Case Study
A healthy nulliparous woman at 27 + 1 weeks’ gestation presented with regular painful uterine contractions and cervical dilation to 2 cm. Her vital signs were normal, and the initial fetal heart rate tracing was Category I. A dose of betamethasone was administered, and IV magnesium sulfate therapy was initiated for fetal neuroprotection. An anesthesiology consult was requested. Early epidural placement was recommended and accepted by the patient. Two hours after an uneventful epidural placement, a Category III fetal heart rate tracing was observed. The tracing did not show any improvement with resuscitative measures, and the patient was transferred to the OR for an urgent cesarean delivery. Surgical T4 level of epidural anesthesia was achieved with 20 ml of a lidocaine, bicarbonate, and epinephrine mixture. Twelve minutes after skin incision, a viable baby boy was born via classical hysterotomy with Apgar scores of 5 and 7 and 1 and 5 minutes, respectively. The newborn was transferred to the NICU for further care. Uterine atony was noted, which failed to respond to an initial IV infusion of oxytocin and an intramuscular injection of methylergonovine 0.25 mg. Uterine tone improved after a single intramyometrial injection of carboprost 0.2 mg. The remainder of the surgery was uneventful, with an estimated blood loss of 1,300 ml. No blood transfusion was required. Morphine 3 mg was administered epidurally for postoperative pain control. The epidural catheter was removed, and the patient was transferred to the PACU in a stable condition.
Key Points
A healthy patient in preterm labor in the absence of any identifiable risk factors commonly presents to the obstetric anesthesiologist for analgesia or anesthesia.
Prompt anesthesiology consultation may allow for the early establishment of epidural analgesia, which can later be converted into epidural anesthesia for an urgent classical cesarean.
Uterine atony initially refractory to IV oxytocin and methylergonovine can sometimes be corrected with prostaglandins such as carboprost.
Discussion
The mean duration of a singleton pregnancy is 40 weeks (280 days) dated from the first day of the last menstrual period. Term is defined as two standard deviations from the mean or, more precisely, 37 completed to 42 weeks (266–294 days) of gestation. Preterm (premature) labor is defined as labor occurring prior to 37 completed weeks of gestation. Preterm is further divided into extreme preterm (<28 weeks), very preterm (28–34 weeks), and late preterm (34–37 weeks).
According to the World Health Organization (WHO), complications of prematurity are the leading cause of death among children younger than 5 years of age worldwide. Preterm birth is also a major cause of perinatal morbidity, and delivery prior to 32 weeks of gestation frequently results in lifelong disability.1 An estimated 15 million premature children are born each year worldwide. In 2010, 517,400 premature babies were born in the United States alone, which ranks sixth highest in the world in regard to the number of babies born too soon.2 In 2013, 11 percent of all live-born babies in the United States were delivered preterm,3 and half of those preterm babies were delivered via cesarean.3 The high likelihood of operative delivery suggests that early anesthesia consultation should be a routine part of the peripartum management of preterm parturients.
Etiology of Preterm Labor
Preterm labor represents a syndrome rather than a single diagnosis because the etiologies are varied. Approximately 20 percent of preterm deliveries are iatrogenic and are performed for maternal or fetal indications, including fetal growth restriction, preeclampsia, placenta previa, and nonreassuring fetal testing.4 Of the remaining cases of preterm birth, around 30 percent occur in the setting of preterm premature rupture of the membranes, 20–25 percent result from intra-amniotic infection, and the remaining 25–30 percent are due to spontaneous (unexplained) preterm labor.
Anesthetic Management and the Preterm Neonate
Preterm babies may be more sensitive to the effects of medications than their term counterparts because they have decreased protein-binding capacity (secondary to hyperbilirubinemia), diminished hepatic clearance, and increased permeability of the blood-brain barrier. Although controversial, it is possible that the choice of anesthesia provided to the mother may affect neonatal outcome. In one prospective population-based cohort study conducted 18 years ago in France, neonatal mortality among 1,338 infants delivered via cesarean before 33 weeks of gestation was 10.1 percent with general, 12.2 percent with spinal, and 7.7 percent with epidural anesthesia. Even after adjustment for gestational age and potential confounding demographic and clinical factors, spinal anesthesia was still associated with a significantly higher risk of neonatal death than general anesthesia (odds ratio [OR] 1.7; 95% confidence interval [CI] 1.1–2.6).5
It was reported more than 20 years ago that compared with epidural anesthesia, general anesthesia at the time of cesarean will lower the Apgar score among preterm babies.6 Similarly, for very preterm babies, cesarean delivery performed under general anesthesia is associated with an increased risk of neonatal intubation compared with spinal anesthesia (48.7 versus 25.2 percent, respectively; OR 2.8; 95% CI 1.8–5.1).7 In addition to these short-term adverse events, much has been written about the potential long-term negative effects of general anesthesia on the developing brain. To specifically address this concern, a consortium called SmartTots (Strategies for Mitigating Anesthesia-Related Neurotoxicity in Tots) was established in 2009 by the Food and Drug Administration (FDA) and the International Anesthesia Research Society. Since that time, animal studies have confirmed that general anesthetic agents are indeed able to induce significant neurotoxicity, acting either via GABA receptors (e.g., propofol, etomidate, sevoflurane, desflurane) or NMDA receptors (e.g., ketamine).8, 9 In one study, for example, significant neuroapoptosis and impairment in synapse development were demonstrated in the brains of primates exposed to general anesthetic agents.10 And data from small observational studies in children suggest that there may indeed be an association between exposure to general anesthesia and subsequent learning difficulties.8, 9 Taken together, these data suggest that epidural anesthesia is likely the safest mode of anesthesia for preterm cesarean deliveries. Well-designed studies in premature infants confirming an improvement in short- and long-term outcome measures with the use of epidural anesthesia are urgently needed.
Epidural administration of chloroprocaine has one additional benefit in that it is associated with a lower incidence of transient fetal heart rate abnormalities compared with bupivacaine or lidocaine.11 It would therefore seem reasonable to use chloroprocaine when the fetus is preterm, especially if rapid induction of epidural anesthesia is required. Lidocaine and bupivacaine remain acceptable choices in nonemergent situations.
Preterm babies have decreased nonenzymatic antioxidant reserve.12 As such, the potential benefit of increasing maternal oxygenation by increasing the percentage of oxygen in the inhaled gaseous mixture must be weighed against the potential harmful effects of increasing the release of oxygen free radicals within the fetoplacental unit.13
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