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Anesth Analg 2001;92:184-188
© 2001 International Anesthesia Research Society

OBSTETRIC ANESTHESIA

The Dose-Range Effects of Sufentanil Added to 0.125% Bupivacaine on the Quality of Patient-Controlled Epidural Analgesia During Labor

Jean-Marc Bernard, MD, PhD*, Daniel Le Roux, MD*, Alexandre Barthe, MD*, Olivier Jourdain, MD{dagger}, Louis Vizquel, MD*, and Claude Michel, MD{dagger}

Département *d’Anesthésie-Réanimation and {dagger}Clinique Gynécologique et Obstétricale, Polyclinique Jean-Villar, Bruges-Bordeaux, France

Address correspondence and reprint requests to Dr. Jean-Marc Bernard, Département d’Anesthésie-Réanimation, Polyclinique Jean-Villar, BP 61, F-33520 Bruges-Bordeaux, France. Address e-mail to jmbmdphd{at}club-internet.fr


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
To determine the minimal sufentanil concentration required to improve the quality of patient-controlled epidural analgesia during labor, we compared the efficacy of a combination of 0.125% bupivacaine with 1:800,000 epinephrine and different concentrations of sufentanil in a double-blinded randomized study. Concentrations were no sufentanil (n = 66), 0.078 µg/mL sufentanil (n = 65), 0.156 µg/mL sufentanil (n = 65), 0.312 µg/mL sufentanil (n = 65), and 0.468 µg/mL sufentanil (n = 67). The patient-controlled epidural analgesia setting was a 12-mL bolus dose and a 25-min lockout interval. Pain was scored at 5–6 cm, 7–8 cm, and full cervical dilation by using a 10-cm visual analog scale. At full cervical dilation, the pain scores were lower in the groups receiving a solution of at least 0.156 µg/mL sufentanil. Few differences were observed when using the larger concentrations, except for increased pruritus intensity. The duration of labor and the mode of delivery were similar in each group. Rescue analgesia, which consisted of 6 mL of 0.25% bupivacaine, was infrequent and comparable between groups. The use of the pump did not differ between groups. Adding a small concentration of sufentanil to 0.125% bupivacaine for patient-controlled epidural analgesia during labor improved the quality of analgesia but did not modify the bupivacaine requirement. Reducing the sufentanil concentrations to 0.156 µg/mL decreased the pruritus intensity without reducing analgesia.

Implications: Adding a small concentration of sufentanil to 0.125% bupivacaine for patient-controlled epidural analgesia during labor improved the quality of analgesia but did not modify the bupivacaine requirement. Reducing the sufentanil concentrations to 0.156 µg/mL decreased the pruritus intensity without reducing analgesia.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
The ability of sufentanil, when added to local anesthetics, to improve the quality and the duration of epidural analgesia for women in active labor has been demonstrated for more than a decade (1–5). This improvement may allow for a significant reduction in the concentration and the total amount of local anesthetics administered during the course of labor. The decreased amounts of local anesthetics may be associated with less motor block and thus may help the rotation and descent of the fetal head (6) and may also reduce the need for instrumental delivery (4,5,7).

Several dose-response studies have been performed to determine the optimal concentrations and doses of adjunctive sufentanil in epidural analgesia during labor (1,5,8,9). Previous studies have used single-bolus or intermittent, staff-administered, epidural injections, but only doses per injection larger than 5 µg (5) and concentrations larger than 0.5 µg/mL (8) have been tested.

This double-blinded, randomized study was designed to determine the sufentanil concentration that improves the quality of analgesia when it is controlled by women during labor by using a patient-controlled epidural analgesia (PCEA) technique.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Our ethics committee approved this study. Parturients of mixed parity who requested epidural analgesia for labor were recruited and gave written informed consent. Exclusion criteria included ASA physical status III–IV parturients, severe medical or obstetric complications, multiple gestation, contraindications to epidural analgesia, and inability to use the PCEA pump.

By use of a computer-generated random number sequence, participants were randomly assigned to five groups of 70 subjects each to receive a combination of 0.125% bupivacaine with 1:800,000 epinephrine and different concentrations of sufentanil via a PCEA pump (APM Abbott, North Chicago, IL). Concentrations of sufentanil were 0 µg/mL, 0.078 µg/mL, 0.156 µg/mL, 0.312 µg/mL, and 0.468 µg/mL, on the basis of the convenience of adding 1/8, 1/4, 1/2, and 3/4 of 1-mL ampule containing 50 µg into an 80-mL reservoir solution. By using a tuberculin syringe, study solutions were prepared by an anesthesiologist not directly involved in the patient’s care or data collection. Because few differences were previously found between an epidural 10-mL bolus injection of 0.125% bupivacaine with epinephrine (1:800,000) with 5, 7.5, and 10 µg sufentanil in laboring women (5), concentrations larger than 0.468 µg/mL, i.e., doses of more than 5 µg per injection, were not selected. We chose 0.125% bupivacaine because many previous studies demonstrated the efficacy of different doses of epidural opioids in combination with this concentration.

Details of the catheter insertion into the epidural space, setting, and instruction in the use of the PCEA pump have been previously described (10). Briefly, an IV infusion of 0.9% saline was started via a forearm cannula, and a 5-port 20-gauge epidural catheter (B. Braun, Melsungen, Germany) was inserted into the epidural space at the L3-4 or L4-5 interspace. All the catheters were aspirated gently for return of blood or cerebrospinal fluid. A test dose of 2 mL of 2% lidocaine with epinephrine was then administered. All catheters were placed in women with a cervical dilation of <=2 cm before the onset of painful contractions and connected to the PCEA pump before inducing labor with an IV oxytocin infusion. The PCEA pump was set to infuse a 12-mL bolus (1.8–2 mL/min) with a 25-min lockout interval (10). The pump did not deliver a background infusion. There was no dose limit. Rescue analgesia consisted of 6 mL of 0.25% epidural bupivacaine at patient request.

Automated maternal blood pressure, heart rate, arterial hemoglobin oxygen saturation (SpO2), tocodynamometry, and continuous fetal heart rate were monitored throughout labor. The labor progress was measured at regular intervals. Hypotension, defined as systolic blood pressure of <100 mm Hg, was treated with left uterine displacement, IV fluid bolus, and 10-mg IV doses of ephedrine, as needed. Episodes of SpO2 less than 90% were treated by oxygen administration via a face mask. Pain was scored at 5–6 cm, 7–8 cm, and full cervical dilation by using a 10-cm visual analog scale. Duration and outcome of labor were noted. Cumulative study solution volumes, PCEA demands, and delivered demand doses were recorded immediately after delivery. At this time, women were asked to complete a questionnaire about their satisfaction with analgesia. Patients were asked to rate the degree of symptoms encountered while using the PCEA pump. Pruritus, nausea, vomiting, and feeling of sleepiness were evaluated with appropriate five-point verbal scores. Data collection was performed by a midwife blinded to group allocation.

It was estimated that a sample size of 70 per group would be sufficient to detect a 30% reduction in pain score with an 80% power at the 5% significance level. Data were presented as mean ± SD, medians and ranges, or numbers and percentages of patients. Associations of discrete variables were tested by {chi}2. Comparisons of nonparametric data were performed by Kruskal-Wallis analysis, followed by Mann-Whitney U-tests for pairwise comparisons. Differences between the groups on continuous data were tested by analysis of variance followed by t-tests with Bonferroni corrections. P < 0.05 was considered significant.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Of the 350 patients enrolled in the study, 22 were excluded because the catheter was displaced or because oxytocin failed to induce labor. The 328 remaining patients did not differ in demographic or obstetric characteristics ( Table 1). The use of the pump, rescue analgesia, and dose of bupivacaine did not differ among the groups. The resulting sufentanil dose differed among groups with the increase in its concentration into the PCEA solution ( Table 2).


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  		Table 1. Demographic and Obstetric Characteristics
 

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  		Table 2. Therapeutic Characteristics
 
At full cervical dilation, pain was decreased in the groups receiving a PCEA solution containing 0.156 µg/mL, 0.312 µg/mL, and 0.468 µg/mL sufentanil, compared with those not receiving sufentanil or receiving 0.078 µg/mL sufentanil. Pain did not differ significantly among the groups receiving 0.156 µg/mL, 0.312 µg/mL, and 0.468 µg/mL sufentanil. Pain did not differ significantly between the groups receiving 0.078 µg/mL sufentanil and no sufentanil ( Fig. 1).



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  		Figure 1. Change in pain score during labor. The box plot displays 10th, 25th, median, 75th, and 90th percentiles of values. Analysis of variance followed by t-test with Bonferroni correction: F = 2.074, P = 0.084 at 5–6 cm cervical dilation; F = 2.694, P = 0.031 at 7–8 cm cervical dilation; and F = 5.541, P = 0.0003 at full cervical dilation. *P < 0.05 vs no sufentanil, and {dagger}P < 0.05 vs 0.078 µg/mL sufentanil.

 
The number of women with criticisms, the degree of sleepiness, the intensity of nausea, and the incidence of vomiting were similar among the groups. There was a significant dose-dependent increase in the incidence and intensity of pruritus with an increasing sufentanil concentration in the PCEA solution ( Table 3). Satisfaction with labor analgesia was better in the groups receiving 0.312 µg/mL and 0.468 µg/mL of sufentanil than in the group receiving no sufentanil ( Fig. 2).


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  		Table 3. Side Effects and Criticism of the Technique
 


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  		Figure 2. Women’s rating of satisfaction with analgesia in a five-point scale (excellent = 5, good = 4, fair = 3, bad = 2, and very bad = 1). No opinion was treated as a missing value. Statistical analyses were performed on raw data sets. For clarity, figure is the percentage of women with excellent, good, and other (fair + bad + very bad). Solutions with 0.312 and 0.468 µg/mL sufentanil were more effective than solutions not containing sufentanil.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
This study is an estimation of the sufentanil concentration improving analgesia when provided by a 12-mL bolus dose of bupivacaine 0.125% with 1:800,000 epinephrine by using a PCEA technique during labor. The results indicate that comparable levels of analgesia were achieved when the concentration of adjunctive sufentanil was smaller than that suggested by other studies (5,9,11).

Although the adjuvant concentration of sufentanil chosen in this study proved effective, it is not possible to comment on the influence of the bolus size, or other patient-controlled analgesia variables, on the efficacy and outcome of our study. The relatively low level of the pain score, associated with the high ratio of successful/total PCEA demands and the small number of supplemental bupivacaine injections, argue for an optimal PCEA setting in our five groups. Previously, we found that conventional PCEA setting, i.e., delivering four milliliters of 0.125% bupivacaine with a lockout interval of eight minutes, could be restrictive and that a setting that allowed a parturient to receive an increased analgesic dose at each valid demand improved her satisfaction with analgesia during labor (10). With a PCEA device delivering a 12-milliliter bolus dose, there is no convincing evidence to support the use of a basal infusion in addition to patient demands.

Under these conditions, PCEA with different incremental doses of sufentanil did not result in a significant reduction in the total bupivacaine dose requirement. This is in contrast to many previous studies. Several groups have observed that staff administration of an epidural solution containing both bupivacaine and sufentanil reduced the total dose of local anesthetics and resulted in less intense motor block (1–3,12). Nevertheless, these investigators used sufentanil doses larger than 10 micrograms, which are more than double our largest dose per injection.

By using an up-down sequential allocation, Polley et al. (8) quantified the bupivacaine-sparing effect of the addition of 10, 20, and 30 micrograms of epidural sufentanil during labor. They observed a larger reduction in the minimum local analgesic concentration, defined as the effective concentration in a 20-milliliter volume in 50% of patients, and demonstrated a significant negative linear relation with increasing doses. In the minimum local analgesic concentration method, the bupivacaine concentration can fluctuate as a dependent variable, in contrast to a PCEA pump delivering a fixed concentration throughout labor, which may have made the local anesthetic-sparing effect difficult to detect in our study. The use of the potent local anesthetic concentration 0.125% bupivacaine, which results in reliable and dense epidural analgesia, may have also made this effect difficult to detect.

The effects of adding 1 µg/mL sufentanil to 0.17% bupivacaine solution for postoperative PCEA after major thoracic and abdominal surgery have been investigated (13). Patients receiving sufentanil required a smaller volume of analgesic solution and self-administered fewer boluses than patients receiving plain solution. In a following study, Brodner et al. (14) showed that 0.75 µg/mL sufentanil added to 0.2% ropivacaine was likely to be the minimum concentration improving postoperative PCEA, but no reduction in the ropivacaine requirement was found when 0.75- and 0.5-µg/mL sufentanil concentrations were compared. Although comparison between different PCEA settings, surgical patients, and parturient women is difficult, these findings (13,14) suggest that self-administration and thus local anesthetic requirement could be reduced by a larger sufentanil concentration in the device. However, as indicated by Brodner et al. (14), it is not known whether varying sufentanil concentrations may influence the risks of sedation and respiratory depression. In view of the degree of placental transfer of epidural sufentanil and its large fetal/maternal blood concentration ratio (0.81) (11), it is conceivable that a large self-administered dose might result in respiratory depression in the neonate. Although clinically significant neonatal depression appears rare and mild after maternal epidural administration of 50–80 micrograms of sufentanil (15,16), a minimum interval between the last injection and birth should further reduce the risk. But this could deprive women of treating painful uterine contractions, increasing their discontent during the second stage.

Our study indicates that comparable levels of analgesia may be achieved by concentrations ranging from 0.156 to 0.468 µg/mL. Few side effects occurred. As has also been reported in other studies, pruritus intensity increased with the sufentanil dose. Satisfaction with analgesia was better with the largest concentration of sufentanil, suggesting that pruritus was not necessarily experienced as a distressing event. Nevertheless, our results indicated that reducing the sufentanil concentration from 0.468 µg/mL to 0.156 µg/mL halved the incidence of pruritus without impeding the quality of analgesia.

In conclusion, adding a small concentration of sufentanil to the 0.125% bupivacaine solution for PCEA improves the quality of analgesia without modifying the bupivacaine requirement during labor. It is likely that the use of PCEA, small-dose sufentanil, and relatively large bupivacaine concentration in our study obscured differences in the local anesthetic-sparing ability. Reducing the sufentanil concentration to 0.156 µg/mL decreased the pruritus intensity without impeding the quality of analgesia. Whether this result is applicable to smaller bupivacaine concentrations and other PCEA settings remains to be determined.


   Acknowledgments
 
We acknowledge the kind assistance and patience provided by the midwife staff in collecting data.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Phillips GH. Epidural sufentanil/bupivacaine combinations for analgesia during labor: effects of varying sufentanil doses. Anesthesiology 1987; 67: 835–8.[Web of Science][Medline]
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  3. Vertommen JD, Vandermeulen E, Van Aken H, et al. The effects of the addition of sufentanil to 0.125% bupivacaine on the quality of analgesia during labor and the incidence of instrumental deliveries. Anesthesiology 1991; 74: 809–14.[Web of Science][Medline]
  4. Steinberg RB, Dunn SM, Dixon DE, et al. Comparison of sufentanil, bupivacaine, and their combination for epidural analgesia in obstetrics. Reg Anesth 1992; 17: 131–8.[Web of Science][Medline]
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  6. Stoddart AP, Nicholson KEA, Popham PA. Low dose bupivacaine/fentanyl epidural infusions in labour and mode of delivery. Anaesthesia 1994; 49: 1087–90.[Web of Science][Medline]
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  9. Herman NL, Sheu KL, Van Decar TK, et al. Determination of the analgesic dose-response relationship for epidural fentanyl and sufentanil with bupivacaine 0.125% in laboring patients. J Clin Anesth 1998; 10: 670–7.[Web of Science][Medline]
  10. Bernard J-M, Le Roux D, Vizquel L, et al. Patient-controlled epidural analgesia during labor: the effects of the increase in bolus and lockout interval. Anesth Analg 2000; 90: 328–32.[Abstract/Free Full Text]
  11. Loftus JR, Hill H, Cohen SE. Placental transfer and neonatal effects of epidural sufentanil and fentanyl administered with bupivacaine during labor. Anesthesiology 1995; 83: 300–8.[Web of Science][Medline]
  12. Van Steenberge A, Debroux HC, Noorduin H. Extradural bupivacaine with sufentanil for vaginal delivery: a double-blind trial. Br J Anaesth 1987; 59: 1518–22.[Abstract/Free Full Text]
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  14. Brodner G, Mertes N, Van Aken H, et al. What concentration of sufentanil should be combined with ropivacaine 0.2% wt/vol for postoperative patient-controlled epidural analgesia? Anesth Analg 2000; 90: 649–57.[Abstract/Free Full Text]
  15. Capogna G, Celleno D, Tomassetti M. Maternal analgesia and neonatal effects of epidural sufentanil for cesarean section. Reg Anesth 1989; 14: 282–7.[Web of Science][Medline]
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Accepted for publication September 26, 2000.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press