A Randomized Control Trial of Bupivacaine and Fentanyl versus Fentanyl-only for Epidural Analgesia during the Second Stage of Labor


Abstract

Background: The purpose of this prospective, double-blinded, parallel-arm, randomized trial was to examine the effects of epidural bupivacaine on the length of the second stage of labor in nulliparous women.

Methods: The authors assessed length of second-stage labor, degree of motor blockade, mode of delivery, and visual analog scores in 310 nulliparous women with labor epidurals randomized to receive either: (1) 0.125% bupivacaine and fentanyl 2 μg/ml or (2) fentanyl 10 μg/ml alone via epidural using double blinding.

Results: The median duration of the second stage was 75 min (41, 128) in the bupivacaine/fentanyl group versus 73 min (42, 120) in the fentanyl-only group (P = 0.17) with a median difference of 6.0 (95% CI, −6.0 to 18.0). Furthermore, there was no difference in degree of motor blockade, incidence of operative delivery, visual analog scores, or neonatal outcomes between the two groups. No adverse events were reported.

Conclusions: Use of epidural bupivacaine/fentanyl or a fentanyl-only infusion during the second stage of labor did not affect the duration of the second stage of labor, degree of motor blockade, mode of delivery, pain relief, and maternal or neonatal outcomes. However, in the fentanyl-only infusion group, there was a fivefold increase in opioid exposure to the fetus with unknown effects on neurobehavior, an outcome not assessed beyond the immediate postnatal period in this study.

What We Already Know about This Topic
  • Epidural analgesia through the second stage of labor is associated in some studies with prolonged second-stage duration and increased instrumental deliveries

  • Whether providing epidural analgesia without local anesthetics alters these outcomes is unknown

What This Article Tells Us That Is New
  • In 310 nulliparous women with epidural analgesia randomized at the onset of second stage to receive epidural fentanyl alone or with bupivacaine, there was no difference in duration of second stage, degree of motor block, or instrumental delivery

  • To achieve similar degrees of analgesia, women receiving epidural fentanyl without bupivacaine required a fivefold increased dose of fentanyl.

Discussion
Historically, when high concentrations of local anesthetic were used in labor epidural infusions, motor blockade was significant during the second stage of labor and often resulted in epidural infusions being turned down or completely off to improve maternal expulsive efforts.11  We highlight three clinical observations from our study of paramount interest and importance that address the aforementioned practices.
First, lower-dose epidural bupivacaine infusions such as that used in this trial moderately impeded lower extremity motor function during childbirth. In fact, all women were able to lift their legs against gravity (motor strength score: 3 or higher), further indication that no woman had an extensive motor block. This counters a previously described theory of epidural local anesthetics resulting in poor maternal expulsive efforts, thought to be a cause of increased operative deliveries.12 
Second, several investigators have reported that a major disadvantage to lowering or discontinuing the epidural infusion during the second stage of labor is the potential for inadequate analgesia.13–16  In two separate studies, Chestnut et al.13,14  randomized women to either bupivacaine-containing solutions or placebo infusion of saline during the second stage. Women randomized to the saline groups reported higher pain scores. Alternatively, Lindow et al.16  infused epidural opioid in lieu of saline in comparison with epidural bupivacaine/fentanyl. Again, results were similar with women reporting higher pain scores and a greater need for rescue analgesia of nitrous oxide and/or perineal infiltration of lidocaine in the fentanyl-only group. Of note, these studies had sample sizes of less than 100 women.
A meta-analysis was performed analyzing the possible consequences of discontinuing epidural analgesia late in labor.17  The only significant finding was an increase in pain. In contrast, our study found that pain scores were equally satisfactory among both groups. This is likely due to the higher concentration of fentanyl (10 μg/ml) used in our studyversus saline and a fentanyl concentration of 1.6 μg/ml used in the study by Lindow et al.16 
Last, substituting epidural bupivacaine with fentanyl-only (10 μg/ml) during the second stage of labor was not associated with deleterious maternal or neonatal effects. Although there was a negligible amount of intravenous meperidine given in both study arms, epidural fentanyl administration was five times greater in the fentanyl-only group. This increase in fetal opioid exposure is because epidural fentanyl is rapidly absorbed systemically. Although the bioavailability is unknown in laboring women, transplacental transfer is approximately 90%.18 
We report three limitations to our study. First, to estimate sample size, from our database, we included women of parity 0 and 1, which would explain the shorter median duration of the second stage at 28 min (15, 58) than what was observed in this study. Our study consisted of all nulliparous women. Second, having a third arm, with subjects that had a placebo infusion started after randomization, would have allowed us to evaluate the effects of discontinuing the epidural entirely on the outcomes of interest. But such a design would have raised ethical concerns regarding the withholding of effective analgesia. Last, parental opioids are known to induce neurobehavioral depression. The literature regarding the effects of epidural opioids remains unclear.19 However, we did not assess the newborn beyond the routine 1- and 5-min Apgar scores, so, there exists the possibility that this exposure could have resulted in neurobehavioral changes, even subtle ones.
In summary, we found that the use of epidural bupivacaine/fentanylversus fentanyl-only neither did lengthen the second stage of labor nor did affect the degree of motor blockade, mode of delivery, satisfaction with pain analgesia, and maternal or neonatal outcomes. However, the use of epidural fentanyl-only resulted in a fivefold increase in fetal opioid exposure. Although not assessed, this exposure could result in neonatal neurobehavioral depression, both short and long term, and should be an outcome of interest in future studies. Therefore, anesthetic management should be tailored to the individual needs of the obstetrical patient, balancing the risks and benefits to the mother and her newborn.

Anesthetic reduced frequency of menopausal hot flashes by half.


Menopausal women treated with a stellate ganglion blockade showed a 50% reduction in moderate-to-severe hot flashes, according to preliminary data presented at Anesthesiology 2013.

Bupivacaine is currently indicated for local or regional anesthesia or analgesia.

“This is the first effective, non-hormonal treatment for hot flashes, which for many women have a serious negative effect on their lives. This treatment will also help breast cancer patients who suffer from hot flashes as a side effect of their treatments of medication. Some breast cancer patients stop taking their medication (tamoxifen) because of hot flashes,”David R. Walega, MD, chief of the division of pain medicine and program director of the multidisciplinary pain medicine fellowship department of anesthesiology at Northwestern University Feinberg School of Medicine, said in a press release.

Researchers randomly assigned 40 menopausal women aged 30 to 65 years with more than 25 vasomotor symptoms per week to an injection of 0.5% bupivacaine 5 mL or sterile saline.

There was a 19% reduction in hot flashes 4 to 6 months after the injection in the bupivacaine group, according to researchers.

Analyses revealed hot flashes decreased 34% from baseline to 6 months among patients in the bupivacaine group vs. placebo. Further, reductions in moderate-to-severe hot flashes were significantly greater among the bupivacaine group vs. the placebo group (RR=0.5; 95% CI, 0.34-0.73), according to data.

“This is a fast, relatively painless, long-lasting and cost-effective treatment for hot flashes,” Walega said. “It has tremendous potential to help not only menopausal women, but also breast cancer patients and women in surgical menopause (whose ovaries have been removed), who have had to put up with ineffective treatments or simply ‘grin and bear it.’”

Source: Endocrine Today.