Neuraxial opioids for labor analgesia: A double-edged sword?

Painful labor triggers unfavorable alterations in maternal physiology and biochemistry.[1] Effective labor analgesia is usually administered in the form of opioids via intrathecal, epidural, and/or intravenous routes. The nonanalgesic effects of intrathecal/epidural or intravenous opioids for obtaining pain relief during labor and delivery have always been associated with controversy. The American College of Obstetricians and Gynecologists Committee in 2006 noted “maternal request is sufficient medical indication for pain relief during labor,” and neuraxial anesthesia is not related to increased incidence of cesarean delivery.[2] Regrettably, this caters to the faction that is focused on evaluating the efficacy of neuraxial analgesia vis-à-vis maternal and fetal complications and not neonatal outcomes. Most often than not, parturients who request analgesia are afflicted by severe pain, or are protracted, and/or have dysfunctional labor; hence, making “pain” a confounding variable in various studies. Thereby, neuraxial or intravenous analgesia though related often has only an associative relation with undesired outcomes.[34] The existing literature is replete with studies, which are challenging to interpret due to improper randomization, inappropriate sample sizes, and erratic dose schedules. Primarily, the research is focused on the effects of neuraxial analgesia on cardiotocography, Doppler flow studies, fetal oxygen saturation, etc. Oddly, none of them have a predictable correlation with neonatal outcome in labor. Future randomized research should concentrate on complete neonatal assessment (Apgar scores, acid-base balance, neurobehavioral scores, and breastfeeding). Because the placental vasculature is devoid of auto-regulation, it is entirely dependent on maternal blood pressure. Fetal heart rate (FHR), which reflects fetal oxygenation, is used to ensure peripartum fetal wellbeing. Fetal distress is detected by loss of variability and deceleration patterns. Maternal, fetal, obstetrical and anesthesiological causes may influence FHR. The fetus may be affected directly by placental transfer of local anesthetics or opioids, or indirectly due to maternal hypotension or uterine hyperactivity/hypotonus. Using continuous cardiotocography, fetal distress can be detected by loss of variability and deceleration patterns. Doppler flow studies done before and after neuraxial analgesia for labor found that uterine and umbilical artery resistance remained unchanged,[56] or increased[7] in normal labor, whereas in preeclampsia,[89] a reduction in resistance was reported. A maternal hemodynamic study concluded that the level of total vascular resistance[10] before combined spinal-epidural (CSE) analgesia in labor might suggest the risk of FHR abnormalities after the procedure. Lower total vascular resistance (<1000 dyne/s/cm−5) was associated with a decreased risk of FHR abnormalities. FHR decelerations seem to occur in women without the ability to upregulate stroke volume and cardiac output in response to the initial effects of analgesia. Tetanic uterine contractions due to intrathecal administration of opioids may lead to fetal bradycardia.[11] Though the mechanisms of action for this are undetermined, perhaps it points toward the hypertonicity of the uterine musculature subsequent to an acute fall in plasma epinephrine (a known tocolytic) levels. Decreased levels of maternal circulating beta-adrenergic agonists facilitate the predominance of alpha activity, which leads to uterine contractions, decreased uteroplacental blood flow, and ensuing fetal bradycardia. Successful management of uterine hyperstimulation (IV nitroglycerine 50–100 mcg or terbutaline 0.25 mg) results in uterine relaxation and subsequent stabilization of uteroplacental perfusion, leading to regularization of FHR abnormalities.[12] Epidural fentanyl and sufentanil, by virtue of their higher lipid solubility, exhibit quicker onset of action, greater systemic absorption, and lower concentration in the fetal circulation. Recent studies investigating the timing of neuraxial analgesia (early or late in labor) described no effect on Apgar score[1314] or umbilical acid-base status,[14] contrary to Chestnut,[1516] who found lower cord pH, higher pCO2 values and increased requirement of neonatal naloxone upon late induction. The neonatal outcome is not affected by the mode of induction (CSE or epidural bolus) nor maintenance with boluses, infusion, or PCEA.[17] No alteration in Apgar scores, cord pH, or NACS was detected in a double-blind comparison of fentanyl and sufentanil by infusion,[18] while less placental transfer, a significantly higher pCO2 but healthier 24 h NACS scores were reported by Loftus who gave sufentanil in relatively larger doses.[19] Leighton compared epidural with systemic analgesia and found no significant difference in FHR abnormalities.[20] A meta-analysis by Mardirosoff reported that fetal bradycardia occurred within 1 hour of intrathecal administration in 7.3% (39 out of 535), compared to 4.8% (19 of 392) of patients, however, it was not related to the increased rate of cesarean delivery.[21] Van de Velde concluded that intrathecal sufentanil (7.5 μg) potentially results in more nonreassuring FHR tracings compared with both intrathecal analgesia using a bupivacaine (2.5 mg)/sufentanil (1.5 μg) mixture and epidural analgesia using bupivacaine, sufentanil, and epinephrine.[22] It is known that larger doses of fentanyl may be associated with slightly impaired breast-feeding,[2324] however, a negligible effect on neonatal respiration was observed in a double-blind comparison of epidural bupivacaine infused alone or with fentanyl.[25] Frequently, obstetricians are concerned about neuraxial anesthesia leading to the slowing of labor, increased incidences of cesarean section, or use of instruments to ensure safe childbirth. In 2001, Cochrane database meta-analysis study explicitly showed that epidural anesthesia had no significant effect on the duration of the first stage of the labor, however, it prolonged the second stage.[26] Thornton has recommended the use of low doses to ameliorate the rate of operative vaginal delivery. No difference in umbilical artery pH was observed in a study comparing umbilical artery acid-base status in 110 matched pairs of women who received either epidural or no analgesia.[27] Interestingly, it showed significantly higher pCO2 and base excess in the epidural group, implying a beneficial effect of epidural analgesia on metabolic acidosis. Obstetric anesthesiologists must be cognizant of the conflicting facts. Informing the worried obstetricians with facts that neuraxial analgesia provides better Apgar scores and variable neurobehavioral changes should console them. Neonatal acid-base status is not only superior with epidural than with systemic opioid analgesia, it is also better than with no analgesia. The evident catecholamine upsurge due to fetal stress response to labor is advantageous for acclimatization to extrauterine life and is not inhibited by maternal neuraxial analgesia.[28] A home run for neuraxial opioids in labor analgesia!