US Pharm. 2006;11:HS-44-HS-52.

A woman in labor is commonly referred to as a parturient in the medical literature. The parturient may be offered various medications to alleviate labor pains. Medications given for analgesia in labor will decrease the pain sensation, while medications used for anesthesia should provide complete pain relief.1 Women of today, especially those living in the United States, certainly have more options than their mothers and grandmothers did.

Stages of Labor
There are three stages of labor. The first begins with the onset of labor, as a woman experiences general abdominal cramping and uterine contractions. Once the cervix has completely dilated, the second stage of labor begins. The woman begins pushing during contractions, with the stage ending when the baby is delivered. Pain in the second stage of labor may be more intense and continuous. During the third stage, the placenta is delivered.2

Labor pain is affected by nerves near the lower thoracic spinal segments (10-12) and the first lumbar spinal segment. Medication administered into either the epidural or subarachnoid spaces can block the pain.3

A woman's perception of labor pain is affected by many factors, including cultural, psychosocial, environmental, and physiologic influences. Nulliparous women may have more pain in early labor, while women who have gone through childbirth previously note more pain in the late first stage and second stage.

Early Use of Labor Analgesia
Early Chinese documents describe the first use of an opioid, opium, in treating labor pain.4 Two British obstetricians pioneered the use of ether as an inhalational anesthetic for labor pain in the 1840s. Chloroform eventually became the anesthetic of choice in place of ether.5 In 1902, morphine and scopol­ amine use for labor pain was reported. There was little benefit in pain relief, although the "twilight sleep" caused maternal confusion and forgetfulness of the event. However, these drugs were also associated with neonatal respiratory depression.6 Meperidine came into use during the early 1940s, eventually becoming the most regularly used opioid for labor pain worldwide.7

The first reported case of regional anesthesia used in labor occurred in 1900, when a physician from Switzerland administered spinal cocaine to six of his patients. Two years later, spinal anesthesia was used for the first time for a cesarean delivery in the U.S.8 In the late 1960s, epidural analgesia became more accepted, especially among academic health centers and private hospitals.

Nonpharmacologic Interventions
There are multiple nonpharmacologic techniques used to reduce labor pain. These interventions include acupuncture, massage, intracutaneous sterile water blocks, water immersion or hydrotherapy, music or audioanalgesia, cold or heat therapy, hypnosis, breath­ ing/focusing, and transcutaneous electrical nerve stimulation.9 However, a primary disadvantage of alternative or nonpharmacologic techniques is the lack of rigorous research to support their use. Advantages to nonpharmacologic interventions include their low cost and wide availability and the fact that they pose low or no risk to the mother and neonate and allow active participation of the mother throughout the labor process.

Routes of Analgesia Administration
There are several routes of analgesia administration used to reduce labor pain. These routes include intravenous (IV), intramuscular (IM), subcutaneous, paracervical blocks, epidural, spinal, and combined spinal epidural.

Parenteral Routes: Opioid derivatives are the agents used for IV and IM analgesia. These agents may moderately reduce labor pains, but they cannot eradicate the pain. IV administration provides a faster onset of analgesia with a shorter duration of action, while IM administration should be considered when pain relief for a longer duration is needed (see Table 1).1 Common side effects of opioids include constipation, dry mouth, urinary retention, sedation, nausea, vomiting, dysphoria, hypoventilation, pruritus, and neonatal depression.1 Several studies have evaluated the benefits of IV analgesia. Soontrapa et al. reported that fewer than 25% of those receiving an IV opioid analgesic had adequate pain relief.10

Parenteral use of opioids may be warranted in those patients who have contraindications to epidural analgesia; previous spinal surgery or deformity, which may make it impossible to place an epidural; or the unavailability of anesthesia or personnel services.

Morphine was the first pure opioid given for relief of labor pain. Doses ranged from 1 to 4 mg with a peak effect at 20 minutes after IV administration. The peak effect for IM dosing was delayed to one to two hours. Side effects with morphine include maternal and neonatal respiratory depression and maternal nausea, vomiting, and sedation. Morphine is rarely used during labor in the U.S. because of its long half-life, high incidence of sedation, and neonatal side effects.11

In the 1940s, meperidine came into use for labor analgesia and is now the most frequently used opioid for labor pain. IV doses are typically 25 to 50 mg and IM doses are 50 to 100 mg. It has a faster onset of action--five to 10 minutes for IV dosing and 45 minutes for IM dosing--than morphine does. As with morphine, meperidine can cause neonatal respiratory depression. The significance of this effect depends on the dose given, as well as the time between dose administration and delivery. A neonate is less likely to suffer respiratory depression if delivery occurs one hour after dosing or more than four hours after dosing. The strongest effects on the neonate tend to occur if delivery takes place two to three hours after the meperidine dose is given. Another disadvantage of meperidine is its metabolism to normeperidine in the neonate, as this metabolite has a much longer half-life (63 hours).11,12

Fentanyl, a synthetic opioid, has several advantages over morphine and meperidine. It has a rapid onset of action of only one to two minutes when it is given intravenously and a short duration of action of 60 minutes. IM and IV doses range from 50 to 100 mcg.1,12 Fentanyl does not readily cross the placenta, as morphine and meperidine do; however, neonatal respiratory depression may still occur. Fentanyl has been noted to cause less maternal sedation, nausea, vomiting, and pruritus as compared to morphine and meperidine.

Butorphanol, an opioid agonist-antagonist, is given in doses of 1 to 2 mg IV or IM. It has an onset of action of two to three minutes after IV dosing and 10 to 30 minutes after IM dosing. It has a three- to four-hour duration of action with either IV or IM administration.1,12 Another opioid agonist-antagonist is nalbuphine, which can be given as either an IV or IM10-mg dose. It has a slightly faster peak effect of two to three minutes when given intravenously and 15 minutes after IM dosing.1,12 Both butorphanol and nalbuphine may cause maternal respiratory depression.1 Patients who may take narcotics for other medical conditions or who are drug abusers may experience withdrawal symptoms due to the antagonistic effects of butorphanol and nalbuphine.11

Paracervical Blocks: Paracervical block was a method commonly used in the 1940s and 1950s; however, its use has decreased with the increasing availability of epidural analgesia. A paracervical block involves the injection of local anesthetics, such as lidocaine or bupivacaine, into either side of the cervix. A major disadvantage seen with paracervical blocks is fetal bradycardia. When this procedure was first implemented, fetal bradycardia was reported to occur 70% of the time.13 However, this incidence has dropped to a rate of 15% with present methods.14

 

Regional Analgesia: Regional analgesia includes epidural, spinal, and combined spinal and epidural procedures that result in partial to complete loss of pain sensation below the T8 to T10 levels of the spine (see Table 2 for contraindications to regional anesthesia).12 In the U.S., there are four million births each year, and nearly 60% of women giving birth receive an epidural.15 Epidural procedures require administration of analgesics or anesthetics via catheter into the area of fibrous connective tissue (dura mater) covering the spinal cord. Spinal analgesia requires piercing the dura into the cerebrospinal fluid–filled cavity, where the spinal cord is located.11 Spinal analgesia is a single dose of a long-acting local anesthetic with or without an opioid agent. For spinal analgesia, small doses of medications are required (e.g., fentanyl 25 mcg with 1 mL bupivacaine 0.25%), whereas, larger doses are needed for epidural use (e.g., fentanyl 50 to 100 mcg with 10 to 15 mL bupivacaine 0.125% to 0.25%).3




Combined spinal and epidural analgesia is a more recent technique that offers the benefit of spinal analgesia's quick onset of action, along with the ability to provide an epidural for an extended period. Combined spinal and epidural administration is accomplished via a "needle-through-needle" technique. Medication is injected via the spinal needle into the subarachnoid space. The spinal needle is removed, leaving the epidural needle in position, and the epidural catheter is threaded through.1 Within three to five minutes, analgesia begins with a duration of 60 to 90 minutes. As the spinal analgesia fades, the anesthesiologist can use the epidural catheter during the remainder of the labor process.

Continuous infusion of an anesthetic with an opioid is commonly used in labor. Continuous infusions offer a more steady level of pain control, compared to bolus administrations. These infusions typically contain bupivacaine or ropivacaine 0.04% to 0.125% and fentanyl or sufentanil.3

Factors that affect rates of epidural use include availability of anesthesia services, conditions or criteria for use (e.g., stage of labor or patient demand), and the size of the hospital.16 Currently, there is debate in the medical literature on whether epidurals should be given early in labor rather than later and what effects this may have on the labor process and delivery. In hospitals with delivery rates of at least 1,500 births per year, the percentage of patients getting epidurals jumped from 22% to 51% from 1981 to 1992.17

Medications given epidurally include opioid analgesics, anesthetics, or more commonly, both. The combination has an additive effect.18 Analgesics commonly used for epidurals include fentanyl and sufentanil, which are better tolerated than morphine and meperidine. The drawbacks for epidural morphine are its long onset time and modest effectiveness.

Local anesthetics used in regional anesthesia include low-dose cocaine derivatives: bupivacaine, lidocaine, and ropivacaine.11 Common side effects include pruritus, inability to urinate, and hypotension.

Bupivacaine is a commonly used local anesthetic, and its advantages include prolonged duration of action, low placental transfer, and efficacy in both early and late stages of labor.19 Bupivacaine was the first anesthetic of choice for several decades; however, it fell out of favor in the mid-1980s after several maternal deaths due to cardiotoxicity of bupivacaine 0.75% solution.20

Lidocaine is used less often than bupivacaine because it offers less pain relief and has a shorter duration of action.11 On the other hand, it has a decreased risk of cardiotoxicity compared to bupivacaine.

Ropivacaine is similar to bupivacaine in onset, duration, and sensory block; however, ropivacaine is the S-enantiomer, and bupivacaine is a racemic mixture of both the R and S forms.21 Ropivacaine, like lidocaine, has less risk of cardiotoxicity than does bupivacaine. Ropivacaine use also reduces the need for instrumental vaginal deliveries. A meta-analysis by Writer et al. noted a 13% reduction in instrumental vaginal deliveries with ropivacaine use compared to bupivacaine.22

Efficacy of ultra-low-dose epidurals and combined spinal epidurals, which are referred to as walking epidurals, was evaluated in several studies. Low concentrations of bupivacaine or ropivacaine in combination with fentanyl allowed for sufficient analgesia along with the majority of patients retaining the ability to ambulate. A study by Breen et al. noted that low-dose bupivacaine at 0.04% with fentanyl and epinephrine produced sufficient analgesia with little motor impairment.23 Campbell et al. reported that 100% of patients receiving epidural ropivacaine 0.08% with fentanyl 2 mcg/mL were able to continue ambulating, compared to 75% of the patients receiving bupivacaine 0.08% with fentanyl 2 mcg/mL.24

There are several precautions to consider for the laboring woman who wishes to ambulate. The patient's blood pressure as well as fetal heart rate should be monitored for 30 to 60 minutes after initiation of the epidural and then at least every 30 minutes thereafter. The patient should demonstrate her ability to walk by either stepping up and down on a stool or performing knee bends. Finally, the patient should never ambulate alone.2

Maternal and Labor Effects of Regional Analgesia

Studies have noted that epidural use is associated with negative effects (see Table 3): increased length of the first and second stages of labor, increased use of forceps or vacuum in deliveries, and maternal fever.





There have also been concerns that epidural use increases the need for cesarean delivery. Two separate meta-analyses noted no change in cesarean rates between epidural and parenteral opioid groups; however, first and second stages of labor were prolonged in patients in the epidural groups compared to those in the parenteral opioid groups.25,26 Several studies by Chestnut et al. have shown that higher concentrations of bupivacaine (0.125% vs. 0.0625% + 0.0002% fentanyl) given epidurally can cause significant motor blockade and increase the risk of forceps delivery.27-29

Epidural analgesia in labor is frequently linked to maternal fever with a body temperature higher than 100.4ºF. One randomized trial observed that 15% of women who received an epidural had a fever, as compared to only 4% of those who did not receive an epidural. This percentage increased for those nulliparous women in the study (24% vs. 5%).30 Neonates born to mothers who have received epidurals are more often assessed and treated with antibiotics due to concerns of possible infection.31

Another concern with epidurals is puncture of the subarachnoid space during positioning of the epidural needle. This early complication causes a minuscule quantity of spinal fluid to seep out into the epidural space, leading to a postdural headache.11 Punctures occur in about 3% of women and account for 70% of severe headaches in postpartum women.32

General Anesthesia
General endotracheal anesthesia for emergency cesarean delivery is indicated when there is severe fetal distress with insufficient time to establish regional anesthesia, as well as cases of coagulopathy, severe maternal hemorrhage, or failure of regional anesthesia.1

General anesthesia involves injection of a rapid-acting induction agent such as thiopental, ketamine, or etomidate and a short-acting muscle relaxant such as succinylcholine or rocuronium to cause deep sedation and analgesia, as well as muscle paralysis and apnea. A tracheal tube is placed, and anesthesia is maintained with oxygen, an inhalational agent, and nitrous oxide.33

Failure of tracheal intubation in obstetric patients is nearly 10 times that in nonobstetric patients.34 Capillary swelling of the mucosa in the trachea due to pregnancy reduces the internal space of the trachea. Anesthesia-related maternal death is the sixth leading cause of pregnancy-associated deaths in the U.S.35 The fatality rate for general anesthesia in cesarean delivery is projected at 32 per one million live births versus 1.9 per one million live births for regional anesthesia.36

Summary
The American College of Obstetricians and Gynecologists offered this statement in a recent bulletin: "Labor results in severe pain for many women. There is no other circumstance in which it is considered acceptable for a person to experience untreated severe pain, amenable to safe intervention, while under a physician's care. In the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labor. Pain management should be provided whenever it is medically indicated."12

For women suffering from labor pain, there are many choices available for pain relief. The route of pain relief will depend on specific circumstances for each patient and the level of pain experienced.

References

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