A comprehensive review states higher bolus dose of remifentanil may provide better analgesia but more maternal side effects while lower bolus doses can produce fewer side effects but inadequate analgesia. One study demonstrated that remifentanil IV patient-controlled analgesia (PCA) with a bolus dose of 0.25-0.5 mcg/kg without a background infusion significantly reduced pain scores from baseline in 90% of the patients with minimal maternal and neonatal adverse effects. [1]
A dose-finding study found the median effective patient-controlled analgesia (PCA) bolus dose of remifentanil to be 0.4 mcg/kg but there was a wide individual variation of 0.2-0.8 mcg/kg. They reported slight sedation in all patients, oxygen desaturation defined by a SpO2 <94% in 59% of the women, fetal heart rate changes in 24% of women and low Apgar scores in 5.8% neonates. More recently, a stepwise increase in the bolus dose of PCA remifentanil for labor analgesia was investigated, starting from 0.15 mcg/kg without a maximum limit. They found a significant reduction in the mean pain scores in the first 3 hours and a high patient satisfaction in 93% of women. They, however, noted a reduction of respiratory rate and oxygen saturation, without any serious complications, in mothers or neonates. [1]
In an attempt to determine the optimum dose of remifentanil IV PCA for labor analgesia,one study compared variable infusion (0.025–0.1 mcg/ kg/min with constant bolus of 0.25 mcg/kg), with variable boluses (0.25–1 mcg/kg with constant infusion at 0.025 mcg/kg/min). The pain scores, satisfaction scores, and cumulative doses of remifentanil were found to be similar between the two groups but maternal side effects such as drowsiness and desaturation were higher in the variable bolus group than the variable infusion group. As a result, they concluded that the regimen of increasing background infusion with a fixed PCA bolus could be more appropriate than fixed background infusion with increasing PCA bolus. [1]
Another study assessed the efficacy and safety of continuous remifentanil infusion, with no boluses, in 205 parturients. They found that infusing remifentanil starting at a rate of 0.025 mcg/kg/min with stepwise increments to a maximum of 0.15 mcg/kg/min resulted in significant reductions in pain scores from baseline, with minimal maternal and neonatal side effects. There was no case of oxygen desaturation or any changes in heart rate variability. A prospective, double-blinded randomized controlled trial comparing maternal and neonatal effects of remifentanil PCA administered using a stepwise increase in the bolus from 0.1 to 0.4 mcg/kg versus continuous infusion increased from 0.05 to 0.2 mcg/kg/min revealed that the adverse effects were similar between both groups. Results from this trial suggest that remifentanil PCA provides better pain relief and similar placental transfer but 6 of the women in the trial chose to cross over to epidural analgesia because their analgesia was unsatisfactory, suggesting that the maximum dose in this trial may have been too low. [1]
Labor analgesia with IV remifentanil has been reported to be associated with excessive maternal sedation and oxygen desaturation, as well as fetal heart decelerations, depending on the dose and administration regimen. There was a case of respiratory arrest with bradycardia reported with remifentanil PCA administered with a PCA bolus of 40 mcg, due to unknown reasons. There was another case of cardiorespiratory arrest in a woman who underwent induction of labor using remifentanil PCA, which consisted of 40 mcg given as a bolus with a maximum dose of 5 mg per 4 hours. She had received 60 mg of oral codeine phosphate and diamorphine 10 mg intramuscularly in addition to Entonox during labor. The patient fully recovered after resuscitation but the exact reason for the arrest remains unclear. Remifentanil readily crosses the placenta and neonates could theoretically experience the same side effects as their mothers but there were no case reports/studies of serious neonatal adverse events. [1]
A meta-analysis compared the efficacy and safety of remifentanil patient-controlled IV analgesia (PCA) and epidural analgesia for labor pain relief from five randomized, controlled trials. It concluded by saying that remifentanil PCA did not provide better analgesic efficacy than epidural analgesia during labor but could be an optional effective alternative for pain relief. The safety of remifentanil still remains controversial but it has been reported that maternal sedation and respiratory depression may occur during labor. Therefore, PCA requires monitoring, one-on-one nursing care throughout labor, and supplemental oxygen in some parturients. [2]
A Cochrane review and meta-analysis included 20 randomized controlled trials of women receiving remifentanil PCA compared to other methods of parental pain management during labor. Evidence showed women in the remifentanil (PCA) group were more satisfied with pain relief than women in the other opioids (IV/IM) group (95% confidence interval [CI] 0.72 to 3.49).There is evidence of effect that remifentanil (PCA) provided stronger pain relief at one hour than other opioids administered IV/IM (95% CI -2.96 to -0.48). [3]
There is no evidence of effect that remifentanil (PCA) was associated with an increased risk for maternal respiratory depression when compared to epidural analgesia (relative risk [RR] 0.91, 95% CI 0.51 to 1.62). There is no evidence of effect that remifentanil (PCA) was associated with an increased risk for newborns with Apgar scores less than seven at five minutes compared to epidural analgesia (RR 1.26, 95% CI 0.62 to 2.57). There is evidence that remifentanil (PCA) was associated with a lower risk for the requirement of additional analgesia when compared to other opioids (IV/IM) (RR 0.57, 95% CI 0.40 to 0.81). [3]
Another meta-analysis provides good evidence that a remifentanil PCA provides better analgesia for labor than intramuscular or intravenous pethidine with almost comparable maternal adverse effects. Epidural analgesia provided better pain relief than remifentanil. The conclusions of the comparison of remifentanil with inhalational nitrous oxide and fentanyl are less clear due to limited data. As there were few randomized trials included in the meta-analysis, with few adverse effects reported, an appropriate risk-to-benefit analysis is currently not possible. Large randomized controlled trials reporting on safety issues and patient satisfaction using appropriate administration modes are needed to complement the knowledge of this alternative method for pain relief during labor. [4]