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anesthesiologist

2015-02-25 01:06 毕业

Effects of Epidural Analgesia on Fetal Well-Being
Yunping Li, M.D.
Dept. of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical
Center, Harvard Medical School, Boston, MA, USA
The use of epidural analgesia has gained popularity among both obstetricians and
parturients in China. Appropriate use of an epidural test dose and fractionation of large
epidural doses of local anesthetics have made epidural anesthesia a very safe modality for
the expecting mother and her fetus.
Meticulous attention to techniques as well as constant vigilance to avoid
preventable errors allow the anesthesiologist to administrate safe labor analgesia and to
insure maternal, fetal and neonatal well-being. Adverse effects of epidural analgesia on
the fetus can originate directly from the drugs used (local anesthetics and opioids) or
indirectly from maternal hemodynamic changes due to loss of vasomotor tone from the
sympathetic blockade of the epidural. The aim of this review is to highlight the influence
of epidural analgesia on fetal and neonatal outcomes and to outline our understanding on
placental drug transfer, uteroplacental blood-flow and acid-base balance and their impact
on neonatal outcome.
1. Epidural opioids and neonatal respiratory depression
Fentanyl and sufentanil are widely used for labor epidural analgesia. Both are
highly lipophilic and able to cross placenta into fetal circulation. Following
administration of 100 μg of fentanyl into the epidural space, a significant amount of
fentanyl rapidly crosses the placenta with a fetal/maternal blood concentration ratio of
0.89 [1]. Therefore, fentanyl poses a potential for producing neonatal respiratory
depression. Sporadic case reports have documented such neonatal respiratory depression
that has been reversed by naloxone injection intramuscularly [2]. In contrast, in vitro
placenta perfusion studies have shown that sufentanil has lower placental transfer due to

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high levels of protein binding in maternal circulation [3, 4]. These studies appear to
suggest that sufentanil could be the opioid of choice for epidural analgesia. It has been
observed in multiple studies there exists a synergy between local anesthetics and opioids
that will significantly improve analgesia and decrease the total opioid requirement,
therefore, increase the safety of using opioids in parturients. Also, it is wise to avoid
bolus of fentanyl and sufentanil if delivery is imminent in 45 minutes. Availability of
naloxone near by the newborn baby warmer is highly recommended in case of neonatal
respiratory depression.
2. Intrathecal opioids and fetal heart rate abnormality
The effect of intrathecal opioids on fetal heart rate (FHR) has remained a
controversial topic in obstetric anesthesia. Abnormal FHR patterns such as late
decelerations and fetal bradycardia have been reported after administration of epidural or
combined spinal and epidural analgesia, especially when high dose of opioids were used.
Van de Velde and colleagues reported that, in a randomized, double-blinded trial,
intrathecal sufentanil in a dose of 7.5 μg is associated with 2 fold higher incidence of
non-reassuring FHR patters and slightly higher Cesarean section rate when compared to
the group received the same dose of sufentanil by epidural [5]. However, despite the
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increased frequency of FHR abnormalities, the neonatal outcomes were favorable in all
groups. There was no emergency Cesarean deliveries needed as a result of non-reassuring
FHR tracing. The epidural fentanyl had similar effects on FHR, but with lower incidence
compared to sufentanil [6]. The presumed mechanism of opioid-induced FHR
abnormality is due to uterine hyperactivity that decreases utero-placental blood flow. It
has been postulated that the uterine hyperactivity is caused by rapid onset of analgesia,
leading to a significant decrease in maternal circulating catecholamine levels. It is highly （转载自科教范文网http://fw.nseac.com）
recommended to utilize the synergistic effect of the combination of local anesthetics and
opioids to reduce the dose of narcotics needed and ultimately minimizing adverse side
effects.
3. Placental transfer of local anesthetics and effect of fetal "ion trapping"
Local anesthetics are weak bases that can cross the placenta in the non-ionized
form only. Bupivacaine is the most widely used local anesthetic in obstetrical analgesia
because of its safety profile for mothers and fetus. Bupivacaine crosses the placenta and
its fetal/maternal ratio varies between 0.2-0.4 because it is highly (96%) bound to
maternal glycoproteins. Neonatal exposure to bupivacaine clearly rises with the duration
of epidural administration. Despite clear evidence of placental transfer, there are no
reported adverse neonatal outcomes.
Lidocaine is frequently chosen for epidural anesthesia for Cesarean delivery due
to its rapid onset when compared to bupivacaine. Lidocaine also traverses the placental
barrier at a fetal/maternal ratio of 0.5-0.7. Repeated epidural injection of large dose of
lidocaine during Cesarean section may result in a greater accumulation of the drug in
newborn, however, any reported effects on newborns have been subtle and are probably
not clinically significant because the term fetus is able to biotransform lidocaine by
hepatic enzymatic activity and make it safe for the fetus.
The use of mepivacaine in obstetric epidural anesthesia fell into disfavor after an
investigation demonstrated that mepivacaine crossed the placenta leading to higher
concentrations in sampled cord blood (36-47% higher) than lidocaine. Furthermore, the
elimination time in newborns of mepivacaine was found to be 9 hrs, three times longer
than lidocaine [7]. In a rare case report, mepivacaine had been accidentally injected into
the fetus in 4 cases following attempts to place a caudal epidural during labor, leading to
intoxication of fetus. All infants were depressed and had convulsions, and two died soon

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after [8]. Currently, a caudal epidural for labor analgesia is not recommended.
For the amide local anesthetics, their pKa values are close enough to maternal
physiologic pH leading to a considerable proportion of them in the non-ionized form in
the maternal circulation and hence making them lipophilic and affording them the ability
to cross the placenta into fetal circulation. In the acidotic fetus (pH<7.2), a greater
proportion of drug is then converted into the ionized form and is unable across the
placenta to be transferred back to the maternal circulation. It results in a larger amount of
local anesthetic in fetal plasma, so called "ion trapping". However, the toxic dose of
local anesthetics in the newborn appears to be similar to that in the adult. The large
volume of distribution and placenta barrier in the fetus are most likely responsible for the
high dose of local anesthetic required to produce toxic effect.
Chloroprocaine has gained popularity in the United States, especially for
emergency Cesarean sections. Rapid hydrolysis by plasma cholinesterase in the mother
and neonate with normal enzyme levels limit its potential for toxicity.
Abboud and colleagues [9] studied the effects of epidural anesthesia on newborn
outcomes in 54 pregnant women undergoing Cesarean section. In this study, epidural
injections of bupivacaine, lidocaine and chloroprocaine for Cesarean sections had no
adverse effect on the newborns' Apgar scores, cord acid-base status, or the early neonatal
neurobehavioral scale.
Newer amide local anesthetics, such as ropivacaine and levobupivacaine, feature
the beneficial blocking properties and lowe

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