New study: Epidural rates in labour could be halved with use of painkiller remifentanil

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Giving pregnant women on-demand access to the synthetic opioid remifentanil during labour could not only halve the number needing an epidural but could also substantially reduce rates of instrumental deliveries, according to the results of a large scale trial in the UK.

Despite having been available for several years, there has been a lack of strong evidence that remifentanil offers advantages over the opioid pethidine, the traditional agent used. There have also been persistent concerns over its potential to cause respiratory depression. 

In the first and largest trial of its kind, the RESPITE trial involved 400 women giving birth at 14 UK hospitals between May 2014 and September 2016. The results of the study, Intravenous remifentanil patient-controlled analgesia versus intramuscular pethidine for pain relief in labour (RESPITE): an open-label, multicentre, randomised controlled trial, were published this week in The Lancet, available through CKN.

Women using remifentanil were half as likely as those given pethidine to progress to an epidural

The RESPITE trial compared remifentanil patient-controlled analgesia (PCA) with pethidine, for women giving birth who had requested opioid pain relief, and assessed how many of the participants later required an epidural. It showed that women using remifentanil were around half as likely as those given pethidine to progress to an epidural (19% compared with 41%) and had marked reductions in average pain scores.

Remifentanil was also associated with a reduction in women needing to have an instrumental delivery (15% versus 26% on pethidine).

While the drug was also linked to a significantly increased rate of low maternal blood oxygen levels, this had no negative effects on either the mother or the baby.

The study’s lead author Dr Matthew Wilson of the School of Health and Related Research at the University of Sheffield, said that past studies had shown that at least 1 in 3 women given pethidine require a subsequent epidural. “While pethidine is commonly used in labour, its effectiveness in terms of pain relief has long been challenged and its shortcomings are more serious when set against known side effects which include women feeling sedated and nauseous. It can also transfer to the baby via the placenta, producing side effects.”

Study details

For the open-label RESPITE trial, the team studied women aged at least 16 years from 14 maternity units across the UK who were beyond 37 weeks' gestation with a single child, and who had requested opioid pain relief.

The women were randomised to either intravenous remifentanil PCA as a 40 µg bolus on demand every two minutes whereas pethidine was given as an injection of 100mg of the drug into a muscle up to every four hours with a maximum of 400mg in 24 hours. 

The women could request an epidural at any time, at which point the other pain relief was stopped.

In the remifentanil PCA group, 93% of women received the drug, and in the pethidine group 77% of women received the drug. The main reasons for not receiving the allocated drug were women giving birth before it could be administered or the mother deciding to immediately request an epidural after randomisation, without receiving the allocated opioid, which only occurred in the pethidine group.

Of the 199 women who were given pethidine, 41% went on to have an epidural, compared to just 19% of the 201 women who were given remifentanil PCA.

On average, women in the remifentanil PCA group rated their pain as less severe than women in the pethidine group. Women’s satisfaction with their pain relief and its effectiveness was also significantly higher within the remifentanil PCA group compared to the pethidine group.

Notably there was a significant difference in rates of instrumental delivery between the two groups, at 15% with remifentanil PCA versus 26% with pethidine. Dr Wilson also added there was no difference in the health of the babies born to women who received remifentanil PCA, which he said was “very reassuring”. He added "we didn't demonstrate any effects on neonatal well-being at birth. There is also the interesting fact that the prevalence of the side effects are not zero with pethidine, which we have shown, and, at the moment, there are no special provisions for monitoring women who receive pethidine [despite] all the years it's been used."

While rates of respiratory depression and excessive sedation were low and similar between the groups, the women received remifentanil PCA were significantly more likely to have low maternal oxygen saturation than those given pethidine, at 14% versus 5%. More women in the remifentanil group were given supplementary oxygen. Dr Wilson noted, however, that the level of reduction in oxygen saturation was "relatively modest, in that it's easily recognised and easily remedied". 

Further studies recommended

The researchers recommended more research to understand the effects of low maternal oxygen levels it can cause, and are planning further studies. Wilson noted that it requires extra equipment and additional supervision by anaesthetists, as well as additional midwifery care. During the trial one-to-one care from a midwife was provided to all women included in the trial where checks on the mother’s breathing, sedation, pain ratings and oxygen levels were carried out every 30 minutes. Dr. Wilson said "remifentanil could only be delivered safely in that context." This same standard of care is reflected in the Queensland Clinical Guideline Short Guide: Remifentanil via PCA in labour

The researchers said that increased staffing requirements would likely be offset against potential reductions in maternal hospital stay and a reduced impact on operating theatres from the reduction in instrumental deliveries.

"The results of the trial provide strong evidence that remifentanil PCA should be routinely offered as an alternative to pethidine"

Study researcher Professor Christine MacArthur, said that “RESPITE essentially set out to examine if there was a more effective alternative to pethidine which is safe, easy to administer and could ultimately reduce the number of women who have an epidural.” The researchers were anticipating fewer women who had remifentanil PCA to then have an epidural, but did not expect to show the epidural rate could be halved, added Professor MacArthur.

“The results of the trial provide strong evidence that remifentanil PCA should be routinely offered as an alternative to pethidine” she said. “Using remifentanil PCA could potentially reduce the financial burden [on health services] if it cut the number of epidurals and the associated higher rates of instrumental birth.”

Dr Wilson said the new study "challenges pethidine as the standard of care". He said that "epidurals are the best form of pain relief we can offer in labour, and not any form of opioid is ever going to be as good as that. But some women don't want epidurals and there is a gap for an effective intervention for pain relief which is associated with maternal satisfaction, and remifentanil seems to fill that gap."