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Diluent Volume for Epidural Fentanyl and Its Effect on Analgesia in Early Labor

Connelly, Neil Roy, MD; Parker, Robert K., DO; Pedersen, Thomas, MD; Manikantan, Thenu, MD; Lucas, Tanya, MD; Serban, Stelian, MD; El-Mansouri, Mervat, MD; DuBois, Scott, MD; Santos, Edgar Delos, MD; Rizvi, Asad, MD; Gibson, Charles, RN MA

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doi: 10.1213/01.ANE.0000061583.77068.0B
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Epidural fentanyl or sufentanil, after a lidocaine-epinephrine test dose, provides approximately 2 h of analgesia while allowing patients to ambulate (1–7). Fentanyl is the most frequently chosen opioid at our institution for early labor ambulatory epidurals based on its inexpensive cost and a lack of significant analgesic difference compared with sufentanil (2). It has been shown that the volume of injectate affects the onset and duration of analgesia of epidural fentanyl in the setting of postoperative pain (8) (a small volume slowed the onset and shortened the analgesic duration). However, it remains unclear what effects would result by varying the volume of injectate of an ambulatory labor epidural. We thus undertook this study to determine the influence of volume on the duration of analgesia and side effects when administered along with fentanyl after a lidocaine and epinephrine test dose in primigravid patients during the early first stage of labor.


Before this study was initiated, IRB approval was obtained. Sixty primigravid ASA physical status I or II obstetric patients, at more than 36 wk of gestation and who had requested labor analgesia, gave written informed consent. Patients were excluded if cervical dilation was more than 5 cm, if they had received opioid agonists or agonist/antagonists, had preeclampsia, or had a contraindication to fentanyl. A normal fetal heart rate pattern (including an absence of decelerations) was required for inclusion in the study.

Before the procedure was begun, the patients’ vital signs (blood pressure, heart rate, and respiratory rate) were documented, and the patients were asked to relate any symptoms of pruritus, nausea, or vomiting. Each patient also completed a baseline assessment using a 100-mm visual analog scale (VAS) for pain, with 0 representing no pain and 100 being the worst possible pain. Each patient received a minimum of 500 mL of Ringer’s lactate solution IV. All procedures were performed with patients in the sitting position. A lumbar epidural catheter was inserted approximately 5 cm into the epidural space by using a Tuohy-Schiff needle (B-Braun Medical, Bethlehem, PA). The patients then received a test dose of 3 mL of 1.5% lidocaine with 1:200,000 epinephrine. If the test dose was negative for intravascular injection (heart rate within 15 bpm of baseline values in 2 min of monitoring) and intrathecal injection (no spinal block after 3 min of monitoring), the patient was given one of three epidural injections, over a 15-s period, in a double-blinded fashion determined by a computer generated randomization list. Group 2 mL received 100 μg of fentanyl in a total volume of 2 mL. Group 10 mL received 100 μg of fentanyl with preservative-free normal saline diluted to a total volume of 10 mL. Group 20 mL received 100 μg of fentanyl with preservative-free normal saline diluted to a total volume of 20 mL.

Patients were placed in the recumbent position with left uterine displacement. VAS scores and the severity of side effects were recorded at 2.5, 5, 7.5, 10, 12.5, 15, and 30 min after the administration of the study infusion and every 30 min thereafter. Observations were performed by an individual blinded to the injected volume. At the time of each assessment, vital signs, modified Bromage motor scale scores (9), pruritus, nausea, vomiting, and sedation were evaluated. Motor block was defined as none, partial (just able to move the knees), almost complete (able to move the feet only), or complete (unable to move the lower extremities). Pruritus was rated as none, minimal (present with minimal symptoms), moderate (bothersome but not requiring therapy), or severe (requiring therapy).

Sedation was categorized as none (awake), mild (drowsy), moderate (sleepy), or severe (unarousable). The fetal heart rate pattern was evaluated at each interval, and any changes were documented. After the first 30 min, patients were allowed to ambulate with assistance provided there was no detectable motor block and the fetal heart rate pattern was reassuring. The time at which each patient requested additional analgesia was recorded, vital signs were documented, pain and side effect assessments were performed, and the study period was concluded. The epidural anesthetics were subsequently managed by the anesthesia team, as appropriate, for the remainder of labor. The length of labor, incidence of cesarean delivery, incidence of postdural puncture headache, and neonatal Apgar scores were recorded.

A plan for treating inadequate analgesia (patient complaint of continued pain) was standardized. If adequate analgesia was not achieved 20 min after the initial study dose (patient stated that pain relief was not adequate), 15 mL of 0.125% bupivacaine was administered via the epidural catheter. If this did not provide relief after an additional 20 min, 10 mL of 2% lidocaine was administered. If this did not result in an adequate level of analgesia, then the epidural catheter would be replaced, and the patient’s data were not included in the analysis.

Before this study was instituted, a power analysis was performed assuming: a duration for 10-mL fentanyl analgesia of 124 ± 42 min (2,5), a 35-min analgesia duration difference; 80% power; and an α of 0.05. This yielded a required sample size of 19 patients per group.

Demographic data were analyzed by using analysis of variance. Pain scores were analyzed by using the Kruskal-Wallis test. Presence or absence of side effects was analyzed by contingency testing. A Kaplan-Meier plot of the patients remaining comfortable over time was generated and analyzed with Cox Mantel. Data are expressed as mean ± SD. Significance was determined at the P < 0.05 level.


Sixty-two patients were enrolled in the study. All patients, except two, achieved adequate initial analgesia with the epidural fentanyl; these two patients did not get comfortable after the administration of epidural local anesthetic, but analgesia was achieved after replacement of the epidural catheter. These two patients were not included in the data analysis. There were no significant differences in demographic variables, cervical dilation at the time of enrollment, rupture of membranes, or oxytocin use among the study groups (Table 1). Baseline VAS pain scores and the incidence of nausea and pruritus were similar in the groups. The median VAS scores were decreased 77.3%, 82.1%, and 83.9% by the 10-min evaluation in the 2-mL, 10-mL, and 20-mL groups, respectively (not significant). At 30 min, VAS scores were reduced by 88.4% (2 mL), 92.0% (10 mL), and 93.5% (20 mL) (not significant). There was no significant difference in pain scores among the groups at any of the time points except for 90 min, at which time the 2-mL group had higher pain scores (P < 0.03) (Figs. 1 and 2). The duration until re-dose was not significantly different among the 2-mL group (108 ± 40 min), the 10-mL group (126 ± 57 min), and the 20-mL group (127 ± 41 min; Fig. 3; not significant).

Figure 1
Figure 1:
The visual analog scale pain scores for the three groups at time intervals up to 15 min. The box represents the 25th–75th percentiles, and the median is represented by the solid line. The extended bars represent the 10th–90th percentiles. There were no significant differences between the groups at any time period.
Figure 2
Figure 2:
The visual analog scale pain scores for the three groups at time intervals up to 2.5 h. The box represents the 25th–75th percentiles, and the median is represented by the solid line. The extended bars represent the 10th–90th percentiles. Pain scores were not obtained after the administration of additional analgesia, and thus, there are <20 patients in each group at the later time periods. The only significant difference in pain scores occurred at 90 min, at which time the 2-mL group had higher pain scores (P < 0.03).
Figure 3
Figure 3:
Kaplan-Meier plot of the percentage of patients in each group who continued to remain comfortable. There were no significant differences among the groups.
Table 1
Table 1:
The Demographic and Outcome Data in the Three Groups

Before administration of the study analgesic, nine patients had experienced nausea (three in the 2-mL, one in the 10-mL, and five in the 20-mL group) (no patients had vomited). During the entire study period, eight patients experienced nausea (three in the 2-mL, two in the 10-mL, and three in the 20-mL group), and two patients vomited (two in the 2-mL, zero in the 10-mL, and zero in the 20-mL group). Twelve patients experienced mild sedation at least once during the study period (three in the 2-mL, five in the 10-mL, and four in the 20-mL group). No patient experienced moderate or severe sedation. At no time did any patient experience severe pruritus. No patient required specific treatment for nausea, vomiting, or pruritus. There were 42 patients who reported at one time interval the presence of mild pruritus (15 in the 2-mL, 13 in the 10-mL, and 14 in the 20-mL group).

No patients delivered without the need for a re-dose. The incidence of cesarean delivery was not significantly different among the groups (five in the 2-mL, four in the 10-mL, and five in the 20-mL group); none of the patients required a cesarean delivery before the need for a re-dose. One patient had an inadvertent dural puncture (20-mL group); no patient, in any group, developed symptoms of a postdural puncture headache.

During the study period, motor block, as reflected by the Bromage score, was absent (score of 0) in all except one of the patients. This patient (2-mL group) complained of mild right knee weakness at 60 and 90 min; she was not allowed to ambulate. Thirty-three patients (55%) ambulated at least once during their labor (9 in the 2-mL, 13 in the 10-mL, and 11 in the 20-mL group). None of these patients chose to ambulate through the hallway; however, they were able to walk to the bathroom. Apgar scores at birth were comparable among groups.


Epidural analgesia allowing ambulation during labor is increasingly popular, in part, because of the perceived improvement in patient satisfaction by preserving motor power. We have successfully used epidural opioids after a lidocaine-epinephrine test dose to provide satisfactory analgesia without a significant motor block (1–5); the diluent volume in these patients has been 10 mL. In treating patients with ambulatory epidural injections, we prefer the epidural opioid technique rather than the combined spinal epidural technique because the former avoids an added step, the expense of a combined spinal epidural needle, and the necessity of an intentional dural puncture. The current study compared 100 μg of fentanyl after a lidocaine and epinephrine test dose in primigravid patients with varying diluent volumes. The mean duration of analgesia in the three groups in the current study was 108, 126, and 127 minutes. These times compare similarly with the analgesic duration previously reported when using epidural fentanyl: 80 minutes (10), 83 minutes (11), and 91 minutes (12). The analgesic duration in all groups in the current study is consistent with that of epidural fentanyl or sufentanil when used for labor pain management (1–3,5).

There were higher pain scores in the 2-mL group at 90 minutes compared with the other two groups. The patients with the higher pain scores were re-dosed shortly after this 90-minute time period (Fig. 2). Despite these patients being re-dosed, the analgesia duration was not significantly shorter in this group. We thus believe that the higher pain scores simply represent a sampling of patients about to be re-dosed and are representative of average higher pain scores in the 2-mL group; similar pain scores at all the other time periods support this contention.

The volume of injectate can influence the efficacy of epidural opioids. The onset and quality of analgesia after cesarean delivery was better when epidural meperidine 25 mg was diluted to a volume of 5 or 10 mL compared with 2 mL; however, the duration of analgesia was not influenced by diluent volume (13). Meperidine, which has intermediate lipid solubility and possesses some local anesthetic characteristics, had its analgesic efficacy affected by diluent volume unlike the hydrophilic drug morphine (14). In contrast to more lipophilic opioids, injectate volume does not seem to be an important factor affecting analgesia from epidural morphine. This probably relates to the greater ability of morphine to spread in cerebrospinal fluid; it is unencumbered by segmental binding. The explanation for the effect on analgesic onset and duration of the diluent volume is related to the intraspinal spread of the opioid. Lipophilic opioids do not spread rostrally in cerebrospinal fluid to any great extent, and they tend to have fairly segmental analgesic profiles (15). The diluent volume is less important with respect to hydrophilic opioids. The quality of lumbar epidural analgesia after cesarean delivery was not significantly influenced by 10-fold dilution (from 2 mL to 20 mL) of 4 mg of morphine (a poorly lipid soluble opioid) (14).

Increasing diluent volume increases spread of the solution in the epidural space resulting in a larger number of opioid receptors affected. This is analogous to injecting local anesthetics for labor pain management in a volume sufficient to achieve block of segmental nerves. It is not only the dose of local anesthetic that is important, but also the volume in which it is given (16). However, when local anesthetic and opioid are administered in a site-specific location, postoperative pain is unaffected by dilution of the medication (17). These two seemingly contradictory results can be explained by the fact that labor epidurals are not placed site specifically and are dependent on spread of the medication to the dermatomal segments. Furthermore, epidural fentanyl may increase the dermatomal level blocked by local anesthetics in laboring patients (18).

The volume of the diluent seems especially important for lipophilic opioids. Decreasing the volume of diluent increased the onset time and shortened the duration of analgesia provided by epidural fentanyl when used for postcesarean delivery pain management (8). These authors showed increased onset time with 1 and 2 mL of fentanyl compared with larger volume dilutions and shorter analgesic duration with 1 mL of fentanyl (8). The authors postulated that lipophilic opioids are more quickly delivered to the opioid receptors by the volume of injectate when the epidural catheters are not placed site specifically (8). We did not find an increased onset time in the small (2 mL) group compared with the larger volume groups. This could be attributed to the use of a 3-mL lidocaine-epinephrine test dose immediately before the opioid bolus in the current study. Early labor analgesia may be provided by the lidocaine 45-mg test dose. Furthermore, the test dose’s volume may have caused further dilution and spread of the fentanyl in the epidural space, resulting in a larger number of opioid receptors being occupied. Despite the literature discussing the concept of avoiding the lidocaine-epinephrine test dose in obstetrical patients (19–22), we believe it remains an important element in detecting intrathecal and intravascular catheter placement.

Our use of epidural opioid after a test dose, without the use of adjuvant local anesthetic, does not result in significant motor block (1–7). Use of a lidocaine and epinephrine test dose has been implicated in a decreased ability for parturients to ambulate (22). However, all the patients in the Cohen et al. study (22) received an initial 12-mL epidural bolus of bupivacaine (0.0625% or 0.125%) in addition to the lidocaine-epinephrine test dose. One patient in the current study and one patient in a previous study (3) complained of motor weakness; these symptoms were presumably caused by the local anesthetic in the test dose. Epidural 0.1% bupivacaine with sufentanil, as part of a patient-controlled epidural analgesia technique, results in detectable motor block in approximately 20% of patients (23). We believe that when sufficient opioid is used initially, and an initial bolus of local anesthesia is avoided, ambulation can be achieved in most patients without eliminating the test dose. Furthermore, we cannot exclude dilution of the fentanyl by the previously administered test dose; however, our usual clinical practice is to administer the opioid after a test dose, and we were investigating the effect of dilution on normal clinical practice.

Previous evaluations of opioid dilution in obstetric patients have primarily investigated postcesarean pain rather than labor pain. The effect of varying the diluent volume of epidural fentanyl on the quality and duration of labor analgesia, based on our study, does not affect the onset of analgesia nor does it prolong the analgesic duration. We have again demonstrated satisfactory results with epidural fentanyl after a lidocaine and epinephrine test dose for the management of laboring patients. When performing an ambulatory epidural in early labor after a lidocaine and epinephrine test dose, we found no advantage or disadvantage in varying the volume from our standard 10-mL injectate volume.

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