title: Patient controlled analgesia with remifentanil versus epidural analgesia in labour: randomised multicentre equivalence trial.
abstract: OBJECTIVE
  To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour.
  
  
  METHODS
  Multicentre randomised controlled equivalence trial.
  
  
  METHODS
  15 hospitals in the Netherlands.
  
  
  METHODS
  Women with an intermediate to high obstetric risk with an intention to deliver vaginally. To exclude a clinically relevant difference in satisfaction with pain relief of more than 10%, we needed to include 1136 women. Because of missing values for satisfaction this number was increased to 1400 before any analysis. We used multiple imputation to correct for missing data.
  
  
  METHODS
  Before the onset of active labour consenting women were randomised to a pain relief strategy with patient controlled remifentanil or epidural analgesia if they requested pain relief during labour.
  
  
  METHODS
  Primary outcome was satisfaction with pain relief, measured hourly on a visual analogue scale and expressed as area under the curve (AUC), thus providing a time weighted measure of total satisfaction with pain relief. A higher AUC represents higher satisfaction with pain relief. Secondary outcomes were pain intensity scores, mode of delivery, and maternal and neonatal outcomes. Analysis was done by intention to treat. The study was defined as an equivalence study for the primary outcome.
  
  
  RESULTS
  1414 women were randomised, of whom 709 were allocated to patient controlled remifentanil and 705 to epidural analgesia. Baseline characteristics were comparable. Pain relief was ultimately used in 65% (447/687) in the remifentanil group and 52% (347/671) in the epidural analgesia group (relative risk 1.32, 95% confidence interval 1.18 to 1.48). Cross over occurred in 7% (45/687) and 8% (51/671) of women, respectively. Of women primarily treated with remifentanil, 13% (53/402) converted to epidural analgesia, while in women primarily treated with epidural analgesia 1% (3/296) converted to remifentanil. The area under the curve for total satisfaction with pain relief was 30.9 in the remifentanil group versus 33.7 in the epidural analgesia group (mean difference -2.8, 95% confidence interval -6.9 to 1.3). For who actually received pain relief the area under the curve for satisfaction with pain relief after the start of pain relief was 25.6 in the remifentanil group versus 36.1 in the epidural analgesia group (mean difference -10.4, -13.9 to -7.0). The rate of caesarean section was 15% in both groups. Oxygen saturation was significantly lower (SpO2 <92%) in women who used remifentanil (relative risk 1.5, 1.4 to 1.7). Maternal and neonatal outcomes were comparable between both groups.
  
  
  CONCLUSIONS
  In women in labour, patient controlled analgesia with remifentanil is not equivalent to epidural analgesia with respect to scores on satisfaction with pain relief. Satisfaction with pain relief was significantly higher in women who were allocated to and received epidural analgesia.
  
  
  BACKGROUND
  Netherlands Trial Register NTR2551.
authors.affiliation: Obstetrics, Leiden University Medical Centre, Leiden, Netherlands l.m.freeman@lumc.nl.
authors.forename: Liv M
authors.initials: LM
authors.lastname: Freeman
authors.affiliation: Obstetrics, Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: Kitty W
authors.initials: KW
authors.lastname: Bloemenkamp
authors.affiliation: Obstetrics and Gynaecology, University Medical Centre Groningen, Groningen, Netherlands.
authors.forename: Maureen T
authors.initials: MT
authors.lastname: Franssen
authors.affiliation: Obstetrics and Gynaecology, Amphia Hospital, Breda, Netherlands.
authors.forename: Dimitri N
authors.initials: DN
authors.lastname: Papatsonis
authors.affiliation: Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, Netherlands.
authors.forename: Petra J
authors.initials: PJ
authors.lastname: Hajenius
authors.affiliation: Anaesthesiology, Academic Medical Centre, Amsterdam, Netherlands.
authors.forename: Markus W
authors.initials: MW
authors.lastname: Hollmann
authors.affiliation: Obstetrics and Gynaecology, Radboud University Medical Centre, Nijmegen, Netherlands.
authors.forename: Mallory D
authors.initials: MD
authors.lastname: Woiski
authors.affiliation: Obstetrics and Gynaecology, Maxima Medical Centre, Veldhoven, Netherlands.
authors.forename: Martina
authors.initials: M
authors.lastname: Porath
authors.affiliation: Anaesthesiology, Maxima Medical Centre, Veldhoven, Netherlands.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: van den Berg
authors.affiliation: Obstetrics and Gynaecology, Saint Antonius Hospital, Nieuwegein, Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: van Beek
authors.affiliation: Anaesthesiology, Saint Antonius Hospital, Nieuwegein, Netherlands.
authors.forename: Odette W H M
authors.initials: OW
authors.lastname: Borchert
authors.affiliation: Obstetrics and Gynaecology, Diakonessen Hospital, Utrecht, Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: Schuitemaker
authors.affiliation: Obstetrics and Gynaecology, Hospital Group Twente, Almelo, Netherlands.
authors.forename: J Marko
authors.initials: JM
authors.lastname: Sikkema
authors.affiliation: Anaesthesiology, Hospital Group Twente, Almelo, Netherlands.
authors.forename: A H M
authors.initials: AH
authors.lastname: Kuipers
authors.affiliation: Obstetrics and Gynaecology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands.
authors.forename: Sabine L M
authors.initials: SL
authors.lastname: Logtenberg
authors.affiliation: Obstetrics and Gynaecology, Meander Medical Centre, Amersfoort, Netherlands.
authors.forename: Paulien C M
authors.initials: PC
authors.lastname: van der Salm
authors.affiliation: Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, Netherlands.
authors.forename: Katrien
authors.initials: K
authors.lastname: Oude Rengerink
authors.affiliation: Paediatrics, Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: Enrico
authors.initials: E
authors.lastname: Lopriore
authors.affiliation: Medical Decision Making, Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: M Elske
authors.initials: ME
authors.lastname: van den Akker-van Marle
authors.affiliation: Medical Statistics and Clinical Epidemiology, Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: le Cessie
authors.affiliation: Obstetrics, Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: Jan M
authors.initials: JM
authors.lastname: van Lith
authors.affiliation: Anaesthesiology, University of Groningen and University Medical Centre Groningen, Groningen, Netherlands.
authors.forename: Michel M
authors.initials: MM
authors.lastname: Struys
authors.affiliation: Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Australia.
authors.forename: Ben Willem J
authors.initials: BW
authors.lastname: Mol
authors.affiliation: Anaesthesiology, Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Dahan
authors.affiliation: Obstetrics, Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Middeldorp
mesh_terms: D000328:Adult; D015360:Analgesia, Epidural; D016362:Analgesia, Obstetrical / Q000379:methods*; D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D009426:Netherlands; D059408:Pain Management / Q000379:methods; D010147:Pain Measurement; D017060:Patient Satisfaction; D010880:Piperidines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011247:Pregnancy; D000077208:Remifentanil; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D000077208:Remifentanil