Learning Objectives: After participating in this continuing professional development activity, the provider should be better able to:
1. Explain considerations for the use of neuraxial analgesia techniques in the management of labor pain.
2. Describe the use of peripheral nerve blocks and/or parenteral and inhalation agents in the management of labor pain.
Labor pain is one of the most stressful experiences that a woman may encounter. According to the American College of Obstetricians and Gynecologists (ACOG), "There is no other circumstance where it is considered acceptable for an individual 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 medically indicated,"1,2 The pain experience has multiple components-physical, emotional, cognitive, social, and cultural. As health care professionals, we are more in tune with patient satisfaction and experience during childbirth than ever before. In this article, we discuss commonly used pharmacologic analgesia modalities to manage labor pain. Pharmacologic analgesic techniques include neuraxial analgesia (eg, epidural and spinal anesthesia), peripheral nerve blocks, parenteral medications, and inhalational agents. Pharmacologic techniques for labor analgesia are summarized in Table 1.
Neuraxial Analgesia Techniques
Neuraxial analgesia techniques include epidural, spinal, and combined spinal-epidural (CSE) analgesia. The primary indication for neuraxial analgesia is the patient's desire for analgesia.2 Neuraxial anesthesia is the preferred modality in patients with anticipated difficult airway, certain cardiopulmonary conditions, preeclampsia, and eclampsia.2 Neuraxial analgesia offers the most effective form of pain relief during labor.5,6 It is the preferred technique in both the United States and Canada.7 A regional technique was used in more than 75% of women who gave birth in US hospitals with a volume of at least 1500 deliveries per year. Forty percent of women who had planned to avoid a labor epidural block received one.7 On the other hand, less than one third of parturients in the UK received neuraxial analgesia. Advantages and disadvantages of neuraxial techniques for labor analgesia are summarized in Table 2.4 Contraindications to neuraxial analgesia are summarized in Table 3.
Epidural Analgesia
Epidural analgesia is the "gold standard" for labor analgesia. It is highly effective for treatment of labor pain and has been demonstrated to reduce the need for additional pain relief, reduce the risk of neonatal acidosis, and naloxone administration (probably by avoiding high amounts of systemic opioids).3,8 However, labor epidural analgesia (LEA) has been associated with increased risk of assisted vaginal birth, maternal hypotension, motor blockade, maternal fever, urinary retention, oxytocin administration, longer second stage of labor, and an increased risk of cesarean delivery for fetal distress. There is no evidence of a significant difference in the risk of cesarean delivery overall, long-term backache, Apgar scores at 5 minutes, and maternal satisfaction with pain relief.3,8 Adverse effects and complications of LEA are summarized in Table 4.
Epidural analgesia is a central nerve block technique that involves injection of a local anesthetic (with or without opioids or other adjuncts) in the lumbar spine targeting spinal nerve roots. It is usually performed with the patient sitting upright or in the lateral decubitus fetal position. Once access is gained into the epidural space, a catheter is threaded, allowing for a continuous infusion of medication. Analgesia is usually apparent within 10 to 20 minutes. In obstetric patients, the goal is to provide sensory blockade below the T8-T10 dermatomes.
Local anesthetics inhibit nerve conduction by blocking sodium channels in the cell membranes. This is a concentration-specific response, usually affecting the smallest nerve fibers first, followed by the larger ones. The order of blockade is as follows: sympathetic, sensory, and then the motor fibers. The reverse is true for recovery. Bupivacaine and ropivacaine are the most commonly used local anesthetics for LEA in the United States. Using dilute local anesthetic solutions (0.125% bupivacaine or 0.2% ropivacaine) can minimize motor blockade.19 Opioids can be added to improve analgesic quality.
Medication delivery modes for LEA include intermittent epidural boluses, continuous epidural infusions, or patient-controlled epidural analgesia. In the past, higher local anesthetic concentrations have been attributed to denser blocks causing motor blockade, decreased pelvic tone, and impairment of "bearing down" during the second stage of labor. The recent trend of using lower concentrations of local anesthetics in combination with opioids mitigates some of these adverse effects. The parturient is able to achieve analgesia while maintaining motor tone, ability to move, and retain her ability to bear down.20
Personal control over decision-making process during labor has consistently been shown to correlate with maternal satisfaction. Early versus late initiation of LEA has similar effects in all measured outcomes.21 At present, there is insufficient evidence to support the hypothesis that discontinuing LEA late in labor reduces the rate of instrumental delivery.22
Intrathecal Technique (Spinal)
Spinal analgesia involves injecting a local anesthetic and/or opioid into the intrathecal space. Traditionally, a single-shot technique was used to provide excellent analgesia and anesthesia. Its limited duration of action precludes its use in extensive and lengthy procedures. Intrathecal opioids act on the central [mu] receptors and do not produce motor blockade seen with local anesthetics. These may be used for rapidly progressing labor and for the second stage of labor. Spinal administration of opioids is associated with greater incidence of pruritus and fetal bradycardia.23 Continuous intrathecal analgesia can be achieved by placing a catheter in the intrathecal space. It offers greater flexibility because duration of action can be prolonged as necessary. Two areas of concern have limited its overall use-risk of nerve injury and postdural puncture headache (PDPH).
Combined Spinal-Epidural Technique
Traditional epidural techniques have been associated with prolonged labor, increased incidence of instrumental vaginal delivery, and use of oxytocin. CSE has gained popularity and was introduced in an attempt to reduce some of these adverse effects.6,7
CSE involves first placing an epidural needle in the lumbar epidural space using a "loss of resistance" technique. Then, a narrow-gauge spinal needle is introduced through the epidural needle into the intrathecal space. Placement is confirmed by free-flowing cerebrospinal fluid (CSF). A single bolus of intrathecal local anesthetic and/or opioid may be injected. The spinal needle is then removed, and the epidural catheter is advanced through the epidural needle into the epidural space. This catheter may then be used for a continuous infusion. A "walking epidural" is a fine balance between providing analgesia and avoiding excessive motor block of the lower extremities. A single-shot intrathecal opioid injection and/or low-dose local anesthetic infusion is common practice.
CSE provides the opportunity to use the best of both techniques-spinal and epidural. It may achieve rapid, profound anesthesia and the ability to prolong the duration of the block. CSE provides similar hemodynamics and equally high maternal satisfaction compared with LEA. Compared with LEA, women who had CSE had less pain on delivery, lower levels of anxiety, and greater satisfaction perioperatively. It has also been suggested that CSE might decrease the risk of conversion of regional to general anesthesia to 0.16%, compared with 4% with use of spinal and epidural techniques.21 CSE, however, also introduces the potential disadvantages of both techniques. Some concerns include fetal bradycardia, adverse effects, and complications associated with the intrathecal administration of local anesthetics and opioids, and the inability to quickly confirm the functional status of the epidural catheter. The incidence of PDPH after a CSE is less than 1%.21
Use of CSE, however, is controversial. In a 2012 Cochrane review, Simmons et al6 concluded that "there appears to be little basis for offering CSE over epidurals in labor with no difference in overall maternal satisfaction despite slightly faster onset of CSE and conversely less pruritus with low-dose epidurals." They reviewed 27 trials involving 3274 women, out of which 5 outcomes showed a significant difference. CSE was more favorable in relation to speed of onset, need for rescue analgesia, urinary retention, and rate of instrumental delivery. Traditional epidural was more favorable in relation to umbilical venous pH and pruritus. No differences between CSE and traditional epidural were identified for mobilization in labor, need for labor augmentation, rate of cesarean birth, incidence of PDPH, maternal hypotension, neonatal Apgar scores, and umbilical arterial pH.
Peripheral Nerve Blocks
Local anesthetic peripheral nerve blocks that can be performed to provide labor analgesia include paracervical (PCB), pudendal, and lumbar sympathetic blocks. A 2012 Cochrane review24 reported 12 randomized controlled trials assessing pain management compared with opioids and nonopioids. Their assessment was that nerve blocks (in particular PCB) are more effective than placebo, opioid, and nonopioid analgesia for pain management. Advantages and disadvantages of peripheral nerve blocks used in the management of labor pain are summarized in Table 5.
Paracervical Block
Early reports of PCB had demonstrated good to excellent pain relief in the first stage of labor in about 75% of the women. Lidocaine or mepivacaine provides relief for about 1 to 2 hours. Complications attributed to the block included hematoma, peripheral vascular collapse, sacral neuritis, fetal acidosis, fetal bradycardia, and death.25
Postparacervical block fetal bradycardia (PPCBB) is fairly common, and its occurrence has limited the use of this technique. Reported incidence is around 15% (range 0%-40%). It is usually a small decrease in fetal heart rate (FHR) for a short duration. Etiology may include aortocaval compression, paracervical manipulation, pressure on fetal scalp, drug absorption, injection into the fetus, increased uterine activity, use of epinephrine to prolong the block, constriction of uterine blood flow in the area adjacent to the block, and local anesthetic toxicity on the fetus.25
Junttila and colleagues26 compared PCB with single-shot spinal (SSS) analgesia for labor pain in multiparous women. They noted that SSS was more effective in pain relief compared with PCB. PCB did decrease the numeric rating scale for pain to 3 or less in 43% parturients using 0.25% racemic bupivacaine. However, 27% of these needed breakthrough analgesia within 1 hour. No difference in FHR abnormalities between the 2 groups was seen. Their rate of PPCBB was mostly less than 2% (range 0%-12%). Risk of fetal bradycardia from the SSS intrathecal opioid was reported to be similar to other studies (5%-7.7%). They did note a higher rate of PDPH than published reports. Risk of pruritus was also higher in the SSS group.
In summary, PCB is an effective modality with a short time frame, limited by the duration of action of the local anesthetic used. Skill and experience of the operator seem to be the most important variable in determining safety of the procedure. A short-duration technique like PCB may be more appropriate for multiparous women in whom the labor is rapidly progressing, as compared with primiparas. PCB may also be considered if access to neuraxial block is not immediately available. ACOG recommends close monitoring before, during, and after PCB and cautions physicians to avoid blocks in cases of uteroplacental insufficiency, nonreassuring FHR tracings, and imminent delivery.27
Pudendal Block
Pudendal nerves provide sensory innervation to the lower vagina, vulva, perineum, and anus. They also provide motor innervation to the perineal muscles, urethral sphincter, and external anal sphincter. Pudendal blocks are helpful for spontaneous vaginal deliveries, outlet forceps, vacuum deliveries, and repair of perineal lacerations. They are not helpful in cases of midpelvic instrumentation, upper vaginal or cervical laceration repairs, or manual removal of retained placenta.4 Pudendal blocks are usually performed by a transvaginal approach during the second stage of labor by the obstetrician in lithotomy position.
Lumbar Sympathetic Block
Bilateral lumbar sympathetic blockade (LSB) may be used to provide analgesia during the first stage of labor without motor blockade. LSB blocks painful stimuli from the uterus, cervix, and upper one third of the vagina. For the second stage of labor, a pudendal nerve block or subarachnoid block must be added to supplement the perineal pain. LSB is technically more difficult to perform and more painful for the patient. It also does not provide analgesia for the second stage of labor. Hence, it is rarely used in obstetrics compared with neuraxial analgesia.
Parenteral Medications
Even though systemic analgesia is not as effective as neuraxial analgesia, its use is still pertinent in our daily practice. The most commonly used systemic agents are mixed opioid agonists-antagonists and opioids. Systemic analgesia is used alternatively if patients refuse neuraxial analgesia or if neuraxial analgesia is contraindicated. Parenteral medications commonly used for labor analgesia are summarized in Table 6.
Opioid Agonists-Antagonists
The opioid agonist-antagonist class of medication has gained traction primarily because of its adverse effect profile of less nausea, vomiting, and respiratory depression. This class of drugs exhibits a ceiling effect for respiratory depression. Nalbuphine (Nubain) and morphine are equipotent, but Romagnoli and Keats29 reported that nalbuphine doses greater than 30 mg/70 kg failed to increase respiratory depression beyond that of morphine at 20 mg/70 kg. Usual nalbuphine doses used in labor are typically 10 to 20 mg every 4 to 6 hours administered via the subcutaneous (SC), intramuscular (IM), or intravenous (IV) route.
Opioids
Opioids commonly used for labor pain include meperidine, morphine, fentanyl, and remifentanil. Opioids are usually administered via the SC, IM, or IV route. Patient-controlled analgesia (PCA) may employ a basal rate along with the bolus dose. A major advantage of PCA is improved satisfaction because the patient feels in control. It also reduces the lag time between the onset of pain and the administration of the medication resulting in smaller frequent doses and a stable plasma drug level. Overall, there is no clear evidence in the current literature that one opioid is superior to the other with regard to pain control in labor. Opioids usually do not provide complete analgesia; however, they improve pain tolerance in the laboring patient. Disadvantages include a myriad of adverse effects both to the mother and the neonate. Adverse effects seen in the mother include nausea, vomiting, dysphoria, pruritus, drowsiness, delayed gastric emptying, and hypoventilation.
Opioids readily cross the placenta by diffusion. In utero, reduced variability in FHR has been reported.4 Respiratory depression and neurobehavioral changes can occur because of the prolonged metabolism and elimination in the neonate. The fetal blood-brain barrier is also less well-developed, leading to additional effects on the respiratory centers in the medulla. In a meta-analysis by Halpern and colleagues,30 parenteral analgesia was associated with a 2- to 3-fold increased risk of Apgar scores lower than 7 at 5 minutes and a 4-fold increase in the need for neonatal naloxone.
Meperidine
Meperidine (pethidine, Demerol) is the most widely used opioid in the world. Half-life is around 2.5 to 3 hours in the mother, but it is prolonged to 18 to 23 hours in the neonate. One of the major concerns is that meperidine is metabolized in the liver to its active metabolite normeperidine, a potent respiratory depressant. Normeperidine can cross the placenta and impact the neonate, where it has a half-life of 60 hours. A study comparing meperidine to remifentanil was terminated early due to poor neonatal Apgar scores in the meperidine group.31 Meperidine is commonly used treat postoperative shivering.
Morphine
Morphine is metabolized in the liver by conjugation to morphine-3-glucuronide (inactive metabolite) and in small amounts to morphine-6-glucuronide (active metabolite). Morphine is known to cause increased respiratory depression in newborns compared with meperidine, probably due to increased permeability through the blood-brain barrier.4
Fentanyl
Fentanyl is highly lipid soluble, 100 times more potent than morphine, and 80 times more potent than meperidine. It has a rapid onset and a short duration of action. In large doses, fentanyl may accumulate. Compared with meperidine, fentanyl has been demonstrated to have less sedation, vomiting, and significantly lower use of naloxone for respiratory depression in neonates. However, no difference was noted in the neurologic and adaptive scores.4,32
Remifentanil
Remifentanil is an ultra-short-acting [mu]-1 opioid receptor agonist and has recently come into vogue. Its popularity is due to its rapid onset, very short half-life, and rapid metabolism by plasma and tissue esterases. Its time of onset is 30 to 60 seconds, with peak activity at 2.5 minutes. The short-context sensitive half-life of 3.5 minutes also alleviates fear of accumulation with use for a lengthy period.33 The effective analgesic half-life is longer at 6 minutes, so a dose initiated at one contraction should last to the subsequent contractions.4 Although remifentanil crosses the placenta rapidly, it is metabolized and redistributed by the fetus quickly and should not produce neonatal depression.
A meta-analysis published by Schnabel and colleagues33 included 8 trials comparing remifentanil with meperidine. In women who received a remifentanil PCA, they report a lower risk of conversion to epidural analgesia, higher satisfaction rates, and lower pain scores after 1 hour. When compared with fentanyl PCA, the remifentanil PCA arm had better pain scores at 1 hour and comparable risk for conversion to epidural analgesia. Epidural analgesia continued to be the "gold standard" with lower pain scores at 1 hour; however, the patient satisfaction scores were similar. In contrast, Freeman et al,34 in their randomized multicenter trial, demonstrated that patient satisfaction was superior with the epidural arm compared with the remifentanil arm.
Because of its unique pharmacodynamic and pharmaco-kinetic profile, one can make the case for remifentanil as possibly the best opioid for labor analgesia. However, remifentanil is a potent respiratory depressant. Several published reports have demonstrated that oxygen desaturation (Spo2 <95% or need for supplemental oxygen) is a common and significant risk factor associated with the use of remifentanil for labor analgesia.4 Continuous pulse-oximetry monitoring, availability of oxygen, one-on-one nursing, and close monitoring by the physicians are therefore imperative.
Inhalational Agents
Inhalation agents are commonly used to achieve surgical anesthesia. In labor, inhaled analgesia involves achieving subanesthetic levels of the agent that the mother self-administers while remaining awake and maintaining her airway reflexes.35 The use of inhalational analgesia in the United States is uncommon, but the interest in increasing. This is in contrast to the United Kingdom, Scandinavia, Canada, Finland, Australia, and other countries where nitrous oxide (NO) has been used for decades. In the UK, NO is available in 100% of obstetric units.
Nitrous Oxide
Entonox is a blend of NO and oxygen (50:50). Usually the gas is inhaled intermittently via a facemask or mouthpiece through a 1-way valve to limit pollution of the labor suite. The parturient is asked to inhale beginning about 30 seconds before each contraction until the end of the contraction. NO can have an anxiolytic effect during labor and provide analgesia; however, it does not eradicate labor pain from uterine contractions. This has caused controversy, with some studies reporting that up to 30% to 40% of women may receive little to no benefit. Proponents of NO tout the high levels of satisfaction for some women.
A 2012 Cochrane database review35 analyzed 26 studies, randomizing 2959 women for inhaled analgesia in labor pain. The studies lacked in quality, and there was significant heterogeneity in the analysis of pain intensity and relief. The researchers concluded that flurane derivatives such as sevoflurane provide better pain relief in the first stage of labor compared with NO. Increased drowsiness was demonstrated in flurane groups, whereas increased nausea was reported with NO. NO provided a better pain relief profile than placebo or no treatment; however, NO resulted in increased nausea, dizziness, vomiting, and drowsiness.
NO does not affect uterine contractions. It undergoes minimal metabolism, and because of its low solubility, it has a rapid onset and offset. It is transmitted across the placenta. After birth, once the neonate begins breathing, NO is rapidly eliminated. No significant differences have been noted in the Apgar scores in neonates whose mothers received NO compared with those in mothers who did not.25 One concern with the use of NO/oxygen blend is the possibility of diffusion hypoxemia in labor. The evidence for this is limited overall, with the suggestion that combined use of NO with opioids increases the risk.36
Conclusion
A variety of pharmacologic analgesia techniques can provide effective labor analgesia. Among these, LEA is the "gold standard" for pain management during labor. Peripheral nerve blocks, IV opioids, and inhaled NO are alternative analgesia modalities that can be used if neuraxial analgesia is contraindicated or declined by the laboring patient.
References