and then compared with each of the dermatome levels. The patient was asked to note when the tested dermatome sensation was the same as the baseline sensation. The anatomic landmarks and correlated dermatome levels were standardized for testing as follows: in the lower extremity, dermatome levels were assessed by stimulating the inguinal crease (L1), anterior thigh (L2), medial knee (L3), medial malleolus (L4), the dorsum web between great and second toe (L5), the lateral heel (S1), and the medial popliteal fossa (S2). On the torso, dermatome levels were assessed in the midclavicular line, with the umbilicus at T10 and the nipples at T4, and the thoracic dermatomes T5 to T9 were considered to be evenly spaced stacked segments in between. The blinded researcher also assessed analgesia using a verbal numeric rating scale (NRS) 0 to 10 (where 0 = no pain, 10 = worst pain imaginable), and motor blockade with a modified Bromage score: 1—complete block (unable to move feet or knees), 2—almost complete block (able to move feet only), 3—partial block (just able to move knees), 4—detectable weakness of hip flexion while supine (full flexion of knees), 5—no detectable weakness of hip flexion while supine, and 6—able to perform partial knee bend.9

The blinded researcher reassessed these parameters (sensory, pain, and motor) at 2.5-minute intervals for the first 10 minutes after intrathecal injection, then every 5 minutes for an additional 20 minutes. The study period ended after the last assessment (30 minutes after intrathecal injection). In addition, the researcher noted the amount of analgesia self-administered by PCEA and any anesthetic interventions, including requests to evaluate analgesia, additional amount of epidural analgesia (“top-ups”) (because of a failed intrathecal injection, for example), or side effects (hypotension, pruritus, nausea, and fetal distress) during those 30 minutes. Hypotension was defined as a 20% reduction in the systolic blood pressure from the admission blood pressure in the absence of uterine contraction or a systolic blood pressure <90 mm Hg. Hypotension was treated with 5 to 10 mg ephedrine IV or 50 to 100 μg phenylephrine IV. Fetal heart rate deceleration was defined as a heart rate that had decreased 15 bpm from the baseline, lasting 2 minutes or more but <10 minutes in duration.10 Nausea and pruritus were evaluated on an NRS ranging from 0 to 10 (where 0 = no nausea/pruritus, 10 = most severe nausea/pruritus requiring treatment) at the end of the 30-minute evaluation period. If therapy was required to treat nausea or pruritus during the study, it was recorded as 10.

In the event of inadequate analgesia, defined as patient requests for supplemental analgesia beyond 2 PCEA self-administered boluses, an assessment was made by an anesthesiologist blinded to group assignment. Supplemental analgesia (“top-up”) was provided by 5 to 10 mL ropivacaine 0.2% (2 mg/mL). In the event of further inadequate analgesia, the anesthesiologist treated patients at their discretion. The blinded researcher recorded maternal demographic and fetal characteristics from the chart (sex, birth weight, and Apgar scores).

The primary outcome measure was the peak sensory dermatome level at 15 minutes, as determined by nontraumatic pinprick test. Secondary outcomes included peak sensory dermatome level at 30 minutes, analgesia assessed by NRS, and motor block using a modified Bromage scale. Additional outcomes included side effects (hypotension, pruritus, nausea, and nonreassuring fetal status), cesarean delivery rates, neonatal outcomes, as well as the need for additional analgesia self-administered by the patient via the PCEA button and the amount of supplemental analgesia (“top-ups”) necessary.

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Statistical Analysis

Maternal demographics were tested by the Student t test (continuous data) or χ2 (categorical data) as appropriate. NRS scores were analyzed by analysis of variance for repeated measures. Times to achieve blocks, NRS end points, and the range of peak dermatome levels and the 95% confidence interval (CI) were tested by the Wilcoxon rank sum test. The median difference between peak dermatome levels at 15 and 30 minutes and the 95% CI for the median difference were found using the Hodges-Lehmann estimator in SPSS 22.0 software (IBM Corp., Armonk, NY). Adverse events were tabulated according to group, severity, and resultant treatment and compared using the Fisher exact test. Statistical significance was assumed when P < 0.05.

Based on previous studies,7,11 an a priori power calculation was performed to identify a sensory block difference of 2 dermatome levels between the 2 independent groups. Calculations were made using G*Power version 3.0.10 (G*Power, University of Düsseldorf). Based on Patel et al.12 and Whitty et al.,13 we assumed a standard deviation of 1 dermatome, an α of 0.05, and a power of 90%, and we calculated that 23 patients in each group sufficed. Based on our previous experience, to address the limitations of our assumptions and potential dropouts and/or withdrawals, we elected to recruit 30 patients per group.

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RESULTS

A total of 92 parturients were assessed for enrollment; 60 parturients were randomly assigned and 54 were analyzed (Figure 2). The groups were similar, and demographic data are presented in Table 1. The median difference in peak dermatome level at 15 minutes (1 dermatome level [95% CI of median difference, 0–2]) and 30 minutes (0 dermatome level [95% CI of median difference, −2 to 2]) were similar with no significant difference between groups. The median time to peak dermatome was similar between groups. The minimal pain score for both groups was 0 of 10, and the median time to achieve the minimal NRS score was 2.5 minutes in both groups. These outcomes were not statistically significant (Table 2).

Table 1

Table 1

Table 2

Table 2

Figure 2

Figure 2

The percentage of parturients with a modified Bromage score <6 was 11.5% for group EVE compared with 32.1% for group NEVE (relative risk, 2.79; 95% CI, 0.85–9.18; P = 0.10). The median peak modified Bromage score was 6 in each group, but with a wider range for group NEVE.4,6 This outcome did not reach statistical significance (P = 0.064) (Table 2).

Table 3

Table 3

Regarding neonatal outcomes, there was no difference between groups with respect to birth weight or the median Apgar scores (9 at 1 minute and 5 minutes for both groups). There was no significant difference in adverse effects between groups, including hypotension, fetal bradycardia, nausea, and vomiting, and no difference in cesarean delivery rate. The incidence of pruritus was not significant between groups and was present in 16 of 28 patients for group NEVE and in 15 of 26 patients for group EVE. Two patients in group NEVE and 1 in group EVE required supplemental analgesia (PCEA). There was no need for top-up analgesia by an anesthesiologist in either group (Table 3). No participants were excluded because of intravascular or intrathecal catheters.

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DISCUSSION

To our knowledge, this is the first clinical trial to study the effect of EVE for labor analgesia. We did not find a significant difference between groups with regard to peak sensory dermatome level or the time to peak dermatome level. There was no difference in minimal pain scores, with a score of 0 of 10 after 2.5 minutes for both groups. Although there was a trend toward less motor block in group EVE, this was not statistically significant.

Most studies in parturients undergoing elective cesarean delivery have not demonstrated an increased block height with EVE using saline.6,7,14–17 However, Blumgart et al.4 demonstrated decreased time to peak sensory block height using EVE, whereas Lew et al.18 demonstrated less motor block and similar block height in group EVE using less bupivacaine compared with the control group. The success of EVE is dependent on several factors that may increase sensory block height, including the timing of epidural injection, the epidural volume injected, patient position, baricity of the local anesthetic, and patient perception.3,5,19–22

Tyagi et al.22 have recently published a literature review on EVE discussing factors that influence EVE. It is recommended that the time of EVE injection should occur soon after intrathecal injection, ideally <5 minutes, to observe an increased sensory level of analgesia.5,22,23 In our study, EVE injection through the Tuohy needle occurred immediately after the removal of the spinal needle after intrathecal injection, suggesting that time lag was not a factor in the lack of difference of sensory block height between groups.

Another factor that can influence EVE is the volume of the injected solution.22 An animal study determined that the volume injected into the epidural space of pregnant ewes should be 50% of that injected in the nonpregnant model, suggesting that sensory block height is higher in pregnancy with the same given volume of solution.24 Most studies on EVE in obstetric patients use a volume between 5 and 10 mL,4,6,7,14,18,22 and it was demonstrated that there is a ceiling effect for EVE at a volume of 15 mL in nonobstetrical patients.25 A recent study demonstrated that a volume of 7.4 mL for EVE is sufficient to raise the level of a spinal sensory block by 2 dermatome levels in adult males.26 Despite using a volume of 10 mL for EVE, which is congruent with these studies, our study failed to demonstrate a difference in sensory block height.

Patient position and baricity of the local anesthetic may affect sensory block height using EVE.22 When using EVE with saline and a hyperbaric local anesthetic in the lateral position, the sensory block level is higher than in the sitting position.20 When CSE is performed with patients in the sitting position, studies show that EVE can increase sensory block level when using plain bupivacaine.8,19 In our study, we standardized the sitting position and injected the same solution of isobaric bupivacaine with fentanyl in all patients. Despite these previous studies, our study did not find a difference between groups using an isobaric solution and the sitting position.

The dose and volume of intrathecal isobaric bupivacaine we used was much smaller than previous studies using EVE, as our goal was to obtain labor analgesia not anesthesia. The quantity of isobaric bupivacaine was probably not sufficient to demonstrate a significant impact on sensory block level using EVE. The trend for less motor block in group EVE may be because of dural compression causing the spread of intrathecal local anesthetic, and thereby decreasing the concentration of local anesthetic at the lumbar dermatomes, the major contributors to lower limb motor function, where injection took place.7 However, this finding is not clinically significant, because the median peak modified Bromage score in both groups was 6.

Pruritus was present in over half the patients in both groups, and there was no significant difference between groups. Although it has been shown that CSE causes more pruritus than low-dose epidural analgesia, our study demonstrates that the use of EVE does not decrease this complication.1

A possible use of EVE may be more stable hemodynamics when using neuraxial anesthesia, as evidenced by case reports of its use in parturients with cardiac comorbidities27,28 or in patients with poor left ventricular function.29 However, it is possible that the greater hemodynamic stability seen with EVE may be attributable to the decrease in local anesthetic dose rather than a direct effect of EVE.22 Further hemodynamic stability may be seen when injecting lower doses of intrathecal medications.

In conclusion, our study demonstrates that EVE does not offer superior analgesia when using a CSE technique for parturients requesting labor analgesia, but any effect on long-term catheter function was not assessed in this study.

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DISCLOSURES

Name: Valerie Zaphiratos, MD, MSc, FRCPC.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Name: Ronald B. George, MD, FRCPC.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Name: Bruce Macaulay, MD, FRCPC.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Name: Prasad Bolleddula, MD, FRCA.

Contribution: This author helped design the study and conduct the study.

Name: Dolores M. McKeen, MSc, MD, FRCPC.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

This manuscript was handled by: Cynthia A. Wong, MD.

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ACKNOWLEDGMENTS

We gratefully acknowledge John Colin Boyd, Obstetric Anesthesia research assistant, and Jaclyn Desroches, Dalhousie University medical student, for their assistance with patient recruitment and data collection. We also acknowledge Kimberly Vella, Obstetric Anesthesia research assistant, for her assistance with manuscript editing and submission. Dr. George acknowledges the Canadian Anesthesiologists’ Society Research Foundation for the Career Scientist Award.

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