We read with interest the articles by Ngan Kee et al.  1and Dyer et al. ,2as well as the editorial by Smiley,3all of which concern comparisons of phenylephrine and ephedrine for the treatment of hypotension associated with spinal anesthesia for cesarean delivery (CD). It is reassuring to know that phenylephrine can be used safely in this setting, something that I (D.R.G.) have advocated to residents and colleagues for more than 10 yr. However, it is important to remember that ephedrine too has been used safely for decades to treat hypotension after induction of spinal anesthesia for CD. Therefore, it is crucial that the results of these recent studies are put into perspective and do not lead to an imposed or voluntary discontinuation of ephedrine use during CD. The reasons for this are as follows:

  1. Phenylephrine is not always effective, and some patients seem to be phenylephrine nonresponders who only get effective response to vasopressor treatment when ephedrine is administered.

  2. Phenylephrine can cause bradydysrhythmias that require treatment with atropine. This seems to be more of a problem when an infusion is used.

  3. The observed differences in neonatal acid–base status demonstrated in many of the studies by Ngan Kee et al . are of unknown clinical significance, but the neonatologists in our center believe that the reported differences are not clinically important. The published normal values for umbilical artery pH after uncomplicated labor and vaginal birth at term are mean pH = 7.28 ± 0.05 (range, 7.15–7.43).4Compare those with the values reported in the two studies recently published in Anesthesiology1,2(table 1).

  4. One study suggests that Apgar scores are a better measure of neonatal outcome than umbilical cord blood gases.5No study that we reviewed on the subject of phenylephrine versus  ephedrine for spinal hypotension during CD has been able to show a significant difference in Apgar scores or in neonatal clinical outcome between groups, despite reported differences in umbilical arterial and venous pH.6–13 

We would not want to see ephedrine discarded based on the evidence reported to date. Instead, we advocate a common sense approach to the treatment of spinal hypotension during CD. For example, phenylephrine could be used as a first-line treatment, with ephedrine being used either as a second-line treatment or in combination with phenylephrine. Maternal heart rate can be used as a guide to therapy. In addition, it may be prudent to use phenylephrine as the first-line agent in nonelective CD because small differences in fetal pH may have greater effect on clinical neonatal outcome in cases of intrauterine fetal stress. To date, however, studies have failed to show a significant difference in pH or clinical neonatal outcome in this setting, regardless of the vasopressor used.10 

Ultimately, more research is necessary to look beyond initial umbilical cord blood gas measurements in the delivery room and instead at more long-term neonatal outcomes. This is especially true for cases of CD in which there is suspected fetal compromise. Until such data are available, do not “throw away” the ephedrine syringe, but rather use a common sense approach based on sound clinical judgment when treating maternal hypotension in this setting.

*Sharp Mary Birch Hospital for Women and Newborns, San Diego, California, and University of California, San Diego, San Diego, California. david.gambling@sharp.com

Ngan Kee WD, Khaw KS, Tan PE, Ng FF, Karmakar MK: Placental transfer and fetal metabolic effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery. Anesthesiology 2009; 111:506–12
Dyer RA, Reed AR, Van Dyk D, Arcache MJ, Hodges O, Lombard CJ, Greenwood J, James MF: Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology 2009; 111:753–65
Smiley RM: Burden of proof. Anesthesiology 2009; 111:470–2
Yeomans ER, Hauth JC, Gilstrap LC III, Strickland DM: Umbilical cord pH, pCO2, and bicarbonate following uncomplicated term vaginal deliveries. Am J Obstet Gynecol 1985; 151:798–800
Casey BM, McIntire DD, Leveno KJ: The continuing value of the APGAR score for the assessment of newborn infants. N Engl J Med 2001; 344:467–71
Cooper DW, Carpenter M, Mowbray P, Desira WR, Ryall DM, Kokri MS: Fetal and maternal effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery. Anesthesiology 2002; 97:1582–90
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Mercier FJ, Riley ET, Frederickson WL, Roger-Christoph S, Benhamou D, Cohen SE: Phenylephrine added to prophylactic ephedrine infusion during spinal anesthesia for elective cesarean section. Anesthesiology 2001; 95:668–74
Moran DH, Perillo M, LaPorta RF, Bader AM, Datta S: Phenylephrine in the prevention of hypotension following spinal anesthesia for cesarean delivery. J Clin Anesth 1991; 3:310–5
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