Dose-Response Study of Phenylephrine for Preventing Spinal-Induced Hypotension During Cesarean Delivery with Combined Spinal-Epidural Anesthesia Under the Effect of Prophylactic Intravenous Ondansetron

Abstract

Background

Ondansetron reduces the median effective dose (ED50) of prophylactic phenylephrine to prevent spinal-induced hypotension (SIH) during cesarean delivery. However, the exact dose response of phenylephrine in combination with prophylactic ondansetron for preventing SIH is unknown. Therefore, this study aimed to determine the dose-response of phenylephrine to prevent SIH in cesarean delivery when 4 mg of ondansetron was used as a preventive method.

Methods

A total of 80 parturients were enrolled and divided randomly into four groups (n = 20 in each group) who received either 0.2, 0.3, 0.4, or 0.5 μg/kg/min of prophylactic phenylephrine. Ten minutes before the initiation of spinal induction, 4 mg prophylactic ondansetron was administered. The effective dose of prophylactic phenylephrine was defined as the dose required to prevent hypotension after the period of intrathecal injection and up to neonatal delivery. The ED50 and ED90 of prophylactic phenylephrine and 95% confidence intervals (95% CI) were calculated using probit analysis.

Results

The ED50 and ED90 for prophylactic phenylephrine to prevent SIH were 0.25 (95% CI, 0.15 to 0.30), and 0.45 (95% CI, 0.39 to 0.59) μg/kg/min, respectively. No significant differences were observed in the side effects and neonatal outcomes between the four groups.

Conclusion

The administration of 4 mg of prophylactic ondansetron was associated with an ED50 of 0.25 (95% CI, 0.15~0.30) and ED90 of 0.45 (95% CI, 0.39~0.59) μg/kg/min for phenylephrine to prevent SIH.

Keywords:

• phenylephrine
• ondansetron
• dose-response
• hypotension
• cesarean delivery
• spinal

Data Sharing Statement

The authors intend to disclose deidentified participant data, including blood pressure, side effects, and demographic data. However, no other documents related to the study will be made accessible. Interested parties can access the data through http://www.chictr.org.cn after a period of 6 months following publication.

Ethics and Consent Statements

This study was approved by the Institutional Review Board of Jiaxing University Affiliated Women and Children’s Hospital’s Institutional Review Board (IRB 2019-119, date of approval: Nov 6. 2019).

This study was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all patients for inclusion in the study.

Acknowledgments

We would like to thank all staff in the operating theater and all obstetric staff involved for their kind help in the study delivery.

Disclosure

The authors declare no conflicts of interest in this work.