Anesthesia for Labor and Delivery

Mccallum R. Hoyt and Elaine Marie Pages-Arroyo

The goal of modern-day obstetric anesthesia practice is to provide the patient with analgesia as she requests it.67,62 That assumes that her choice is appropriate to the labor process, to the current conditions as evaluated by her obstetric provider, and has as little impact on the fetus as possible.⁵⁹ Depending on the patient’s predilections, labor might be approached with prepared responses to modify pain perception, a plan to use systemic medications or nerve blocks, or some combination of these. How and whether a mother’s choice has an impact on fetal well-being and neonatal outcome is the focus of this chapter and includes a discussion of the newer anesthetic techniques because the neonatologist should understand them. It also reviews some of the more established pain relief approaches as well as the more popular alternatives currently in vogue.

Labor Pain Characteristics and Challenges

Research has shown that the experience of pain is a complex, subjective, multidimensional response to sensory stimuli.²⁵ The perception of pain in pregnancy is influenced by numerous factors such as fear of pain, increased susceptibility to pain because of generalized anxiety, level of education, and age or parity.¹¹ To appreciate the complexity of providing analgesia to the laboring patient and better understand successes and expectations when doing so, a considerably abbreviated and simplistic discussion of pain is in order. A clinically useful classification is to define it as being visceral or somatic. Stated very simply, visceral pain originates from the viscera and is often described as cramping, dull, and steady.^25,11 Somatic pain is related to nonvisceral structures and is commonly described as sharp, intermittent, and well localized.^25,11 During the dilation phase of labor, or first stage, visceral pain predominates.^25,11 This pain stimulus arises from mechanical distention of the lower uterine segment and cervical dilation. Somatic pain prevails during the descent phase of labor, or second stage, and it is attributed to the distention and traction on pelvic structures surrounding the vagina and from distention of the pelvic floor and perineum.^25,11

The challenge with labor pain is in understanding that the very dynamic nature of it requires adaptation of pain techniques to adequately manage it. Pain can evolve rapidly over a relatively short period of time, changing not only in intensity, but also from a visceral to a somatic source. To add to the challenge, not all medications are effective for all types of pain. Local anesthetics block nerve conduction and are effective where the nerves responsible for pain transmission are accessible. In labor, the nerves transmitting the pain are well described, and most of them can be reached with a needle, making some form of nerve block with a local anesthetic a common choice. On the other hand, opioids are very effective for visceral pain, but are of little value for somatic pain.⁵⁸ Therefore, systemic opioids can aid a patient reasonably well during the first stage of labor, but have little effect if used during the second stage.

Neuraxial analgesia is widely accepted as the most effective and least depressant method of providing pain relief in labor.⁶⁷ The term encompasses epidural, spinal, and combined spinal-epidural nerve blocks that can be administered only by those trained in anesthetic methods.⁴¹ With modern-day techniques, dosing can be reduced to such low levels that an analgesic state, which diminishes pain while minimizing the effect on other sensory pathways such as touch and proprioception, is possible and often the goal.⁶ The lower doses result in less absorption into the maternal bloodstream than occurs with heavier dosing regimens, and in some cases levels are nondetectable. These methods allow the parturient to experience pain-free labor with minimal side effects to both the mother and the fetus while permitting the patient to actively participate in the labor process.⁴¹ However, all procedures carry some risk, and dosing methods vary widely across the United States such that there can remain a fetal or neonatal effect from the medications used.

Despite the proven safety and efficacy of the lower-dose neuraxial techniques, not all obstetric patients wish to use them, nor are there always practitioners available to perform the procedures.⁵⁹ Also, an obstetric patient may not be a reasonable candidate for a neuraxial block for a myriad of reasons. As a result, many of the tried-and-true approaches for managing labor pain are still commonplace in obstetric suites, as are some interesting alternative therapies.

Techniques That Modify Pain

Although nonpharmacologic techniques do not alter the actual transmission of pain sensation, they attempt to alter the person’s perception and response to it, with some measured success. Many of these approaches require preparation beforehand, and their effectiveness is subject to several variables. As a result, studies comparing controlled breathing techniques, hypnosis, and other nonpharmacologic methods to nerve blocks and medications are hard to evaluate.

The assumption held by proponents of alternative pain management techniques and many expectant mothers is that nonpharmacologic techniques to control pain without the use of medications and nerve blocks will not have any adverse effect on the neonate and therefore are the safest and healthiest choices for themselves and their babies. Clinical studies have not proved this assumption to be true. Although most techniques are as benign as they appear, some can carry unintended consequences if not performed properly, making this pertinent knowledge for the well-informed neonatologist.

Nonpharmacologic Approaches

Natural Childbirth

Natural childbirth is a technique that was first defined by Ferdinand Lamaze in the 1950s and began its popular rise in the 1960s as an alternative to the heavy sedation that was often used at the time. The technique of controlled breathing and focal points to stay in a relaxed state during a contraction is based on the theory that one can modify the sensation of pain and one’s response to it. Building upon the popularity of the Lamaze approach to labor pain, the Bradley technique was introduced in the 1970s as a variant and incorporated the woman’s partner as her active coach. Today the term natural childbirth applies to any controlled breathing technique that the mother uses during labor to cope with pain and avoid pharmacologic methods.

Is natural childbirth an effective way to manage pain during labor? There is some objective evidence that Lamaze training as originally practiced is associated with β-endorphin elevations, which may help alter pain sensation.²² What is not always appreciated by those who teach and by couples who use this technique to prepare for labor is that incorrect performance can have negative consequences. Maternal and fetal Pco₂ levels are positively correlated.⁵³ If the mother deviates from the defined breathing technique and hyperventilates during her contractions, she will lower her Pco₂ levels as a result.⁵⁰ This situation has two effects. First, maternal hypocapnia causes uterine vasoconstriction, thereby reducing blood flow to the fetus; second, the fetus also develops hypocapnia in response to the maternal hypocapnia. As the fetal Pco₂ falls, the fetal oxyhemoglobin dissociation curve shifts leftward, causing a reduction in fetal oxygenation and setting the stage for hypoxia and metabolic acidosis. If fetal acidosis develops during the first stage of labor, it will worsen during the second stage, especially if that stage exceeds 1 hour.⁷¹ Once hypoxia and a base deficit are present during the second stage of labor, it is difficult to reverse in utero.⁷¹ The result is a neonate who is in need of resuscitation. Obviously this series of events does not occur in every case, but the fetal tracing associated with this scenario can resemble that of cord compression and result in obstetric maneuvering.⁵³ Effective analgesic techniques have been shown to improve these conditions if applied before the second stage.⁵³

With the boom of the Internet, patients today are able to find a variety of information online about natural childbirth practices without any means to determine if the information presented is accurate. A common thread is to suggest that natural childbirth is empowering for women and has little potential for harm to the baby. Several factors have come to bear upon modern-day childbirth courses that teach the Lamaze or Bradley techniques and the information that is provided. Couples are no longer willing to take the full 6-week training course. Instead, weekend courses are offered that try to present all the information in 2 days. This alternative makes it nearly impossible to practice and learn the pain-controlling techniques that Lamaze and Bradley described. Additionally, information on all available forms of pain relief options is variable, because of not only some potential personal biases by the instructor, but also the instructor’s knowledge of what is available at the maternity units in the area. As a result, couples may approach labor with a rigid plan that does not take into consideration informed alternatives for pain management should the fetus show signs of compromise. Unfortunately, a mother who envisions a natural childbirth for her labor often views resorting to any form of analgesia, especially an epidural, as a failure on her part. Studies show that natural childbirth preparation, including training in breathing and relaxation, did not decrease the use of epidural analgesia during labor.⁷ It has been shown that when mothers who planned for an unmedicated labor resort to a neuraxial block, it is as a result of labors that are frequently longer and associated with higher pain scores, which may catch them unprepared for the intensity of the process.³⁷

Hypnosis

Hypnobirthing, or self-hypnosis for labor and delivery, enjoys a devoted following among those for whom the process has been successful, but certainly it is a technique that not many individuals can use. It requires time for training and practice, and is not a choice for those with only a weekend set aside for learning it. There are two main methods of providing hypnosis in the context of pain management for childbirth: hypnotherapy delivered in person by a known practitioner, and self-hypnosis, in which the mother is previously trained to self-induce a state of altered consciousness. Under such a state, there is less awareness of the environment and an increased susceptibility to suggestion. These may be verbal and nonverbal communications used to achieve specific therapeutic goals.¹⁵ In the context of childbirth, suggestions may focus on increasing feelings of safety, relaxation, and comfort, as well as potentially developing sensations of numbness.⁴³

Further studies are warranted to clarify the impact of hypnosis on labor pain. The evidence available is difficult to evaluate.⁹³ Studies lack randomization, hypnotic methods are not well described and may vary between studies, and the study populations are relatively small. A recent Cochrane Database review examined seven trials with a total of 1213 women comparing the use of hypnosis during labor with other existing therapies.⁸⁶ Such therapies included placebo use, no treatment, or any other analgesic drug or technique.⁴³ The review authors found no statistical differences between women in the hypnosis group and those in the control group with regard to several outcomes: use of pharmacologic pain relief, spontaneous vaginal birth, and satisfaction with pain relief. There was some evidence of benefits for women in the hypnosis group compared with the control group for pain intensity, length of labor, and maternal hospital stay, although these findings were based on studies with small numbers of women.

Water Birth

The water birth movement holds that submersion for labor, delivery, or both reduces the sensation of pain. It also holds that birthing from one water environment into another is less stressful for the infant. Unfortunately, there are no substantive studies supporting this claim. Like most alternative methods, almost everything reported in the literature is anecdotal. A Cochrane Database review article indicates that immersion in water during the first stage decreases maternal requests for neuraxial analgesia and can be supported for women at low risk of complications.¹³ However, immersion during the second stage of labor needs further investigation. At present, there is no clear evidence whether to support or reject a woman’s decision to give birth in water.¹³ Questions regarding infection and neonatal outcomes are not addressed, and large collaborative trials are needed to answer these critical issues. A 2004 review article considered three clinical concerns: water aspiration, neonatal/maternal infection, and neonatal/maternal thermoregulation in the practice of water birthing. They also looked at two practical concerns: skills and education of midwives or health professionals assisting the water birth, and emergency procedures in case of maternal collapse. They did not find sufficient evidence to caution women away from this practice.⁹⁹

Acupuncture, Saline Injections, and Transcutaneous Electrical Nerve Stimulation

This group of techniques has most often been used to address the issue of low back pain during labor and not that of labor pain management in general. In controlled trials, acupuncture has been demonstrated to be beneficial ⁸⁵ but time consuming and without consistent results.⁸⁴ In addition, the study sizes have been small, indicating that more research is needed.⁸⁵

Intracutaneous or subcutaneous injection of sterile water is rapidly gaining popularity as a method of pain relief in labor. The outcomes reported severely limit conclusions for clinical practice.¹⁹ There is little robust evidence that sterile water is effective for low back or any other labor pain. Present studies found no difference in delivery or other maternal or fetal outcomes. Further large, methodologically rigorous studies are required to determine the efficacy of sterile water to relieve pain in labor.¹⁹

Transcutaneous electrical nerve stimulation (TENS) for the management of back pain involves the placement of electrodes over the sacrum. A low electrical pulse is then transmitted that modifies the sensation of pain. Again, this method has been demonstrated to work well for low back pain in general but does not lessen the request for other analgesics in labor pain management. There is insufficient evidence to make judgments on whether TENS is more effective than placebo or other interventions for pain management in labor. None of these aforementioned techniques appears to have any negative effect on the neonate.

Systemic Medications

There are two classes of drugs commonly used by obstetric providers in modern practice for labor pain management that fall under the scope of this segment. They are opioids for pain relief and sedatives to relax and reduce anxiety. Under emergent surgical conditions, anesthesiologists use other classes of drugs, but these are not reviewed in any detail here. When considering the effect of any medication on the fetus, it is worth noting whether that medication has produced a cerebral effect on the mother. If so, that medication has the properties to cross the lipid blood-brain barrier and likely will cross the placental barrier to reach the fetus as the necessary transport mechanisms are the same.¹⁰⁰ However, the extent to which a fetus is exposed depends on many factors, such as the drug’s pharmacokinetic and pharmacodynamic properties, the dose, and the mode of delivery. The following segment reviews a few of the pharmacologic principles pertinent to medication choices and fetal exposure. A more complete discussion can be found elsewhere or in any major pharmacology text.

Pharmacokinetics, Pharmacodynamics, and the Fetus

Three pharmacologic characteristics are considered when weighing whether or not a medication has the properties to enter the maternal circulation from its primary site of administration and then leave that circulation to cross the placenta (see Chapter 51). These are how much of the drug is in the ionized versus the nonionized state as determined by its pH, whether it has lipophilic or hydrophilic tendencies, and whether it prefers to bind to protein. A medication that is ionized cannot cross a membrane barrier. If a drug’s pH is physiologic (pKa = pH = 7.4), it means that 50% of the drug is ionized and 50% is nonionized. For the purposes of discussion, local anesthetics are a class of weak bases (pKa = 7.6-9.1), so they are more ionized when exposed to the physiologic pH. The ratio by which a local anesthetic is ionized as opposed to nonionized in the circulation depends on how great is the base of the drug. For instance, a local anesthetic with a pKa of 9.1 is mostly ionized, and more will stay in the maternal circulation than a local anesthetic with a pKa of 7.6. Because it is the nonionized portion of a drug that can cross a membrane barrier, the amount that crosses will reproportion itself into ionized and nonionized forms when in the fetal circulation. If the fetal pH is lower than the maternal pH because of acidosis, more of the drug converts to the ionized form while in the fetal circulation and cannot return to the maternal circulation. If maternal exposure to the medication persists, more of the drug passes from the mother to the fetus, and increasing amounts accumulate in the fetal circulation. This phenomenon is called fetal ion trapping and has been associated with some of the deleterious effects produced by medications in the compromised fetus.

Of the other pharmacodynamic properties mentioned, drugs that possess lipophilic properties as opposed to hydrophilic are more capable of crossing lipid-rich membranes. Most medications used in obstetrics are lipophilic, but to varying degrees. For example, fentanyl and sufentanil are lipophilic opioids, but sufentanil is much more so. As a result, epidural doses of sufentanil more readily leave the epidural space to enter the maternal circulation than fentanyl.

Protein binding is the third important pharmacologic principle. A drug that binds with protein molecules remains in the maternal circulation because when bound, it becomes a bulky molecule. Only the unbound drug is free to cross a membrane and produce an effect. So excluding active transport mechanisms, it is the unbound, nonionized portion of a lipophilic medication that can cross a membrane barrier to produce an effect.

The pharmacokinetic effects of metabolism and elimination are yet another regulator of how much or even whether a drug will exert an effect on the fetal brain. Most medications undergo extensive metabolism into inactive metabolites in the maternal circulation. As a result, very little if any effect may be found. One example of a rapidly metabolized medication is succinylcholine, a depolarizing muscle relaxant. This medication is metabolized to benign metabolites by pseudocholinesterase in the maternal plasma and has a half-life of about 90 seconds. As a result, nothing reaches the fetus. However, if a drug is metabolized into an active metabolite in the maternal system and then crosses into the fetal system, that metabolite can have fetal effects. Such is the case with normeperidine, the active metabolite of meperidine.

A useful measurement that helps estimate fetal medication exposure is the ratio of the umbilical vein drug concentration to the maternal vein (UV : MV). A ratio of 1 (UV : MV = 1) means that the amounts of medication in the umbilical vein equal those in the maternal vein. A low ratio means that a small amount has crossed the placenta to reach the umbilical vein. For example, the nondepolarizing muscle relaxants used in general anesthesia are highly ionized, hydrophilic compounds that do not cross the membrane barrier. Their UV : MV ratios tend to be on the order of 0.1. Table 28-1 lists the UV : MV ratios of some common anesthetics.

TABLE 28-1

Placental Passage of Commonly Used Anesthetic Medications

Drug	Umbilical Vein to Maternal Vein Ratio (UV : MV)
Induction Agents
Thiopental	1.08 (range, 0.5-1.5)
Ketamine	0.54 (range, 0.4-0.7)
Propofol	0.7
Etomidate	0.5
Nondepolarizing Neuromuscular Blocking Agents
Pancuronium	0.19
Vecuronium	0.11
Opioids
Morphine	0.92
Meperidine	0.81 (may exceed 1.0 after 2-3 hours)
Fentanyl	0.57
Sufentanil	Levels too low to measure in humans
Butorphanol	0.84
Nalbuphine	0.97

Adapted from data from Glosten B. Anesthesia for obstetrics. In: Longnecker DE, et al., eds. Principles and practice of anesthesiology, 2nd ed. St. Louis: Mosby; 1998.

Even if the umbilical vein levels are significant, they may not be great enough to produce any important neurobehavioral effect because two more protective barriers exist to shield the fetal brain from medication exposure. Approximately 40% to 60% of any medication entering the fetal circulation passes through the liver first and then travels through the inferior vena cava to the heart and into the circulation. The mature or nearly mature fetal liver can metabolize most drugs, and this first pass through the liver buffers the fetal brain from exposure.²⁷ Additionally, the unique fetal circulation dilutes most of any drug as it travels into the general circulation, and this dilutional effect can be quite protective of the fetal brain.²⁷

One final clinical note for the neonatologist: Not only does the dose have an impact on how much medication enters the maternal circulation for eventual fetal distribution, but so does the mode of administration. Although it is obvious that intravenous administration achieves the highest maternal blood levels, all blocks and injections distribute some level of the drug into the maternal circulation, and they differ markedly from one another. From the greatest to the least effect on maternal blood levels, drug administration modes have the following ranking ²⁷:

Intravenous>Paracervical>Intramuscular >Epidural>Spinal

It should be noted that maternal local anesthetic levels after a spinal delivery are so low as to be clinically irrelevant.

Sedatives

The routine use of heavy sedatives in the active phase of labor has markedly diminished, making it unlikely that a neonatologist will be caring for a neonate with a recent exposure. In modern practice, the primary purpose of sedatives is to help the parturient rest during a prolonged latent phase of labor, as a sleep aid before starting an induction in a few hours, or as administered during a cesarean section either to an anxious patient or before the induction of a general anesthetic. Other than in the cesarean section scenario, enough time usually passes between administration and delivery so that any significant drug amounts clear the maternal and fetal circulations. The classes of medications most often encountered today are benzodiazepines.

Benzodiazepines are most likely encountered in an acute situation either because of maternal self-administration or from the anesthesia provider during a cesarean section. The two most commonly encountered benzodiazepines are diazepam and midazolam. Midazolam has a low UV : MV ratio, so it does not cross to the fetus well at all, making it essentially without clinical effect when given acutely. The most common use of midazolam is during a cesarean section that is unplanned. It is given by the anesthesia provider, and although a very good anxiolytic, it unfortunately causes maternal amnesia that will impair the mother’s recall of the delivery if given beforehand. Therefore it is usually reserved for the highly anxious patient, and most providers attempt to delay administration until after delivery. Unfortunately diazepam has a high UV : MV ratio that reaches 1 within minutes and can increase to 2 within hours.¹⁰⁰ Metabolites are active and can remain in the system for up to 8 days. When given in the intrapartum setting for eclamptic seizures, this medication can cause hypotonia, hypothermia, and respiratory depression in the neonate.^21,46,94 Once thought to cause oral cleft malformations when used chronically during the first trimester, more recent prospective studies do not support this assertion.^24,78 Regardless, diazepam is not as commonly prescribed by the obstetric provider as it once was, and its use is usually limited to the acute management of maternal seizures.

Barbiturates are used less commonly than before. Phenobarbital is rarely used, but remains an option for treatment of partial or generalized tonic-clonic seizures and status epilepticus.²¹ Thiopental is another barbiturate that used to be a common anesthetic induction agent; however, propofol is now more frequently used. The two have similar profiles as far as neonatal effects are concerned.

Some clinicians, even more in the past, felt that sedatives such as phenothiazines had value in early labor in reducing a woman’s anxiety and promoting sleep, and thereby contributed to pain relief.⁶⁰ Phenergan, also used for its antiemetic qualities, could be useful if there is a need to treat vomiting as well as provide pain relief.⁶⁰

Opioids

The definition of an opioid is any natural, synthetic, or semisynthetic compound that acts on the same receptors as morphine and produces similar effects. Those agents that stimulate opioid receptors are known as pure agonists and include morphine, meperidine, and fentanyl. Those that act on only some of the receptors and may even block action on others are known as agonist-antagonists and include nalbuphine and butorphanol. Pure antagonists block action on all receptors and are not considered opioids but can reverse their actions. Naloxone defines this class.

Opioids do not block the transmission of pain, but rather stimulate receptors to alter the perception of pain and one’s response to that perception. For that reason, opioids are considered incomplete analgesics. There are three known opioid receptor types and a possible fourth on which these drugs act.58,79 The µ-receptor provides the most complete analgesia, but also most of the known side effects of opioids such as pruritus, nausea and vomiting, euphoria, dysphoria, and respiratory depression to the point of apnea. The κ-receptor mediates less intense analgesia because of what is known as a “ceiling effect.” The dose-response studies performed early in the investigation of medications that stimulate this receptor determined that the curve stopped rising at a particular dose. This flattening of the dose-response curve means that more of the drug does not produce more of an expected effect. This “ceiling effect” holds not only for analgesia but also for respiratory depression. No other side effects appear to be associated with this receptor type. Both the µ- and κ-receptors have been divided into multiple subgroups. The δ-receptor mediates the effects of the endogenous endorphins, especially as they act on the spinal cord. The final receptor, named the σ-receptor, may be responsible for some of the side effects occasionally seen with some opioids. However, the existence of this receptor is dubious. Box 28-1 lists some of the opioids commonly used in labor and their classifications.

Box 28-1 Opioids Commonly Used During Labor

Opioids appear to be more effective on visceral pain than somatic pain.⁵⁸ As a result, they are more useful during the first stage of labor, which tends to be visceral in nature, than the second stage, which is more somatic.⁴¹ Because all opioids can cross the placenta and produce an effect in the fetus, systemic opioid use has traditionally been limited to the first stage so that the opioid is metabolized from the fetus before delivery. However, not only has the selection of opioids expanded over the years, but also the thoughts on how they can be delivered. Intermittent intravenous administrations are still the mainstay on most units, but now intravenous patient-controlled analgesia (IV-PCA) is being offered on some obstetric units. Once thought to be taboo because of the depressive effects of opioids on the neonate, studies show that this administration technique can be provided reasonably well.^63,83 But most agree that because of the neonatal effects, this method should be reserved for situations in which a regional technique is either not available or contraindicated.²⁴

There are several reports in the literature describing the IV-PCA technique with meperidine, fentanyl, nalbuphine, alfentanil, and remifentanil.61,63,83,89 Those neonates whose mothers use this technique should be watched for signs of sedation, respiratory depression, and low oxygen saturation.

Opioid Agonists

Opioid agonists that may be used on the obstetric unit are morphine, meperidine, fentanyl, sufentanil, and remifentanil.⁸⁸ Although formerly used, studies have shown that alfentanil is less effective than other opioids, such as fentanyl, for first-stage labor analgesia. In addition, when used in doses of 10 µg/kg in the mother, it can cause severe neonatal respiratory depression.⁴⁵ Morphine is the only naturally occurring agonist and, if used at all during labor, is used early. The reason is that not only is it more depressive than any other opioid to the neonate, but it may also depress uterine contractions, making it a questionable choice for labor management.⁷⁹

Meperidine (Demerol) is a synthetic opioid with some very interesting properties. This opioid is the one most commonly used systemically, and there is evidence that it enhances the effacement and dilation of the cervix.⁴⁸ It has atropine-like properties that can produce tachycardia and myocardial depression in the mother. Also, when injected into the epidural or spinal space, it can produce a block similar to that seen with local anesthetics.¹² For this reason, there are case reports that describe the use of meperidine in this manner in patients with a documented allergy to all forms of local anesthetics.

When used to provide systemic analgesia, meperidine is traditionally dosed in such a way as to limit fetal exposure before delivery. The drug’s duration of action is 2 to 4 hours, with a half-life of 3 to 4.5 hours. Based on that and knowing that intramuscular administration requires about 45 minutes to an hour to absorb and have an effect, meperidine is not given unless delivery is expected within the hour or beyond 3 hours. Unfortunately, estimates of delivery time are an imprecise science, and sometimes the neonate is delivered during peak exposure. Even so, the need for naloxone to reverse the depressive effects is uncommon under this scenario. In any case, it would probably be best to closely observe neonates exposed to this form of analgesia. Meperidine is metabolized to an active metabolite called normeperidine. The fetal liver is capable of metabolizing meperidine into its active metabolite, or it can cross the placenta and accumulate. Its half-life is 15 to 40 hours, so its neurologic and depressive effects can be evident for some time after delivery.

Several commonly used opioids are analogues of meperidine. They are fentanyl, sufentanil, alfentanil, and remifentanil. Although only fentanyl and sufentanil are used for anesthetic nerve blocks, fentanyl, alfentanil, and remifentanil have been used systemically in the obstetric setting. All these meperidine analogues are lipid soluble and can cross the placenta. However, they are rapidly metabolized by the first pass through the liver to inactive metabolites, thereby making any depressive effects uncommon when these drugs are given as intermittent intravenous boluses.⁶⁸ Because of its pharmacokinetic properties, remifentanil is so short-acting that it can be used only in a continuous infusion mode. In one study, fentanyl was injected as a maternal intravenous dose of 1 µg/kg just before the start of the cesarean section, and no neonatal depressive effects were detected.⁶¹

Fentanyl has been used in the IV-PCA format,49,76 as have alfentanil⁴⁹ and remifentanil,^24,36,61 with mild neonatal depression a common occurrence. This mode of administration is growing in use as more is reported in the literature and obstetric providers find it a more acceptable alternative to intermittent injections when anesthetic services are limited or neuraxial blocks are contraindicated. Remifentanil in particular may be well suited to the IV-PCA format because its half-life is only 4 minutes. Generally, oxygen supplementation and observation are all that is required for the neonate after such exposure.^37,75

One final note about the opioid agonists: All of them are associated with the suppression of fetal beat-to-beat variability, which returns to normal as the drug is eliminated, suggesting a causal effect.