Intravenous Remifentanil Patient-controlled Analgesia Versus Intramuscular Pethidine for Pain Relief in Labour (RESPITE): An Open-label, Multicenter, Randomized Controlled Trial

Abstract

Objective Approximately a third of women receiving pethidine during labour subsequently require an epidural, which provides effective pain relief but increases the risk of instrumental delivery. Remifentanil patient-controlled analgesia (PCA) is a potent synthetic opioid with an ultra-short half-life, making it a potential alternative to pethidine. The RESPITE trial aimed to determine epidural rates among women using remifentanil PCA compared to pethidine. Design Randomised, parallel, open-label trial in 14 UK maternity units (ISRCTN2965460). Methods Women at term gestation, in labour with a singleton cephalic presentation, requesting opioid pain relief, were randomly assigned (1:1) to remifentanil PCA (40 lg bolus with a 2 minutes 'lock-out') or intramuscular pethidine (100 mg, 4-hourly, up to 400 mg). 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 randomisation. 400 women were required to detect a reduction in epidural conversion from 30% to 15% with 90% power, with a 15% anticipated attrition from emergency caesarean section. Primary analyses were unadjusted and by intention to treat. A meta-analysis of all trials comparable to RESPITE was performed. Results Between May 2014 and September 2016, 201 women were randomised to remifentanil PCA and 200 to pethidine. Epidural conversion rates were 19% (39/201) and 41% (81/199), respectively (RR 0.48, 95% CI 0.34 to 0.66, P < 0Á0001). Adding the results of RESPITE to previous studies gave a pooled risk ratio of a requirement for 'rescue' analgesia with remifentanil, relative to pethidine, of 0.54 (95% CI 0.42 to 0.68). Instrumental delivery rates were 15% in the remifentanil PCA group and 26% in the pethidine group, with equal proportions of caesarean deliveries in each group (P = 0.02). Maternal respiratory depression and excessive sedation did not differ between groups, although women randomised to remifentanil PCA were more likely to receive supplemental oxygen. There were no differences between the groups in Apgar scores < 7 at 5 min. Conclusion The use of remifentanil PCA as a first-line opioid for labour analgesia, instead of pethidine, would reduce epidural rates, instrumental delivery, and the risk of incontinence for significant numbers of women worldwide. The increased low maternal oxygen saturation rates with remifentanil did not result in adverse sequelae. The robust design of this study, combined with all other available evidence, suggests a fundamental re-evaluation of labour analgesia is needed and the use of pethidine as standard care should be challenged.Conclusion It is feasible to recruit women to a study where the new OD may be used to assist birth. The preliminary data, particularly maternal experience and neonatal outcomes, are very positive. More information is required on both the OD use and the technique, before moving on to an RCT. Abstracts 1696Maternal monitoring of the fetal heart rate dur...

SP22.1 Remifentanil PCIA has no place in labor analgesia

“…Despite underreporting of serious adverse events was likely, the conclusion was that the risk of potentially lifethreatening adverse events seems to be low 31 When Remifentanil PCIA was compared to pethidine, maternal desaturation was 3 times more frequent with Remifentanil in the RESPITE trial. 12 This result is in line with the results of another randomized trial demonstrating a significantly higher incidence of maternal desaturation with Remifentanil than with fentanyl and meperidine 10 Conclusion Maternal respiratory depression is more common with Remifentanil than with other opioids or epidural analgesia.…”

“…However, Apgar scores, incidence of fetal acidosis, need for neonatal resuscitation and NICU admission were similar. 12 Remifentanil vs Fentanyl In a 2010 prospective, randomized, double-blind study comparing PCIA with Remifentanil meperidine or fentanyl, no difference was found in Apgar scores, cord pH and BE, NACS and CTG reactivity. 10 In a 2012 retrospective cohort study comparing Remifentanil vs Fentanyl PCIA, Fentanyl was found to be associated with a higher need for neonatal resuscitation 13…”

“…pethidine (50 vs 65), the reduction in VAS pain scores was similar in both groups (-25) and was corresponding to a mild analgesic effect in line with previous studies. 12 Compared with fentanyl, Remifentanil PCIA provides either no analgesic benefit or only a transient benefit limited to the first hour of administration 10 13 Remifentanil vs neuraxial analgesia Several randomized controlled trials and two meta-analysis have compared the analgesic efficacy of Remifentanil PCIA with epidural analgesia for pain relief during labour.…”