Labor pain relief using bupivacaine and sufentanil: Patient controlled epidural analgesia versus intermittent injections

European Journal of Obstetrics & Gynecology and Reproductive Biology 59 Supp!. (1995) S47-S54 Labor pain relief using bupivacaine and sufentanil: Patient controlled epidural analgesia versus intermittent injections Erik P. Vandermeulen, Hugo Van Aken*, Jan D. Vertommen Department ofanesthesiology, Universitair Ziekenhuis Gasthuisberg, Herestraat 49. B-3 Leuven, Belgium Abstract Objectives: To determine whether the use of patient-controlled epidural analgesia versus intermittent injections resulted in local anesthetic dose reduction. Study Design: PCEA and CIT using a mixture ofo.125% bupivacaine with sufentanil lor.75 JLglml were compared in 6 and 195 parturients, respectively. Assessments included pain scores, local anesthetic consumption, degree of motor blockade, type of delivery and neonatal outcome. Statistical analysis was done using Student's t test and Chi-squares. Results: PCEA and CIT provided effective analgesia during labor and delivery. A higher dose of opioid significantly reduced the use of local anesthetic solution in PCEA-patients. There was no difference in motor blockade, type of delivery and neonatal outcome. Conclusion: Patient-controlled epidural analgesia is an effective, safe and acceptable alternative to conventional intermittent epidural injections for pain relief during labor and delivery. Keywords: Epidural anesthesia; Bupivacaine; Sufentanil; Patient-controlled analgesia 1. Introduction In a previous study our group demonstrated that the addition of sufentanil I /Lg/ml to intermittent 1 ml epidural injections of.125% bupivacaine with epinephrine 1:8 significantly enhanced the quality and duration of maternal labor analgesia without depressing the neurobehavioral status of the newborn. Also, the use of sufentanil reduced the total dose of local anesthetic, the degree ofmotor block and the incidence ofinstrumental deliveries [I]. In addition, we have recently shown that the sufentanil concentration can be further reduced to.75 /Lg/ml without compromising the quality of analgesia [2]. Meanwhile, an increasing number of studies have reported the efficacy and safety of patientcontrolled epidural analgesia for labor analgesia [3,4]. A significant reduction in local anesthetic consumption was found when PCEA was compared to continuous infusion epidural analgesia (CIEA) [5-7], or to PCEA supplemented by a continuous epidural background infusion [8,9]. Only few studies have prospectively compared PCEA with conventional intermittent "top-up" injections [6,1]. The aim of these two study protocols was to deter- Corresponding author, Tel.: +32 1634427; Fax: +32 16344245. mine, in a prospective, randomized and controlled manner, if bolus-only patient-controlled epidural analgesia (without continuous background infusion), using a mixture of.125% bupivacaine with sufentanil, can further reduce the total dose of bupivacaine without altering the quality of analgesia when compared to CIT. In a first trial, we used bupivacaine.125% with epinephrine (l:8 ) plus sufentanil 1 /Lg/ml, while the second study included the use of sufentanil.75 /Lg/ml. The design and results of both studies will be presented separately, followed by a common discussion and conclusion. 2. Materials and methods 2.1. Bupivacaine.125% + Epinephrine 1:8 + Sufentanil 1 /Lg/ml After Institutional Review Board approval and obtaining written informed consent, 6 pregnant women at term (ASA physical status I or II) in spontaneous or induced labor, all of whom requested epidural analgesia, were included in the protocol. Only women who had not received sedatives, analgesics or any drug other than oxytocine or prostaglandin E2 and who had singleton fetuses in the vertex position were studied. After hydration by intravenous infusion of 1 ml lactated 28-2243/95/$9.5 1995 Elsevier Science Ireland Ltd. All rights reserved SSDl 28-2243(95)2 63-X

548 E.P. Vandermeulen el al. / European Journal of ObSlerrics & Gynecology and Reproducrive Biology 59 Suppl. (/995) 547-S54 Ringer's solution, an epidural puncture was performed at either the L3-L4 or L2-L3 interspace with the women in a lateral decubitus position. The epidural space was identified by a loss of resistance to saline technique using an 18 G Tuohy needle and a multiorifice catheter (Portex, UK) was inserted into the epidural space. Analgesia was induced in all patients by epidural injection of 1 ml of an anesthetic mixture containing 12.5 mg bupivacaine, 12.5 p.g epinephrine and 1 p.g sufentanil. This injection served as both test dose and analgesic dose (I]. After the extent of the sensory block was assessed, the patients were randomly assigned into one of two treatment groups of equal size. Patients in group A were instructed to maintain analgesia by self administration of4 ml boli ofbupivacaine.125% with epinephrine (1:8) plus sufentanil 1 p.g/ml. The patientcontrolled analgesia (PCA) device used was an Abbott Lifecare 42 Infuser and a lockout interval of 2 min was selected. A background infusion was not provided. It was explained to all patients that there was no limit on the number of demands that could be made and that it would be impossible to overdose themselves as the PCA devices were programmed with safe dosing parameters. If more than 3 ml of the local anesthetic mixture was necessary, bupivacaine without sufentanil was used. In group B, analgesia was maintained by intermittent injections of 1 ml bupivacaine.125% with epinephrine 1:8 plus sufentanil I p.g/ml on request, given by an anesthesiologist. Similarly, if more than 3 ml of the anesthetic mixture was necessary, bupivacaine without sufentanil was used. The quality ofanalgesia was assessed on a linear visual analog scale, using a line of 1 mm, before the first epidural injection, then every hour and during episiotomy, delivery and suturing. In addition, the quality of analgesia was evaluated again I hand 5 days following delivery. The degree of motor blockade and the total volume of anesthetic mixture were also recorded. Abdominal muscle motor block was assessed before the first epidural injection and immediately before delivery by the Rectus Abdominis Muscle-test (R.A.M.-test) (II]. The R.A.M.-test is performed by asking the parturient to rise slowly (arms extended - back curled) from the complete supine position to a sitting position. Weakness of the abdominal musculature will prevent the woman from completely reaching the sitting position. The degree to which she succeeds to sit will be allocated a score ranging from 2% (only an increase in abdominal wall tension) to 1% (complete sitting position). The type of delivery and neonatal Apgar scores at 1 and 5 min were noted. Statistical analyses were performed by Student's t test and Chi-squares where appropriate. A P value <.5 was considered significant. 2.2. Bupivacaine.125% + Epinephrine 1:8 + Sufentani/.75 p.g/m/ After obtaining approval by the Institutional Review Board and written informed consent 195 ASA physical status I or II parturients in spontaneous or induced labor, all of whom had requested painfree labor and delivery, were included in the protocol. Only patients who had not received sedatives, analgesics or any drug other than oxytocine or prostaglandin E2 and who had singleton fetuses in the vertex position were included in this prospective study and randomly allocated into one of two treatment groups. Epidural anesthesia was performed using the same standardized technique as described previously. Briefly, after identification of the epidural space by a loss ofresistance to saline technique, an epidural multiorifice catheter (Portex, UK) was inserted through the 18 G Tuohy needle at the L3-L4 or L2-L3 interspace. Analgesia was induced by epidural injection of 1 ml bupivacaine.125% with epinephrine (I :8 ) plus sufentanil.75 p.g/ml. After evaluation of the spread ofthe sensory block, the patients were randomly assigned to one of two treatment groups. Patients in group A could maintain analgesia by selfadministration of 4 ml boli of bupivacaine.125% with epinephrine (1:8 ) plus sufentanil.75 p.g/ml with a lockout interval of 2 min, using a similar PCA device as in the first study. Patients in group B had their analgesia maintained by supplementary epidural injections of 1 ml of the same local anestheticlopioid mixture on request, given by an anesthesiologist. If more than 3 ml of this anesthetic mixture was necessary,.125% bupivacaine with adrenaline (1:8) but without sufentanil was used. The quality ofanalgesia was assessed on a linear visual analog scale of 1 mm before the first epidural injection, then every hour and following episiotomy, delivery and suturing. One hour after delivery, maternal satisfaction with the technique was also evaluated on a 1 mm visual analog scale. Motor block in the abdominal muscles was evaluated before the first epidural injection and immediately before delivery by means of the R.A.M. test. The amount ofanesthetic mixture used and the type of delivery were noted. The neonates were evaluated at I and 5 min after birth by Apgar scores. Statistical analyses were done by Student's t test and Chi squares. A P value <.5 was considered significant. 3. Results 3.1. Bupivacaine.125% + Epinephrine 1:8 + Sufentani/ I p.g/m/ Each group included 3 patients. However, one patient in group A was excluded during the study because she failed to understand the principles of patientcontrolled analgesia. Maternal age, weight, height, par-

E.P. Vandermeulen et al./ European Journal of Obstetrics & Gynecology and Reproductive Biology 59 5uppl. (1995) 547-554 549 ity, ASA physical status, cervical dilation at the start of the epidural, contraction rate, baseline pain scores and the baby's gestational age and weight did not differ significantly between the two groups (Table 1). Labor was induced in about 2/3 of the women in both groups. There were no differences in pain scores between the two groups at any time during labor, nor were there differences during episiotomy, delivery, suturing and at I and 5 h after delivery (Fig. 1). The degree of motor paralysis in the abdominal muscles, measured before delivery, remained virtually unchanged from its pre-injection values and was similar in each of the groups (Table 2). Significantly less anesthetic mixture was used by the patients in group A than by the patients in group B (Table 3). A comparable number of patients was given an additional infiltration of the perineal area with lidocaine by the obstetrician prior to episiotomy. 1 Table I Maternal and neonatal demographics Variable Age (yr) Weight (kg) Height (em) Gestational age (weeks) Cervical dilation before epidural (em) Time between contractions before epidural (min) Pain score before 1st epidural injection (mrn) Birth weight (g) Parity Nul1iparous Parous Labor Spontaneous Induced Group A Group B (n = 29) (n = 3) 28 ~ 4 29 ~ 4 78 ~ 14 77~13 165 ~ 6 165 ~ 6 39 ~ 2 39 ± I 4~1 4±1 3~1 3 ± I 74 ± 18 74 ~ 15 3845 ~ 339 3449 ± 373 17 16 12 14 7 II 22 19 CIT, conventional intennitlent "top-up" injections; PCEA. patientcontrol1ed epidural analgesia. Values are mean :l: S.D. 9 8 7 w 6 a: (J en 5 II Group A III Group B z < 4 a.. 3 2 1 c:.r:..r:..r:..r:. >. ~.~ - - - en W ) '>= ~ ~,... C\J ('t) 'V E c:.~ (,)............ ::J.~,~ ~ ~ ~ ~ ::J 'c ' ex: ex: ex: ex: (f) -c -c '.......,... ~ ctl 'iij....r:. ' a..- L() - III Fig. I. Pain scores (mean ~ S.D.) obtained throughout the study as measured by visual analog scale (mrn).

S5 E.P. Vandermeulen et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 59 5uppl. (1995) 547-554 Table 2 Motor blockade (R.A.M.-test) Table 4 Type of delivery Time Before 1st injection Before delivery Power (%) Type of delivery Group A Group B Group A Group B (n = 29) (n = 3) (n = 29) (n = 3) Spontaneous 22 24 Vacuum 7 5 66 ± 2 63 ± 23 Cesarean section I 68 ± II 64 ± 14 CIT, conventional intermittent "top-up" injections; PCEA, patientcontrolled epidural analgesia. CIT, conventional intermittent "top-up" injections; PCEA, patientcontrolled epidural analgesia; R.A.M.-test, rectus abdominis muscle test. Finally, the methods of delivery were comparable in both groups (Table 4), most of the patients delivering spontaneously. All newborns had Apgar scores of more than 7 at 1 and 5 min after birth. 3.2. Bupivacaine.125% + Epinephrine 1:8 + Sufentanil.75 IJ.g/ml The total patient population consisted of 195 women. The mothers age, weight, height, parity, ASA physical status, duration of pregnancy, cervical dilation at the start of the epidural, contraction rate, baseline pain scores, and neonatal birth weight did not differ between the two groups (Table 5). Labor was induced in a comparable number of women in both groups. In patients with spontaneous labor, the epidural anesthetic was started at a higher average pain score (72 mm ± 17) than in patients in whom labor was induced (62 mm ± 24, P <.5). Therefore, the results were further analyzed according to the type of labor. Once epidural anesthesia was induced, all previously existing differences in pain scores disappeared and remained so for the remainder of labor and also during episiotomy, delivery or suturing (Fig. 2). Table 3 Total volume of local anesthetic mixture used and number of patients requiring additional infiltration of local anesthetics Total volume anesthetic (ml) Additional local anesthesia Group A (n = 29) 19 ± 6 8/29 Group B (n = 3) 24 ± 11* 5/29 CIT, conventional intermittent "top-up" injections; PCEA. patientcontrolled epidural analgesia. P <.5 A comparable amount of local anesthetic was used in both groups for a similar duration oflabor and comparable maternal satisfaction (Table 6). There was no difference in the degree ofmotor blockade between the two treatment groups, both before the first epidural injection and prior to delivery (Table 7), nor was there a difference in the type of delivery (Table 8). Although abdominal muscle strength (R.A.M.-test) was found lower prior to delivery when compared to pre-injection values, this difference was not significant. More than 75% ofpatients in both treatment groups delivered spontaneously. Finally, all neonates had Apgar scores of more than 7 at I and 5 min after delivery. Table 5 Maternal and neonatal demographics Variable Age (yr) Weight (kg) Height (em) Gestational age (weeks) Cervical dilation before epidural (em) Time between contractions before epidural (min) Pain score before 1st epidural injection (mm) Birth weight (g) Parity Nulliparous Parous Labor Spontaneous Induced Group A Group B (n = 16) (n = 89) 28 ± 4 29 ± 4 76 ± 12 75 ± 13 166 ± 5 165 ± 7 39 ± I 39 ± I 4 ± I 4±1 4±2 3 ± 2 63 ± 23 7 ± 2 3355 ± 411 3394 ± 488 67 44 39 45 39 46 67 43 CIT, conventional intermittent "top-up" injections; PCEA, patientcontrolled epidural analgesia.

E.P. Vandermeulen et 1. / European Journal of Obstetrics & Gynecology and Reproductive Biology 59 Suppl. (1995) 547-S54 551 1 9 8 7 w a: 6 () C/') z 5 < 4 ll. 3 Group A Spontaneous Labor Group B - Spontaneous Labor Group A - Induced Labor II Group B - Induced Labor 2 1 c:.r::.r:: C\J U...... :~ iii ~ E CO +: +: c:( c:(.r::.r::.r:: >. ~ Ol (W) v II) E c:.;::...... Q>.2: OJ :::J OJ +: +: +: Qi 'ii) 5 c:( c:( c:( Cl (/) 'Q. w Fig. 2. Pain scores (mean ± S.D.) obtained throughout the study as measured by visual analog scale (mm). 4. Discussion Although multiple studies have compared PCEA with PCEA supplemented by a continuous epidural background infusion and/or a continuous infusion epidural analgesia, only few studies have prospectively compared the effects of bolus-only PCEA and conventional intermittent "top-up" injections in the same obstetrical context. Epidural analgesia during labor is often managed by the intermittent injection of local anesthetic solutions (± opioids) by anesthesiologists, nurse anesthetists or midwives, on demand by the parturient. As labor progresses, the painful episodes will become more frequent, more severe and longer lasting, thus increasing analgesic requirements. Any delay in the administration ofa "topup" injection or failure to promptly recognize the return of pain in a parturient will cause significant discomfort in the latter and make it more difficult to catch up with the increasing pain [12]. Continuous epidural infusion analgesia may overcome this problem but will use significantly higher doses oflocal anesthetic [5,7,13-15] Table 6 Total volume of local anesthetic mixture used, duration of labor, and maternal satisfaction Spontaneous labor Induced labor Group A Group B Group A Group B (n = 39) (n =46) (n = 67) (n = 43) Total volume of anesthetic (ml) 22 ± I I 2 ± 9 22 ± 8 22 ± 9 Duration oflabor (min) 213 ± 178 153 ± 114 186 ± 112 156 ± 82 Satisfaction (mm) 88 ± 18 89 ± 16 94 ± 16 92 ± 12 CIT, conventional intermittent "top-up" injections; PCEA, patient-controlled epidural analgesia. Values are mean * S.D.

S52 E.P. Vandermeulen et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 59 5uppl. (/995) 547-554 Table 7 Motor blockade (R.A.M-test) Time Power ("!o) Spontaneous labor Induced labor Group A (n =39) Group B (n = 46) Group A (n =67) Group B (n =43) Before 1st injection Before delivery 7 ± 19 55 ± 19 7 ± 22 54 ± 2S 71 ± 21 S3 ± 23 7 ± 18 52 ± 22 CIT, conventional intermittent "top-up" injections; PCEA, patient-controlled epidural analgesia; R.A.M.-test, rectus abdominis muscle test. and may increase the risk for the development of higher blocks, motor paralysis and tachyphylaxis [16]. Patient-controlled analgesia (PCA) for postoperative analgesia has been shown to provide better pain relief than more conventional techniques without an increase in side effects (17). Often patients are the best managers oftheir own pain as they can best detect when they need pain relief. Transposing the concept of PCA to epidural labor analgesia may provide a solution to the ever changing pain conditions during labor and delivery. In 199, Gambling et al. studied 58 nulliparous parturients and compared the effects of bolus-only PCEA and CIT [1] using bupivacaine.125% with epinephrine 1:4 during first stage labor. Initially, all patients received a 3-ml test dose with.25% bupivacaine followed by 5 ml of the same solution to produce a sensory block extending to at least TlO. Thereafter, PCEA-patients could self-administer 4-ml boli (lockout interval of 2 min) of.125% bupivacaine with epinephrine. CIT-patients received 12-ml boli of.125% bupivacaine from the anesthesiologist upon request. In the event of inadequate analgesia, supplementary analgesia was available. Gambling et al. found a similar pain relief in both groups but significantly greater patient satisfaction in PCEA patients. Comparable hourly amounts of local anesthetic solution were used in both groups. Purdie et al. compared bolus-only PCEA, intermittent midwife administered epidural "top-up" injections and Table 8 Type of delivery Method Spontaneous Vacuum Forceps Cesarean section Group A (n =16) 8 18 2 6 Group B (n = 89) 69 15 2 3 CIT, conventional intermittent "top-up" injections; PCEA, patient controlled epidural analgesia. continuous infusion epidural analgesia in 33 parturients requiring epidural analgesia during labor [6]. A lumbar epidural block was initiated in all patients with 1 ml bupivacaine.25%. Parturients in the PCEA group were able to maintain analgesia via selfadministration of 3-ml boli of.25% bupivacaine with a lockout interval of 5 min and an hourly maximum of 4 boli. Intermittent "top-up"-patients received 3-ml epidural injections of bupivacaine.25% followed by 7 ml of the same solution administered by a midwife on request. Finally, the continuous infusion group received bupivacaine.125% at a rate of 1 ml/h. If necessary, supplementary analgesia was available and administered via additional epidural injections by the anesthesiologist. Each technique provided comparable analgesia and maternal satisfaction, with no difference in the mode of delivery and no complications. However, there was a significantly increased consumption of bupivacaine in the continuous infusion group. Both of our own studies have shown that bolus-only PCEA, using.125% bupivacaine with epinephrine 1:8 containing one of two different sufentanil concentrations (l or.75 /Lg/ml), provides similar pain relief during labor and delivery when compared with CIT. The technique was associated with a high degree of safety and acceptability among all patients. Although in our first study, the application of PCEA was associated with a significantly reduced consumption of local anesthetic, this did not result in reduction ofabdominal muscle motor blockade upon delivery nor in the number of instrumental deliveries. The second protocol found no differences in the amount of local anesthetic used nor was there a difference in patient satisfaction. The similarities in pain relief when PCEA was compared to CIT in both ofour studies may be explained by the fact that an anesthesiologist was always available, thus avoiding long delays in providing a top-up injection. Similar results were found in the above studies by Gambling et al. [1] and Purdie et al. [6], as anesthesiologists or midwives, respectively, were always readily available. It is interesting to note that patients in spontaneous labor have higher pain scores before asking for

E.P. Vandermeulen et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 59 Suppl. (1995) S47-S54 S53 anepidural anesthetic. Perhaps, this can be explained by the fact that patients in spontaneous labor do feel more in control than women in whom labor was induced and are willing to endure more pain. In patients receiving intravenous patient-controlled analgesia for postoperative pain relief, analgesia was found to be only minimally-improved over that of more conventional techniques [17]. However, patient satisfaction was often significantly improved by PCA. Similar results were reported when PCEA was used for labor analgesia [1,13), although most studies did not find a significant difference. No difference in patient satisfaction (not measured in our first protocol) was noted in our second study in both PCEA- and CIT-treated patients. A comparable result was noted by Purdie et al. [6], while Gambling et al. found a significantly improved maternal satisfaction when PCEA was employed [1). Differences in the anesthetic technique and in the methodology used for the evaluation of patient satisfaction by all of these investigators may account for some of the variability in these results. Purdie et at. used higher concentrated solutions of bupivacaine (without opioid) in the patients treated with PCEA and measured maternal satisfaction on a three point scale [6]. In contrast, Gambling et al. used.25% bupivacaine as a loading dose and.125% bupivacaine (both without opioid) for maintenance, while patient satisfaction was scored using a satisfaction index [1]. Possible explanations for improved patient satisfaction when PCEA is used include psychological factors [18], a certain placebo effect, reduction of anxiety by decrease of the time between analgesia demand and onset of analgesia and, finally, a better titration of analgesia towards the individual patient's needs as only the patient knows how bad the pain is and how much she can tolerate [19]. When we used a local anesthetic solution containing sufentanil.75 tlg/ml in our second study, no difference was found in the amount of local anesthetic used during labor, nor was there a difference in the extent ofabdominal muscle paralysis or the incidence of instrumental deliveries when PCEA was compared to CIT. These results are similar to those in previously cited papers [6,1]. In contrast, our first study detected a significant reduction in local anesthetic use in PCEA-treated patients. As the use ofa higher sufentanil concentration in our first study (I tlg/ml vs..75 Itg/ml in the second protocol) was the only factor in the study design that differed from the second study, it is possible that the presence ofa higher dose ofopioid in a dilute local anesthetic solution may prove critical in the reduction of the local anesthetic requirements. In the studies by Gambling et al. and Purdie et al., no opioid was added to the local anesthetic solution and no differences in the local anesthetic requirements were found [6,1]. However, further studies are necessary to clearly distinguish the effect of the opioid dose on the efficacy of PCEA. In our hands, PCEA proved to be very safe when used in pregnant patients. No unwanted effects were noted while neonatal Apgar scores were comparable in all treatment groups. These results are confirmed by those ofother investigators [8-1,13,2]. Although PCA technology has proven to be extremely reliable [21], rare mishaps may occur, usually secondary to erroneous programming or loading of the device, or even to misfunctioning of the device [22-24]. Furthermore, a recent case report discussed the risks ofa patient handing over the controls of the PCA-device to her husband and let him trigger analgesic administration [25]. Therefore, the standards of patient monitoring applied to PCEAtreated patients should be at least as high as those used with all other epidural anesthesia techniques. The extent of the block must be monitored at regular time intervals as a sensory block cephalad to T6 [26J or T7 [6], although without complications, has been reported in association with PCEA. Finally, intravascular migration of the epidural catheter remains a possibility and has been described in a patient treated with PCEA [27]. In summary, our two studies have shown that bolusonly PCEA is capable of producing effective pain relief during all stages of labor and delivery. The technique is associated with a high degree of acceptability and satisfaction among patients and has proven to be safe in both mothers and neonates. However, careful monitoring of the extent ofthe block and continuous awareness ofpossible unwanted effects are mandatory. Therefore, the P in PCEA should not only stand for patient-controlled epidural analgesia but also for physician-controlled analgesia. These physicians should be thoroughly trained in the management of regional anesthesia and its possible complications. References [I] Vertommen JD, Vandenneulen E, Van Aken H et aj. The effects ofthe addition ofsufentanil to.125% bupivacaine on the quality ofanalgesia during labor and on the incidence ofinstrumental deliveries. Anesthesiology 1991; 74: 89-814. (2) Vertommen JD, Lemmens E, Van Aken H. Comparison of the addition of three different doses of sufentanil to.125% bupivacaine given epidurally during labour. Anaesthesia 1994; 49: 678-681. [3] Crowhurst JA. Analgesia for labour. Curr Opin Anaesthesiol 1994; 7: 224-23. [4] Crowhurst JA, Simmons SW. Patient-eontrolled analgesia in pregnancy. Int Anesthesiol Clin 1994; 32(2): 45-67. [5] Ferrante MF, Lu L, Jamison SB, Datta S. Patient-eontrolled epidural analgesia: Demand dosing. Anesth Analg 1991; 73: 547-552. [6] Purdie J, Reid J, Thorburn J, Asbury AJ. Continuous extradural analgesia: Comparison ofmidwife top-ups, continuous infusions and patient controlled administration. Br J Anaesth 1992; 68: 58-584.

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