Per 2019 guidance from the American College of Obstetricians and Gynecologists (ACOG), commonly used opioids for labor analgesia include fentanyl, morphine, remifentanil, nalbuphine, and butorphanol (Table 1). While parenteral opioids provide poor maternal pain relief and have common adverse events, they do appear to have a role in peripartum analgesia. There is no consensus on an ideal parenteral opioid during labor, as there are no great differences among studied agents. All opioids cross the placenta, which can also induce adverse effects on the newborn. Due to prolonged drug elimination in newborns, meperidine is generally not recommended due to a long-acting metabolite (normeperidine) that cannot be antagonized by naloxone. Nalbuphine and butorphanol are associated with lower incidences of respiratory depression due to being mixed agonists-antagonists. Remifentanil, administered via intravenous patient-controlled analgesia (PCA), seems to provide better pain relief during labor than other opioids. It is becoming a popular option due to its ultra-short duration of action without active metabolites. However, apneic episodes are common among women who received remifentanil PCA during labor, so respiratory monitoring is necessary. Non-opioid agents are also an option, but they appear to be less effective than opioids. If opioids are to be used via epidural analgesia, fentanyl or sufentanil are the options of choice. [1]
A 2018 Cochrane Review aimed to assess the effectiveness, safety, and acceptability of various parenteral opioid analgesia in labor. A total of 70 studies were included, with 61 of these contributing to the data, involving more than 8,000 patients. Intramuscular meperidine (50-100 mg) was compared to placebo in four studies. One study involving 50 women showed no differences in maternal satisfaction 30 minutes after administration (RR 7.00; 95% CI 0.38 to 128.87). Pain relief (defined as reduction in visual analog scale [VAS] of at least 40 mm), was greater with meperidine 100 mg compared with placebo (RR 25; 95% CI 1.56 to 400.54). Additional analgesia was required in both groups, but fewer in the meperidine group (RR 0.71; 95% CI 0.54 to 0.94). One study that included 116 women reported more women in the meperidine group reported “fair” or “good” pain relief within an hour of administration (RR 1.75; 95% CI 1.24 to 2.47) compared to placebo. No differences were observed in the number of women requiring an epidural (RR 0.5; 95% CI 0.14 to 1.78]). Another study found IM tramadol to be associated with poor pain relief compared with IM meperidine (RR 1.56; 95% CI 1.1 to 2.21); however, no difference was seen when in regards to the need for additional analgesia (RR 1.07; 95% CI 0.6 to 1.91). No difference in pain relief was observed between 50 mg IM dihydrocodeine and 100 mg IM meperidine (RR 1.09; 95% CI 0.64 to 1.86). When comparing IM pentazocine with IM meperidine, no difference was seen in maternal satisfaction with analgesia in two studies (RR 1.08; 95% CI 0.92 to 1.27) and four studies reported poor pain relief, with no difference for women who received promazine (RR 1.53; 95% CI 0.66 to 3.58). No difference was observed in the need for additional analgesic drugs in two studies between pentazocine and meperidine (RR 0.91; 95% CI 0.5 to 1.65). Compared to IM meperidine, IM nalbuphine was associated with better satisfaction with analgesia (RR 0.73; 95% CI 0.55 to 0.96) in one study, although another study reported no clear difference (RR 6; 95% CI 0.79 to 45.42). No difference in maternal pain intensity was observed between meperidine and nalbuphine, one evaluating severe pain at 30 minutes (RR 0.86; 95% CI 0.59 to 1.26) and the other at 60 minutes (mean difference -8; 95% CI -18.55 to 2.55). No difference in requirement of additional analgesia was seen in one study (RR 1.26; 95% CI 0.49 to 3.27) or use of epidural (RR 1.65; 95% CI 0.55 to 4.94). When comparing IM phenazocine to IM meperidine, no difference was seen regarding use of epidural (RR 1.31; 95% CI 0.58 to 2.97). When comparing IM butorphanol to IM meperidine, no difference was observed for additional analgesia required (RR 0.89; 95% CI 0.55 to 1.45). In regards to the efficacy of opioids during labor, no one opioid was clearly more effective than the others (including meperidine, tramadol, dihydrocodeine, pentazocine, butorphanol, fentanyl, nalbuphine, morphine, remifentanil, and alfentanil), but they overall were associated with some pain relief. Maternal satisfaction was unreported, but opioids were associated with maternal nausea, vomiting, and drowsiness. It is unclear which opioid was associated with the best pain relief, or least adverse effects. [2]
Another Cochrane Review, published in 2017, included 20 randomized controlled trials (N= 3,569) that evaluated the use of remifentanil PCA for labor pain. Ten trials compared remifentanil to an epidural, four compared to another opioid (IV/IM), three compared to another opioid PCA, two compared remifentanil PCA to continuous remifentanil, and one study compared two different remifentanil PCA regimens. When compared to other IV/IM opioids (i.e., meperidine or fentanyl), a significant difference was found in maternal pain relief satisfaction scores favoring remifentanil (mean difference 2.11; 95% CI 0.72 to 3.49); however, this came with substantial heterogeneity (I2= 93%). By contrast, women were significantly less satisfied with remifentanil PCA than epidural analgesia (mean difference -0.22; 95% CI -0.40 to -0.04). Remifentanil PCA also resulted in lower pain scores at one hour compared to other opioids given via IV/IM (mean difference -1.58; 95% CI -2.69 to -0.48) or via PCA (mean difference -0.51; 95% CI -1.01 to -0.00). Again, the change in pain scores was significantly higher with remifentanil compared to epidural analgesia (mean difference 0.57; 95% CI 0.31 to 0.84). Likewise, remifentanil reduced the risk of requiring additional analgesia compared to other opioids, but was associated with a higher risk of requiring additional analgesia compared to epidural. There was no difference in neonates with an Apgar score <7 at five minutes between remifentanil and epidural analgesia; no reliable conclusions could be drawn on Apgar score compared to other opioids. No difference was also found in risk of Cesarean delivery between remifentanil and any other agent compared. The included studies were not able to compare the rates of adverse events of remifentanil during labor on mothers or newborns. [3]