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Canadian Journal of Anesthesia 49:72-80 (2002)
© Canadian Anesthesiologists' Society, 2002
Obstetrical and Pediatric Anesthesia

Epinephrine reduces the sedative side effects of epidural sufentanil for labour analgesia

[L’épinéphrine réduit les effets secondaires sédatifs du sufentanil épidural administré pour l’analgésie pendant le travail]

Kevin P. Armstrong, MD FRCPC*, Brent Kennedy, MD FRCPC*, James T. Watson, MD FRCPC*, Patricia K. Morley-Forster, MD FRCPC*, Irvan Yee, MD FRCPC* and Ronald Butler, MD FRCPC{dagger}

1 From the Department of Anesthesiology,
2 St. Joseph's Health Care London, and the London Health Science Centre, London, Ontario, Canada.

Address correspondence to: Dr. Kevin Armstrong, Department of Anesthesiology, St. Joseph' Health Care London, 268 Grosvenor St., London, Ontario N6A 4L6, Canada. Phone: 519-646-6000, ext. 64219; Fax: 519-646-6116; E-mail: Kevin.armstrong2{at}sympatico.ca


   Abstract
TOP
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Purpose: The use of opioids in labour analgesia has primarily been as an adjuvant to local anesthetics. For early labour, satisfactory analgesia with epidural sufentanil alone is possible. This study evaluates the impact of epinephrine on sedative side effects and analgesia related to the latter technique.

Methods: After Institutional Review Board approval and informed consent this prospective, randomized, double-blind study evaluated 43 nulliparous subjects requesting epidural analgesia. The study site, a tertiary care obstetric unit, accommodates 3500–4500 deliveries annually. Group selection was randomized and blinded by selection of a sealed envelope containing a number which corresponded to a premixed labelled syringe of saline or epinephrine (100 µg•mL-1). An epidural catheter was placed in a standardized fashion. All subjects received 40 µg of sufentanil and 0.5 mL from the premixed syringe, diluted to 10 mL with NaCl. A blinded observer collected data on maternal sedation, lightheadedness, hemodynamics, oxygenation, and fetal heart rate over a one-hour period following sufentanil injection.

Results: The addition of epinephrine significantly (P <0.05) reduced the incidence of sedation and lightheadedness after epidural sufentanil at all data collection points, except two. Analgesic duration was also significantly prolonged by this addition (120 ± 56 vs 84 ± 32 min). Maternal satisfaction was high regardless of solution.

Conclusion: Forty micrograms of epidural sufentanil produces satisfactory analgesia in early labour. The addition of epinephrine improves the side effect profile of this technique while prolonging the duration of analgesia. Epidural sufentanil requires attention to maternal monitoring of oxygenation as maternal desaturation occurred in both groups.


   Introduction
TOP
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
EPIDURAL opioids continue to be an integral part of labour analgesia. Sufentanil has been evaluated in combination with local anesthetics in the epidural1,2 and intrathecal space.1,3,4 As a sole epidural agent, its use is less prevalent but studies have evaluated its analgesic effectiveness and pharmacokinetics in the obstetric2,5,6 and non-obstetric7,8 populations. Dunn et al. concluded that 40 µg of sufentanil administered epidurally, after a test dose of lidocaine and epinephrine, is as effective as 10 µg of intrathecal sufentanil.9

Based on previous experience at our institution, we found that 40 µg of sufentanil, diluted to 10 mL with normal saline, provided good analgesia when injected epidurally. However, lightheadedness and sedation were noted to be significant. Central nervous system (CNS) side effects2,10 and respiratory depression,11,12 have been described after intrathecal sufentanil. We postulated that this alteration in CNS status was due to systemic uptake of sufentanil via the epidural vasculature.8,13 Thus we hypothesized that the addition of 50 µg of epinephrine would reduce absorption and decrease CNS side effects. Our secondary hypothesis was that reduced systemic uptake would lead to a greater delivery of sufentanil to the cerebrospinal fluid (CSF), resulting in an increase in the duration as well as the intensity of analgesia.


   Methods
TOP
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
With Ethics Board approval, a prospective, randomized, and double-blind trial was undertaken. After informed consent, 43 nulliparous women requesting epidural labour analgesia were randomized to receive either epidural sufentanil alone (Group C), or epidural sufentanil with epinephrine (Group E). The Family Birthing Centre at St. Joseph' Health Care London was the lone site during this investigation. This centre is a high-risk obstetric unit with 3500–4500 deliveries per year; the nulliparous epidural rate is approximately 80%. Subject inclusion criteria were nulliparity, ASA I or II, age greater than 18 yr, weight less than 100 kg, gestational age greater than 34 weeks, no use of oral or im opioids, a normal fetal heart rate (FHR) tracing, and no contraindication to an epidural. A sufentanil solution was then prepared. Forty micrograms (0.8 mL) of sufentanil were combined with 8.7 mL of normal saline and 0.5 mL of a numbered study solution, to bring the final volume to 10 mL. The study solution contained either NaCl or one in 10 000 epinephrine (100 µg•mL-1). The study solutions were prepared in sterile syringes and randomized by the Department of Pharmacy. Each syringe was numbered, and the code was known only to the Department of Pharmacy. The syringes were kept on the labour ward and replaced every seven days.

An epidural was established at the L2–3 or L3–4 interspace by loss of resistance to air. The absence of CSF or blood in the catheter after negative aspiration, and to gravity flow was taken to indicate that the catheter was not in the intrathecal or vascular space. Monitors were then applied [blood pressure (BP), pulse oximetry, and FHR monitor], baseline readings taken, and the sufentanil solution injected in two 5-mL doses. This was considered to be time zero (T0). For each subject there were seven data points recorded for most variables, time zero (baseline) and then five, ten, 15, 30, 45 and 60 min post-injection. Data were collected and subsequently entered into a database for future analysis.

Measurement of primary outcomes included the presence of sedation, lightheadedness, the duration and intensity of analgesia, respiratory depression, motor blockade, pruritus, nausea and/or vomiting. Sedation was assessed using a visual analog scale for sedation (VASS). A score of 0 indicated the subject felt fully awake; a score of 100 meant the subject was unable to keep her eyes open or did not respond. Scores were recorded at T0, T5, T10, T15, T30, T45, and T60. An increase of 50% from baseline or an absolute score of 55 was considered to be of clinical relevance. Pain relief was measured similarly using the visual analog scale for pain (VASP) where 0 indicated no pain and 100 the worst pain imaginable. Scores were recorded at the same intervals as for VASS. A decrease in VASP of 50% from baseline or an absolute score of less than 25 was considered to be clinically significant pain relief. The presence or absence of lightheadedness, pruritus, and nausea were determined by direct questioning at the above time intervals. Treatment was available on request for pruritis, nausea, or vomiting. Duration of analgesia was measured as the time between epidural initiation (T0) and the subject' request for additional analgesia.

Motor blockade was assessed using the modified Bromage score, where 0 indicated no perceivable motor blockade and 3, no motor function in the lower limb. FHR was recorded continually for 45 min prior to epidural initiation and for 60 min after time 0 (T0). BP, respiratory rate (RR) and oxygen saturation (O2 Sat) were measured throughout the study period. The lowest saturation in an interval was recorded for each data point. An O2 Sat of less than 93% was considered clinically meaningful,14 less than 90%, hypoxemia.

Secondary data consisted of oxytocin use, time to 5 and 10 cm cervical dilation, time and method of delivery, and neonatal APGAR scores at one and five minutes. A maternal questionnaire to assess satisfaction was administered on the first post-partum day. The questionnaire attempted to determine the effectiveness of pain control, the presence of side effects, and whether or not the subject would choose this method of pain relief in the future.

Statistical analysis
Data are reported as mean ± standard deviation for continuous variables and the frequency of occurrence for categorical variables. The student two-sample t test was used to analyze group differences for continuous measures and Fisher' exact test was used for categorical data. A P-value of 0.05 was considered significant. All tests of significance were two tailed. All analyses were performed with SPSS 8.0 (Chicago IL, USA).


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Between March 1998 and April 1999, 44 subjects were recruited into the study; 22 in Group C and 22 in Group E. One subject in the epinephrine group was omitted and no data gathered after a recognized intravascular injection of half the dose. No ill effects resulted. Three subjects required a second epidural (inserted after the one hour study period) because of inadequate pain relief after a "rescue" dose of 10 mL of 0.25% bupivacaine. Two of these parturients were in Group E and one in Group C. Data from these subjects are included in the final analysis. Four mothers did not complete the maternal questionnaire; three of these in Group C. Forty-three of the 44 subjects recruited contributed data for final analysis. There were no demographic differences between the groups, with respect to maternal age, use of oxytocin, cervical dilation at epidural insertion, number of subjects requiring Cesarean delivery, or neonatal depression as determined by Apgar score (Table IGo).


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  		TABLE I Subject demographics
 
Sedation
CNS side effects, namely, sedation (VASS) and lightheadedness were greater in the subjects receiving sufentanil alone (Group C). At each data point there was a statistical difference in the number of subjects reporting a greater than 50% increase in sedation by VASS in Group C (P <0.034; Figure 1Go). Having defined clinically significant sedation at an absolute VASS of greater than 55,15 more subjects in the control group exceeded this threshold statistically (P <0.001; Figure 2Go). A comparison of the subjects that exceeded this VASS is presented in Table IIGo. Similarly, the incidence of lightheadedness was significantly more frequent in Group C, at each time point, with the exception of T15 (Figure 3Go).



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  		FIGURE 1 Number of subjects reporting a greater than 50% increase in visual analog scale for sedation following epidural sufentanil.

 


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  		FIGURE 2 Number of patients experiencing significant sedation, a visual analog scale for sedation greater than 55.

 

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  		TABLE II Deep sedation (VASS >55) and the relationship to initial sedation (VASS at T0)
 


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  		FIGURE 3 Number of subjects reporting lightheadedness after epidural sufentanil.

 
Pain control
The addition of epinephrine to epidural sufentanil statistically and clinically extended the duration of pain control. Time to request for additional analgesia after initiation of the epidural was significantly (P=0.012) longer in the epinephrine group (30%). The duration in Group E was 120 ± 56 min while in Group C it was 84 ± 32 min (Figure 4Go). There was no difference in the reduction of VASP between groups. The results are presented in Figure 5Go.



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  		FIGURE 4 Duration of analgesia following epidural sufentanil with or without epinephrine.

 


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  		FIGURE 5 Patients reporting a 50% reduction in visual analog scale for pain following epidural sufentanil with and without epinephrine.

 
Maternal questionnaire
Thirty-nine mothers (19 in Group C, 20 in Group E) completed a maternal questionnaire on the first post-partum day. They rated their satisfaction with pain control, the presence of side effects and if these side effects were tolerable. The final question asked whether or not they would choose this method of pain relief in the future. The results are presented in Table IIIGo.


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  		TABLE III Results of maternal questionnaire on the first post-partum day
 
Maternal and fetal monitoring
During the study, maternal O2 Sat, RR, and BP were measured. There was no difference in RR, BP, pruritus, nausea, maternal O2 Sat or fetal bradycardia between groups. These results are presented in Table IVGo. Maternal desaturation to 93% or less occurred in five subjects (23%) from Group C and six (28%) of Group E subjects. FHR decelerations were observed in five Group C subjects (23%) and four subjects (19%) from Group E. Table VGo shows the association of maternal desaturation and FHR decelerations. Back pain on injection of sufentanil was significantly greater (P <0.021) in Group E (five in Group E vs 0 in Group C).


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  		TABLE IV Effects and side effects of epidural sufentanil for labour analgesia
 

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  		TABLE V Association of maternal hypoxia and fetal heart rate decelerations
 

   Discussion
TOP
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Both sufentanil and epinephrine have been utilized in epidural labour pain management.2,4,16–18 In this study the addition of epinephrine to sufentanil reduced the number of subjects reporting sedation and lightheadedness in the first 45 min after epidural initiation. The number of subjects reporting a greater than 50% increase in VASS was significantly higher in the control group. The same was seen for an absolute VASS greater than 55. The degree of sedation between the groups is further highlighted by the fact that in the subset of those subjects that exceeded a VASS of 55, there was a difference in the mean VASS at T0 between the study groups. The mean VASS at T0 in the epinephrine group is 40 ± 23 compared to 22 ± 17 in the control group. The mean VASS at T0 for each population was 25 ± 25 in Group E and 24 ± 22 in Group C. A VASS of 55 was chosen to indicate deep sedation because subjects in another study assessing propofol sedation for regional anesthesia reported this VASS (55) when a 0.7 mg•kg-1 bolus was given followed by a 4 mg•kg-1•hr-1 infusion. This VASS of 55 correlated to an observer VASS of 73.15 We attribute the measured increase in sedation to be secondary to higher systemic absorption of sufentanil in the control group. This is of significance if patients wish to be ambulatory. Additionally, deep sedation may alarm the parturient or her labour partner(s).

Sufentanil administered into the epidural space potentially exerts its analgesic effect through spinal cord receptors located in the substantia gelatinosa,17,19 but the possibility of supraspinal action, via CSF or systemic circulation, needs to be considered.10 Stevens et al., using dogs20 has shown a rapid rise in lumbar and cisterna magna CSF levels of sufentanil following large epidural doses. The investigators concluded that high levels of sufentanil in the central CSF cannot be explained by systemic uptake, since concentrations in the cisterna magna were 1/12 that of lumbar levels, but six times greater than those of the plasma. This suggests that analgesia (and side effects) may occur at the supraspinal level and are due to cephalad migration in the CSF, not vascular delivery. Klepper et al. studied the impact of epinephrine on epidural sufentanil in human volunteers.7 No difference in plasma sufentanil levels was evident whether epinephrine was used or not. They concluded that there was no change in systemic levels when epinephrine was utilized. Our data supports decreased systemic uptake and less central CNS effect, since side effects actually decreased and analgesia improved with the addition of epinephrine. Neither the Klepper7 nor the Stevens20 study involved pregnant subjects, where an increased epidural vasculature may explain the effect of epinephrine in our study. Furthermore, the decrease in CNS side effects with epinephrine does not suggest CSF migration of sufentanil as in the dog study, but this may be explained on the basis of the larger dose of sufentanil per kilogram used by Stevens.

Studies in postoperative subjects have demonstrated that significant plasma levels occur following epidural administration of sufentanil. The investigators were unable to demonstrate any difference in pain scores when the same dose of sufentanil was given either intravenously or epidurally.8,21 These findings have led some clinicians to question the concept of a spinal cord effect with lipid soluble epidural opioids, and suggest that any improvement in analgesia is secondary to systemic uptake. To distinguish between systemic effect and direct spread in CSF, and any impact the addition of epinephrine has on systemic levels, plasma sufentanil levels would be required. We decided against this because of the lack of acceptability to subjects.

It is common for sedation to occur following epidural initiation, especially when opioids are used.13 The proposed mechanisms for these side effects include, 1) systemic uptake2,7,11,21,22 or 2) cephalic spread in the CSF.13,23 Individually or together, these two mechanisms can also lead to respiratory depression as sufentanil reaches opioid receptors in the respiratory centre. The resulting rise in carbon dioxide may itself lead to sedation.13 Our study suggests systemic uptake to be the mechanism responsible in the pregnant subject.

If epinephrine, through its vasoactive properties, decreases the systemic uptake there are four potential outcomes: 1) sufentanil is absorbed into the epidural fat resulting in less systemic side effects but little or no change in analgesia; 2) increased delivery of sufentanil to the CSF with decreased side effects and increased analgesia; 3) increased delivery of sufentanil to the CSF; and decreased side effects, but no change in analgesia, because of a "ceiling effect" to increasing dose; and 4) increased delivery of sufentanil to the CSF with improved analgesia, but paradoxically, an increase in CNS depressive side effects secondary to high supraspinal concentrations of sufentanil. Our data suggest the second outcome was occurring.

Duration of analgesia was prolonged (84 vs 120 min) with a trend towards greater intensity, and faster onset at the various data points. This suggests that epinephrine increases sufentanil concentrations available to the spinal cord. The number of subjects reaching an absolute VASP of less than 25 appears to be greater in Group E. The lack of a statistical difference between groups on pain scores five to 45 min post-injection, may indicate that epidural sufentanil with or without epinephrine will produce good analgesia, or that a larger sample size is required. Other causes of poor analgesia include technical failure, that is, the epidural catheter is not in the epidural space. There was one restart of an epidural in Group C and two in Group E. Advanced or rapid labour24 requires more intense analgesia. Six subjects in Group C and eight in Group E had their epidural placed with a cervical dilation of greater than 5 cm. Can sequestration of sufentanil in the epidural fat produce less than satisfactory analgesia? Hansdottir et al. provided some evidence for this when they found lower than expected CSF levels when plasma concentrations were taken into account and inferred that the unaccounted sufentanil was bound in the epidural space.25

It is possible that any changes in VASP may be due to the alpha2 agonist effect of epinephrine.3,17 We are aware of one animal study26 which concluded that epidural epinephrine is metabolized by the dura of pigs and monkeys therefore limiting its transfer into the CSF. This finding makes it seem unlikely that the added epinephrine had any impact on the recorded pain scores.

Oxyhemoglobin desaturation to less than 93% occurred in each group, five in Group C and six in Group E with no clear correlation to sedation. An O2 Sat of 93% is clinically relevant because manufactures of these monitors report an error of ± 2%.14 Therefore a reading of 93% may represent a real O2 Sat of 91%. At 90% the PaO2 approximates 60 mmHg. This is the steep part of the oxygen dissociation curve where small decreases in PaO2 result in relatively large decreases in hemoglobin saturation. A potential consequence of this reduced oxygen content is a subsequent decrease in delivery of oxygen to the uteroplacental unit. This degree of desaturation occurred in both groups, but the number of data points recorded where the O2 Sat was less than 93% is greater in the control group. No subject had a recorded RR of less than 12 beats•min-1. Other investigators have demonstrated that RR is a less sensitive measure of respiratory depression13 than the carbon dioxide response curve. However, the carbon dioxide response curve is not easily applied in the clinical situation. O2 Sat monitoring is not a routine part of labour analgesia but Porter et al.27 have shown maternal desaturation occurs during epidural labour analgesia when fentanyl (2.5 µg•mL-1) is used compared to bupivacaine alone. Bourne et al.28 were able to show that 25% of pregnant non-labouring subjects desaturate to an O2 Sat <90% at night. This suggests that oxygen desaturation may occur on labour and delivery wards, especially when epidural opioids are used.

Muscle rigidity or leg pain has been reported with intrathecal sufentanil.29,30 The mechanism of this is unknown. In our study, five parturients in the epinephrine group described moderately severe back pain on injection of the sufentanil dose. On further questioning, it appears that the pain was in the lumbar region and was coincident with a contraction. In some subjects there was a subjective sense of increased uterine activity, possibly indicating a hypertonic state. However, there was no demonstration of fetal bradycardia associated with this back pain. We are uncertain of the significance of these findings, but epinephrine may accentuate the action of sufentanil with respect to this side effect.

Fetal bradycardia following epidural/CSE analgesia has been described with an incidence of approximately 10 to 25%.31,32 The etiology of these events during times of stable maternal hemodynamics remains unclear. Rapid pain relief and decreased endogenous epinephrine relative to norepinephrine has been suggested as the mechanism for uterine hypertonus leading to fetal bradycardia.31 In this study, if fetal bradycardia occurred, it did so without a fall in BP and no definitive evidence of a hypertonic state by uterine tocometry. Fetal bradycardia may also be due to fetal hypoxia secondary to maternal hypoxemia. In this study O2 Sat was recorded continually for one hour. A total of 11 mothers, five in Group C and six in Group E, had at least one recorded O2 Sat of less than 93%. Two subjects in this subset had a deceleration in FHR with a coincident low O2 Sat. Subject nine in Group E had an O2 Sat of 92% recorded in the T30–T45 interval. At this time, variable FHR decelerations to 80 beats•min-1 were recorded. O2 Sat and FHR recovered with positional change and supplemental O2 as per the protocol for fetal bradycardia. Subject 36 in Group C experienced a fall in O2 Sat to 90%, observed over the T15–T45 min interval; there were also variable FHR decelerations to 90 beats•min-1. Treatment included supplemental O2, positional change and cessation of oxytocin. There were no operative deliveries as a result of FHR changes within the study period.

The maternal questionnaire administered on the first post-partum day confirmed that the majority of subjects in our study were satisfied with their pain management, and that the side effects, when present, were tolerable to the parturients.

Epidural sufentanil as a sole agent for labour analgesia raises some interesting issues. At present, methods of labour analgesia are capable of producing safe, high quality pain control with minor side effects while maintaining motor function. Epidural sufentanil in the dose we have used, produced good pain control, maintained motor function, and had a side effect profile that was acceptable to parturients. Additional advantages include: 1) no necessity for dural puncture; 2) a useful alternative for short-term pain relief in patients allergic to local anesthetics; 3) a means of improving analgesia in a less than satisfactory epidural; or 4) an aid in managing first to second stage transition of labour. However, large doses of such a potent medication deserves special consideration with respect to intravascular or intrathecal injection. Injection must be done carefully, in divided doses and with oxyhemoglobin saturation monitoring. Ten micrograms of intrathecal sufentanil will produce rapid analgesia in someone with first stage labour.9 Ten micrograms of intravascular sufentanil will also have a rapid analgesic effect and may itself serve as a test for intravascular injection, as Morris demonstrated with fentanyl.33 This same 2.5 mL bolus contains 12.5 µg of epinephrine and will increase maternal heart rate. Like any technique involving relatively large doses of opioid in neuraxial analgesia, an opioid antagonist must be readily available.12

We conclude that the addition of 50 µg of epinephrine to 40 µg of sufentanil diluted to 10 mL for epidural labour analgesia increases intensity and duration of analgesia while decreasing side effects, specifically the incidence of lightheadedness and sedation. This provides a good level of analgesia for the parturient without motor blockade and avoids the necessity for dural puncture. In addition, a marker for intravascular injection is available. It is, however, not without its drawbacks. Most significant is the short-lived mild hypoxia noted in 25% of our subjects. We therefore recommend that this technique requires O2 Sat monitoring and the availability of naloxone. The incidence of side effects was tolerable to the majority of mothers in our study.


   Acknowledgments
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
The authors would like to acknowledge the contribution of the following in the conduct of this study: Lee-Ann van Derhaeghe, Department of Pharmacy, SJHC, the nursing staff of the Family Birthing Centre SJHC, and the Department of Obstetrics SJHC, London, Ontario, Canada.


   Footnotes
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Funding through the Department of Anesthesiology St. Joseph' Health Care London, London Ontario, Canada. Presented as a poster and abstract at the 1999 Society for Obstetric Anesthesia and Perinatology (SOAP) Annual meeting 19-22/05/1999. Denver, Colorado, USA.

Revision received November 16, 2001. Accepted for publication July 30, 2001.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
1 Camann W, Abouleish A, Eisenach J, Hood D, Datta S. Intrathecal sufentanil and epidural bupivacaine for labor analgesia: dose-response of individual agents and in combination. Reg Anesth Pain Med 1998; 23: 457–62.[Medline]

2 Steinberg RB, Powell G, Hu X, Dunn SM. Epidural sufentanil for analgesia for labor and delivery. Reg Anesth 1989; 14: 225–8.[Medline]

3 Campbell DC, Banner R, Crone L-A, Gore-Hickman W, Yip RW. Addition of epinephrine to intrathecal bupivacaine and sufentanil for ambulatory labor analgesia. Anesthesiology 1997; 86: 525–31.[Medline]

4 Mardirosoff C, Dumont L. Two doses of intrathecal sufentanil (2.5 and 5 mg) combined with bupivacaine and epinephrine for labor analgesia. Anesth Analg 1999; 89: 1263–6.[Abstract/Free Full Text]

5 Steinberg RB. Dunn SM, Dixon DE, Rehm KL, Pastides H, Hu X. Comparison of sufentanil, bupivacaine and their combination for epidural analgesia in obstetrics. Reg Anesth 1992; 17: 131–8.[Medline]

6 Connelly NR, Parker RK, Vallurupalli V, Bhopatkar S, Dunn S. Comparison of epidural fentanyl versus epidural sufentanil for analgesia in ambulatory patients in early labor. Anesth Analg 2000; 91: 374–8.[Abstract/Free Full Text]

7 Klepper ID, Sherrill DL, Boetger CL, Bromage PR. Analgesic and respiratory effects of extradural sufentanil in volunteers and the influence of adrenalin as an adjuvant. Br J Anaesth 1987; 59: 1147–56.[Abstract/Free Full Text]

8 Ionescu TI, Taverne RHT, Houweling PL, Drost RH, Nuijten S, Van Rossum J. Pharmacokinetic study of extradural and intrathecal sufentanil anaesthesia for major surgery. Br J Anaesth 1991; 66: 458–64.[Abstract/Free Full Text]

9 Dunn SM, Connelly NR, Steinberg RB, et al. Intrathecal sufentanil versus epidural lidocaine with epinephrine and sufentanil for early labor analgesia. Anesth Analg 1998; 87: 331–5.[Abstract/Free Full Text]

10 de Leon-Casasola OA, Lema MJ. Postoperative epidural opioid analgesia: what are the choices?. Anesth Analg 1996; 83: 867–75.[Abstract]

11 Greenhalgh CA. Respiratory arrest in a parturient following intrathecal injection of sufentanil and bupivacaine. Anaesthesia 1996; 51: 173–5.[Medline]

12 Katsiris S, Williams S, Leighton BL, Halpern S. Respiratory arrest following intrathecal injection of sufentanil and bupivacaine in a parturient. Can J Anaesth 1998; 45: 880–3.[Abstract/Free Full Text]

13 Chaney MA. Side effects of intrathecal and epidural opioids. Can J Anaesth 1995; 42: 891–903.[Abstract/Free Full Text]

14 Barker SJ, Tremper KK. Pulse oximetry. In: Ehrenwerth J, Eisenkraft JB (Eds.). Anesthesia Equipment. St. Louis: Mosby, 1993: 249–63.

15 Smith I, Monk TG, White PF, Ding Y. Propofol infusion during regional anesthesia: sedative, amnestic, and anxiolytic properties. Anesth Analg 1994; 79: 313–9.[Abstract/Free Full Text]

16 Grieco WM, Norris MC, Leighton BL, et al. Intrathecal sufentanil labor analgesia: the effects of adding morphine or epinephrine. Anesth Analg 1993; 77: 1149–54.[Abstract/Free Full Text]

17 Camann WR, Minzter BH, Denney RA, Datta S. Intrathecal sufentanil for labor analgesia. Effects of added epinephrine. Anesthesiology 1993; 78: 870–4.[Medline]

18 Camann WR, Denney RA, Holby ED, Datta S. A comparison of intrathecal, epidural, and intravenous sufentanil for labor analgesia. Anesthesiology 1992; 77: 884–7.[Medline]

19 Brown DL. Spinal, epidural, and caudal anesthesia: anatomy, physiology, and technique. In: Chestnut DH (Ed.). Obstetric Anesthesia Principals and Practice, 2nd ed. St Louis: Mosby Publishers, 1999: 187–208.

20 Stevens RA, Petty RH, Hill HF, et al. Redistribution of sufentanil to cerebrospinal fluid and systemic circulation after epidural administration in dogs. Anesth Analg 1993; 76: 323–7.[Medline]

21 Sinatra RS, Ayoub CM. Postoperative analgesia: epidural and spinal techniques. In: Chestnut DH (Ed.). Obstetric Anesthesia Principals and Practice, 2nd ed. St Louis: Mosby Publishers, 1999: 521–55.

22 Norris MC, Fogel ST, Holtmann B. Intrathecal sufentanil (5 vs. 10 mg) for labor analgesia: efficacy and side effects. Reg Anesth Pain Med 1998; 23: 252–7.[Medline]

23 Miguel R, Barlow I, Morrell M, Scharf J, Sanusi D, Fu E. A prospective, randomized, double-blind comparison of epidural and intravenous sufentanil infusions. Anesthesiology 1994; 81: 346–52.[Medline]

24 Viscomi CM, Rathmell JP, Pace NL. Duration of intrathecal labor analgesia: early versus advanced labour. Anesth Analg 1997; 84: 1108–12.[Abstract]

25 Hansdottir V, Woestenborghs R, Nordberg G. The cerebrospinal fluid and plasma pharmacokinetics of sufentanil after thoracic or lumbar epidural administration. Anesth Analg 1995; 80: 724–9.[Abstract]

26 Kern C, Mautz DS, Bernards CM. Epinephrine is metabolized by the spinal meninges of monkeys and pigs. Anesthesiology 1995; 83: 1078–81.[Medline]

27 Porter JS, Bonello E, Reynolds F. The effects of epidural opioids on maternal oxygenation during labour and delivery. Anaesthesia 1996; 51: 899–903.[Medline]

28 Bourne T, Ogilvy AJ, Vickers R, Williamson K. Nocturnal hypoxaemia in late pregnancy. Br J Anaesth 1995; 75: 67–82.

29 Newman LM, Patel RV, Krolick T, Ivankovich AD. Muscular spasm in the lower limbs of laboring patients after intrathecal administration of epinephrine and sufentanil. Anesthesiology 1994; 80: 468–71.[Medline]

30 Malinovsky J-M, Lepage J-Y, Cozian A, Lechevalier T. Transient muscular spasm after a large dose of intrathecal sufentanil. Anesthesiology 1996; 84: 1513–5.[Medline]

31 Neilsen PE, Erickson JR, Abouleish EI, Perriatt S, Sheppard C. Fetal heart rate changes after intrathecal sufentanil or epidural bupivacaine for labor analgesia: incidence and clinical significance. Anesth Analg 1996; 83: 742–6.[Abstract]

32 Gambling DR, Sharma SK, Ramin SM, et al. Randomized study of combined spinal-epidural analgesia versus intravenous meperidine during labor: impact on cesarean delivery rate. Anesthesiology 1998; 89: 1336–44.[Medline]

33 Morris GF, Gore-Hickman W, Lang SA, Yip RW. Can parturients distinguish between intravenous and epidural fentanyl? Can J Anaesth 1994; 41: 667–72.[Abstract/Free Full Text]





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