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Anesthesia for Labor and Delivery
The goal of modern-day obstetric anesthesia practice is to provide the patient with analgesia as she requests it. That assumes her choice is appropriate to the labor process and to the current conditions as evaluated by her obstetric provider, and has as little impact on the fetus as possible. 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, which includes a discussion of the newer anesthetic techniques. 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. Labor pain in particular has been shown to be more intense than almost any other known pain syndrome. 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 of pain is to define it as being visceral or somatic. Visceral pain originates from the viscera and is often described as cramping, dull, and steady. Somatic pain is related to nonvisceral structures and is commonly described as sharp, intermittent, and well localized. During the dilation phase, or first stage, of labor, visceral pain predominates, arising from mechanical distention of the lower uterine segment and cervical dilation. Somatic pain prevails during the descent phase, or second stage, of labor and is attributed to the distention and traction on pelvic structures surrounding the vagina as well as distention of the pelvic floor and perineum.
The challenge when managing labor pain is to understand its very dynamic nature that may require adaptation of pain techniques to adequately manage it. Labor pain evolves 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 some form of nerve block, making this a common choice. On the other hand, opioids are very effective for visceral pain but are of little value for somatic pain. 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. The term encompasses epidural, spinal, and combined spinal-epidural (CSE) central nervous system blocks that are only administered by those trained in anesthetic methods. 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. The lower doses result in less absorption into the maternal bloodstream, making levels barely or non-detectable. This allows the parturient to experience pain-free labor with minimal side effects to both her and the fetus while still allowing for active participation in the labor process. However, all procedures carry some risk, and as dosing methods can vary across the United States, a fetal or neonatal effect from the medications used can occur.
Despite the proven safety and efficacy of the lower-dose neuraxial techniques, not all parturients wish to use them, nor are there always practitioners available to perform these procedures. Also, not all patients are reasonable candidates for a neuraxial block for a myriad of reasons. As a result, many of the traditional, non-neuraxial approaches for labor pain management are still utilized in obstetric suites, as are some newer 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 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. What is not always appreciated is that incorrect performance can have negative consequences. If the mother deviates from the defined breathing technique and hyperventilates during her contractions, she will lower her P co 2 levels. The maternal hypocapnia and resulting acute alkalosis causes the maternal oxy-hemoglobin curve to shift toward the fetal curve, thereby reducing the release of oxygen to the fetus. It also may reduce umbilical blood flow. If fetal acidosis develops during the first stage of labor, it will worsen during the second stage, especially if that stage exceeds 1 hour. Once hypoxia and a base deficit are present during the second stage of labor, it is difficult to reverse in utero. 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. Effective analgesic techniques have been shown to improve these conditions if applied before the second stage.
With the popularity of the Internet, patients today are able to find a variety of information about natural childbirth practices without any means to determine if the information presented is accurate. 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 course but try to learn the techniques in a matter of hours, if they train at all. This makes it nearly impossible to learn the pain-controlling techniques that Lamaze and Bradley described. Additionally, information provided in courses on available forms of pain relief options is variable, not only due to potential personal biases by the instructor, but also the instructor's knowledge of what is available at the local maternity units. 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. Also, mothers who planned for an unmedicated labor but resorted to a neuraxial block frequently experienced longer labors associated with higher pain scores, which may catch them unprepared for the intensity of the process.
Hypnosis
Self-hypnosis for labor and delivery, or hypnobirthing, enjoys a devoted following among those for whom the process has been successful. It requires time for training and practice and is not a choice for those with only a weekend set aside to learn 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 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. In the context of childbirth, suggestions may focus on increasing feelings of safety, relaxation, and comfort, as well as potentially developing sensations of numbness.
Further studies are warranted to clarify the impact of hypnosis on labor pain as current studies lack randomization, hypnotic methods are not well described, and the study populations are relatively small. A recent Cochrane database review examined 9 trials with a total of 2954. The review authors found hypnosis may reduce the overall use of analgesics but not epidural use. Also, there were no clear 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.
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. 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. 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.
Acupuncture
This technique 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 but time consuming and without consistent results. In addition, the study sizes have been small, indicating that more research is needed, although there appears to be no negative effect on the neonate.
Pharmacokinetics, Pharmacodynamics, and the Fetus
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. 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.
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 45 ). 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. A drug's pKa means that 50% of the drug is ionized and 50% is nonionized. Local anesthetics as a class are weak bases (pKa = 7.6-9.1), so at physiologic pH (7.4) more of the drug is in the ionized state. The ratio by which a local anesthetic is ionized in the circulation depends on how much higher the pKa is from 7.4. 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 only the nonionized portion of a drug will cross a membrane barrier, the amount that crosses will reproportion itself into ionized and nonionized forms once 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 and cannot return to the maternal circulation. If maternal exposure to the medication persists, more of the drug passes from mother to 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 27.1 lists the UV:MV ratios of some common anesthetics.
TABLE 27.1
Placental Passage of Commonly Used Anesthetic Medications
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.
| 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 |
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%-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. 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.
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 :
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, but may be administered during a cesarean delivery either to an anxious patient or before the induction of a general anesthetic. Other than in the cesarean delivery scenario, enough time usually passes between administration and delivery so that any significant drug amounts clear the maternal and fetal circulations. The class of medications most often encountered today is benzodiazepines.
Benzodiazepines are most likely used 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 delivery that is unplanned. Given by the anesthesia provider for its excellent anxiolytic properties, it unfortunately causes maternal amnesia that will impair the mother's recall of the delivery if administered beforehand. It is usually reserved for the highly anxious patient, and most providers attempt to delay administration until after delivery. Diazepam is another benzodiazepine that might be encountered. Unfortunately, diazepam has a high UV:MV ratio that reaches 1 within minutes and can increase to 2 within hours. 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. Once thought to cause oral cleft malformations when used chronically during the first trimester, studies do not support this assertion. 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. A discussion of other benzodiazepines can be found in any general pharmacologic text.
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. Thiopental is an anesthetic induction agent that is no longer available in the United States, making propofol the most frequently used. The two have similar profiles as far as neonatal effects are concerned.
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 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. The µ-receptor provides the most complete analgesia but also produces 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, called the σ-receptor, may be responsible for supraspinal effects and little is known about it to date, but research is ongoing. Box 27.1 lists some of the opioids commonly used in labor and their classifications.
Box 27.1
Opioids Commonly Used During Labor
Opioids appear to be more effective on visceral pain than somatic pain. 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. 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 intravenous patient-controlled analgesia (IV-PCA) is offered on most obstetric units. Once thought to be taboo because of neonatal opioid-induced depression, studies show that this administration technique can be provided reasonably well. However, because of the depressive effects, this method should be reserved for situations in which a regional technique is either not available or contraindicated.
There are several reports in the literature describing the IV-PCA technique with meperidine, fentanyl, alfentanil, and remifentanil. 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. 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. 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 to the neonate than any other opioid, but it may also depress uterine contractions, making it a questionable choice for labor management.
Meperidine (Demerol) is a synthetic opioid with some very interesting properties. This opioid was one of the most commonly used systemically, but its use has dropped off. There is evidence that it enhances the effacement and dilation of the cervix and has atropine-like properties that can produce tachycardia and myocardial depression in the mother. When injected into the epidural or spinal space, it can produce a block similar to that seen with local anesthetics, making it an option when a patient has 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 2-4 hours, with a half-life of 3-4.5 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 15-40 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. 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.
Fentanyl has been used in the IV-PCA format, as have alfentanil and remifentanil, with mild neonatal depression a common occurrence. This mode of administration is a more acceptable alternative to intermittent injections when anesthetic services are limited or neuraxial blocks are contraindicated. Generally, oxygen supplementation and observation are all that is required for the neonate after such exposure.
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.
Opioid Agonist-Antagonists
All medications in this category stimulate the κ-receptor and thus have a ceiling effect on respiratory depression, as previously described. However, the ceiling effect also applies to analgesic capabilities, making this class of drug limited in its effectiveness. The two most commonly used formulations on obstetric units in the United States are nalbuphine (Nubain) and butorphanol (Stadol). Both produce sedation in the mother and degrade to inactive metabolites, and although both cross the placenta, the fetal effects seem limited. However, nalbuphine reduces fetal beat-to-beat variability and can produce a sinusoidal pattern when used.
It is important to note that these two medications are markedly different in how they act on the µ-receptor. Whereas butorphanol has essentially no effect on the µ-receptor, nalbuphine actively blocks it. As a result, it can be used in small doses in lieu of naloxone to counter µ-receptor side effects such as pruritus. The danger with nalbuphine is that it can place an opioid-addicted patient into acute withdrawal at doses commonly used for labor analgesia. It can do the same to the addicted neonate. Therefore, caution should be exercised when using this medication if there is any indication of opioid abuse in the mother or if she is in an opioid addiction maintenance program.
Because of the sedative and respiratory depressive effects of these drugs as well as the inability to produce complete analgesia, heavy intrapartum use can lead to a situation in which maternal hyperventilation during a contraction is followed by hypoventilation as the contraction recedes. This condition will produce predictable consequences for maternal oxygen and carbon dioxide levels and shifts in the oxy-hemoglobin curve that can end in significant fetal acidosis that begins during the first stage and worsens during the second.
Opioid Antagonists
The opioid antagonist, naloxone (Narcan), blocks the action of an opioid on all of the receptors and is commonly used to reverse adverse side effects and excessive dosing. It has a short half-life (30-45 minutes), which means that repeated boluses may be necessary at times. Naloxone is not a benign drug and has been known to cause pulmonary edema and cardiac failure in some situations, so caution should be exercised when using it. It crosses the placenta, so it will reverse any opioid effect in the fetus. As with nalbuphine, it is not a medication that should be given to a mother with an opioid addiction or who is in an opioid addiction maintenance program. Not only will it produce withdrawal in the mother but in the addicted fetus as well.
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