2: Obstetric Anesthesia and the Neonate

During birth, the status of the fetus can be influenced by obstetric analgesia and anesthesia. Care in choosing analgesic and anesthetic agents can often prevent respiratory depression in the newborn, especially in high-risk deliveries.

Drugs administered to the mother may affect the fetus via placental transfer or may cause a maternal disorder that affects the fetus (eg, maternal drug-induced hypotension producing fetal hypoxia). All anesthetic and analgesic drugs cross the placenta to some degree. Flow-dependent passive diffusion is the usual mechanism.

Most anesthetic and analgesic drugs have a high degree of lipid solubility, low molecular weight (<500), and variable protein-binding and ionization capabilities. These characteristics lead to rapid placental transfer. Local anesthetics and narcotics (lipid-soluble, unionized) cross the placenta easily; neuromuscular blocking agents (highly ionized) do not.

1. Inhalation analgesia. Inhalation analgesia is rarely used in the United States as a result of the wide availability of regional anesthesia (Note: Entonox, a mixture of 50% oxygen and 50% nitrous oxide, is used outside the United States). In addition, several problems associated with inhalational anesthesia limit its routine use:

   1. The need for specialized vaporizers

   2. Potential pollution of the labor and delivery environment with waste anesthetic gases

   3. Incomplete analgesia

   4. Maternal childbirth amnesia

   5. Possible loss of maternal protective airway reflexes and pulmonary aspiration of gastric contents

2. Pudendal block and paracervical block. Paracervical blocks are rarely used today because they may precipitate severe fetal bradycardia or increased uterine activity or cause a direct vasoconstrictive effect of the local anesthetic, resulting in decreased uteroplacental/fetoplacental perfusion. If a paracervical block is performed, the fetal heart rate (FHR) must be monitored. Paracervical blocks are effective in the first stage of labor, and pudendal blocks are effective during the second stage. Pudendal blocks have little direct effect on the fetus; however, seizures have been reported after both.

3. Opioids. All intravenously administered opioids are rapidly transferred to the fetus and cause dose-related respiratory depression and alterations in Apgar and neurobehavioral scores.

   1. Meperidine. Meperidine can cause severe neonatal depression (measured by Apgar scoring) if the drug is administered 2–3 hours before delivery as a result of maximum fetal uptake. Depression is manifested as respiratory acidosis, decreased oxygen saturation, decreased minute ventilation, and increased time to sustained respiration. Fetal normeperidine, a long-acting meperidine metabolite and significant respiratory depressant, accumulates after multiple doses or a prolonged dose-delivery interval.

   2. Morphine. Morphine has a delayed onset of action and may generate greater neonatal respiratory depression than meperidine.

   3. Butorphanol and nalbuphine. These are agonist-antagonist narcotic agents that may be safer than morphine because they demonstrate a ceiling effect for respiratory depression with increasing doses. Unlike butorphanol, maternal administration of nalbuphine can result in decreased FHR variability, sinusoidal FHR patterns, fetal tachycardia, and fetal bradycardia.

   4. Fentanyl and remifentanil. These are synthetic opioids, best administered via patient-controlled analgesia during labor. Both are short acting and have no active metabolites. Fentanyl may cause low 1-minute Apgar scores, but neonatal neurobehavioral scores are normal. Remifentanil requires careful monitoring and one-on-one maternal nursing care.

4. Opioid antagonist (naloxone). Naloxone should never be administered to neonates of women who have received chronic opioid therapy because it may precipitate acute withdrawal symptoms. It can be used to reverse respiratory depression caused by acute maternal opioid administration during labor.

5. Sedatives and tranquilizers

   1. Barbiturates. Barbiturates cross the placenta rapidly and can have pronounced neonatal effects (somnolence, flaccidity, hypoventilation, failure to feed) that may last for days. Effects are intensified if opioids are used simultaneously. This is rarely an issue when barbiturates are used to induce general anesthesia for an emergent cesarean delivery. Barbiturates rapidly redistribute into maternal tissues before placental transfer and, when they cross the placenta, are preferentially uptaken by the fetal liver.

   2. Benzodiazepines (diazepam, lorazepam, and midazolam). These agents promptly cross the placenta and equilibrate within minutes after intravenous administration. Fetal levels are often higher than maternal levels. Diazepam given in low doses (<10 mg) may cause decreased beat-to-beat variability and tone, but has little effect on Apgar scores and blood gas levels. Larger doses of diazepam may persist for days and can result in hypotonia, lethargy, poor feeding, and impaired thermoregulation. Benzodiazepines are not frequently administered during labor because they induce maternal childbirth amnesia.

   3. Phenothiazines. Phenothiazines are rarely used today because they may produce hypotension via central α-blockade, but are sometimes combined with a narcotic (neuroleptanalgesia).

   4. Ketamine. Ketamine induces dissociative analgesia. Doses >1 mg/kg may cause uterine hypertonia, neonatal depression (low Apgar scores), and abnormal neonatal muscle tone. Doses normally used in labor (0.1–0.2 mg/kg) are relatively safe, producing minimal maternal or neonatal effects.

6. Lumbar epidural analgesia. Lumbar epidural analgesia is the most frequently used neuraxial anesthetic technique for childbirth. Maternal pain and catecholamine levels are reduced, decreasing maternal hyperventilation and improving fetal oxygen delivery (excessive catecholamines can cause prolonged incoordinate labor and decreased uterine blood flow). Vasospasm of uterine arteries, common in preeclampsia, may be lessened. Labor epidural analgesia lasting >4 hours is associated with benign maternal temperature increases of up to 1°C. Unfortunately, this may lead to unnecessary neonatal sepsis evaluations.

   Local anesthetic (eg, bupivacaine, ropivacaine) is injected incrementally and/or infused continuously through an epidural catheter placed in a lumbar (L2–3, L3–4, L4–5) interspace to block the T10–L1 and S2–S4 spinal cord segments. Small doses of an opioid may be added as well; these have little effect on the neonate. Maternal hypotension caused by sympathetic blockade is easily treated with fluid administration and/or intravenous ephedrine.

7. Intrathecal opioid analgesia/combined spinal epidural. Intrathecal opioids (sufentanil or fentanyl ± morphine) provide rapid labor analgesia with minimal motor and sympathetic blockade. They are usually administered in combination with an epidural (combined spinal epidural; CSE) via a “needle-through-needle” technique (spinal needle through epidural needle, opioid injected, epidural catheter placed). When intrathecal analgesia recedes, epidural analgesia takes over. Indications include early first-stage labor (opioid alone) or when labor is very advanced (opioid + bupivacaine). Transient FHR changes occur in 10–15% of cases, usually without adverse neonatal outcomes.

8. Caudal epidural analgesia. Caudal epidural analgesia blocks the sacral nerve roots and provides excellent pain relief in the second stage of labor. Use is limited during the first stage because the larger doses of local anesthetic needed increase pelvic muscle relaxation and impair fetal head rotation. Fetal intracranial local anesthetic injection can occur also.

9. Continuous spinal analgesia. A catheter is placed directly into the spinal space either through or over the top of an introducer needle. Usually the introducer is large, making the incidence of spinal headache unacceptably high. An infusion of opioid (fentanyl or sufentanil) ± bupivacaine is maintained throughout labor. The catheter may be readily dosed for emergent cesarean delivery.

10. Local anesthetics. All of the neuraxial anesthetic/analgesic techniques (eg, epidural, spinal) and local blocks (eg, pudendal, paracervical) depend on the use of local anesthetic agents.

    1. Lidocaine. Placental transfer of lidocaine is significant, but Apgar scores are not affected in healthy neonates. Acidotic fetuses accumulate larger amounts of lidocaine through pH-induced ion trapping.

    2. Bupivacaine. Bupivacaine is theoretically less harmful than lidocaine for the fetus because it has a higher degree of ionization and protein binding. Maternal toxicity leading to convulsions and cardiac arrest has been reported after inadvertent intravascular injection. Bupivacaine, in very low concentrations, is the most commonly used local anesthetic agent for continuous labor analgesia because it provides excellent sensory analgesia with minimal motor blockade.

    3. 2-Chloroprocaine. After systemic absorption, 2-chloroprocaine is rapidly broken down by pseudocholinesterase; therefore, very little reaches the placenta or fetus. However, because of its short duration and significant motor blockade, 2-chloroprocaine is not useful for continuous labor analgesia.

    4. Ropivacaine. Ropivacaine is similar to bupivacaine but produces less motor block and maternal cardiotoxicity. The Neonatal Neurologic and Adaptive Capacity Score (NACS) is slightly better in infants whose mothers received epidural ropivacaine compared with bupivacaine for labor analgesia.

    5. Levobupivacaine. Levobupivacaine is the purified levorotary enantiomer of racemic bupivacaine. Like ropivacaine, it has less potential for cardiotoxicity than bupivacaine.

11. Psychoprophylaxis. The Lamaze technique of prepared childbirth involves class instruction for prospective parents. The process of childbirth is explained, and exercises, breathing skills, and relaxation techniques are taught to relieve labor pain. However, the popular assumption that the neonate benefits if the mother receives no drugs during childbirth may not be true. Pain and discomfort may cause psychological stress and hyperventilation in the mother, which can negatively impact the neonate. Approximately 50–70% of women who have learned the Lamaze method request medications or an anesthetic during labor. Other analgesic techniques include transcutaneous electric nerve stimulation (TENS), hypnosis, and acupuncture.

Aortocaval compression may decrease placental perfusion if the mother is positioned supine; the bed must be tilted left side down or a wedge placed under the right hip. Regional anesthesia is chosen for most cesarean deliveries because it is usually safer for mother and baby. If immediate delivery is indicated, general anesthesia is often used because it has the shortest induction time.

1. Spinal anesthesia. Spinal anesthesia (injection of local anesthetic directly into cerebrospinal fluid) requires one-tenth of the drug needed for epidural anesthesia. Maternal and fetal drug levels are low. Hypotension occurs rapidly but can be attenuated by administering 1.5–2.0 L of a balanced salt solution intravenously and treated with intravenous ephedrine or phenylephrine. Better quality anesthesia, more rapid placement, and faster onset make spinal preferred over epidural anesthesia for cesarean delivery. Abnormalities in neurobehavioral scores are more common after general anesthesia than spinal.

2. Lumbar epidural anesthesia. Placental transfer of local anesthetics occurs to a small degree, but drug effects can only be detected by neurobehavioral testing. Maternal hypotension may also occur, as with spinal anesthesia, but more slowly and to a lesser extent.

3. Combined spinal epidural. If a cesarean delivery of prolonged duration is anticipated, a CSE may be used. Rapid, good-quality spinal anesthesia is obtained with the ability to initiate epidural anesthesia when the spinal wanes.

4. General anesthesia. General anesthesia is used in the following circumstances: strong patient preference, emergency delivery (eg, maternal hemorrhage, fetal bradycardia), and contraindications to regional anesthesia (eg, maternal coagulopathy, neurologic problems, sepsis, infection). After induction, anesthesia is maintained with a combination of nitrous oxide in oxygen and low doses of inhaled halogenated agents or intravenous drugs. Opioids or benzodiazepines are rarely necessary before the cord is clamped.

   1. Agents used in general obstetric anesthesia

      1. Premedication. Cimetidine or ranitidine (H₂ receptor antagonists) may be administered to help prevent aspiration pneumonitis by decreasing gastric volume and increasing gastric pH; metoclopramide speeds gastric emptying. The neonate is not affected by these agents. Premedications traditionally used in surgery (eg, atropinics, opioids, benzodiazepines) are rarely given.

      2. Propofol. Propofol (2–2.5 mg/kg), another induction agent, is currently not approved for use in pregnancy, as well-controlled studies in humans have not been done. It rapidly crosses the placenta and distributes into the fetus. Most investigators have reported no difference in Apgar scores or NACS of infants exposed to propofol alone or with other anesthetic agents.

      3. Ketamine. Ketamine (1 mg/kg) is typically reserved for induction in severe asthmatics because of its bronchodilator properties and in patients with mild to moderate hypovolemia when cesarean delivery is emergent. Neonatal neurobehavioral scores after ketamine administration are similar to those after thiopental.

      4. Muscle relaxants. Muscle relaxants, which are highly ionized, cross the placenta only in small amounts and have little effect on the neonate.

         1. Succinylcholine. Succinylcholine crosses the placenta in minimal amounts. In twice-normal doses, it is detectable in the fetus, but no respiratory effects are seen until the dose is 5 times normal or both mother and fetus have abnormal pseudocholinesterase levels or activity.

         2. Atracurium, cisatracurium, vecuronium, and rocuronium. These are medium-duration nondepolarizing muscle relaxants. In clinical doses, an insufficient amount of drug crosses the placenta to affect the neonate.

         3. Pancuronium. Pancuronium is a long-duration muscle relaxant that does not affect the neonate when administered in clinical doses.

      5. Nitrous oxide. Nitrous oxide has rapid placental transfer. Prolonged administration of high (>50%) concentrations of nitrous oxide can result in low Apgar scores because of neonatal anesthesia and diffusion hypoxia. Concentrations of up to 50% are safe, but neonates may need supplemental oxygen after delivery.

      6. Halogenated anesthetic agents (isoflurane, enflurane, sevoflurane, desflurane, and halothane). These are used to maintain general anesthesia. Beneficial effects include decreased maternal catecholamines, increased uterine blood flow, and improved maternal anesthesia compared with nitrous oxide alone. Low concentrations of these agents rarely cause neonatal anesthesia and are readily exhaled. High concentrations may decrease uterine contractility. The lowest effective concentration is chosen, and the agent is usually discontinued after delivery to decrease uterine atony and prevent excessive blood loss.

   2. Neonatal effects of general anesthesia. Maternal hypoxia resulting from aspiration or failed endotracheal intubation can cause fetal hypoxia. Maternal hyperventilation (Paco₂ <20 mm Hg) decreases placental blood flow and shifts the maternal oxyhemoglobin curve to the left, which can also lead to fetal hypoxia and acidosis.

   3. Interval between incision of the uterus and delivery. Incision and manipulation of the uterus produces reflex uterine vasoconstriction, which may result in fetal asphyxia. Long intervals between uterine incision and delivery (>90 seconds) are associated with significant lowering of Apgar scores. If the interval is >180 seconds, low Apgar scores and fetal acidosis could result. Regional anesthesia decreases reflex vasoconstriction, so the incision-to-delivery interval is less important. The interval may be prolonged with a breech, multiple gestation, or preterm delivery; uterine scarring; or a large fetus.

   4. Regional versus general anesthesia

      1. Apgar scores. Early studies showed that neonates were less depressed at 1- and 5-minute Apgar scores when regional rather than general anesthesia was used. New general anesthetic techniques lower Apgar scores at 1 minute only. This represents transient sedation (temporary neonatal general anesthesia), not asphyxia. If the interval between induction and delivery is short, the difference between regional and general anesthesia is less, but regional anesthesia is preferred if a prolonged delivery time is anticipated. However, low Apgar scores from sedation do not have the negative prognostic value that low Apgar scores from asphyxia do, provided the neonate is adequately resuscitated.

      2. Acid-base status. The differences in acid-base status are minimal and probably not significant. Infants of diabetic mothers may be less acidotic with general than with regional anesthesia because regional anesthesia-induced hypotension may exacerbate any existing uteroplacental insufficiency.

      3. Neurobehavioral examinations. These are used to detect subtle changes in the neonate during the first few hours after birth. The goal is to detect central nervous system depression from drugs and to differentiate it from effects associated with birth trauma and perinatal asphyxia. Neonates are complex, and using only one assessment tool (Apgar score, acid-base balance, neurobehavioral testing) cannot predict developmental outcome.

         1. The Brazelton Neonatal Behavioral Assessment Scale (NBAS). Developed in 1973, this scale consists of 47 individual tests; 27 evaluate behavior, and 20 evaluate elicited responses. The NBAS evaluates the ability of the newborn to perform complex motor behaviors, to alter its state of arousal, and to suppress meaningless stimuli. However, it requires at least 45 minutes, an experienced examiner, and does not generate a single number indicating a depressed neonate; it is rarely used in the immediate postnatal setting.

         2. The Scanlon Early Neonatal Neurobehavioral Scale (ENNS). Developed in 1974, this scale includes 15 observations of muscle tone, primary reflexes, and decrement response to stimulation; 11 observations on states of consciousness; and one general assessment of neurobehavioral status. It uses noxious stimuli (repeated pin-prick and Moro maneuvers), is complicated, and although faster to perform than the NBAS, still does not yield a single number signifying a depressed neonate.

         3. The Neonatal Neurologic and Adaptive Capacity Score (NACS). This score was developed in 1982 by Amiel-Tison, Barrier, and Shnider and is used worldwide to examine neonatal effects of peripartum medications. The NACS includes 20 criteria to evaluate 5 areas: adaptive capacity (response to sound, habituation to sound, response to light, habituation to light, consolability), passive tone (scarf sign, recoil of elbows, popliteal angle, recoil of lower limbs), active tone (active contraction of neck flexors, active contraction of neck extensors), primary reflexes (palmar grasp, response to traction, supporting reaction, automatic walking, placing reaction, sucking, Moro reflex), and general neurologic status (alertness, crying, motor activity). A single number is generated that immediately identifies a depressed or vigorous neonate. It is rapid (3–15 minutes), simple, and avoids the use of noxious stimuli.