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Journal of Obstetrics and Gynaecology, February 2011; 31(2): 134138 2011 Informa UK, Ltd.

. ISSN 0144-3615 print/ISSN 1364-6893 online DOI: 10.3109/01443615.2010.542840

OBSTETRICS

Comparison of intermittent and continuous epidural analgesia on delivery and progression of labour
S. SKRABLIN1, O. GRGIC2, S. MIHALJEVIC3 & J. BLAJIC1
Department of Obstetrics and Gynecology, 1School of Medicine, 2Clinical Hospital Sestre Milosrdnice and 3 Anesthesiology, Reanimatology and Intensive Care, School of Medicine, University of Zagreb, Croatia Summary In this study, 205 nulliparous parturients were enrolled to receive either intermittent (n 101) or continuous (n 104) type of epidural analgesia in labour. The primary outcome was rate of caesarean deliveries, whereas secondary outcomes included rate of fundal pressure manoeuvres, duration of labour from application of analgesia, dose of anaesthetic and short-term maternal and neonatal outcome between two groups. Rate of caesarean deliveries was signicantly increased in the continuous group (15/104 vs 5/101, p 0.02), as well as rate of fundal pressure manoeuvres (24/104 vs 11/101, p 0.02) and dose of fentanyl (100 [100300] vs 187.5 [125450] mg, p 5 0.001 and levobupivacaine (40 [4060] vs 75 [5090] ml, p 5 0.001). Duration of labour from analgesia to delivery was not signicantly different between the two groups (414 + 101 vs 432 + 94 min, p 0.12). Keywords: Continuous, epidural analgesia, intermittent, length of labour, maternal outcome, neonatal outcome, operative delivery

Introduction
Satisfactory epidural analgesia for labour and delivery poses several challenges to the obstetrician and anaesthesiologist. The ideal analgesia has to be effective in providing adequate pain relief without unintended side-effects and negative interference with the process of labour and delivery (Eltzschig et al. 2003). Intermittent and continuous types of epidural analgesia have been commonly and widely used during labour (Fettes et al. 2006; Salim et al. 2005; Smedstad and Morison 1988; Wong et al. 2006). Continuous infusion is associated with more consistent analgesia without excessive uctuations in the level of anaesthetic, improved patient satisfaction but it may be related with either insufcient analgesia or excessive blockade (Fettes et al. 2006; Halpern et al. 2005; Salim et al. 2005; Smedstad and Morison 1988; Vallejo et al. 2007). In the presence of excessive sensory blockade, a parturient may not appreciate a strong urge to push upon reaching the second stage of labour, and this stage could be prolonged (Lamont et al. 1989). Additionally, the majority of previous studies found that the continuous type was associated with a higher total dose of anaesthetic (Boutros et al. 1999; Eddleston et al. 1992; Fettes et al. 2006; Quinn et al. 1993; Smedstad and Morison 1988; Wong et al. 2006). On the other hand, with the intermittent technique, a delay in bolus administration may cause incomplete or suboptimal analgesia with higher uctuations in anaesthetic level (Lamont et al. 1989; Salim et al. 2005). Moreover, in a retrospective study, an intermittent in comparison with the continuous type was associated with higher incidence of caesarean deliveries (CD) (Driver et al. 1996). Therefore, in this prospective trial, our objective was to determine the effect of intermittent and continuous type of

epidural analgesia on the CD rate, rate of fundal pressure (FP) manoeuvre, progression and duration of labour, dose of anaesthetic in labour and short-term maternal and neonatal outcome in a nulliparous population.

Materials and methods


The local and national ethical committee approved the study protocol, and all women included in the study gave their informed written consent. Low risk nulliparous parturients in term pregnancy were admitted to the labour and delivery unit at the University department of Obstetrics and Gynecology, KBC Zagreb, Croatia. The exclusion criteria for enrolment were: 1. Pre-term delivery (delivery 537 weeks) 2. Cervical dilatation 2 and 45 cm 3. Parturients with systemic disease (e.g. heart disease, renal disease, asthma, diabetes mellitus, hypertension) and with chronic analgesic use 4. Parturients who had contraindications to neuraxial blocks (e.g. coagulopathy, thrombocytopenia) 5. Multiple pregnancies 6. Absolute indication for caesarean delivery (e.g. strait pelvis, placenta praevia, etc.) 7. Breech presentation or other malpresentation 8. A failure to achieve adequate analgesia. At the time of request for labour analgesia, the cervix was examined to determine the cervical status and each parturient received a 1,000 ml i.v. preload of Ringers lactate solution (TEVA, Petach Tikva, Israel) for hydration. The parturients

Correspondence: O. Grgic, Department of Obstetrics and Gynecology, Vinogradska 29, 10000 Zagreb, Croatia. E-mail: ozren.grgic@gmail.com

Intermittent versus continuous epidural in labour


did not receive systemic analgesia before randomisation. Baseline pain was assessed with the visual analogue scale (VAS) (10 cm unmarked line with end-points labelled 0 cm no pain and 10 cm worst pain imaginable), and systolic blood pressure (BP) measured non-invasively on the right arm with the parturient supine and with left uterine displacement. The use of cervical prostaglandin E2, oxytocin, meconium stained amniotic uid, number of contractions, degree of cervical dilatation and effacement were also recorded. Every parturient received an epidural analgesia in the left lateral recumbent position. The epidural catheter was placed in sterile fashion and introduced with an 18- or 16-gauge needle in the L23 or L45 intravertebral space using the loss of resistance technique to saline. After that, a multi-orice epidural catheter was inserted 34 cm into the epidural space. Before enrolment, all parturients received an initial bolus of 20 ml of levobupivacaine (Chirocaine, Abbott Laboratories Ltd, Queensborough, Kent, UK) with fentanyl of 2 mg/ml (Fentanyl, Janssen-Cilag EMEA, Beerse, Antwerp, Belgium). The levobupivacaine concentration was 0.07%. If VAS remained 41 cm at 15 min after the administration of initial bolus dose or the parturient complained of pain at that time, a dose of epidural supplementation equal to the initial dose was offered. If there was no improvement after the second dose, a failure to achieve adequate analgesia was diagnosed and these parturients were excluded from further analysis. If there was satisfactory analgesia after the initial bolus dose for 30 min parturients were randomly assigned by obstetrician in delivery ward to receive either a continuous infusion or intermittent bolus doses. In the intermittent group, the dose of 20 ml of levobupivacaine with fentanyl of 2.5 mg/ml was given 60 min after the initial dose. The next dose was admitted when the parturient felt and reported a presence of abdominal discomfort or contractions. In the continuous group, the infusion of levobupivacaine with fentanyl in the identical concentration was started through the infusion pump (Perfusor compact type 201 499, B. Braun Medical Inc, Bethlehem PA, USA). The infusion rate was increased up to 14 ml/h when analgesia was inadequate, and analgesia was continued until delivery. After application of epidural analgesia every enrolled parturient received oxytocin (Syntocinon 5 IU, Novartis, Basel, Switzerland) infusion (5 IU Syntocinon 500 ml 5% glucose solution), starting with a rate of 4 mIU/min. The rate was increased by 2 mIU/min every 30 min to a maximum of 40 mIU/min. Cervical examinations were performed every 2 h or when the parturients complained of rectal pressure. At any time during the study, the parturients were instructed to ask for immediate help if they felt contractions or any other form of discomfort from obstetrician and/or anaesthesiologist. VAS for pain evaluation was obtained every 60 min with the beginning 15 min after the initial bolus dose until delivery. A modied Bromage score (0 no impairment; 1 unable to raise extended leg but able to move knees and feet; 2 unable to raise extended leg as well as ex knees, able to move foot; 3 not able to ex ankle, feet or knees complete block) was determined every 60 min. Fetal heart rate was monitored continuously during the whole labour. Blood pressure was monitored every 5 min for the rst 15 min after initial bolus and every 30 min thereafter during labour. If the systolic BP decreased 20% from baseline,

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200 ml of Ringers acetate solution was administered. If the systolic pressure decreased to 80 mmHg or 30% from baseline, ephedrine 5 mg was administered. Data were collected for each parturient and included demographic characteristics, labour data and method of delivery. The primary outcome was: 1. The incidence of CD between two groups. The secondary outcomes were: 1. Incidence of FP manoeuvres 2. Dose of anaesthetic and oxytocin per parturient 3. Duration of labour from beginning of epidural anesthesia to delivery between the two groups 4. Neonatal status: neonatal weight, Apgar score at 1 and 5 min, umbilical pH

Table I. Demographic characteristics. Continuous (n 104) Maternal age (years) (mean) IQR Range Gestational age at delivery (cw) (mean) IQR Range Onset of labour Spontaneous ROM Induction Cervical effacement at time of randomisation Partial Full Cervical dilatation (cm) at time of randomisation (mean) IQR Range Amniotic uid Normal Meconium Contractions per 10 min at time of randomisation (mean) IQR Range VAS before randomisation (cm) IQR Range 28 2630 1840 40 Intermittent (n 101) 28 2533 1842 40 p value 0.48*

0.33*

3840 3742 50 28 26

3941 3742 54 24 23 0.25{ 0.29{ 0.48{

49 55 4

50 51 4

0.42{ 0.53{

45 35 82 22 2

45 35 87 14 2 0.09{ 0.34{

12 13 6.2

12 13 6.5

0.33*

5.38.2 3.110

5.38.2 2.29.9

M, median; IQR, interquartile range; cw, completed weeks; ROM, rupture of membranes; BMI, body mass index; VAS, visual analogue scale. *MannWhitney test. {w2-test. {Cochran MantelHaenszel test.

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Table II. Primary and secondary outcomes. Statistical analysis Continuous (n 104) Intermittent (n 101) 5 11 2 23 14 40 4060 2080 100 100300 100600 414 + 101 140720 7.1 + 0.3 0.318 3,545 + 482 2,1304,600 5 3 3 23 1 5.4 1.731.2 33 78 4 3 1 p value 0.03* 0.02*,jj NA
,jj

RR 2.91 2.12 NA

95%CI 1.097.72 1.094.09

Caesarean delivery Fundal pressure No. of doses (mean) IQR Range Dose of Levobupivacaine (ml) IQR Range Dose of Fentanyl (mg) IQR Range Length of labour from epidural to delivery (min) (AM + SD) Range Dose of Oxytocin (IU) Range Neonatal status Weight (g) AM + SD Range Apgar 7 at 1 min Apgar 7 at 5 min pH 57.1 Maternal status Intrapartum fever Motor blockade AUVAS Range Hypotension Episiotomy Perineal tears 3rd/4th degree Retained placenta Postpartum haemorrhage

15 24

75 5090 40180 187.5 125450 1251,350 432 + 94 145735 7.3 + 0.3 0.318.5 3,510 + 459 2,3404550 4 2 2 21 11 4.3 1.324.5 22 80 4 4 2

50.001{,jj

NA

50.001{,jj

NA

0.12{

NA

0.34{

NA

0.36{ 0.48* 0.48* 0.48* 0.38x 0.01*,jj 0.36{ 0.56x 0.54x 0.62* 0.51* 0.51*

NA 1.28 1.54 1.54 1.12 10.68 NA 1.53 1.01 1.03 0.77 0.51 0.354.65 0.269.06 0.269.06 0.671.91 1.4081.24

0.783.78 0.881.15 0.264.01 0.173.36 0.045.59

AM, arithmetic mean; SD, standard deviation; NA, not applicable; M, median; IQR, interquartile range; IU, international unit; AUVAS, area under visual analogue score curve from start of epidural infusion to delivery. *Fishers exact test. {Wilcoxon signed ranks test. {Mann Whitney test. x 2 w -test. jjStatistically signicant.

5. Maternal status: intrapartum fever (temperature 438.58C); motor blockade (modied Bromage score 40); hypotension in labour (systolic pressure 520% from baseline); episiotomy; perineal tears 3rd/4th degree; retained placenta; postpartum bleeding (bleeding 4500 ml); intrapartal VAS score.

Statistics
As a part of the study design, a sample size calculation was performed (Sample size calculator, MaCorr Inc., Toronto, Ontario, Canada). The calculation was designed to detect at least 20% difference in the rate of CD between the groups. Condence interval was determined using the condence level (CL) of 95%. The programme calculated that the condence interval is 7.8%. Using the CL of 95% and condence interval of 7.8%, the programme calculated that for our population, the sample size needed to be 158 participants. Data were analysed using SPSS version 15.0 (SPSS Inc., Chicago IL, USA). We analysed the data based on intention to treat analysis. The w2 and Fisher exact tests were used to evaluate categorical data where appropriate. Additionally, for comparison of the categorical data between the two groups, we calculated a risk ratio (RR) with 95% condence interval.

A MannWhitney test was used to evaluate continuous variables where appropriate and normality of distribution was assessed using the KolmogorovSmirnov test. Comparison between the groups for cervical dilatation and number of contractions in 10 min before enrolment was made by CochranMantelHaenszel test. Comparison for total dose of anaesthetic between the groups was made by with Wilcoxon signed ranks test. Two-tailed p values are reported throughout and statistical signicance was dened as p  0.05.

Results
Totally, 266 nulliparous parturients between 3742 weeks of pregnancy with fetus in cephalic presentation and cervical dilatation of 25 cm consented to participate in the study between May 2009 and February 2010. Of the parturients, 61 were excluded (18 due to failure to achieve adequate analgesia; 11 because of chronic systemic disease; 11 due to the feto-pelvic disproportion; eight because of different contraindications to neuraxial blockade; seven because of breech presentation; four parturients refused to participate; and nally two had other malpresentations). Therefore, the nal results were based on 205 parturients.

Intermittent versus continuous epidural in labour


The demographic characteristics and enrolment details are presented in Table I. There was no statistically signicant difference among the parameters assessed. Primary and secondary outcome measures are presented on Table II. In the continuous group, the number of CDs and number of FPs were signicantly higher in comparison to the intermittent group. In the continuous group, the indication for 13 CDs was prolongation of labour (dystocia). In the remaining two cases, the indication was fetal distress according to the CTG status. In the intermittent group, four CDs were performed because of prolongation of labour, and in the remaining one case, the indication was threatened fetal distress. The length from application of epidural analgesia to delivery was not statistically signicant between the two groups. Total dose of opioid as well as non-opioid anaesthetic was signicantly higher in the continuous group. There was no statistically signicant difference among other secondary outcomes except a higher rate of motor blockade in the continuous group.

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Discussion
The results of our study showed that continuous compared with intermittent epidural analgesia in labour is associated with a higher dose of anaesthetic, higher rate of CDs and increased rate of FP manoeuvre, as well as higher incidence of motor blockade during labour, without any difference in duration of labour. Several changes have occurred in the past few decades regarding the drugs, methods, and strategies used to provide epidural analgesia for labour. Improvements in parturients satisfaction and safety have contributed to the increasing use of epidural analgesia during labour but, as almost all medical treatments, it has been associated with a number of unintended effects (Eltzschig et al. 2003). In a previously reported trial in nulliparous population, Fettes et al. (2006) randomised 40 parturients to receive continuous or intermittent doses but the duration of rst (467 + 273 vs 587 + 267 min) and second stage (99 + 66 vs 103 + 62 min) of labour was equal in both groups (Fettes et al. 2006). Additionally, Salim and colleagues randomised 130 parturients and did not nd signicant differences in duration of the rst (4.4 + 2.1 vs 4.6 + 2.5 h) and second stage (1.6 + 0.9 vs 1.4 + 0.9 h) of labour between these two groups (Salim et al. 2005). Our study in comparison to the previously reported trials showed similar results regarding the duration of labour. Results of study of Boutros et al. (1999) showed that the total dose of anaesthetic in the primiparous population was not different between the two groups (58.5 + 18.1 vs 49.5 + 26.6 mg) but the hourly dose of local anaesthetic was signicantly higher in the continuous group (13.8 + 3.7. vs 10.2 + 2.1 mg/h). Fettes et al. (2006) showed that the total dose of non-opioid anaesthetic was increased in the continuous group (124.2 + 17.9 mg vs 104.7 + 29.2 mg, p 0.02). In a recent study published by Wong and co-workers (2006), a total dose of opioid as well as non-opioid anaesthetic was statistically signicantly higher in a continuous group. Our study, as all previous trials regarding the total and hourly dose of anaesthetic between the two types of anaesthesia, conrmed that continuous infusion is associated with a signicantly increased dose of anaesthetic. Because of the higher dose of anaesthetic in the continuous group, the rate of motor blockade was statistically signicantly higher.

According to the method of delivery, parturients in the continuous group had almost a three times higher relative risk for CD. Our nding is different from the results of a retrospective study by Driver and co-workers published 15 years ago (Driver et al. 1996). They showed that parturients who received a continuous epidural analgesia were signicantly less likely to have an emergency CD (p 0.002). The difference could be because in the continuous group, parturients may not have a strong urge to push, and this could lead to signicant prolongation of the second stage of labour. Some other new trials that compared these two types of epidural analgesia have not found higher rates of CD or operative vaginal deliveries in either group (Eddleston et al. 1992; Fettes et al. 2006; Quinn et al. 1993; Salim et al. 2005; Smedstad and Morison 1988; Wong et al. 2006). In the continuous group, the incidence of FP to achieve delivery was signicantly higher. Results of a recent study showed that there were no data available to determine whether or not FP was of benet, but this manoeuvre did not appear to increase the rate of spontaneous vaginal births in women with epidural analgesia (Torvaldsen et al. 2004). A major limitation in our study was that it was not completely blind, which could have led to observer bias. Participation in the study did not change the standard obstetric procedure. The decision for delivery induction, cervical examination, indications for CD or for FP was made by the senior consultant and not by any of the investigators. In conclusion, our results show that continuous type of epidural anaesthesia might be associated with a higher rate of CD, a higher dose of anaesthetic and increased rate of FP manoeuvres, without any difference in the duration of labour. Declaration of interest: The authors report no conicts of interest. The authors alone are responsible for the content and writing of the paper.

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