Ephedrine, phenylephrine and fetal acidosis

Field: Medicine (Health Sciences)

I was interested to read the editorial by Clyburn [1]. He discussed the causes of fetal acidosis during spinal anaesthesia for Caesarean section, which vasopressor to use and how best to give it. At our hospital we have several years of experience of using phenylephrine infusions in obstetric anaesthesia. In a study of low-risk Caesarean sections, we compared the incidence of fetal acidosis when phenylephrine, ephedrine, or a combination of both was given to try and maintain maternal arterial pressure at baseline levels during spinal anaesthesia [2]. Giving phenylephrine was associated with a reduction in fetal acidosis, compared with ephedrine. We could not explain this difference on the basis of differences in maternal arterial pressure, so we had to consider alternative mechanisms. Clyburn mentioned that as ephedrine crosses the placenta it is possible that acidosis is the result of a direct fetal effect. We believe this to have been the most likely mechanism for the ephedrine-induced fetal acidosis in our study and we found indirect evidence of an ephedrine-induced increase in fetal metabolic rate. With ephedrine, the umbilical arterial − venous Pco2 difference was greater than with phenylephrine, and it appeared to be dose dependent. With ephedrine, but not phenylephrine, decreasing umbilical artery pH was associated with an increasing umbilical vessel Pco2 difference. This suggests that ephedrine-induced fetal acidosis was associated with increasing fetal metabolic rate. In the pregnant ewe there is evidence that a beta-adrenergic induced increase in fetal metabolic rate can increase fetal oxygen demand, leading to anaerobic metabolism and lactic acidosis [3]. Increased fetal metabolic rate would also be expected to reduce fetal pH by increasing fetal Pco2. Is the difference in fetal pH that can occur between ephedrine and phenylephrine clinically significant? Probably not when moderate doses are given. The meta-analysis by Kee et al. [4] found a 0.03 (95% CI, 0.02–0.04) difference only in umbilical artery pH and no difference in the incidence of acidosis, or difference in Apgar scores. It is only when relatively large doses of vasopressor are given to try and maintain arterial pressure at baseline that the incidence of acidosis increases with ephedrine, compared with alpha-agonists [2, 5]. However, the clinical significance of the increased acidosis is questionable for the low-risk pregnancies studied, because there was no evidence of any difference in Apgar scores. One study has even provided evidence that maternal beta-adrenergic administration before delivery by Caesarean section can improve the clinical condition of the neonate [6]. It improved respiratory function and reduced hypoglycaemia, even though it was associated with increased fetal acidosis. The relatively large doses of ephedrine that are required when baseline maternal arterial pressure is the goal probably have direct fetal effects. It is also possible that there may be direct fetal effects from the increasingly large doses of phenylephrine that are being given. If phenylephrine does cross the placenta in significant amounts, it may not induce fetal acidosis, because of its lack of beta-adrenergic activity. However, it could possibly have other fetal effects, such as increased fetal arterial pressure, or even induce changes in the fetal pattern of circulation. Early in 2002 we introduced guidelines in our hospital for the routine use of phenylephrine for Caesarean section. The guidelines have been used elsewhere in our region [7, 8]. In common with Clyburn, we start a prophylactic phenylephrine infusion immediately after spinal anaesthesia. However, our initial infusion rate (33 μg.min−1) is one-third of that referred to by Clyburn (100 μg.min−1) [9]. We then adjust the rate up or down by factors of two (maximum rate 67 μg.min−1), as required, to keep the arterial pressure at baseline level. Additional phenylephrine boluses are occasionally needed, but the median overall phenylephrine dose required is only 33 μg.min−1 (IQR 24–47). This is associated with a low-incidence of maternal nausea and vomiting and fetal acidosis [2]. There is also evidence from recent research that it does not significantly reduce maternal cardiac output, or alter umbilical artery pulsatility index [8]. However, giving 100 μg.min−1 of phenylephrine can reduce maternal cardiac output [10]. Perhaps the routine use of our (or a similar) more conservative regimen would be advisable until further work is carried out to assess possible placental transfer and fetal side-effects of phenylephrine. I would also recommend caution with glycopyrronium. Clyburn recommended giving it if maternal heart rate decreased below 80 bpm. Maternal arterial pressure also needs to be taken into consideration. In our experience, if the decrease in heart rate is associated with an increase in arterial pressure above baseline levels, giving glycopyrronium can cause severe hypertension.