Remifentanil intravenous patient controlled analgesia (PCA) versus intramuscular Pethidine for pain relief in labour


Childbirth can be extremely painful and the majority of women who deliver in modern obstetric units choose a pharmacological method of pain relief.  The commonest opioid used in labour is intramuscular pethidine, however, its effectiveness in pain relief has long been challenged and has known side effects including maternal sedation, nausea and potential transfer across the placenta to the foetus. More than a third of women who receive pethidine subsequently require an epidural due to inadequate pain relief. Epidurals provide highly effective pain relief, but increase the risk of a forceps or suction delivery which may extend hospital stay. Therefore there is a clear need for a safe, effective, easy to administer analgesic alternative.

We propose to compare remifentanil intravenous PCA to intramuscular pethidine (normal care) in a randomised controlled trial. Women in established labour, requesting systemic opioid pain relief will be randomised to either remifentanil intravenous PCA or pethidine intramuscular injection (im). Our primary aim is to determine the proportion of women who have an epidural placed for pain relief in labour, in each group. We will also consider the effectiveness of pain relief by visual analogue score, maternal sedation and any effects on the baby and mother at delivery.  This multicentre study will recruit 400 women in childbirth over approximately 24 months. The results will be used to make recommendations on the use of remifentanil in childbirth via publications and clinical guidelines.

What was the RESPITE trial?

We undertook the RESPITE trial, a pragmatic, multicentre, randomised controlled trial designed to assess the effectiveness of pain relief provided by intravenous remifentanil PCA compared to intramuscular pethidine. The primary outcome was the proportion of women who had an epidural placed for pain relief in labour in each group. Secondary outcomes included the effectiveness of pain relief provided by each technique quantified by Visual Analogue Scale taken every 30 minutes after time zero, until epidural placement, delivery or transfer to theatre. Other secondary outcomes included the incidence of maternal side effects, up to the end of 3rd stage, including excessive sedation score (not rousable to voice), oxygen Saturation <94% whilst breathing room air, nausea requiring anti-emetic administration, requirement and indication for supplemental oxygen, respiratory depression (respiratory rate < 8 breaths/minute), delivery mode (spontaneous vaginal, instrumental vaginal, caesarean Section), incidence of foetal distress requiring delivery, neonatal status at delivery and rate of initiation of breast feeding within the first hour of birth. Randomisation was done on a 1:1 individual, unblinded basis.

Women who were admitted to labour ward who fulfilled the following criteria were eligibile to be randomised: requesting systemic opioid analgesia, 16 years of age or older, beyond 37+0 weeks’ gestation, in established labour, defined as regular painful contractions, irrespective of cervical dilatation, with vaginal birth intended, able to understand all information (written and oral) presented (using an interpreter if necessary) and provide signed consent, not participating in any other clinical trial of a medicinal product and having a live, singleton pregnancy with cephalic presentation.


 1. Wilson M, MacArthur C, Gao Smith F, et al. 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. Trials 2016;
17(1): 591

2. Wilson M, MacArthur C, Smith F, Homer L, Hewitt C, Handley K, Daniels J, A randomised controlled trial of remifentanil intravenous patient controlled analgesia (PCA) versus intramuscular pethidine  or pain relief in labour (RESPITE trial), International Journal of Obstetric Anaesthesia. Abstract 4873, exported on 11/01/2017

3. Wilson, M.J.A., MacArthur, C., Hewitt, C. A., Handley, K., Gao, F., Beeson, L., Daniels, J. (2018) Intravenous remifentanil patient-controlled analgesia versus intramuscular pethidine for pain relief in labour (RESPITE): an open label, multi-centre, randomised controlled trial. The Lancet, 392(10148), 662-672. doi: 

 4. Wilson, M.J.A., MacArthur, C., Daniels, J. (2019) Pain relief during labour - Authors' reply. The Lancet, doi:

5. Wilson, MJA; MacArthur, C; Hewitt, C; Handley, K; Smith, FG; Beeson, L; Daniels, J. Remifentanil-patient controlled analgesia versus intramuscular pethidine for pain relief in labour: the RESPITE randomised controlled trial. BJOG. 2019; 126(S2);128

6. Moran VH, Thomson G, Cook J, et al Qualitative exploration of women’s experiences of intramuscular pethidine or remifentanil patient-controlled analgesia for labour pain BMJ Open 2019;9:e032203. doi: 10.1136/bmjopen-2019-032203

EudraCT Number: 2012-005257-22

ISRCTN Number: 29654603

Funder: National Institute for Health Research

Chief Investigator: Dr Matthew Wilson

Sponsor: University of Birmingham

Trial Coordinating Centre: Birmingham Clinical Trials Unit, University of Birmingham