The ideal labor analgesic technique is safe for both the mother and the infant, does not interfere with the progress of labor and delivery, and provides flexibility in response to changing conditions. In addition, the ideal technique provides consistent pain relief, has a long duration of action, minimizes undesirable side effects (e.g., motor block), and minimizes ongoing demands on the anesthesia provider’s time. No single technique or anesthetic agent is ideal for all parturients during labor. The American Society of Anesthesiologists (ASA) has published practice guidelines for obstetric anesthesia, as well as guidelines for neuraxial anesthesia in obstetric patients. Guidelines promulgated by professional organizations in other countries also address obstetric anesthesia care. All obstetric anesthesia providers should review their country’s respective guidelines. Specific neuraxial techniques for labor analgesia, including their advantages, disadvantages, side effects, and complications, are considered in this chapter.
KeywordsNeuraxial labor analgesia, Epidural analgesia, Combined spinal-epidural analgesia, Vaginal delivery, Neuraxial opioid analgesia
Preparation for Neuraxial Analgesia, 475
Indications and Contraindications, 475
Types of Neuraxial Analgesia, 476
Informed Consent, 478
Equipment and Monitors, 478
Intravenous Hydration, 479
Maternal Positioning, 479
Initiation of Epidural Analgesia, 479
Initiation of Spinal Analgesia, 487
Choice of Drugs, 487
Maintenance of Analgesia, 490
Analgesia/Anesthesia for Vaginal Delivery, 497
Side Effects of Neuraxial Analgesia, 498
Nausea and Vomiting, 499
Urinary Retention, 501
Recrudescence of Herpes Simplex Virus, 501
Delayed Gastric Emptying, 501
Complications of Neuraxial Analgesia, 502
Inadequate Analgesia, 502
Unintentional Dural Puncture, 503
Respiratory Depression, 504
Intravascular Injection of Local Anesthetic, 504
High Neuroblockade and Total Spinal Anesthesia, 505
Extensive Motor Blockade, 506
Prolonged Neuroblockade, 507
Sensory Changes, 507
Back Pain, 507
Pelvic Floor Injury, 507
Effects of Neuraxial Analgesia on the Progress of Labor, 508
Cesarean Delivery Rate, 509
Instrumental Vaginal Delivery Rate, 513
Duration of Labor, 516
Other Factors and Progress of Labor, 520
Effects of Neuraxial Analgesia on the Fetus and Neonate, 520
Conclusions and Recommendations, 522
Epidural analgesia and spinal analgesia are the most effective methods of intrapartum pain relief in contemporary clinical practice. During the first stage of labor, pain results primarily from distention of the lower uterine segment and cervix (see Chapter 20 ). Painful impulses are transmitted by means of visceral afferent nerve fibers, which accompany sympathetic nerve fibers and enter the spinal cord at the 10th, 11th, and 12th thoracic and first lumbar spinal segments. As labor progresses and the fetus descends in the birth canal, distention of the vagina and perineum results in painful impulses that are transmitted via the pudendal nerve to the second, third, and fourth sacral spinal segments. Neuraxial analgesia is the only form of analgesia that provides complete analgesia for both stages of labor. During the first stage of labor, visceral pain impulses entering the spinal cord at T10 to L1 must be blocked. During the late first stage of labor and the second stage of labor, somatic impulses entering the spinal cord from S2 to S4 must also be blocked (see Chapter 20 ).
In a survey of 1000 consecutive women who chose a variety of analgesic techniques for labor and vaginal delivery (including nonpharmacologic methods, transcutaneous electrical nerve stimulation, intramuscular meperidine [pethidine], inhalation of nitrous oxide, epidural analgesia, and a combination of these techniques), pain relief and overall satisfaction with the birth experience were greater in patients who received epidural analgesia. Similarly, randomized studies that have compared epidural analgesia with systemic opioids and/or inhalation analgesia (i.e., nitrous oxide) have shown that pain scores are lower and patients are more satisfied with neuraxial analgesia.
The provision of analgesia for labor may result in other benefits. Effective epidural analgesia reduces maternal plasma concentrations of catecholamines ( Fig. 23.1 ). Decreased alpha- and beta-adrenergic receptor stimulation may result in better uteroplacental perfusion and more effective uterine activity. Painful uterine contractions result in maternal hyperventilation. The hyperventilation, in turn, leads to maternal respiratory alkalosis, a leftward shift of the oxyhemoglobin dissociation curve, increased maternal hemoglobin affinity for oxygen, and reduced oxygen delivery to the fetus. Hypocarbia also leads to hypoventilation between contractions, which may cause a decrease in maternal Pa o 2 . Effective epidural analgesia blunts this “hyperventilation-hypoventilation” cycle. Additionally, one study showed that paternal anxiety levels were lower, and both paternal involvement in the childbirth process and paternal satisfaction were greater, in men whose partners received epidural analgesia than in those whose partners did not. Finally, the presence of an epidural catheter and effective epidural analgesia facilitate the rapid initiation of epidural anesthesia for emergency cesarean delivery. Neuraxial anesthesia for cesarean delivery is associated with greater overall maternal safety than emergency administration of general anesthesia (see Chapter 26 ).
Neuraxial analgesia is not used by all laboring women, although surveys of obstetric anesthesia practice in the United States have shown that the use of neuraxial analgesia has grown over the past four decades. Data collected from the U.S. Standard Certificate of Live Birth in 27 states in 2008 indicated that 61% of women who had a singleton vaginal delivery received neuraxial analgesia. The rate was higher among white women than in women of other races/ethnicities, and it was also higher in larger maternal units than in smaller units. In a 2011 to 2013 survey of 2400 American women, 67% used spinal or epidural analgesia or anesthesia. In France in 2016, over 80% of laboring women used neuraxial analgesia.
The availability of skilled anesthesia providers influences the neuraxial analgesia rate. Other factors include the information and advice provided to pregnant women by obstetricians, nurses, and childbirth education instructors. The personal and cultural expectations of a laboring woman, as well as obstetric complications, also affect the childbirth experience and the use of neuraxial analgesia (see Chapters 20 and 21 ).
Ideally, the anesthesia provider should tailor the analgesic technique to meet the individual parturient’s needs. Factors that should be considered in formulating an analgesic plan for individual parturients include the parturient’s preferences for analgesia, coexisting maternal disease, the airway examination, fetal status, spontaneous versus induced labor, stage of labor, and anticipated risk for operative delivery. The risks and benefits of the various epidural and spinal analgesic techniques should be assessed for each parturient. Good technique requires thoughtful preparation and meticulous attention to detail to ensure maternal and fetal safety.
The ideal labor analgesic technique is safe for both the mother and the infant, does not interfere with the progress of labor and delivery, and provides flexibility in response to changing conditions. In addition, the ideal technique provides consistent pain relief, has a long duration of action, minimizes undesirable side effects (e.g., motor block), and minimizes ongoing demands on the anesthesia provider’s time. No single technique or anesthetic agent is ideal for all parturients during labor. The American Society of Anesthesiologists (ASA) has published practice guidelines for obstetric anesthesia (see Appendix B ), as well as guidelines for neuraxial anesthesia in obstetric patients (see Appendix A ). Guidelines promulgated by professional organizations in other countries also address obstetric anesthesia care. All obstetric anesthesia providers should review their country’s respective guidelines. Specific neuraxial techniques for labor analgesia, including their advantages, disadvantages, side effects, and complications, are considered in this chapter.
Preparation for Neuraxial Analgesia
Indications and Contraindications
Epidural analgesia is indicated to treat the pain experienced by a woman in labor. In its 2017 Practice Bulletin, Obstetric Analgesia and Anesthesia, the American College of Obstetricians and Gynecologists (ACOG) reaffirmed an earlier opinion jointly published by the ASA and ACOG, which stated that “in the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labor.” Furthermore, the ACOG has stated that “decisions regarding analgesia should be closely coordinated among the obstetrician-gynecologist or other obstetric care provider, the anesthesiologist, the patient, and skilled support personnel.” Neuraxial analgesia is an appropriate treatment for the pain of labor, including early labor (defined as regular uterine contractions that cause progressive effacement and dilation of the uterine cervix). Randomized controlled trials and a meta-analysis have confirmed that initiation of neuraxial analgesia in early labor does not increase the risk for cesarean delivery (see later discussion).
Neuraxial analgesia may facilitate an atraumatic vaginal breech delivery, the vaginal delivery of twin infants, and vaginal delivery of a preterm infant (see Chapters 33 and 34 ). By providing effective pain relief, epidural analgesia facilitates blood pressure control in preeclamptic women (see Chapter 35 ). Epidural analgesia also blunts the hemodynamic effects of uterine contractions (e.g., sudden increase in cardiac preload) and the associated pain response (tachycardia, increased systemic vascular resistance, hypertension, hyperventilation) in patients with other medical complications (e.g., mitral stenosis, spinal cord injury, intracranial neurovascular disease, asthma; see Chapter 41 , Chapter 48 , Chapter 52 ).
Box 23.1 lists the contraindications to administration of epidural or spinal analgesia. Some anesthesiologists have suggested that systemic maternal infection, preexisting neurologic disease, or severe stenotic heart lesions are relative contraindications to neuraxial analgesia. However, most cases of systemic infection (especially if properly treated), or neurologic or cardiac disease, do not contraindicate the administration of neuraxial analgesia (see Chapter 36 , Chapter 41 , Chapter 48 ). It is also controversial whether mild or isolated abnormalities in tests of blood coagulation preclude the use of neuraxial analgesia. The dose and timing of administration of drugs administered for thromboprophylaxis must also be considered (see Chapter 44 ). The anesthesia provider should consider the risks and benefits of neuraxial analgesia for each patient individually.
Patient refusal or inability to cooperate
Increased intracranial pressure secondary to a mass lesion
Skin or soft tissue infection at the site of needle placement
Recent pharmacologic anticoagulation a
Uncorrected maternal hypovolemia (e.g., hemorrhage)
Inadequate training in or experience with the technique
Inadequate resources (e.g., staff, equipment) for monitoring and resuscitation
Thorough preparation for neuraxial labor analgesia involves several steps ( Box 23.2 ). These include (1) a review of the parturient’s obstetric history; (2) a focused preanesthetic evaluation that includes maternal obstetric, anesthetic, and health history; and (3) a brief physical examination (i.e., vital signs, airway, heart, lungs, and back). Routine measurement of the platelet count is not necessary; however, assessment of the platelet count and other laboratory measurements may be indicated in selected patients. Similarly, routine intrapartum blood typing and screening or cross-matching is not necessary in healthy parturients, although consideration should be given to sending a blood sample to the blood bank (to facilitate the rapid availability of blood products in case of emergency need). For parturients at increased risk for hemorrhage, intrapartum typing and screening or cross-matching should be performed. Fetal well-being should be assessed by a skilled provider, and equipment (including resuscitation equipment) should be checked by the anesthesia provider (see Box 12.1 ). Informed consent should be obtained (see Chapters 12 and 32 ). Early and ongoing communication among the obstetric and anesthesia providers, nursing staff, and other members of the multidisciplinary team is encouraged.
Communicate (early) with the obstetric provider.
Review parturient’s obstetric history.
Perform focused preanesthetic evaluation.
Review maternal obstetric, anesthetic, and health history.
Perform targeted physical examination (vital signs, airway, heart, lungs, back).
Review relevant laboratory measurements and imaging studies.
Consider need for blood typing and screening or cross-matching.
Formulate analgesia plan.
Obtain informed consent.
Perform equipment check:
Check routine equipment.
Check emergency resuscitation equipment.
Obtain peripheral intravenous access.
Apply maternal monitors (blood pressure, heart rate, pulse oximetry).
Monitor fetal heart rate.
Perform a team time-out.
Types of Neuraxial Analgesia
The technical aspects of neuraxial analgesic/anesthetic techniques are discussed in detail in Chapter 12 . These techniques include continuous epidural, combined spinal-epidural, and caudal analgesia and continuous and single-shot spinal analgesia. Continuous epidural and combined spinal-epidural analgesia are the most common techniques used for neuraxial labor analgesia. There are advantages and disadvantages to each technique ( Table 23.1 ).
|Continuous epidural||Continuous analgesia |
No dural puncture required
Ability to extend analgesia to anesthesia for cesarean delivery
|Slow onset of analgesia |
Larger drug doses required when compared with spinal techniques
Greater risk for maternal local anesthetic systemic toxicity
Greater fetal drug exposure
|Combined spinal-epidural||Continuous analgesia |
Low doses of local anesthetic and opioid
Rapid onset of analgesia
Rapid onset of sacral analgesia
Ability to extend analgesia to anesthesia for cesarean delivery
Complete analgesia with opioid alone
Decreased incidence of failed epidural analgesia
|Increased incidence of pruritus |
Possible higher risk for fetal bradycardia
|Continuous spinal||Continuous analgesia |
Low doses of local anesthetic and opioid
Rapid onset of analgesia
Ability to extend analgesia to anesthesia for cesarean delivery
|Large dural puncture increases risk for post–dural puncture headache |
Possibility of overdose and total spinal anesthesia if the spinal catheter is mistaken for an epidural catheter
|Continuous caudal||Continuous analgesia |
Avoids need to access neuraxial canal through lumbar interspace in patients with previous lumbar spine surgery
|Requires large volumes/doses of drugs |
May be technically more difficult than other neuraxial techniques
Possible higher risk for infection than with other neuraxial techniques
Risk for inadvertent fetal injection
|Single-shot spinal||Technically simple |
Rapid onset of analgesia
Immediate sacral analgesia
Low drug doses
|Limited duration of analgesia|
Continuous lumbar epidural analgesia has been the mainstay of neuraxial labor analgesia for several decades. Placement of an epidural catheter allows analgesia to be maintained until after delivery. No dural puncture is required. The presence of a catheter and effective analgesia allow the conversion to epidural anesthesia should cesarean delivery be necessary. Injection of a local anesthetic in the lumbar epidural space allows both cephalad and caudad spread of the anesthetic solution.
Analgesia is initiated by bolus injection of drug(s) through the epidural needle, catheter, or both. Analgesia is maintained with anesthesia provider-, patient-, or infusion pump–administered intermittent bolus injections or a continuous epidural infusion, or a combination of these techniques. The catheter is removed after delivery when there is no further need for analgesia or anesthesia.
Combined Spinal-Epidural Analgesia
Combined spinal-epidural (CSE) analgesia has become increasingly popular in the past 20 years. Onset of complete analgesia is significantly faster than with epidural techniques (2 to 5 minutes versus 10 to 15 minutes, respectively). In a meta-analysis of the onset time of CSE compared with low-dose epidural analgesia, the mean difference in onset was –5.4 minutes (95% confidence interval [CI], –7.3 to –3.6). More women with spinal analgesia than with epidural analgesia had effective analgesia at 10 minutes (relative risk [RR], 1.9; 95% CI, 1.5 to 2.5). In particular, the onset of sacral analgesia is significantly slower after the initiation of lumbar epidural analgesia than with spinal analgesia. It may take several hours of lumbar epidural infusion, or several bolus injections of local anesthetic into the lumbar epidural space, to achieve sacral analgesia. Rapid onset of sacral analgesia is advantageous in the parturient in whom analgesia is initiated late in the first stage of labor or in a parous parturient with rapid progress of labor. Spinal analgesia requires significantly lower drug doses to attain effective analgesia than does epidural analgesia; therefore, the risk for local anesthetic systemic toxicity is decreased. In addition, there is less systemic absorption of spinal anesthetic agents into the maternal circulation, so maternal and fetal plasma drug concentrations are lower with spinal than with epidural analgesia.
An additional advantage of spinal analgesia is that complete analgesia for early labor can be accomplished with the intrathecal injection of a lipid-soluble opioid without the addition of a local anesthetic. Thus, motor blockade is avoided and the risk for hypotension is lower. This method is ideal for patients who wish to ambulate or for those with preload-dependent cardiac conditions such as stenotic heart lesions. Finally, use of the CSE technique may lower the incidence of failure of epidural analgesia (e.g., a nonfunctioning epidural catheter). The likelihood of an epidural catheter placed for labor analgesia failing to provide satisfactory anesthesia for a subsequent cesarean delivery was more than five times higher for catheters placed as part of an epidural technique than for catheters placed as part of a CSE technique.
Several studies have described a modification of CSE analgesia in which a dural puncture is made with a small-gauge spinal needle but no drug is injected into the subarachnoid space (dural puncture epidural analgesia). Results of studies are inconsistent, but two studies found that blockade of sacral dermatomes occurred more frequently after injection of epidural local anesthetic and opioid in parturients with a dural puncture than in those without. Presumably, enhanced sacral analgesia occurs because of increased migration of anesthetic solution across the dural puncture site.
CSE analgesia has several possible undesirable side effects. Dural puncture is required to initiate CSE analgesia, although puncture with a small-gauge pencil-point needle does not appear to increase the risk for post–dural puncture headache. A more serious concern, however, is that dural puncture during labor may be a risk factor for postpartum neuraxial infection, a rare but potentially life-threatening complication (see Chapter 31 ).
The incidence of pruritus is higher with intrathecal opioid administration than with epidural opioid administration. Another purported disadvantage of the CSE technique is that the correct placement of the epidural catheter in the epidural space cannot be verified until spinal analgesia or anesthesia wanes. Therefore, it has been suggested that if a functioning epidural catheter is important to the safe care of the mother and fetus (e.g., in the setting of a suspected difficult airway or nonreassuring fetal status), an epidural rather than CSE technique is indicated. However, in a retrospective study that included 2395 neuraxial labor analgesia procedures, the CSE technique did not result in delayed recognition of epidural catheter failure, and the overall catheter failure rate was lower when the catheter was sited as part of CSE analgesia.
The most common CSE technique for labor analgesia is the needle-through-needle technique in a midlumbar interspinous space (see Chapter 12 ). Analgesia is maintained via the epidural catheter, as with traditional epidural analgesia.
Continuous Spinal Analgesia
Continuous spinal analgesia is used occasionally for labor analgesia but is not practical for most parturients. Several spinal catheters are commercially available in the United States and Europe, but their use for continuous labor analgesia has not been well studied. Because the available catheters require dural puncture with a large-gauge needle, the technique may be associated with an unacceptably high incidence of post–dural puncture headache. However, continuous spinal analgesia is a management option in patients with unintentional dural puncture. Continuous spinal analgesia can readily be converted to surgical anesthesia if necessary.
Continuous caudal epidural analgesia is used infrequently in modern obstetric anesthesia practice. It is technically more difficult to place a caudal catheter than a lumbar epidural catheter. Large volumes of anesthetic solution are required to extend neuroblockade to the low thoracic spinal segments, resulting in higher maternal plasma concentrations of drug. There is a risk for needle/catheter misplacement and direct injection into the fetus. However, this technique is useful for parturients in whom access to the lumbar spinal canal is not possible (e.g., because of a fused lumbar spine).
In general, single-shot techniques (spinal, lumbar epidural, or caudal) are not useful for most laboring women because of their limited duration of action. These techniques may be indicated for parturients who require analgesia or anesthesia shortly before anticipated vaginal delivery or in settings in which continuous neuraxial analgesia is not possible. Intrathecal morphine has been combined with bupivacaine and sufentanil or fentanyl in an attempt to prolong analgesia. A 2016 meta-analysis of five randomized-controlled trials comparing single-shot spinal labor analgesia (bupivacaine and sufentanil or fentanyl) with and without morphine concluded that more adequately powered trials are necessary to determine the benefits and harms of the technique.
Informed consent is an important aspect of preparation for neuraxial labor analgesia (see Chapters 12 and 32 ). The preanesthetic evaluation and informed consent process allow the anesthesia provider to allay the parturient’s concerns and to demonstrate a commitment to her care. Most laboring women understand the need for informed consent and appreciate the opportunity to participate in decisions about their care.
Equipment and Monitors
Resuscitation equipment, drugs, and supplies must be immediately available for the management of serious complications of neuraxial analgesia (e.g., hypotension, total spinal anesthesia, local anesthetic systemic toxicity) (see Box 12.1 ). Emergency airway equipment should be checked before the administration of neuraxial analgesia.
During the initiation of neuraxial analgesia, the parturient’s oxygen saturation is measured continuously and the blood pressure is assessed every 2 to 3 minutes for 15 to 20 minutes after the neuraxial anesthetic administration, or until the mother is hemodynamically stable (see Chapter 12 ). The fetal heart rate (FHR) should be monitored before and after the initiation of neuraxial analgesia; it may be difficult to monitor the FHR during the actual procedure. During maintenance of neuraxial analgesia, maternal blood pressure is measured every 15 to 30 minutes, or more frequently if hypotension ensues. The sensory level of analgesia and the intensity of motor block ( Box 23.3 ) are assessed after the administration of the test and therapeutic doses of local anesthetics. Subsequently, sensory level, motor block, and pain control are assessed at regular intervals.
Complete: patient unable to move feet or knees
Almost complete: patient able to move feet only
Partial: patient just able to move knees
None: patient capable of full flexion of knees and feet
Before the initiation of neuraxial analgesia, ultrasonographic imaging of the back may be helpful, especially in parturients whose landmarks are difficult to palpate.
Placement of an intravenous catheter (preferably 18-gauge or larger) and correction of hypovolemia with intravenous hydration are necessary before the initiation of neuraxial analgesia to mitigate hypotension that can result from sympathetic blockade. Data from small studies are conflicting as to whether a fluid bolus administered immediately before the initiation of analgesia decreases the risk for nonreassuring FHR patterns. The ASA Task Force on Obstetric Anesthesia is silent on intravenous fluid management, although many anesthesia providers administer approximately 500 mL of lactated Ringer’s solution (without dextrose) immediately before or during the initiation of analgesia. Severe hypotension is less likely with the contemporary practice of administering a dilute solution of local anesthetic for epidural analgesia or an intrathecal opioid for spinal analgesia.
Studies of intravenous hydration and spinal anesthesia for cesarean delivery suggest that there is no advantage to administering the fluid before the initiation of anesthesia (preload) compared with administering the fluid at the time of initiation of anesthesia (co-load). Rarely, hydration should be guided by serial assessment of intravascular fluid volume (e.g., central venous pressure, transthoracic echocardiography). Fluid administration should be judicious in parturients at risk for pulmonary edema (e.g., women with preeclampsia with severe features). Anesthesia and obstetric providers should avoid the bolus administration of dextrose-containing solutions in laboring women.
Either the lateral decubitus or the sitting position can be used during initiation of neuraxial analgesia (see Chapter 12 ). Factors to consider when positioning the parturient for the procedure include patient comfort, avoidance of aortocaval compression, ability to monitor the FHR, provider comfort and experience, and optimal positioning of the spine and palpation of landmarks. Patient position relative to the baricity of the anesthetic solution should be considered during initiation of spinal analgesia/anesthesia. There is little evidence that patient position influences the extent of neuroblockade during initiation of epidural analgesia/anesthesia. After completion of the procedure, parturients should be assisted to the lateral position for the first 15 to 30 minutes after the neuraxial injection to alleviate aortocaval compression.
Initiation of Epidural Analgesia
A procedure for initiating epidural labor analgesia is outlined in Box 23.4 . Commonly, after siting the epidural catheter in the epidural space, a test dose is administered to rule out intrathecal or intravascular placement of the epidural catheter. After a negative test, epidural analgesia is established with the incremental injection of a local anesthetic, usually in combination with a lipid-soluble opioid. Maternal vital signs are monitored, and clinical analgesia is verified.
Complete preparation for neuraxial analgesia checklist (see Box 23.2 ).
Position patient with the help of an assistant (lateral decubitus or sitting).
Initiate maternal blood pressure and pulse oximetry monitoring and fetal heart rate monitoring.
Initiate an intravenous fluid bolus (500 mL of lactated Ringer’s solution).
Site epidural catheter in epidural space using sterile technique.
Administer an epidural test dose (see Table 12.2 ).
If the test dose is negative, secure epidural catheter and position patient in the lateral position.
Administer 5 to 15 mL of epidural local anesthetic, in 5-mL increments (usually low concentration of local anesthetic combined with a lipid-soluble opioid [see Table 23.2 ]).
Monitor maternal blood pressure every 2 to 3 minutes for 15 to 20 minutes, or until parturient is hemodynamically stable.
Assess pain score and extent of sensory blockade (cephalad and caudad).
Initiate maintenance epidural analgesia (see Table 23.5 ).
Epidural Test Dose
The purpose of the test dose is to help identify unintentional cannulation of a vein or the subarachnoid space. The test dose should contain a dose of local anesthetic and/or another marker sufficient to allow the recognition of intravenous or subarachnoid injection but not so large as to cause systemic toxicity or total spinal anesthesia. The most common intravascular test dose contains epinephrine (adrenaline) (see Chapter 12 ).
The use of the epinephrine test dose in obstetrics is not without detractors. Some anesthesia providers fear that intravenous injection of epinephrine may decrease uteroplacental perfusion and precipitate fetal compromise. However, there has been no report of adverse neonatal outcome after intravenous injection of an epinephrine-containing test dose. Another argument against routine use of a test dose is that aspiration of multi-orifice catheters is 98% sensitive in identifying their intravascular location. (The sensitivity of aspiration is significantly lower for single-orifice catheters.) The epidural test dose contributes to undesirable motor blockade. Finally, because modern epidural labor analgesia involves the infusion of a low concentration of local anesthetic solution, unintentional intravascular or intrathecal administration is not likely to result in cardiovascular collapse or total spinal anesthesia.
Others argue that the test dose still has a role in obstetric anesthesia practice. Large volumes of a concentrated local anesthetic solution are still routinely administered for emergency cesarean delivery. Although not a safety issue, it is easier for the parturient and anesthesia provider to identify a misplaced catheter at the time of initial placement and to replace the catheter at that time rather than identify the misplaced catheter after the sterile field has been breached and the parturient repositioned.
The epinephrine test dose is less specific in laboring women because cyclic changes in maternal heart rate complicate interpretation of its effects. For this reason, if used, the test dose should be given immediately after a uterine contraction so there is less confusion as to whether tachycardia is caused by pain or intravenous epinephrine. Other methods of detecting intravascular injection are discussed in Chapter 12 .
No matter whether a formal test dose is used or not, it is imperative that the anesthesia provider take the time to look for evidence of unintentional intrathecal or intravascular injection of local anesthetic. Finally, every anesthesia provider should remember that no single test dose regimen can exclude every case of unintentional intravenous or subarachnoid injection. Box 12.3 summarizes steps that may be taken to decrease the risk for unintentional intravenous or subarachnoid injection of local anesthetic.
Choice of Drugs
The ideal analgesic drug for labor would provide rapid onset of effective analgesia with minimal motor blockade, minimal risk for maternal toxicity, and negligible effect on uterine activity and uteroplacental perfusion. It would undergo limited transplacental transfer and thus have minimal direct effect on the fetus. Finally, this ideal agent would have a long duration of action. Although this perfect analgesic drug does not exist, the combination of a local anesthetic with an opioid allows us to approach this goal.
Traditionally, local anesthetics were administered to block both the visceral pain of labor (lower uterine segment distention and cervical dilation) and the somatic pain (descent of the fetus in the birth canal). More than 40 years ago, investigators identified dense concentrations of opioid receptors in the dorsal horn of the spinal cord. The application of small doses of an opioid to these receptor sites generates a specific and profound opioid response. The introduction of neuraxial opioids to the armamentarium of the obstetric anesthesia provider moved us closer to the prediction made by Benjamin Rush in 1805: “A medicine would be discovered which should suspend sensibility altogether and leave irritability or powers of motion unimpaired.” Intrathecal opioids effectively relieve the visceral pain of the early first stage of labor, although they must be combined with a local anesthetic to effectively relieve the somatic pain of the late first stage and the second stage of labor. The combination of a local anesthetic with a lipid-soluble opioid allows for the use of lower doses of each agent, thus minimizing undesirable side effects. For example, when used alone without an opioid, the local anesthetic dose required for effective epidural analgesia is associated with an unacceptably high incidence of motor blockade. Similarly, used alone, high doses of epidural opioid are required for satisfactory analgesia during early labor, and such doses are associated with significant systemic absorption and systemic side effects. The addition of an opioid to the local anesthetic also shortens latency, an important aspect of labor analgesia, especially with the use of long-acting (and therefore, long-latency) local anesthetics. Thus, contemporary epidural labor analgesia practice most often incorporates low doses of a long-acting local anesthetic combined with a lipid-soluble opioid.
Traditionally, the amide local anesthetic bupivacaine has been the most commonly used agent for epidural labor analgesia. Bupivacaine is highly protein-bound, a feature that limits transplacental transfer. The umbilical vein–to–maternal vein concentration ratio is approximately 0.3. After epidural administration of bupivacaine (without opioid) during labor, the patient first perceives pain relief within 8 to 10 minutes, but approximately 20 minutes are required to achieve the peak effect. Duration of analgesia is approximately 90 minutes. Bupivacaine 6.25 to 12.5 mg (e.g., 10 to 20 mL of a 0.0625% solution, or 5 to 10 mL of a 0.125% solution) combined with fentanyl or sufentanil is adequate to initiate labor analgesia in most parturients ( Table 23.2 ).
|Drug||Epidural Analgesia a||Spinal Analgesia|
|Local Anesthetics b|
|Fentanyl||50–100 µg||15–25 µg d|
|Sufentanil||5–10 µg||1.5–5 µg d|
|Morphine c||NA||125–250 µg d|
|Meperidine c||NA||10–20 mg|
b The local anesthetic dose/concentration and the fentanyl or sufentanil dose are reduced if the drugs are combined or if a local anesthetic-containing epidural test dose is administered before the initial therapeutic dose. The dose of opioid should be reduced or the opioid omitted if the parturient has recently received systemic opioid analgesia.
c Lidocaine, morphine, and meperidine are not commonly used for labor analgesia because of their short duration of action (lidocaine), long latency (morphine), and high incidence of nausea and vomiting (morphine and meperidine).
The potency of local anesthetics for neuraxial labor analgesia is often assessed by determining the median effective concentration of local anesthetic solution when administered as a 20-mL epidural bolus (this concentration is sometimes referred to as the minimum local anesthetic concentration [MLAC]). It is lower for women in early labor than in late labor, and it is also lower when the local anesthetic is combined with a lipid-soluble opioid.
It is important to consider both the local anesthetic dose and concentration for initiation and maintenance of epidural analgesia. Christiaens et al. randomly assigned parturients to receive epidural bupivacaine 20 mg diluted in 4 mL, 10 mL, or 20 mL (0.5%, 0.2%, and 0.1% solutions, respectively). Analgesia in the 10-mL and 20-mL groups was superior to that in the 4-mL group, and duration of analgesia was longest in the 20-mL group. Lyons et al. compared the minimum local anesthetic volume (MLAV) and minimum local anesthetic dose (MLAD) for 0.125% and 0.25% bupivacaine for epidural labor analgesia. Bupivacaine 0.125% produced analgesia equivalent to that provided by bupivacaine 0.25%, with a 50% increase in required volume and a 25% reduction in dose ( Table 23.3 ). Stated differently, a dose-sparing effect is achieved by administering a 0.125% solution of bupivacaine rather than a 0.25% solution. Ginosar et al. randomized parturients to receive maintenance of analgesia with an epidural infusion of either bupivacaine 0.25% at 5 mL/h or bupivacaine 0.0625% at 20 mL/h (10 mg/h in both groups). The median bupivacaine dose was lower and patient satisfaction was greater with bupivacaine 0.0625% than with bupivacaine 0.25%. Together, these data suggest that epidural analgesia and safety are improved with the use of low concentration–high volume local anesthetic solutions.
|Median Effective Volume a|
|Up-down analysis (mL)||13.6 (12.4–14.8)||9.2 (6.9–11.5)|
|Probit analysis (mL)||13.5 (11.4–15.9)||8.6 (7.2–10.3)|
|Median Effective Dose b|
|Up-down analysis (mg)||17.0 (15.5–18.5)||23.1 (17.2–28.9)|
|Probit analysis (mg)||16.8 (14.2–19.9)||21.5 (17.9–25.7)|
Ropivacaine, a relatively newer amide local anesthetic, is similar to bupivacaine in structure and pharmacodynamics (see Chapter 13 ). It is a homologue of bupivacaine and mepivacaine, but unlike these other local anesthetics it is formulated as a single-levorotary enantiomer rather than a racemic mixture. Studies of pregnant sheep have demonstrated that clinically relevant plasma concentrations of ropivacaine do not adversely affect uterine blood flow.
Studies in vitro and in vivo have shown that ropivacaine is less cardiodepressant and arrhythmogenic than bupivacaine when doses of equal mass are compared. Ropivacaine is cleared more rapidly than bupivacaine after intravenous administration in both pregnant and nonpregnant sheep. Consequently, a larger dose of drug—but not a higher plasma concentration—is required to produce systemic toxicity. These findings suggest that ropivacaine may have a greater margin of safety than bupivacaine if unintentional intravenous injection occurs in pregnant women. However, many early investigations assumed that ropivacaine and bupivacaine are equipotent; subsequent studies have demonstrated that ropivacaine is 25% to 40% less potent than bupivacaine. In one study that characterized the full dose-response curves, the slope of the bupivacaine and ropivacaine curves were similar, suggesting that the nature of the drug-receptor interaction is not different between the two drugs. When ropivacaine concentrations are adjusted for this difference in potency, there is a less clear advantage for ropivacaine in terms of the risk for systemic toxicity. In reality, systemic toxicity is not a major concern with the contemporary administration of a dilute solution of local anesthetic for epidural labor analgesia.
Several studies that compared equal concentrations of ropivacaine and bupivacaine given by patient-controlled epidural analgesia (PCEA) have not found any significant difference in clinical efficacy between the two local anesthetics. Other studies that adjusted for the potency difference and compared equipotent concentrations (e.g., 0.0625% bupivacaine versus 0.1% ropivacaine) also found no difference in clinical efficacy. It is important to recognize that potency is an unchanging property of a drug, whereas clinical efficacy is influenced by multiple variables. For example, ropivacaine has a longer duration of analgesia than bupivacaine, which may offset its lesser potency when it is administered by continuous epidural infusion.
Early clinical studies suggested that ropivacaine is associated with less motor block than bupivacaine ; avoidance of motor blockade is a desirable characteristic of neuraxial analgesia during labor. However, these studies also compared equal concentrations of ropivacaine and bupivacaine, and the observed lower degree of motor blockade may reflect the lesser potency of ropivacaine. A study of the relative motor-blocking potencies of epidural ropivacaine and bupivacaine showed that ropivacaine was less potent than bupivacaine in terms of motor blockade, a finding that corresponded to the relative analgesic potencies of the two drugs. The differences in potency of motor blockade may not be relevant with the use of low concentrations of local anesthetic. Several clinical studies and a well-conducted meta-analysis of studies that compared epidural ropivacaine and bupivacaine did not demonstrate an advantage for ropivacaine in terms of outcome of labor (see later discussion), although the incidence of motor blockade was less in the ropivacaine groups.
There is no clear evidence of greater patient safety, lower risk for instrumental vaginal delivery, or other improved outcomes when ropivacaine is used to provide epidural labor analgesia. A 2010 review concluded that there is no advantage to the routine use of ropivacaine compared with bupivacaine for labor analgesia. In contrast, ropivacaine offers greater patient safety in settings in which high concentrations and greater volumes of drugs are administered (e.g., brachial plexus blockade or epidural anesthesia for cesarean delivery).
Like bupivacaine, ropivacaine is often combined with fentanyl or sufentanil for labor analgesia. Ropivacaine concentrations used to initiate epidural analgesia range from 0.08% to 0.2% (see Table 23.2 ). Higher concentrations are used if the drug is administered without an opioid.
Levobupivacaine is the levorotary enantiomer of bupivacaine (which is a racemic mixture). It is not available in the United States. Both preclinical and clinical studies have suggested that, like ropivacaine, levobupivacaine has less potential for cardiotoxicity than bupivacaine when equal doses of the two drugs are compared. One study found that levobupivacaine was essentially equipotent to bupivacaine with a potency ratio of 0.98; however, the 95% CI was wide (0.67 to 1.41). Other studies have suggested that levobupivacaine and ropivacaine have similar potency. In an MLAC study that compared the motor blocking potency of bupivacaine and levobupivacaine, levobupivacaine was less potent than bupivacaine (potency ratio, 0.87; 95% CI, 0.77 to 0.98). Beilin et al. compared epidural bupivacaine, ropivacaine, and levobupivacaine (0.0625% with fentanyl 2 µg/mL *
* The Institute of Safe Medicine Practices (ISMP) has recommended that health care providers never use µg as an abbreviation for micrograms, but rather they should use mcg ( www.ismp.org/tools/errorproneabbreviations.pdf , accessed October 2017). The use of the symbol µg is frequently misinterpreted and involved in harmful medication errors. The abbreviation may be mistaken for mg (milligrams), which would result in a 1000-fold overdose. The symbol µg should never be used when communicating medical information, including pharmacy and prescriber computer order entry screens, computer-generated labels, labels for drug storage bins, and medication administration records. However, most scholarly publications have continued to use the abbreviation µg. The editors have chosen to retain the use of the abbreviation µg throughout this text. However, the editors recommend the use of the abbreviation mcg in clinical practice.) for labor analgesia. There were no differences among groups in obstetric outcomes, although the incidence of motor blockade was lower in the ropivacaine and levobupivacaine groups. Therefore, although epidural bupivacaine is more potent than ropivacaine for both sensory and motor blockade during labor, and may be more potent than levobupivacaine, there do not appear to be any clinical advantages of one drug over the other two drugs for epidural labor analgesia.
Lidocaine is an amide local anesthetic with a duration of action intermediate between those of bupivacaine and 2-chloroprocaine. During labor, the administration of a 0.75% to 1.0% solution of lidocaine typically provides satisfactory analgesia. However, lidocaine is not commonly used for initiation or maintenance of epidural labor analgesia, in part because of its shorter duration of action in comparison with bupivacaine, ropivacaine, and levobupivacaine. Lidocaine is less protein-bound than these other amide local anesthetics, and at delivery, the umbilical vein–to–maternal vein lidocaine concentration ratio is approximately twice that of bupivacaine. Early studies discouraged the epidural administration of lidocaine in pregnant women because epidural lidocaine was associated with abnormal neonatal neurobehavioral findings. Subsequently, larger, more carefully controlled studies have demonstrated that the epidural administration of lidocaine, bupivacaine, and 2-chloroprocaine have similar neonatal outcomes. Although some investigators have observed subtle differences in neurobehavior between infants exposed to lidocaine and those exposed to other local anesthetics, these differences are within the inherent variability of the examinations and are not clinically significant. Other factors (e.g., mode of delivery) appear to be much more important determinants of neonatal condition.
An ester local anesthetic, 2-chloroprocaine has a rapid onset of action. Epidural administration of 10 mL of 2% 2-chloroprocaine provides effective analgesia for approximately 40 minutes. The short duration of action limits its usefulness during labor. In addition, the epidural administration of 2-chloroprocaine may adversely affect the efficacy of subsequently administered epidural bupivacaine and opioids, although it is unclear whether the mechanism is related to pharmacokinetic or pharmacodynamic properties of the drug. In obstetric practice, 2-chloroprocaine is most commonly used for extension of epidural labor analgesia for instrumental vaginal delivery (see later discussion) or emergency cesarean delivery (see Chapter 26 ).
Lipid-soluble opioids: fentanyl and sufentanil.
Morphine was one of the first opioids to be studied for labor analgesia. However, because of its long latency, side effects, and inconsistent analgesia, morphine has largely been replaced by the lipid-soluble opioids fentanyl and sufentanil (see Chapter 13 ). The lipid-soluble agents have a rapid onset of action. Permeability (of the dura-arachnoid) is not a rate-limiting factor, and increasing the concentration gradient (by administration of a larger dose) facilitates faster entry into the spinal cord. The high lipid solubility of these agents also results in a shorter duration of action and greater systemic absorption than occurs with water-soluble drugs.
Some investigators have suggested that the improved analgesia results from a supraspinal action rather than a primary spinal action. However, several studies have refuted this theory, including studies of epidural opioid administration by bolus and continuous infusion. Vella et al. observed that the initiation of epidural analgesia with 0.25% bupivacaine with epidural fentanyl 80 µg resulted in more rapid, complete, and prolonged analgesia than intravenous fentanyl 80 µg, even though plasma fentanyl concentrations were higher in the intravenous group. Similarly, D’Angelo et al. demonstrated that a continuous epidural infusion but not an intravenous infusion of fentanyl reduced epidural bupivacaine requirements in laboring women. Polley et al. determined that the MLAC of epidural bupivacaine administered as a 20-mL bolus in laboring women was reduced from 0.064% to 0.034% when epidural rather than intravenous fentanyl was co-administered with bupivacaine. Ginosar et al. determined that the MLAC of bupivacaine administered by continuous epidural infusion during labor was lower by a factor of three when it was co-administered with an epidural (rather than intravenous) fentanyl infusion. Finally, in a volunteer study, lumbar epidural administration of fentanyl resulted in tolerance to experimental pain at a lumbar but not a cranial dermatome, whereas intravenous fentanyl administration resulted in pain tolerance at both dermatomes. These studies strongly suggest that during labor, epidural fentanyl provides analgesia primarily through a spinal site of action.
Epidural fentanyl alone provides moderate analgesia in early labor, but the dose needed to provide complete analgesia is accompanied by significant side effects (e.g., pruritus, nausea, maternal sedation, perhaps neonatal depression). In addition, epidural administration of an opioid alone provides inadequate analgesia during the late first stage as well as the second stage of labor. In a study comparing sufentanil alone, sufentanil with bupivacaine, and bupivacaine alone, women randomly assigned to the sufentanil-alone (30 µg) group experienced satisfactory analgesia after the initial dose but not after subsequent doses. However, the initial dose was administered after an epidural test dose that contained lidocaine 60 mg. In clinical practice, epidural fentanyl and sufentanil are usually administered with a local anesthetic for the initiation of analgesia (at a minimum, with a local anesthetic–containing epidural test dose).
In clinical practice, either fentanyl or sufentanil is frequently combined with a low-concentration, long-acting amide local anesthetic to initiate epidural labor analgesia. Epidural opioid administration allows the anesthesia provider to use a more dilute solution of local anesthetic to provide epidural labor analgesia. Epidural fentanyl and sufentanil decrease epidural bupivacaine requirements during labor in a dose-dependent fashion ( Fig. 23.2 ). The reduction in MLAC by the addition of fentanyl or sufentanil is observed with levobupivacaine, ropivacaine, and 2-chloroprocaine as well as bupivacaine.
The addition of a lipid-soluble opioid to a local anesthetic for neuraxial labor analgesia decreases latency, prolongs the duration of analgesia, and improves the quality of analgesia. For example, Reynolds and O’Sullivan showed that epidural bupivacaine 10 mg combined with fentanyl 100 µg was more effective for the treatment of breakthrough pain and had a faster onset and longer duration of action than either bupivacaine 25 mg or fentanyl 100 µg administered alone. Van Steenberge et al. observed that the mean (± SD) onset of analgesia was 10.3 ± 3.8 minutes in women randomly assigned to receive bupivacaine 12.5 mg without sufentanil, whereas it was 8.7 ± 2.6 minutes in women who received bupivacaine combined with sufentanil 7.5 µg. Duration of analgesia was longer in the sufentanil group (131 minutes versus 86 minutes without sufentanil). In another study, the addition of fentanyl 100 µg to 0.125% bupivacaine prolonged the mean duration of analgesia from 55 minutes to 106 minutes.
The quality of analgesia is also better with the addition of an opioid to the local anesthetic. For example, 86% of women rated their analgesia as excellent after epidural analgesia was initiated with bupivacaine combined with sufentanil, compared with 50% of those who received bupivacaine without sufentanil. The percentage of women who experienced no or short periods of pain during the first stage of labor was 94% in women who received sufentanil and 76% in women who did not. After initiation of analgesia with 0.125% bupivacaine with epinephrine 1.25 µg/mL, 43% of women randomly assigned to receive epidural fentanyl 100 µg rated their analgesia as excellent, compared with 6% in a control group that did not receive fentanyl.
The dose-sparing effects of fentanyl and sufentanil are also evident when the drugs are combined with a low-concentration solution of bupivacaine used for the maintenance of analgesia throughout labor. For example, the total bupivacaine dose (mean ± SD) was 34 ± 17 mg in laboring women who received 0.125% bupivacaine/epinephrine 1.25 µg/mL with sufentanil, compared with 42 ± 19 mg in those who received bupivacaine/epinephrine without sufentanil. Similarly, in women randomly assigned to receive bupivacaine/epinephrine with or without fentanyl 100 µg, the total bupivacaine dose was 55 mg or 110 mg, respectively. Advantages of a lower total dose of local anesthetic include (1) decreased risk for local anesthetic systemic toxicity, (2) decreased risk for high or total spinal anesthesia, (3) decreased plasma concentrations of local anesthetic in the fetus and neonate, and (4) decreased intensity of motor blockade.
Several studies have directly compared the administration of epidural fentanyl or sufentanil combined with a local anesthetic for the initiation of labor analgesia. There were no differences in analgesia in women in early labor randomly assigned to receive either fentanyl 100 µg or sufentanil 20 µg immediately after a lidocaine 45-mg/epinephrine 15-µg test dose. In contrast, a second study demonstrated slightly better analgesia 20 minutes after injection of 0.125% bupivacaine (15 mg) with sufentanil 15 µg than after the same dose of bupivacaine with fentanyl 75 µg.
In the United States, fentanyl is more commonly used because historically it had a lower acquisition cost than sufentanil. Additionally, the concentration of the commercially available sufentanil preparation (50 µg/mL) may make drug errors more likely with sufentanil than with fentanyl because sufentanil doses significantly lower than 50 µg are used for initiation of epidural analgesia.
There are few rigorous dose-response studies of epidural fentanyl or sufentanil combined with bupivacaine for initiation of epidural labor analgesia. Herman et al. randomly assigned 100 laboring women with a cervical dilation of 5 cm or less to receive 0.125% bupivacaine 10 mL, combined with fentanyl 0 to 100 µg (in 25-µg increments) or sufentanil 0 to 25 µg (in 5-µg increments), injected after a negative epidural test dose (bupivacaine 7.5 mg with epinephrine 15 µg). Using a probit dose-response analysis, these researchers calculated the effective dose in 95% of subjects (ED 95 ) to be 50 µg for fentanyl and 8 µg for sufentanil; these figures equate to a sufentanil-to-fentanyl potency ratio of 6.3 : 1. Capogna et al. sought to determine the median effective analgesic dose (ED 50 ) of epidural fentanyl and sufentanil alone (no local anesthetic) for the initiation of epidural analgesia in nulliparous women with a cervical dilation between 2 and 4 cm. The ED 50 of fentanyl was 124 µg (95% CI, 118 to 131), and the ED 50 of sufentanil was 21 µg (95% CI, 20 to 22), with a potency ratio of 5.9 : 1. The potency ratio in volunteers subjected to an electrical stimulus was approximately 5 : 1. Taken together, these data suggest that the potency ratio of sufentanil to fentanyl administered into the epidural space is approximately 6 : 1.
Several studies have compared bupivacaine combined with fentanyl 50 µg and 100 µg. No differences in the onset, duration, and quality of analgesia were noted in Asian women randomly assigned to receive 0.125% bupivacaine (10 mg) combined with either 50 or 100 µg of fentanyl. In contrast, when 0.125% bupivacaine (15 mg) with epinephrine 15 µg was administered to laboring Italian women with either 50 or 100 µg of fentanyl, there was no difference in the onset or duration of analgesia, but more women in the 100-µg group had excellent analgesia.
There were no differences in latency, duration of analgesia, and quality of analgesia when analgesia was induced with 0.125% bupivacaine (12.5 mg)/epinephrine 12.5 µg and either 7.5 or 15 µg of sufentanil. Similarly, after injection of a lidocaine 60-mg/epinephrine 15-µg test dose, another study found no differences in latency and quality of analgesia among epidural sufentanil doses of 5, 10, 20, 30, 40, and 50 µg. However, the duration of analgesia was longer after the higher doses of sufentanil.
The range of fentanyl and sufentanil doses used for the initiation of epidural labor analgesia is shown in Table 23.2 . Pain and analgesic requirements vary depending on several factors, including parity, stage of labor, presence of ruptured membranes, oxytocin augmentation, and whether the opioid is administered in combination with a local anesthetic. One study reported that the ED 50 of epidural sufentanil was higher in women undergoing prostaglandin induction of labor than in women with spontaneous labor. Conell-Price et al. developed a model of labor pain in nulliparous women and found that the use of oxytocin was associated with 48% more pain at the start of labor. Preliminary evidence suggests that pharmacogenetics may also play a role in dose requirements. Camorcia et al. reported that nulliparous women who were heterozygous or homozygous for the single nucleotide polymorphism (SNP) A118G (substitution of guanine for adenine at position 118) of the gene encoding the µ-opioid receptor (OPRM1) had a lower ED 50 for epidural sufentanil administered for labor analgesia.
Several early studies suggested that the duration of epidural and spinal analgesia may exhibit circadian rhythm (chronobiology), possibly secondary to human biologic rhythms. However, in a secondary analysis of data from a large study, Scavone et al. found no evidence of a circadian response to intrathecal fentanyl or intravenous opioid labor analgesia. In a detailed analysis of data from a study designed to test whether parturient response to intrathecal bupivacaine exhibited a circadian rhythm, Shafer et al. demonstrated that external daily rhythms, such as nursing shifts, may contribute to the appearance of biologic rhythm. Thus, whether a circadian response to neuraxial local anesthetic or opioid exists, or is clinically significant, requires further study.
Current evidence supports the administration of epidural opioid doses at the lower end of the dose range for nulliparous women, for women in early labor, or when the opioid is co-administered with a local anesthetic. Higher doses are associated with a higher incidence of maternal side effects and the potential for neonatal depression (see later discussion). The major maternal side effect of epidural fentanyl and sufentanil for labor analgesia is pruritus. Neonatal outcomes do not appear to be adversely affected by the addition of fentanyl or sufentanil to a local anesthetic for epidural analgesia (see later discussion). In fact, the combination of drugs allows lower doses of both drugs to be administered, resulting in lower concentrations of both drugs in the neonate.
Two studies found that the diluent volume (2 to 20 mL) did not affect the onset and duration of epidural labor analgesia when fentanyl was injected into the epidural space after the injection of a local anesthetic solution.
Morphine was one of the first opioids used for labor analgesia. Hughes et al. compared analgesia using epidural administration of morphine (2.0, 5.0, and 7.5 mg) with that using epidural bupivacaine 0.5%. Morphine was effective in 7 of 11 parturients until the end of the first stage of labor, but all parturients required bupivacaine for adequate analgesia during the second stage of labor. Subsequently, investigators combined morphine with bupivacaine and observed a longer duration of analgesia compared with that for bupivacaine alone. However, the inconsistent analgesia, long latency (30 to 60 minutes), and high incidence of side effects of morphine (which continued after delivery), along with the introduction of lipid-soluble opioids and epidural infusion pumps into clinical practice, have made the use of epidural morphine for labor analgesia largely obsolete.
Several studies described the use of alfentanil with bupivacaine for labor analgesia. Alfentanil has lower lipid solubility than both fentanyl and sufentanil. Only a few small studies have compared alfentanil with other opioids for labor analgesia.
Several groups of investigators have reported the use of epidural hydromorphone for labor analgesia. The lipid solubility of hydromorphone lies between those of morphine and fentanyl, but is closer to that of morphine. In a large prospective observational study, effective labor analgesia was obtained by initiating analgesia with 0.25% bupivacaine (20 to 25 mg) with epinephrine (40 to 50 µg), followed by hydromorphone 100 µg. However, Mhyre observed that effective labor analgesia could not be provided by 0.035% bupivacaine (7 mg) with hydromorphone 100 to 110 µg. In another trial, parturients were randomly assigned to receive either epidural hydromorphone 300 µg or saline-control immediately after the initiation of analgesia with lidocaine 45 mg, epinephrine 15 µg, and fentanyl 100 µg. Duration of analgesia and side effects were similar in the two groups. At the current time, further investigation is required before hydromorphone can be recommended for epidural labor analgesia.
Meperidine may be used effectively alone (without a local anesthetic), in part because it possesses local anesthetic properties. When given during labor, epidural meperidine 100 mg provides analgesia similar to that provided by 0.25% bupivacaine, with less motor blockade. However, this dose of epidural meperidine produces more sedation, nausea, and pruritus than epidural bupivacaine. Handley and Perkins observed that the addition of meperidine 25 mg to 0.125%, 0.187%, or 0.25% bupivacaine (10 mL) provided adequate analgesia for the first stage of labor. Epidural administration of meperidine effectively prevents or treats the shivering that often occurs during labor. Investigators from Saudi Arabia randomly allocated women to receive 0.1% bupivacaine with either meperidine 1 mg/mL or fentanyl 2 µg/mL. No differences were noted between groups in analgesic characteristics, except that women in the meperidine group had a higher incidence of nausea and vomiting. Currently there is no evidence that meperidine alone or in combination with bupivacaine has any advantages over a combination of a long-acting amide local anesthetic and a lipid-soluble opioid.
Butorphanol is a lipid-soluble opioid agonist-antagonist, with weak µ-receptor and strong κ-receptor activity. Because κ-opioid receptors appear to be involved in the modulation of visceral pain, κ-receptor agonists should be useful agents for the relief of labor pain, which has a significant visceral component (see Chapter 20 ). Somnolence is the most prominent side effect of epidural butorphanol. The addition of butorphanol 1, 2, or 3 mg to 0.25% bupivacaine (25 mg) shortened latency and prolonged the duration of analgesia in comparison with epidural bupivacaine alone in one study. The investigators concluded that the optimal dose of butorphanol was 2 mg. Of concern was the observation of a transient sinusoidal FHR pattern in the 3-mg group that was not unlike that seen after the intravenous administration of butorphanol. However, there was no difference among groups in Apgar scores, umbilical cord blood gas and pH measurements, or neurobehavioral scores. Similarly, Abboud et al. observed that the addition of butorphanol 1 or 2 mg to 0.25% bupivacaine resulted in better quality and longer duration of analgesia than the epidural administration of bupivacaine alone, without maternal or neonatal side effects. However, some anesthesia providers have noted that the epidural administration of butorphanol results in somnolence and occasional dysphoria, which are side effects of κ-receptor stimulation.
Diamorphine (heroin) is available for epidural analgesia in the United Kingdom. Using isobolographic analysis, McLeod et al. concluded that the combination of diamorphine and levobupivacaine is additive when used for first-stage labor analgesia. Several studies from the United Kingdom have reported diamorphine doses between 250 and 500 µg/h (i.e., diamorphine 25 to 50 µg/mL combined with a low concentration of bupivacaine). Whether diamorphine offers any advantages over fentanyl or sufentanil has not been studied. It is not available for clinical administration in the United States.
Although the contemporary mainstay of epidural labor analgesia includes administration of a long-acting amide local anesthetic combined with a lipid-soluble opioid, other drugs may be added as adjuvants. Adjuvants may prolong the duration of analgesia or decrease the required anesthetic dose, thus reducing the risk for specific side effects.
Some anesthesia providers add a low dose of epinephrine (1.25 to 5 µg/mL [1 : 800,000 to 1 : 200,000]) to the local anesthetic solution ( Table 23.4 ). The addition of epinephrine shortens the latency and prolongs the duration of epidural bupivacaine analgesia. The MLAC of bupivacaine with epinephrine (66 µg) is 29% lower than that of bupivacaine without epinephrine, perhaps as a result of the stimulation of alpha-adrenergic receptors in the spinal cord.
|Adjunct Drug||Epidural Analgesia||Spinal Analgesia|
|INITIATION BOLUS DOSE a||MAINTENANCE INFUSION DOSE a||INITIATION BOLUS DOSE|
|Epinephrine||25–75 µg b||25–50 µg/h b||2.25–200 µg|
|Clonidine||75–100 µg||10–30 µg/h c||15–30 µg|
|Neostigmine||500–750 µg||25–75 µg/h d||NR|
|Morphine||NA||NA||100–250 µg (0.1–0.25 mg)|
a Adjuncts are usually co-administered with a low-concentration local anesthetic solution (e.g., bupivacaine < 0.08%), often with a lipid-soluble opioid. There is extensive experience with epidural clonidine for labor analgesia in some European countries but less overall experience with epidural neostigmine.
The addition of epinephrine to the local anesthetic has a variable effect on the systemic uptake of the local anesthetic in obstetric patients. The systemic absorption of epinephrine may increase maternal heart rate and transiently decrease uterine activity as a result of beta-adrenergic receptor stimulation. However, some studies have shown that the addition of epinephrine to bupivacaine, lidocaine, or levobupivacaine does not result in longer labor than the epidural administration of bupivacaine or lidocaine without epinephrine or levobupivacaine-sufentanil without epinephrine. Epidural administration of an epinephrine-containing local anesthetic solution does not adversely affect intervillous blood flow or neonatal outcome. One disadvantage of the use of epinephrine is that it increases the intensity of motor blockade. The addition of epinephrine may improve the efficacy of epidural opioids, but the enhanced effect is insufficient to make use of epidural opioids (without local anesthetic) an attractive regimen for the duration of labor. Finally, the addition of a third drug to the local anesthetic/opioid solution may increase the risk for drug error and contamination. For these reasons, at our institution my colleagues and I do not routinely administer epinephrine-containing local anesthetic solutions during labor. However, other anesthesia providers have a different view, and some consider epinephrine a useful adjuvant, especially when added to a very dilute solution of local anesthetic with an opioid.
Analgesia is enhanced by the direct stimulation of alpha 2 -adrenergic receptors and the inhibition of neurotransmitter release in the dorsal horn of the spinal cord (see Chapter 20 ). Epidural administration of clonidine alone provides modest analgesia. Studies have evaluated the epidural administration of clonidine as an adjuvant to a local anesthetic alone, to local anesthetic and opioid combinations, to fentanyl, and to neostigmine (see later discussion). In an MLAC study, clonidine 60 µg, but not 30 µg, decreased the MLAC of ropivacaine by approximately two-thirds. In another study, clonidine 75 µg and sufentanil 5 µg both reduced the MLAC of ropivacaine by about two-thirds. Unlike epinephrine, clonidine does not increase the motor blockade that results from the epidural administration of a local anesthetic, but it does potentiate both the quality and duration of analgesia. However, in a “black box” warning on the package insert, the manufacturer of Duraclon (the epidural clonidine formulation approved by the U.S. Food and Drug Administration [FDA]) recommends against its use in obstetric patients because of the risk for hypotension and bradycardia. Most studies, however, have found that the hypotension is readily amenable to treatment. An additional side effect is maternal sedation. High doses (greater than 150 µg) may be associated with FHR changes, although no adverse fetal effects have been observed with lower doses.
Clonidine is not often used for labor analgesia in North America, but it is more widely used in some European countries. It may be particularly useful in women in whom other epidural analgesics are contraindicated or in those who have breakthrough pain with standard local anesthetic/opioid solutions, despite a functioning epidural catheter. In this circumstance, additional local anesthetic will result in motor blockade but clonidine will not.
Neostigmine inhibits the breakdown of acetylcholine within the spinal cord. Acetylcholine binds to muscarinic receptors, leading to a reduction in neurotransmitter release and subsequent analgesia. Roelants et al. randomly assigned parturients to receive either epidural ropivacaine (20 mg) alone or epidural neostigmine (4 µg/kg) combined with ropivacaine 10 mg, with or without sufentanil 10 µg. The magnitude and duration of analgesia in the ropivacaine/neostigmine group were similar to that of the plain ropivacaine group but less than in the ropivacaine/sufentanil group. Neostigmine is hydrophilic, and the researchers hypothesized that only a small portion of the epidural dose penetrates the spinal cord. In a subsequent study, the same researchers compared epidural sufentanil 20 µg with sufentanil 10 µg combined with neostigmine 250, 500, or 750 µg. Neostigmine 250 µg with sufentanil was ineffective, but both 500 and 750 µg of neostigmine produced effective analgesia similar in duration to that obtained with sufentanil alone.
In another study, maintenance of epidural analgesia with a solution of neostigmine 4 µg/mL combined with bupivacaine 0.125% resulted in a 19% reduction in bupivacaine consumption compared with administration of bupivacaine alone. However, maternal sedation was noted in the neostigmine group in the first 5 to 20 minutes after initiation of epidural analgesia with bupivacaine and neostigmine 60 µg. Booth et al. randomized laboring women to receive initiation and maintenance of epidural analgesia with 0.125% bupivacaine, combined with fentanyl 2 µg/mL or neostigmine 2, 4, or 8 µg/mL. The primary outcome, hourly bupivacaine consumption, did not differ among groups, nor did patient satisfaction. Pruritus was less common in the neostigmine groups, but other adverse effects did not differ, suggesting that there is no advantage to replacing the lipid-soluble opioid with neostigmine when combined with a local anesthetic.
Because animal studies suggest a synergistic antinociceptive effect of spinal alpha 2 -adrenergic agonists and cholinesterase inhibitors, researchers have also investigated epidural neostigmine combined with clonidine. The combination of clonidine 75 µg with neostigmine 500 or 750 µg provided acceptable analgesia (visual analogue scale pain score less than 30/100 mm in 30 minutes) in approximately 80% of parturients. Epidural neostigmine 500 µg combined with clonidine 75 µg prolonged labor analgesia initiated with spinal ropivacaine and sufentanil. In a follow-up study, the same investigators initiated analgesia with spinal ropivacaine and sufentanil and maintained analgesia with ropivacaine/sufentanil PCEA. Study subjects were randomized to receive a 10-mL epidural bolus injection of a solution containing neostigmine 500 µg combined with clonidine 75 µg or placebo saline solution 15 minutes after the intrathecal injection. Hourly ropivacaine use and the incidence of breakthrough pain were less in the group that received the epidural neostigmine/clonidine bolus. Systolic blood pressures were lower in the treatment group, but the incidence of hypotension did not differ.
Taken together, the studies have not identified any significant adverse maternal or neonatal effects; however, the number of studies is small and further study is required to determine the role of epidural neostigmine for routine labor analgesia. Neostigmine is not approved for neuraxial injection in the United States.
Epidural labor analgesia is usually initiated with the bolus injection of a local anesthetic combined with a lipid-soluble opioid. The advantages of the addition of an opioid to an epidural solution of local anesthetic include (1) lower total dose of anesthetic, (2) decreased motor blockade, (3) reduced shivering, and (4) greater patient satisfaction. Some anesthesia providers contend that local anesthetic–opioid techniques result in a lower risk for hypotension, but this belief is unproven. There are no clinically significant differences among the three commonly used, long-acting amide local anesthetics (bupivacaine, ropivacaine, levobupivacaine), or between fentanyl and sufentanil. Other adjuvants (e.g., epinephrine, clonidine, neostigmine) may prove useful in selected patients. High-volume/low-concentration local anesthetic solutions compared with low-volume/high-concentration solutions are associated with lower dose requirements and better analgesia.
Initiation of Spinal Analgesia
Initiation of neuraxial analgesia with the intrathecal injection of an opioid, or an opioid combined with a local anesthetic, usually performed as part of a CSE technique, results in a rapid onset of analgesia with a low dose of drug(s) (see Table 23.2 ). The onset of effective spinal analgesia occurs faster than epidural analgesia, and more women have effective analgesia at 10 minutes. Intrathecal opioids can provide complete analgesia during early labor when the pain stimuli are primarily visceral. An intrathecal local anesthetic without an opioid is not commonly used for labor analgesia. Doses high enough to provide analgesia are associated with significant motor blockade, and lower doses either do not provide satisfactory analgesia or are associated with an unacceptably short duration of analgesia. A lipid-soluble opioid is combined with a local anesthetic (bupivacaine, ropivacaine, or levobupivacaine) when sacral analgesia is necessary for complete analgesia (e.g., initiation of analgesia during the active first stage or the second stage of labor). The interaction between intrathecal local anesthetics and opioids is synergistic. Like the combination of an epidural local anesthetic with an opioid, the combination of an intrathecal opioid with a local anesthetic results in better quality and longer duration of analgesia, as well as a lower dose requirement for both drugs, compared with either drug used alone.
Choice of Drugs
Fentanyl and sufentanil.
The two opioids most commonly used for initiation of spinal labor analgesia are fentanyl and sufentanil. When administered alone in early labor, intrathecal fentanyl and sufentanil provide complete analgesia without a sympathectomy or motor blockade. This is a particularly useful technique for patients in whom a sudden decrease in preload (secondary to neuraxial local anesthetic–induced sympathectomy) might not be well tolerated (e.g., patient with a stenotic heart lesion).
Studies suggest that the ED 50 of intrathecal fentanyl varies from 5.5 to 18 µg. The wide range of published values may be explained by differences in patient population (e.g., parity), cervical dilation at initiation of analgesia, and definition of successful analgesia. Nelson et al. hypothesized that acute mixing of fentanyl in cerebrospinal fluid (CSF) may explain the large interindividual variability observed after the injection of intrathecal opioid. In an elegant study, the investigators determined CSF fentanyl concentration at the site of the lumbar injection 60 seconds after the fentanyl injection. CSF fentanyl concentration did not correlate with onset, sensory level, or duration of analgesia. Instead, decreased diastolic and increased systolic blood pressure correlated with duration of analgesia. The authors hypothesized that hemodynamic characteristics may influence the distribution of drug in the CSF and, hence, block characteristics.
Herman et al. determined that the ED 95 of intrathecal fentanyl for parturients of mixed parity in early labor (cervical dilation less than or equal to 5 cm) was 17.4 µg (95% CI, 13.8 to 27.1). The duration of analgesia is dose dependent but plateaus at 80 to 90 minutes after administration of 15 to 25 µg of fentanyl ( Fig. 23.3 ). There does not appear to be any reason to administer doses higher than 25 µg, because side effects (e.g., pruritus, respiratory depression) are also dose dependent.
The reported ED 50 of intrathecal sufentanil varies from 1.8 to 4.1 µg, and the ED 95 is 8 to 10 µg. A comparison of the potencies of fentanyl and sufentanil using ED 50 estimates from different studies is difficult because of differences in patient populations and the definition of efficacy. In a single-center study, the relative potency ratio of intrathecal sufentanil to fentanyl for labor analgesia was estimated to be 4.4 : 1. When the drugs were administered at twice the ED 50 (fentanyl 36 µg, sufentanil 8 µg), the duration of sufentanil analgesia was 25 minutes longer than that of fentanyl analgesia (104 versus 79 minutes), although the incidence of side effects was not different.
Landau et al. investigated the influence of genetic variability of the µ-opioid receptor OPRM1 on the ED 50 of intrathecal fentanyl for labor analgesia. Nulliparous women who were heterozygous or homozygous for A118G had a lower ED 50 for intrathecal fentanyl (18 µg, 95% CI, 13 to 22) than women homozygous for the wild-type allele (A118) (27 µg, 95% CI, 23 to 31). Additionally, women in the group with the A118G allele requested analgesia at a more advanced cervical dilation. However, in two other studies assessing duration of intrathecal fentanyl labor analgesia, there was no difference in the duration of analgesia in women with the A118G allele compared with women who were homozygous for the wild-type allele. Thus, the clinical implications of genetic polymorphisms of OPRM1 on labor analgesia remain unclear.
Typically, an intrathecal opioid injection for labor analgesia is administered as part of a CSE technique. Maintenance epidural analgesia is usually initiated soon after initiation of spinal analgesia. Therefore, the duration of intrathecal analgesia is relatively less important. Nelson et al. concluded, and we concur, that the longer duration of sufentanil analgesia in comparison with fentanyl analgesia does not necessarily justify the former’s use. Other factors, such as cost and the greater risk for a drug dose error with sufentanil (because of its greater potency), should be considered. In some European countries sufentanil is available in a dilute concentration (5 µg/mL), possibly making it easier and safer to use.
Intrathecal fentanyl (or sufentanil) is often co-administered with an amide local anesthetic (see later discussion), most commonly bupivacaine (see Table 23.2 ). The addition of a local anesthetic to intrathecal fentanyl or sufentanil markedly decreases the dose of opioid necessary to produce analgesia. Wong et al. randomly assigned parous women to receive intrathecal bupivacaine 2.5 mg and intrathecal sufentanil 0, 2.5, 5, 7.5, or 10 µg, followed by a standard epidural test dose. There were no differences among the sufentanil groups in quality and duration of analgesia. These results suggest that a sufentanil dose as small as 2.5 µg is effective when combined with bupivacaine 2.5 mg. In current clinical practice, it is common to combine bupivacaine 2.5 mg with sufentanil 1.5 to 2 µg. Stocks at al. demonstrated that three different doses of intrathecal fentanyl (5, 15, and 25 µg) led to similar reductions in the ED 50 of intrathecal bupivacaine, although both the duration of analgesia and the incidence of pruritus were dose dependent. As with sufentanil, the dose of intrathecal fentanyl is usually reduced when combined with bupivacaine. Intrathecal fentanyl 10 to 15 µg, combined with bupivacaine 2.5 mg, provides effective analgesia for most parturients.
Early studies demonstrated that the intrathecal administration of 0.5 to 2 mg of morphine reliably produced analgesia during the first stage of labor, but the analgesia was less reliable during the second stage of labor and during instrumental vaginal delivery. However, intrathecal administration of these relatively large doses of morphine resulted in a high incidence of side effects, including somnolence, nausea and vomiting, pruritus, and respiratory depression. In addition, the onset of analgesia is slower with intrathecal morphine than with lipid-soluble opioids, and the long duration of action may be a disadvantage (i.e., the parturient may deliver before the regression of side effects). Abouleish reported a case of life-threatening respiratory depression 1 hour after delivery and 7 hours after the administration of 1 mg of hyperbaric intrathecal morphine.
In several studies, low-dose morphine (0.1 to 0.25 mg) was successfully combined with intrathecal bupivacaine (2 to 2.5 mg) and fentanyl (12.5 to 25 µg); the combination resulted in short latency of onset and a prolonged duration of analgesia. In contrast, a single study from Sweden found no advantage to adding morphine 0.05 or 0.1 mg to bupivacaine 1.25 mg and sufentanil 5 µg. The addition of low-dose morphine to intrathecal bupivacaine and a lipid-soluble opioid may be useful in low-resource settings in which continuous epidural infusion techniques are impractical. When used as part of a CSE technique, the addition of intrathecal morphine to bupivacaine and fentanyl has been shown to result in less breakthrough pain during labor as well as decreased analgesic use in the first 24 hours postpartum, compared with intrathecal bupivacaine and fentanyl without morphine. The incidence of intrapartum side effects was similar ; however, the morphine group had a higher incidence of postpartum nausea (17% versus 0% for no morphine).
An alternative drug is meperidine. Meperidine is unique among the opioids in that it possesses weak local anesthetic properties, and it has been used in large doses (e.g., 1 mg/kg) as the sole agent to provide spinal anesthesia for surgical procedures. Intrathecal administration of meperidine (10 to 20 mg) results in effective labor analgesia within 2 to 12 minutes, with a duration of 1 to 3 hours. Honet et al. compared the efficacy of intrathecal meperidine 10 mg, fentanyl 10 µg, and sufentanil 5 µg in 65 laboring women. The three drugs were similar in onset of analgesia (less than 5 minutes) and duration of effective analgesia (80 to 100 minutes). However, the meperidine group had significantly lower pain scores after cervical dilation had progressed beyond 6 cm. As labor advances, the nature of pain becomes increasingly somatic; only meperidine also functions as a local anesthetic. This fact helps explain why meperidine provided more effective analgesia during advanced labor, including the second stage. Booth et al. observed that intrathecal meperidine was associated with a significantly higher incidence of nausea and vomiting than a combination of fentanyl and bupivacaine for labor analgesia. Therefore, intrathecal meperidine does not seem to offer any advantages over bupivacaine-fentanyl for routine intrathecal analgesia, although it may be useful for the rare patient with a contraindication to bupivacaine-fentanyl administration.
In the United Kingdom, some anesthesia providers have advocated the intrathecal administration of diamorphine (heroin) for labor analgesia, although it is not commonly used for this purpose. This drug is not available for clinical use in the United States. Kestin et al. observed that the intrathecal administration of diamorphine (0.2 to 0.5 mg) provided good to excellent analgesia in 90% of laboring women. The mean duration of analgesia was approximately 100 minutes. However, 75% of patients had pruritus, nausea, and vomiting. In contrast, Vaughan et al. randomly assigned parturients to receive intrathecal bupivacaine 2.5 mg with either fentanyl 25 µg or diamorphine 0.25 mg. Duration of analgesia was longer in the diamorphine group, but the incidence of side effects was low in both groups.
In the late first stage and the second stage of labor, a local anesthetic must be added to the spinal opioid to block somatic stimuli from the vagina and perineum caused by descent of the fetus. The local anesthetic works synergistically with the opioid, so lower doses of both drugs can be used. Bupivacaine is most commonly combined with fentanyl or sufentanil. The ED 95 of bupivacaine was 3.3 mg when combined with sufentanil 1.5 µg and 1.7 mg when combined with fentanyl 15 µg. Intrathecal bupivacaine doses between 1.25 and 2.5 mg are commonly used (see Table 23.2 ). Levobupivacaine and ropivacaine are not usually used for intrathecal injection in the United States. They are less potent than bupivacaine for intrathecal labor analgesia ( Fig. 23.4 ). Spinal lidocaine has not been studied for use in labor analgesia, but it is unlikely to have any advantages compared with other, longer-acting amide local anesthetics. Common doses of spinal local anesthetics are shown in Table 23.2 .