SEE Question 2023

You are administering spinal anesthesia during an urgent cesarean delivery for a nonreassuring fetal heart rate. According to a recent study, which of the following outcomes is MOST likely in this parturient if you administer norepinephrine for maternal hypotension, compared to a similar parturient receiving phenylephrine?

• □ (A) Lower risk of nausea and vomiting
• □ (B) Higher risk of maternal tachycardia
• □ (C) No difference in fetal umbilical arterial pH

Guidelines from ASA and the Society for Obstetric Anesthesia and Perinatology recommend ephedrine or phenylephrine for treating maternal hypotension following spinal anesthesia for cesarean delivery. However, the guidelines also cite evidence that phenylephrine may more effectively treat hypotension and improve umbilical artery pH compared to ephedrine. Thus, phenylephrine – via preemptive infusion or rescue bolus – has gained favor in this setting.

More recently, norepinephrine, with both α- and β-adrenergic agonist properties, has been explored as a potential replacement for phenylephrine. However, outcomes in relatively uncomplicated cesarean deliveries have been equivocal, and essentially no studies have compared these agents in the setting of potential or confirmed fetal distress. Investigators in India compared phenylephrine and norepinephrine when used to treat hypotension in parturients undergoing spinal anesthesia for emergency cesarean delivery with potential or confirmed fetal distress. Inclusion criteria included a nonreassuring fetal heart rate, meconium-stained amniotic fluid, intra-uterine growth restriction, oligohydramnios, antepartum hemorrhage, fetal prematurity (gestation <37 weeks), or fetal postmaturity (gestation >42 weeks). Parturients were excluded if they had conditions associated with hypertension, cardiovascular disease, or hypotension (systolic blood pressure <100 mm Hg).

Parturients were randomized to receive either intravenous phenylephrine (100 μg) or norepinephrine (8 μg) with any systolic blood pressure reading less than 100 mm Hg following spinal anesthesia. The patient, the investigator collecting the data, and the provider caring for the neonate were blinded to the treatment. Only patients who required these pressors were included in the analysis (50 patients in each group).

In both groups, the mean time from administration of spinal anesthesia to delivery was approximately 10.5 minutes, and the mean time from uterine incision to delivery was approximately 36 seconds. No difference was observed between groups in the median number of hypotensive episodes resulting in treatment (phenylephrine, 2 [IQR, 1-2]; norepinephrine, 1 [IQR, 1-1]). Eleven parturients (22%) in the phenylephrine group had multiple hypotensive episodes compared to 14 (28%) in the norepinephrine group. Seven parturients (14%) in the phenylephrine group had bradycardia (defined as heart rate <60 beats/min) compared to 5 (10%) in the norepinephrine group. For bradycardia, only one patient (2%) in the phenylephrine group and two (4%) in the norepinephrine group received treatment (i.e., 0.2 mg of glycopyrrolate). Three parturients in each group (6%) experienced tachycardia.

There were no differences detected between groups in mean fetal umbilical arterial pH (phenylephrine, 7.251 ± 0.081; norepinephrine, 7.252 ± 0.082) or mean arterial Po₂ (phenylephrine, 21.1 ± 7.5 mm Hg; norepinephrine, 21.4 ± 6.7 mm Hg). No differences were noted in other arterial blood gas measures (Pco₂, O₂ saturation, HCO₃, base excess). Umbilical venous blood gas values did not differ between groups. Other secondary measures that were similar between groups were maternal heart rate, systolic blood pressure, the occurrence of nausea or vomiting, Apgar scores, and neonatal intensive care unit admission. Umbilical artery blood lactate levels, a better indicator of fetal well-being than pH, were not measured.

In summary, for emergency cesarean delivery in the presence of confirmed or potential fetal distress, the maternal hemodynamic responses and markers of fetal well-being did not differ between parturients receiving intravenous phenylephrine versus norepinephrine for hypotension following spinal anesthesia. This relatively small study did not demonstrate a pharmacodynamic argument for norepinephrine to avoid bradycardia, as both agents similarly increased systolic blood pressure with a baroreflex-mediated decrease in heart rate. Both agents produced similarly desired maternal and fetal outcomes in the setting of emergency cesarean delivery. The authors emphasized that the evidence remains insufficient to claim that either norepinephrine or phenylephrine is superior for treatment of hypotension during elective or emergency cesarean delivery.