New drug for labor pain may reduce dependency on epidurals: Lancet

A new drug called remifentanil when given intravenously reduced the need for a subsequent epidural for the management of pain in about half of the women in labor as compared to the women who were given the current standard of care -- pethidine. This is the finding from an open-label randomized controlled trial published in The Lancet journal.

About a third of women who receive pethidine for management of labor pain require an epidural, which increases the risk of instrumental vaginal delivery. Remifentanil patient-controlled analgesia (PCA) in labor is an alternative to pethidine but is not widely used. Matthew Wilson, University of Sheffield, UK, and colleagues conducted the study to evaluate the progression of epidural analgesia among women using remifentanil PCA compared with pethidine.

Epidurals - injections of pain relief drugs around the spinal cord - provide effective pain relief but increase the risk of needing instrumental delivery (forceps or vacuum) during birth, which in turn can increase the risk of trauma and long-lasting problems for the mother, such as incontinence and sexual dysfunction.

"Using remifentanil instead of pethidine could reduce the need for epidurals, instrumental deliveries, and consequent morbidity for large numbers of women worldwide, but more research is recommended to understand the effects of low maternal oxygen levels it can cause," write the authors.

"Previous studies have shown that at least one in three women given pethidine to manage pain during labor requires a subsequent epidural as the drug is not always effective. It also has unwanted side effects such as sedation and nausea for the mother, and it may pass into the baby's bloodstream through the placenta," says lead author Dr. Wilson "Our findings challenge the routine use of pethidine for pain relief during labor. Remifentanil reduced the need for an epidural by half and there were no lasting problems for the mothers and babies in our trial, although the effect of remifentanil on maternal oxygen levels needs to be clarified in further studies."

For the study, the researcher analyzed 400 women aged over 16 years old who were giving birth after 37 weeks and had requested opioid pain relief. The participants were told about the trial during antenatal visits or when admitted to the hospital to have labor induced and could sign up to take part when they were in active labor.

Also Read: Easing labor pain may help reduce postpartum depression in some women

Half of the women were allocated to receive remifentanil and half were allocated to pethidine. Remifentanil was given as a patient-controlled drip and women could receive 40μg of the drug every two minutes by pressing a handheld device, 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. Because of the difference in how the drugs were given, participants and healthcare professionals knew which drug was being used.

All women in the trial received one-to-one care from a midwife, with checks on the mother's breathing rate, sedation, pain ratings and oxygen levels every 30 minutes. The women could request an epidural at any time, and other pain relief was stopped if an epidural was given.

Key Findings:

• Half as many women in the remifentanil group went on to have an epidural (19% [39/201]) than in the pethidine group (41% [81/199]) and this remained the same even when the women who did not receive the drug they were meant to be excluded.


• On average, women in the remifentanil group rated their pain as less severe than women in the pethidine group.


• Women given remifentanil were also less likely to need forceps and vacuum during labor than women given pethidine (15% [31/201] vs 26% [52/199]).


• remifentanil was associated with twice as many mothers having low oxygen levels than pethidine (14% [26/189] vs 5% [8/154]), and more women in the remifentanil group were given supplementary oxygen. Despite this increase, it did not cause any negative effects on the mother or baby.


• Breathing problems and sedation in the mother were rare in both groups.

In the remifentanil group 93% (186/201) of women received the drug, and in the pethidine group 77% (154/200) of women received the drug. The main reasons for not receiving the allocated drug were women giving birth before it could be administered (12 women in the remifentanil group and 17 women in the pethidine group) or the mother deciding to immediately request an epidural after randomisation, without receiving the allocated opioid, which only occurred in the pethidine group (in 22 women).

The authors note some limitations, including that the higher number of women in the pethidine group opting for an epidural immediately could be because they had preconceptions about pethidine's effectiveness. Once a woman requested an epidural, it would have been unethical to withhold it.

Women whose labor was induced were more common in the study than in the general population as this provides extra time before labor and meant they were more easily recruited into the study. However, being induced is very common so the authors believe their findings are still relevant.

"Intravenous remifentanil PCA halved the proportion of epidural conversions compared with intramuscular pethidine. This finding challenges routine pethidine use as a standard of care in labor," concluded the authors.

For more information log on to https://doi.org/10.1016/S0140-6736(18)31613-1