A Randomised Controlled Trial of Remifentanil Intravenous Patient Controlled Analgesia (PCA) Versus Intramuscular Pethidine for Pain Relief in Labour (RESPITE)

University of Birmingham

Status and phase

Completed

Phase 4

Conditions

Pain Relief in Labour

Treatments

Drug: Remifentanil

Drug: Pethidine

Study type

Interventional

Funder types

Other

Identifiers

NCT02179294

RG_12-151

2012-005257-22 (EudraCT Number)

Details and patient eligibility

About

Childbirth can be an extremely painful and the provision of pain relief during labour is a vital component of a positive maternal experience. The majority of women who deliver in modern obstetric units choose a pharmacological method of pain relief, including Entonox, the injection of opioids or epidural placement. The commonest opioid used in labour is pethidine administered by intramuscular (im) injection. The effectiveness of pain relief provided by pethidine has long been challenged. Its shortcomings are more serious when set against 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 resulting in prolonged hospital stay. Therefore, there is a clear need for a safe, effective, easy to administer analgesic alternative.

Full description

Patient Controlled Analgesia (PCA) comprises drug administration into an intravenous drip with a small dose given each time a woman presses a button, giving her control over her own pain relief. The pump is programmed to ensure that the maximum dose allowable is within the safe range. This form of delivery of pain relief matches the drug dose to pain sensation within the relevant time frame, which is not possible using a single dose intramuscular injection. Whilst PCA is in widespread use for acute pain relief it has only a limited role in obstetrics. The most common drug given by PCA is morphine, however, since it has a long duration of action and crosses the placenta, the potential for accumulation in the foetus and consequent neonatal sedation at delivery restricts its utility (within obstetrics) to contexts where neonatal status is not relevant, such as intra-uterine foetal death or foetal abnormality incompatible with survival.

Remifentanil is a novel synthetic opioid with a very rapid onset (blood-brain equilibration 1.2-1.4 minutes) and short duration of action (context specific half-life 3 minutes), giving it an analgesic profile which potentially makes it ideal for providing pain relief over 1-2 uterine contractions after a single intravenous dose. It is subject to rapid redistribution and metabolism by non-specific blood and tissue esterases negating the potential for accumulation in mother or foetus. Administration of remifentanil by PCA has been investigated in several small studies in comparison to pethidine and shown to provide useful, although not complete, pain relief in labour.10-12 Thus far, there is no evidence of detrimental neonatal effects in comparison to other opioids.

Enrollment

401 patients

Sex

Female

Ages

16+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Women who are admitted to labour ward who fulfil all the following criteria will be eligible to be randomised:

Requesting systemic opioid analgesia
16 years of age or older
Beyond 37 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)
Not participating in any other clinical trial of a medicinal product
Live, singleton pregnancy with cephalic presentation

Exclusion criteria

Contraindication to epidural analgesia
Contraindication to intramuscular injection
History of a previous adverse reaction to pethidine or remifentanil
Patients taking long term opioid therapy including Methadone
Systemic pain relief opioid in the last 4 hours administered by intravenous or intramuscular injection. (Oral medications comprising opioids alone or in combination preparations, administered in this 4 hour period, are permitted).