Prophylactic Norepinephrine and Phenylephrine Boluses to Prevent Postspinal Anesthesia Hypotension During Cesarean Section: A Randomized Sequential Allocation Dose-Finding Study

Drug Des Devel Ther. 2023 May 23:17:1547-1555. doi: 10.2147/DDDT.S406671. eCollection 2023.

Abstract

Background: Norepinephrine and phenylephrine are widely used for obstetric anesthesia. Our central objective was to determine the ED (effective dose) 90 and potency ratio of prophylactic norepinephrine and phenylephrine boluses for preventing postspinal anesthesia hypotension during cesarean section.

Methods: Patients scheduled for elective cesarean section (n = 80) were randomly allocated to receive prophylactic norepinephrine (NE) or phenylephrine (PE) boluses immediately after induction of spinal anesthesia. An initial dose of NE (3 μg) and PE (37.5 μg) was given to the first patient, and an up-and-down sequential allocation method was used to determine the next dose level according to the responses (the effectiveness for preventing postspinal anesthesia hypotension [defined as SBP < 80% of baseline value]). Primary outcomes were ED90 and the potency ratio of prophylactic norepinephrine and phenylephrine boluses. Secondary outcomes were the incidence of postspinal anesthesia hypotension, severe postspinal anesthesia hypotension, nausea, vomiting, bradycardia, hypertension, umbilical artery blood gas values, and Apgar scores.

Results: The ED90 values for prophylactic norepinephrine and phenylephrine boluses were 8.0 μg (95% CI 7.1-11.0 μg) and 90.9 μg (95% CI 82.0-123.9 μg), respectively. The estimated relative potency ratio was 11.4:1. The incidence of bradycardia was lower in the NE group (2.5% vs 20%, P = 0.034). Other outcomes were comparable between the two groups.

Conclusion: An 8-μg prophylactic bolus of norepinephrine and a 90-μg prophylactic bolus of phenylephrine can effectively prevent postspinal anesthesia hypotension in patients during cesarean section.

Keywords: cesarean section; norepinephrine; phenylephrine; postspinal anesthesia hypotension.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Anesthesia, Obstetrical* / adverse effects
  • Anesthesia, Spinal* / adverse effects
  • Anesthesia, Spinal* / methods
  • Bradycardia
  • Cesarean Section / adverse effects
  • Cesarean Section / methods
  • Double-Blind Method
  • Female
  • Humans
  • Hypotension* / chemically induced
  • Hypotension* / prevention & control
  • Norepinephrine
  • Phenylephrine
  • Pregnancy
  • Vasoconstrictor Agents

Substances

  • Phenylephrine
  • Norepinephrine
  • Vasoconstrictor Agents

Grants and funding

This work was supported by the Key Research and Development Program of Ningxia (grant number: 2021BEG03039) and Ningxia Natural Science Foundation (grant number: 2022AAC03591).