Intravenous remifentanil patient-controlled analgesia versus intramuscular pethidine for pain relief in labour (RESPITE): an open-label, multicentre, randomised controlled trial

Abstract

Background: Approximately a third of women receiving pethidine for labour pain subsequently require an epidural, which provides effective pain relief but increases the risk of instrumental delivery. Remifentanil patient controlled analgesia (PCA) in labour is an alternative to pethidine, but not widely utilized. We sought to determine epidural rates amongst women using remifentanil PCA compared to pethidine.
Methods: We conducted a randomised, parallel, open-label trial in 14 UK maternity units. Women at term gestation, in labour with a singleton cephalic presentation, requesting opioid pain relief, were randomly assigned (1:1) to remifentanil PCA (40μg bolus with a two minute “lock-out”) or intramuscular pethidine (100mg, four-hourly, up to 400mg). Web-based or telephone randomisation minimised allocations by parity, age, ethnicity and mode of labour onset. The primary outcome was the proportion of women who received epidural analgesia after enrolment. To detect a reduction in epidural conversion from 30% to 15% with 90% power, with a 15% anticipated attrition from urgent delivery by emergency caesarean section, required 400 women. Primary analyses were unadjusted and by intention-to-treat. ISRCTN29654603.
Findings: Between May 13, 2014, and Sept 2, 2016, 201 women were randomly assigned to the remifentanil PCA group and 200 to the pethidine group. One participant in the pethidine group withdrew consent, leaving 199 for analyses. The proportions of epidural conversion were 19% (39 of 201) in the remifentanil PCA group and 41% (81 of 199) in the pethidine group (risk ratio 0·48, 95% CI 0·34–0·66; p less 0·0001). There were no serious adverse events or drug reactions directly attributable to either analgesic during the study.
Interpretation: Intravenous remifentanil PCA halved the proportion of epidural conversions compared with intramuscular pethidine. This finding challenges routine pethidine use as standard of care in labour.