Determination of the 90% Effective Dose of Phenylephrine Boluses to Treat Spinal Anesthesia-Induced Hypotension in Patients with Severe Preeclampsia during Cesarean Delivery: A Pilot Study

Abstract

Purpose

Treatment of spinal anesthesia-induced hypotension in patients with severe preeclampsia assumes special concern as hypotension may further reduce placental perfusion. Phenylephrine is still the first-line vasopressor for treating spinal anesthesia-induced hypotension. However, the optimal dose of phenylephrine used as intravenous (IV) boluses in patients with severe preeclampsia has not been clearly determined. We aim to calculate the 90% effective dose (ED₉₀) of phenylephrine as IV boluses for treating spinal anesthesia-induced hypotension in patients with severe preeclampsia undergoing cesarean delivery.

Patients and Methods

Forty patients with severe preeclampsia were enrolled in this prospective sequential allocation dose-finding trial. Using the biased coin up-and-down (BCUD) method, all patients in our study received an IV bolus phenylephrine of either 40, 50, 60, 70, or 80 µg when the mean arterial pressure (MAP) decreased to less than 80% of the baseline level and the ED₉₀ was determined. The primary outcome was the success of the assigned phenylephrine bolus to maintain the MAP at or above 80% of baseline value between the induction of spinal anesthesia and delivery of the fetus. Secondary outcomes included hypertension, nausea, vomiting, bradycardia, upper sensory level of anesthesia, umbilical blood gases, and Apgar score. Estimating of the ED₉₀ with 95% confidence interval (CI) was achieved by isotonic regression method.

Results

The ED₉₀ of phenylephrine was estimated as 62.00 µg (95% CI=50.00–67.40 µg) using the isotonic regression method. No patients enrolled in our study experienced bradycardia and those patients who developed hypertension were all observed at the dose level 70 µg.

Conclusion

For clinical practice, we recommend that phenylephrine 60 µg may be both effective and safe for treatment of spinal anesthesia-induced hypotension in severe preeclampsia during cesarean delivery.

Keywords:

• phenylephrine
• hypotension
• preeclampsia
• biased coin up-and-down method
• ED₉₀

Acknowledgments

The authors thank the teachers and colleagues in the Department of Anesthesiology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Abbreviations

ED₉₀, the 90% effective dose; BCUD, biased coin up-and-down; MAP, mean arterial pressure; IV, intravenous; CI, confidence interval; ASA, American Society of Anesthesiologists; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; CO, Cardiac output; PAVA, pooled-adjacent-violators algorithm; SVR, systemic vascular resistance.

Data Sharing Statement

The data that support the findings of the study are available from the corresponding author upon reasonable request.

Ethics Approval and Informed Consent

The authors declare that the study have obtained approval from the Ethical Committee of Women’s Hospital, Zhejiang University School of Medicine (Hangzhou, China) (no. 20180010) and was registered at Chinese Clinical Trials.gov (ChiCTR1800015805). Written informed consent was obtained from all patients before enrollment in our study. We confirm that our study complies with the Declaration of Helsinki.

Consent for Publication

All authors have read and approved the manuscript, and agreed to submit to your journal.

Disclosure

The authors declared no external funding or competing interests.