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Anesth Analg 2002;94:927-932
© 2002 International Anesthesia Research Society


OBSTETRIC ANESTHESIA

A Comparison of Epidural Infusions in the Combined Spinal/Epidural Technique for Labor Analgesia

Yaakov Beilin, MD*{dagger}, Ashalatha Nair, MD*, Ittamar Arnold, BA*, Howard H. Bernstein, MD*{dagger}, Jeffrey Zahn, MD*, Sabera Hossain, MS{ddagger}, and Carol A. Bodian, DrPH{ddagger}

Departments of *Anesthesiology, {dagger}Obstetrics, Gynecology & Reproductive Sciences, and {ddagger}Biomathematical Sciences, Mount Sinai School of Medicine, New York, New York

Address correspondence and reprint requests to Yaakov Beilin, MD, The Mount Sinai Medical Center, Department of Anesthesiology, Box 1010, One Gustave L. Levy Place, New York, NY 10029-6574. Address e-mail to YBeilin{at}mountsinai.org


    Abstract
 Top
 Abstract
 Introduction
 Discussion
 References
 
We compared the clinical effects of three epidural infusions initiated after subarachnoid medication was administered as part of the combined spinal/epidural technique for labor analgesia. Fifteen minutes after administering subarachnoid fentanyl 25 µg and 1 mL of bupivacaine 0.25%, and 5 min after an epidural test dose of 3 mL of bupivacaine 0.25%, women were randomized to receive an epidural infusion of saline, bupivacaine 0.125%, bupivacaine 0.0625%, or bupivacaine 0.04% with epinephrine 1:600,000. All epidural infusions were started at 10 mL/h, and all except the Saline Group also received fentanyl 2 µg/mL. The end point of the study was delivery or request for additional medication for analgesia. We found that time until request for additional analgesia was longest in women who received bupivacaine 0.125% (median duration, 300 min) versus saline (median duration, 118 min) (P = 0.0001) and was intermediate for bupivacaine 0.0625% and bupivacaine 0.04% (median duration, 162 and 180 min, respectively) (P = 0.0001 versus saline). Women who received bupivacaine 0.125% had the most motor block. We conclude that all the bupivacaine-based infusions we tested maintained the analgesia from subarachnoid medication longer than saline, with the longest duration, but the most motor block, from bupivacaine 0.125%.

IMPLICATIONS: In this prospective, randomized, and double-blinded study we found that initiating an epidural infusion of bupivacaine 0.125% with fentanyl 2 µg/mL at 10 mL/h 15 min after subarachnoid fentanyl 25 µg with 1 mL of bupivacaine 0.25%, followed by an epidural test dose of 3 mL of bupivacaine 0.25%, maintained the analgesia for longer but with more motor block than with either bupivacaine 0.04% or bupivacaine 0.0625%.


    Introduction
 Top
 Abstract
 Introduction
 Discussion
 References
 
T he combined spinal/epidural technique (CSE) has become a popular modality for labor analgesia. Analgesia is initially produced with medication injected into the subarachnoid space and is then maintained with epidural medication. The most commonly used subarachnoid medications are fentanyl and sufentanil, with or without bupivacaine. The duration of action of the subarachnoid medications is approximately 1.5–2 h (1). Management of the epidural component of the CSE technique varies among practitioners. Some initiate the epidural medication shortly after the subarachnoid medication has been administered, even though the woman is not yet experiencing pain, whereas others wait until the labor pain returns. Initiating an epidural infusion of ropivacaine 0.1% with fentanyl 2 µg/mL and epinephrine 1:400,000, 5 min after the subarachnoid medication, without an epidural test dose, maintains the analgesia for longer (approximately 60 min) than initiating an epidural saline solution (2). The purpose of this study was to determine whether a bupivacaine-based epidural infusion maintains the analgesia achieved by subarachnoid fentanyl 25 µg and bupivacaine 2.5 mg for a longer duration than epidural saline and to compare the clinical effects of three commonly used epidural infusions.

Methods
The protocol was approved by our IRB, and written, informed consent was obtained from each parturient before she requested labor analgesia. Nulliparous women who were experiencing contractions at least once every 5 min and who had <5 cm cervical dilatation at the time they requested labor analgesia were enrolled in this prospective, randomized, and double-blinded study. All of the women had agreed to receive a CSE anesthetic for labor analgesia.

Before placement of the CSE anesthetic, the woman was randomly assigned to one of four groups on the basis of which epidural infusion would be used after the subarachnoid medication had been administered. Patients in the Placebo group received 0.9% saline; Group_0.125 received bupivacaine 0.125% with fentanyl 2 µg/mL; Group_0.04 received bupivacaine 0.04% with fentanyl 2 µg/mL and epinephrine 1:600,000; and Group_0.0625 received bupivacaine 0.0625% with fentanyl 2 µg/mL.

A computer-generated random-number program was used to assign the patients to each group. The results of the randomization were sealed in opaque envelopes and opened sequentially by the anesthesiologist after the woman requested labor analgesia. The research assistant, who performed all the patient assessments, and the patient were unaware of group assignment.

Before placement of the anesthetic, the woman was asked to assess her pain level with a verbal 0 to 10 pain scale, with 0 being no pain and 10 being the worst imaginable pain. With the woman in the sitting position, a CSE anesthetic was then administered at the L2-3 or L3-4 interspace by use of the loss of resistance to air technique. Once the epidural space was identified with an 18-gauge Hustead needle, a 123-mm-long, 25-gauge Sprotte needle was inserted through the epidural needle until cerebrospinal fluid was returned. Both the epidural needle and the spinal needle were directed with the bevel in a cephalad direction. Each woman received a subarachnoid injection of fentanyl 25 µg with 1 mL of bupivacaine 0.25%. The spinal needle was then removed, and a 20-gauge, closed-tip epidural catheter was threaded 5 cm into the epidural space. The patient was then positioned supine with left uterine displacement, and blood pressure (BP) was measured. The patient remained supine with left uterine displacement for the course of the study. Pain levels were assessed with the same 0 to 10 scale 5 and 10 min after the subarachnoid medication was administered. After 10 min, the woman was also asked if she was satisfied with her degree of pain relief or if she needed more medication. If she required more medication at this point, her participation in the study was concluded.

If the woman was satisfied with the degree of pain relief 10 min after the subarachnoid medication was given, the degree of motor block in the lower extremities was assessed with the modified Bromage scale (0 = no motor block; 1 = unable to raise extended leg, able to move knees and foot; 2 = unable to raise extended leg or knees, able to move foot; 3 = complete motor block of lower limb). An epidural test dose consisting of 3 mL of bupivacaine 0.25% was then administered to check for subarachnoid and intravascular catheter placement. The presence of clinical symptoms of an intravascular injection were sought for the next 2–3 min by asking the woman if she felt dizzy, had tinnitus, or had a metallic taste in her mouth. Five minutes after the test dose, if there were no clinical signs of a subarachnoid injection, as evidenced by the woman’s ability to move her legs and the absence of hypotension, an epidural infusion based on group assignment was started at a rate of 10 mL/h. For this study, the time at which the infusion was started was considered Time 0 (t0).

Assessments of maternal BP, pain score (0–10), Bromage score (0–3), pruritus (none, moderate, mild, or severe), and nausea (yes or no) were made hourly. Hypotension was defined as a >20% decrease from t0 in systolic BP. Fetal heart rate was monitored continuously by an obstetrician who was blinded to group assignment.

The duration of the epidural anesthetic was measured from the time the infusion was started (t0) either until the patient requested additional analgesia or, if the patient never requested additional medication, until delivery time. Delivery may have been vaginal or by cesarean delivery. For each group, a Kaplan-Meier life table was calculated to estimate the cumulative probability that patients would request additional analgesia the longer they remained in labor. Comparisons among groups were made by the log-rank test. Expected median durations of the epidural for each group were estimated from the life tables. The Kruskal-Wallis test was used to compare pain scores among groups. Differences among groups in motor blockade (percentage positive) were evaluated by using the {chi}2 test for trend.

We designed the study to provide 80% power to detect a difference of 30 min between each dose group and the Placebo group, assuming that the analgesia in the Placebo group would last an average of 110 min with an SD of 20 min (1). Approximate sample sizes were estimated assuming all patients would request additional medication before they delivered, for three two-tailed tests, each at the 0.017 significance level, for an overall Type I error of 5%. Twenty-two patients per group provided 80% power under those assumptions.

Results
We enrolled 104 patients and studied 89. Twelve patients were not included in the study either because they did not request labor analgesia or because they requested analgesia when the research team was unavailable. In addition, two were excluded because of protocol deviations (one each in Group_0.125 and Group_0.0625), and one was excluded from Group_0.04 because the catheter was found to be intravascular. The patient developed tinnitus after she received 5 mL of bupivacaine 0.25% after negative aspiration on the catheter. This occurred 2 h after epidural placement, when the patient complained of pain and additional medication was administered. No patient was excluded because the epidural catheter was threaded into the subarachnoid space, nor was any patient excluded because of inadequate pain relief 10 min after the spinal medication was administered. Demographic data and initial labor characteristics of the four groups are presented in Table 1. The groups were similar except that fewer women in Group_0.0625 were receiving oxytocin at the beginning of the study. However, all patients were receiving oxytocin for augmentation of contractions by the end of the study.


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Table 1.  Patient Demographics and Labor Characteristicsa
 
The duration of analgesia was significantly longer in each of the three bupivacaine groups as compared with the Placebo group (Fig. 1). The estimated median duration (and 95% confidence interval) for the Placebo group was 118 min (102–125 min); for Group_0.125, 300 min (180–384 min); for Group_0.04, 180 min (156–222 min); and for Group_0.0625, 162 min (126–240 min) (P = 0.0001 for each bupivacaine group separately versus the Placebo group). No patient in the Placebo group delivered before requesting additional medication; eight delivered without requesting additional medication in Group_0.125, as did four in Group_0.04 and five in Group_0.0625. The pain scores at the time of request for additional medication did not differ significantly (P = 0.25) (Table 2). The four groups differed significantly in motor block (Bromage scale score >0) at the first and second hours. Motor block was most common in Group_0.125 (Fig. 2). Only two patients, both in Group_0.125, developed a Bromage scale score >1. In one woman it occurred at the third hour, and in one it occurred at the sixth and seventh hour. No patient had a Bromage scale score of 3, and no patient in Group_0.04 had any motor block at any time point. Most patients in all groups developed pruritus, but this was primarily from the subarachnoid medication, because the incidence was most frequent at t0 and waned with time. No patient experienced moderate or severe pruritus after the third hour (Fig. 3). Only four patients developed hypotension during the study period: two in Group_0.04 at the second hour and two patients at the third hour, one in Group_0.125 and one in Group_0.0625. Also, very few patients developed nausea at any time point. No patient required an urgent cesarean delivery—all cesarean deliveries were secondary to dystocia. All Apgar scores were >7 at 1 min except for two in Group_0.125, which were 4 and 6, and one each in Group_0.04 and Group_0.0625, which were scores of 7. At 5 min, all Apgar scores were >=8.



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Figure 1. Kaplan-Meier curves of the probability that analgesia remains effective over time.

 

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Table 2.  Duration of Analgesia
 


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Figure 2. Percentage of patients at each hour with any motor block (Bromage scale score >0).

 


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Figure 3. Percentage of patients at each hour with pruritus. The darker regions represent patients who complained of moderate or severe pruritus, and the lighter regions represent patients with any pruritus.

 

    Discussion
 Top
 Abstract
 Introduction
 Discussion
 References
 
We found that initiating a bupivacaine-based epidural infusion maintains the analgesia afforded by subarachnoid fentanyl 25 µg plus bupivacaine 2.5 mg and an epidural test dose of 3 mL of bupivacaine 0.25% for longer (at least 40 minutes) than an epidural saline infusion. We also found that an epidural infusion of bupivacaine 0.125% combined with fentanyl 2 µg/mL maintains the analgesia for longer, but with more motor block, than either bupivacaine 0.04% or bupivacaine 0.0625%.

The CSE technique has become popular because of its rapid onset of analgesia and high patient satisfaction (3). After the spinal medication is administered, some anesthesiologists start the epidural infusion immediately, some offer the patient controlled epidural analgesia, and some manage the patient with boluses without an infusion. Collis et al. (4) compared the three techniques and found similar analgesia and high satisfaction in all three groups. However, which epidural infusion should be used after the spinal medication has been administered has not been adequately studied. The subarachnoid medication will provide analgesia for approximately 90–120 minutes (1), after which time the epidural catheter must be used. The two questions posed in this study are 1) does initiating an epidural infusion 15 minutes after subarachnoid medication is administered maintain the analgesia from the subarachnoid medication? and 2) what are the clinical effects of three commonly used epidural infusions?

We found that all the infusions tested maintained the analgesia for longer than epidural saline. Gaiser et al. (2) also found that initiating a ropivacaine-based epidural infusion five minutes after the administration of subarachnoid medication, without first administering an epidural test dose, maintains the labor analgesia for longer (by approximately one hour) than epidural saline. A difference in study design between our study and that of Gaiser et al. (2) is that we used an epidural test dose that may have affected the duration of analgesia. We found that those in Group_0.125 had a longer duration of analgesia as compared with those in the Placebo group and as compared with those in Group_0.04 or Group_0.0625. In hindsight this may seem to be intuitive, because the more concentrated local anesthetic conferred the longest duration of analgesia. However, Chestnut et al. (5) have demonstrated that bupivacaine 0.0625% with fentanyl provides similar analgesia as bupivacaine 0.125%, and Pratt et al.1 showed that an infusion of bupivacaine 0.04% with fentanyl 2 µg/mL and epinephrine 1:600,000 provides analgesia similar to that from an infusion of bupivacaine 0.125% with fentanyl 2 µg/mL.

The longer duration of analgesia in Group_0.125 may be of benefit to the anesthesiologist on a busy labor floor or where anesthesia personnel are scarce. However, the more frequent incidence of motor block in Group_0.125 may mitigate its time advantage even though the motor block was minimal. Only two patients had a Bromage scale score >1; this occurred after three hours in one patient and at six hours in another. Whether a small amount of motor block affects the course of labor is unknown, although more concentrated infusions are associated with an increased rate of instrumental deliveries (7). In this study, we followed the patient only until she requested additional medication. It is possible that the degree of motor block may have increased after additional medication was administered. We did not enroll enough patients to draw any conclusions about the course or outcome of labor with different epidural infusions, nor was the study designed to address this issue. The only way to attribute outcome to a particular infusion is to avoid or control for all other epidural medications used during labor for analgesia, and we did not believe that this was realistic.

It is possible that there were other differences in motor block among the groups that were not detectable with the Bromage scale. More sophisticated tests, such as isometric abdominal wall assessment (8), may have detected subtle differences in motor block among the groups, but this assessment is difficult to use, and any such subtle differences are probably not of clinical significance. We chose the Bromage scale because it is easy to use and is clinically effective in detecting gross differences in motor block.

Other complications, such as hypotension, pruritus, nausea, and low Apgar scores, were rare and did not differ among the groups. Although the incidence of hypotension in our study was infrequent, Gaiser et al. (2) noted a 20% decrease in BP 60 minutes after the epidural infusion was started. However, the clinical significance of the decrease that they noted was minimal, because only one patient required ephedrine to treat the decrease in BP. Consistent with the results of Palmer et al. (1), most patients in all groups developed pruritus immediately after placement of the CSE anesthetic (Fig. 3). Thus we were not able to assess the effect of different infusions, if any, on pruritus.

Most of our patients were in relatively early labor (median cervical dilatation <3 cm). We chose such patients to minimize the number who would deliver before requesting additional medication. However, the duration of analgesia from the subarachnoid medication is longer when the patient is in early labor (9), and our results may have been different if the women had been at a more advanced stage of labor.

We used a test dose before the start of the epidural infusion. Norris et al. (10) have recommended eliminating the intravascular test dose completely if dilute concentrations of bupivacaine are used through a multiorifice catheter. However, most anesthesiologists agree that a subarachnoid test dose should be administered, and some anesthesiologists disagree with the recommendation of Norris et al. and prefer to administer an intravascular test dose (11). Foss and D’Angelo2 found that a test dose with lidocaine 1.5% and epinephrine 15 µg is adequate with the CSE technique. We do not routinely use epinephrine as part of our test dose because it may decrease uteroplacental blood flow and because 15 µg of epinephrine IV does not reliably cause an increase in heart rate in the parturient (12). We chose bupivacaine for the test dose because we preferred to use one local anesthetic for the entire study and not use one local anesthetic (lidocaine) for the test dose and a different one for the infusions. Although there may have been some failures with our test dose, as there are with all test doses, 3 mL of bupivacaine 0.25% has been found to be a satisfactory subarachnoid test dose (13). Furthermore, small IV doses (10 mg) of bupivacaine have been found to cause tinnitus (14) and therefore may be a satisfactory intravascular dose. We certainly believe it is worth attempting to elicit the symptoms of an intravascular injection. Indeed, the one patient treated with an intravascular catheter in our study was noted to have the symptom of tinnitus after a negative aspiration.

In conclusion, initiating an epidural infusion 15 minutes after subarachnoid medication is administered and 5 minutes after an epidural test dose will maintain the analgesia with minimal side effects. Using an infusion of bupivacaine 0.125% with fentanyl 2 µg/mL maintains the analgesia for longer than either bupivacaine 0.0625% with fentanyl 2 µg/mL or bupivacaine 0.04% with fentanyl 2 µg/mL and epinephrine 1:600,000, but it produces more motor block.


    Acknowledgments
 
Supported by the Department of Anesthesiology, Mount Sinai School of Medicine, New York, NY.

The authors are grateful to James B. Eisenkraft, MD, Professor of Anesthesiology at The Mount Sinai School of Medicine, New York, NY, for his help with the study design and for his critical review of the manuscript.


    Footnotes
 
Presented in part at the annual meeting of the Society for Obstetric Anesthesia and Perinatology, San Diego, CA, April 21, 2001.

1 Pratt SD, Soni AK, Sarna MC, et al. Ultra low dose labor epidural solution affects obstetric outcome but not anesthesiologist workload: a preliminary report of a review of 2511 patients [abstract]. Anesth Analg 1997;84:S403. Back

2 Foss M, D’Angelo R. Development of effective epidural test dose following administration of CSE analgesia [abstract]. Anesthesiology 1998;89:A1040. Back


    References
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 Abstract
 Introduction
 Discussion
 References
 

  1. Palmer CM, Van Maren G, Nogami WM, Alves D. Bupivacaine augments intrathecal fentanyl for labor analgesia. Anesthesiology 1999; 91: 84–9.[Web of Science][Medline]
  2. Gaiser RR, Lewin SB, Cheek TG, Gutsche BB. Effects of immediately initiating an epidural infusion in the combined spinal and epidural technique in nulliparous parturients. Reg Anesth Pain Med 2000; 25: 223–7.[Web of Science][Medline]
  3. Collis RE, Davies DW, Aveling W. Randomised comparison of combined spinal-epidural and standard epidural analgesia in labour. Lancet 1995; 345: 1413–6.[Web of Science][Medline]
  4. Collis RE, Plaat FS, Morgan BM. Comparison of midwife top-ups, continuous infusion and patient-controlled epidural analgesia for maintaining mobility after a low-dose combined spinal-epidural. Br J Anaesth 1999; 82: 233–6.[Abstract/Free Full Text]
  5. Chestnut DH, Bates JN, Choi WW. Continuous infusion epidural analgesia with lidocaine: efficacy and influence during the second stage of labor. Obstet Gynecol 1987; 69: 323–7.[Web of Science][Medline]
  6. Deleted in proof.
  7. Effect of low-dose mobile versus epidural techniques on mode of delivery: a randomised controlled trial. Lancet 2001; 358: 19–23.[Web of Science][Medline]
  8. Axelsson K, Hallgren S, Widman B, et al. A new method for measuring motor block in the lower extremities. Acta Anaesthesiol Scand 1985; 29: 72–8.[Web of Science][Medline]
  9. Viscomi CM, Rathmell JP, Pace NL. Duration of intrathecal labor analgesia: early versus advanced labor. Anesth Analg 1997; 84: 1108–12.[Abstract]
  10. Norris MC, Fogel ST, Dalman H, et al. Labor epidural analgesia without an intravascular "test dose." Anesthesiology 1998; 88: 1495–501.[Web of Science][Medline]
  11. Birnbach DJ, Chestnut DH. The epidural test dose in obstetric patients: has it outlived its usefulness? Anesth Analg 1999; 88: 971–2.[Free Full Text]
  12. Leighton BL, Norris MC, Sosis M, et al. Limitations of epinephrine as a marker of intravascular injection in laboring women. Anesthesiology 1987; 66: 688–91.[Web of Science][Medline]
  13. Poblete B, Van Gessel EF, Gaggero G, Gamulin Z. Efficacy of three test doses to detect epidural catheter misplacement. Can J Anaesth 1999; 46: 34–9.[Web of Science][Medline]
  14. Eldor J, Frankel DZ, Olshwang D, Davison JT. Tinnitus as an early diagnostic sign of inadvertent intravenous injection of bupivacaine epidural test dose. Resuscitation 1988; 16: 303–4.[Medline]
Accepted for publication December 7, 2001.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2002 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press