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The Effect of Prophylactic Phenylephrine and Ephedrine Infusions on Umbilical Artery Blood pH in Women With Preeclampsia Undergoing Cesarean Delivery With Spinal Anesthesia: A Randomized, Double-Blind Trial

Higgins, Nicole*; Fitzgerald, Paul, C.*; van Dyk, Dominique; Dyer, Robert, A.; Rodriguez, Natalie*; McCarthy, Robert, J.*; Wong, Cynthia, A.*

doi: 10.1213/ANE.0000000000002524
Research Report: PDF Only

BACKGROUND: Spinal anesthesia for cesarean delivery is associated with a high incidence of hypotension. Phenylephrine results in higher umbilical artery pH than ephedrine when used to prevent or treat hypotension in healthy women. We hypothesized that phenylephrine compared to ephedrine would result in higher umbilical artery pH in women with preeclampsia undergoing cesarean delivery with spinal anesthesia.

METHODS: This study was a randomized double-blind clinical trial. Nonlaboring women with preeclampsia scheduled for cesarean delivery with spinal anesthesia at Prentice Women’s Hospital of Northwestern Medicine were randomized to receive prophylactic infusions of phenylephrine or ephedrine titrated to maintain systolic blood pressure >80% of baseline. Spinal anesthesia consisted of hyperbaric 0.75% bupivacaine 12 mg, fentanyl 15 µg, and morphine 150 µg. The primary outcome was umbilical arterial blood pH and the secondary outcome was umbilical artery base excess.

RESULTS: One hundred ten women were enrolled in the study and 54 per group were included in the analysis. There were 74 and 72 infants delivered in the ephedrine and phenylephrine groups, respectively. The phenylephrine:ephedrine ratio for umbilical artery pH was 1.002 (95% confidence interval [CI], 0.997–1.007). Mean [standard deviation] umbilical artery pH was not different between the ephedrine 7.20 [0.10] and phenylephrine 7.22 [0.07] groups (mean difference −0.02, 95% CI of the difference −0.06 to 0.07; P = .38). Median (first, third quartiles) umbilical artery base excess was −3.4 mEq/L (−5.7 to −2.0 mEq/L) in the ephedrine group and −2.8 mEq/L (−4.6 to −2.2mEq/L) in the phenylephrine group (difference −0.6 mEq/L, 95% CI of the difference −1.6 to 0.3 mEq/L; P = .10). When adjusted for gestational age and infant gender, umbilical artery pH did not differ between groups. There were also no differences in the umbilical artery pH stratified by magnesium therapy or by the severity of preeclampsia.

CONCLUSIONS: We were unable to demonstrate a beneficial effect of phenylephrine on umbilical artery pH compared with ephedrine. Our findings suggest that phenylephrine may not have a clinically important advantage compared with ephedrine with regard to improved neonatal acid-base status when used to prevent spinal anesthesia–induced hypotension in women with preeclampsia undergoing cesarean delivery.

From the *Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and Department of Anaesthesia and Perioperative Medicine, University of Cape Town, Cape Town, South Africa.

Accepted for publication August 24, 2017.

Funding: This study was supported by the Department of Anesthesiology at Northwestern University Feinberg School of Medicine.

Conflicts of Interest: See Disclosures at the end of the article.

The study was presented at the 2015 Annual Meeting of the American Society of Anesthesiologists, October 24–28, San Diego, California.

Cynthia A. Wong, MD, is currently affiliated with Department of Anesthesia, University of Iowa Carver College of Medicine, Iowa City, Iowa.

Clinical trial registry: (NCT00458003).

Reprints will not be available from the authors.

Address correspondence to Robert J. McCarthy, PharmD, Department of Anesthesiology, Northwestern University Feinberg School of Medicine, 251 E Huron St F5-704, Chicago, IL 60611. Address e-mail to

© 2018 International Anesthesia Research Society
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