title: The RESPITE trial: remifentanil intravenously administered patient-controlled analgesia (PCA) versus pethidine intramuscular injection for pain relief in labour: study protocol for a randomised controlled trial.
abstract: The commonest opioid used for pain relief in labour is pethidine (meperidine); however, its effectiveness has long been challenged and the drug has known side effects including maternal sedation, nausea and potential transfer across the placenta to the foetus. Over a third of women receiving pethidine require an epidural due to inadequate pain relief. Epidural analgesia increases the risk of an instrumental vaginal delivery and its associated effects. Therefore, there is a clear need for a safe, effective, alternative analgesic to pethidine. Evidence suggests that remifentanil patient-controlled analgesia (PCA) reduces epidural conversion rates compared to pethidine; however, no trial has yet investigated this as a primary endpoint. We are, therefore, comparing pethidine intramuscular injection to remifentanil PCA in a randomised controlled trial.
  
  
  
  Women in established labour, requesting systemic opioid pain relief, will be randomised to either intravenously administered remifentanil PCA (intervention) or pethidine intramuscular injection (control) in an unblinded, 1:1 individual randomised trial. Following informed consent, 400 women in established labour, who request systemic opioid pain relief, from NHS Trusts across England will undergo a minimised randomisation by a computer or automated telephone system to either pethidine or remifentanil. In order to balance the groups this minimisation is based on four parameters; parity (nulliparous versus multiparous), maternal age (<20, 20 < 30, 30 < 40, 40+ years), ethnicity (South Asian (Pakistani/Indian/Bangladeshi) versus Other) and induced versus spontaneous labour. The effectiveness of pain relief provided by each technique will be recorded every 30 min after time zero, until epidural placement, delivery or transfer to theatre, quantified by Visual Analogue Scale. Incidence of maternal side effects including sedation, delivery mode, foetal distress requiring delivery, neonatal status at delivery and rate of initiation of breastfeeding within the first hour of birth will also be recorded. Maternal satisfaction with her childbirth experience will be determined by a postpartum questionnaire prior to discharge from the delivery ward.
  
  
  
  The RESPITE trial's primary outcome is the proportion of women who have an epidural placed for pain relief in labour in each arm.
  
  
  
  Current Controlled Trials registration number: ISRCTN29654603 . Registered on 23 July 2013.
authors.affiliation: Anaesthesia, School of Health and Related Research (ScHARR), University of Sheffield, 30 Regent St, Sheffield, South Yorkshire, S1 4DA, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Wilson
authors.affiliation: Maternal and Child Epidemiology, Public Health Building, Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: MacArthur
authors.affiliation: Anaesthesia, Critical Care and Pain, Perioperative, Critical Care and Trauma Trials Group, Institute of Inflammation and Ageing, Centre of Translational Inflammation Research, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Edgbaston, Birmingham, B15 2WB, UK.
authors.forename: Fang
authors.initials: F
authors.lastname: Gao Smith
authors.affiliation: Birmingham Clinical Trials Unit (BCTU), Public Health Building, Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Leanne
authors.initials: L
authors.lastname: Homer
authors.affiliation: Birmingham Clinical Trials Unit (BCTU), Public Health Building, Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Kelly
authors.initials: K
authors.lastname: Handley
authors.affiliation: Birmingham Clinical Trials Unit (BCTU), Public Health Building, Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. j.p.daniels@bham.ac.uk.
authors.forename: Jane
authors.identifier: 0000-0003-3324-6771
authors.initials: J
authors.lastname: Daniels
mesh_terms: D000328:Adult; D016362:Analgesia, Obstetrical / Q000009:adverse effects / Q000379:methods*; D016058:Analgesia, Patient-Controlled / Q000009:adverse effects / Q000379:methods*; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D002985:Clinical Protocols; D004739:England; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D048949:Labor Pain / Q000175:diagnosis / Q000188:drug therapy*; D008614:Meperidine / Q000008:administration & dosage* / Q000009:adverse effects; D010147:Pain Measurement; D017060:Patient Satisfaction; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D011247:Pregnancy; D000077208:Remifentanil; D012107:Research Design; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D008614:Meperidine; D000077208:Remifentanil
keywords: Childbirth; Epidural; Labour; Pain relief; Pethidine; Remifentanil