U.K. Study Finds Remifentanil Leads to Fewer Epidurals Than Meperidine

Author: Andrew Goldstein

Anesthesiology News

Women given remifentanil for labor pain were less likely to need a subsequent epidural compared with women given meperidine, the current standard for labor pain relief in the United Kingdom, according to a study published in the Lancet (2018;392(10148):662-672.).

“What I think the study has shown rigorously for the first time, in the context of a well-conducted, controlled trial, is that remifentanil results in progression to epidural about half as often as [meperidine], and that’s significant,” said lead author Matthew J.A. Wilson, MD, FRCA, an anesthesiologist and a senior lecturer at the University of Sheffield, in England. “But it also challenges whether [meperidine] should remain—in the U.K., at least—our standard opioid care for labor, because we’ve now demonstrated that there is something out there that is potentially far superior.”

The open-label, randomized controlled study was conducted over two years, from 2014 to 2016, at 14 hospitals in the United Kingdom. Of the 401 patients recruited, 201 were assigned to receive IV patient-controlled remifentanil (40 mcg with a two-minute lockout), whereas 200 were assigned to receive intramuscular meperidine (100 mg every four hours with up to 400 mg per 24 hours), according to Dr. Wilson.

All women in the trial received one-to-one care, with checks on their breathing rate, sedation, pain ratings and oxygen levels every 30 minutes. The women could request an epidural at any time. Because the study was open-label, neither the consenting physicians nor the midwives were involved in the decision to proceed to epidural analgesia. The primary outcome was progression to epidural analgesia, with secondary outcomes pertaining to maternal analgesia, maternal well-being and neonatal outcomes to monitor neonatal well-being, Dr. Wilson said.

In the remifentanil arm 186 patients (93%) received the drug, while in the meperidine arm 154 patients (77%) received the drug. Upon being randomly assigned to the meperidine arm, 22 women immediately requested epidural analgesia. A sensitivity test was performed and showed that this did not significantly affect the results of the trial, Dr. Wilson said.

“What we demonstrated was, for women randomized to remifentanil, they progress to epidural about half as often (19% vs. 41%; 95% CI, 0.34-0.66) as the women in the [meperidine] group.” Dr. Wilson said. Other important outcomes included a lower chance of requiring instrumental vaginal delivery with or without an epidural (15% vs. 26%), a similar rate of cesarean deliveries, superior rated pain relief, better visual analog scores, higher satisfaction and a higher risk for requiring supplementary maternal oxygen (14% vs. 5%) for women receiving remifentanil patient-controlled analgesia (PCA), according to Dr. Wilson.

In the United States, about 60% to 65% of laboring patients receive epidural analgesia as first-line pain relief, compared with about 30% in the United Kingdom, according to Ellen S. Steinberg, MD, a professor of obstetric anesthesia at Stony Brook University School of Medicine, in New York, who was not affiliated with the study. Meperidine is not frequently used in this setting in the United States, whereas it is the standard labor pain relief treatment in the United Kingdom.

In a 2017 article in Anesthesia and Analgesia, researchers surveyed directors of obstetric anesthesia in American academic medical centers and found that only 30% used IV remifentanil PCA for labor pain management. Of those, most departments used the drug around five times, and none of them used it more than 20 times annually, according to Dr. Steinberg.

Although the epidural rate in the United States is high, this still leaves a third of women who may wish to use another form of labor pain management, Dr. Wilson said, and the study is relevant in other countries with lower epidural rates.

“I would say that it doesn’t have relevance for us because intramuscular [meperidine] is not a labor pain relief medication that is widely used, or even barely used, in the United States,” Dr. Steinberg said. “This kind of comparison doesn’t really do anything for us. IV PCA remifentanil has some value for patients who can’t get epidurals—in my mind it’s still very questionable; we still have a lot more things we need to work out before we could use that safely.”