The ED50 and ED95 of Prophylactic Norepinephrine for Preventing Post-Spinal Hypotension During Cesarean Delivery Under Combined Spinal-Epidural Anesthesia: A Prospective Dose-Finding Study

Background: Hypotension commonly occurs with spinal anesthesia during cesarean delivery. Norepinephrine is an alternative to phenylephrine which can be used to prevent or treat hypotension, with better maintained cardiac output and less bradycardia. However, an appropriate initial prophylactic infus...

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Main Authors: Wenping Xu, Dan Michael Drzymalski, Ling Ai, Hanqing Yao, Lin Liu, Fei Xiao
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.691809/full
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author Wenping Xu
Dan Michael Drzymalski
Ling Ai
Hanqing Yao
Lin Liu
Fei Xiao
author_facet Wenping Xu
Dan Michael Drzymalski
Ling Ai
Hanqing Yao
Lin Liu
Fei Xiao
author_sort Wenping Xu
collection DOAJ
description Background: Hypotension commonly occurs with spinal anesthesia during cesarean delivery. Norepinephrine is an alternative to phenylephrine which can be used to prevent or treat hypotension, with better maintained cardiac output and less bradycardia. However, an appropriate initial prophylactic infusion dose of norepinephrine remains unclear. The aim of this study was to describe the dose-response relationship of prophylactic norepinephrine infusion during cesarean delivery under combined spinal-epidural anesthesia.Methods: We performed a prospective, randomized, double-blinded dose-finding study. One hundred patients undergoing elective cesarean delivery were randomly assigned to receive an infusion of norepinephrine at 0, 0.025, 0.05, 0.075 or 0.1 μg/kg/min initiated immediately after intrathecal injection of 10 mg bupivacaine combined with 5 µg sufentanil. An effective dose was considered when there was no hypotension (systolic blood pressure < 90 mm Hg or < 80% of baseline) during the time period from injection of intrathecal local anesthetic to delivery of the neonate. The primary aim was to determine the dose-response relationship of norepinephrine to prevent spinal anesthesia-induced hypotension. The median effective dose (ED50) and 95% effective dose (ED95) for norepinephrine were calculated utilizing probit analysis.Results: The proportion of patients with hypotension was 80, 70, 40, 15 and 5% at norepinephrine doses of 0, 0.025, 0.05, 0.075 and 0.1 μg/kg/min, respectively. The ED50 and ED95 were 0.042 (95% CI, 0.025–0.053) µg/kg/min and 0.097 (95% CI, 0.081–0.134) µg/kg/min, respectively. There were no differences in the Apgar scores (p = 0.685) or umbilical arterial pH (p = 0.485) measurements of the newborns among the treatment groups.Conclusion: A norepinephrine infusion of 0.1 μg/kg/min as an initial starting dose was effective for the prevention of spinal-induced hypotension.
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spelling doaj.art-3b2058d3974c42998419b44c47becc122022-12-21T21:28:12ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-07-011210.3389/fphar.2021.691809691809The ED50 and ED95 of Prophylactic Norepinephrine for Preventing Post-Spinal Hypotension During Cesarean Delivery Under Combined Spinal-Epidural Anesthesia: A Prospective Dose-Finding StudyWenping Xu0Dan Michael Drzymalski1Ling Ai2Hanqing Yao3Lin Liu4Fei Xiao5Department of Anesthesia, Jiaxing University Affiliated Women and Children Hospital, Jiaxing, ChinaDepartment of Anesthesiology and Perioperative Medicine, Tufts Medical Center, Boston, MA, United StatesDepartment of Anesthesia, Jiaxing University Affiliated Women and Children Hospital, Jiaxing, ChinaDepartment of Anesthesia, Jiaxing University Affiliated Women and Children Hospital, Jiaxing, ChinaDepartment of Anesthesia, Jiaxing University Affiliated Women and Children Hospital, Jiaxing, ChinaDepartment of Anesthesia, Jiaxing University Affiliated Women and Children Hospital, Jiaxing, ChinaBackground: Hypotension commonly occurs with spinal anesthesia during cesarean delivery. Norepinephrine is an alternative to phenylephrine which can be used to prevent or treat hypotension, with better maintained cardiac output and less bradycardia. However, an appropriate initial prophylactic infusion dose of norepinephrine remains unclear. The aim of this study was to describe the dose-response relationship of prophylactic norepinephrine infusion during cesarean delivery under combined spinal-epidural anesthesia.Methods: We performed a prospective, randomized, double-blinded dose-finding study. One hundred patients undergoing elective cesarean delivery were randomly assigned to receive an infusion of norepinephrine at 0, 0.025, 0.05, 0.075 or 0.1 μg/kg/min initiated immediately after intrathecal injection of 10 mg bupivacaine combined with 5 µg sufentanil. An effective dose was considered when there was no hypotension (systolic blood pressure < 90 mm Hg or < 80% of baseline) during the time period from injection of intrathecal local anesthetic to delivery of the neonate. The primary aim was to determine the dose-response relationship of norepinephrine to prevent spinal anesthesia-induced hypotension. The median effective dose (ED50) and 95% effective dose (ED95) for norepinephrine were calculated utilizing probit analysis.Results: The proportion of patients with hypotension was 80, 70, 40, 15 and 5% at norepinephrine doses of 0, 0.025, 0.05, 0.075 and 0.1 μg/kg/min, respectively. The ED50 and ED95 were 0.042 (95% CI, 0.025–0.053) µg/kg/min and 0.097 (95% CI, 0.081–0.134) µg/kg/min, respectively. There were no differences in the Apgar scores (p = 0.685) or umbilical arterial pH (p = 0.485) measurements of the newborns among the treatment groups.Conclusion: A norepinephrine infusion of 0.1 μg/kg/min as an initial starting dose was effective for the prevention of spinal-induced hypotension.https://www.frontiersin.org/articles/10.3389/fphar.2021.691809/fullcesarean deliveryanesthesiaspinalnorepinephrinehypotension
spellingShingle Wenping Xu
Dan Michael Drzymalski
Ling Ai
Hanqing Yao
Lin Liu
Fei Xiao
The ED50 and ED95 of Prophylactic Norepinephrine for Preventing Post-Spinal Hypotension During Cesarean Delivery Under Combined Spinal-Epidural Anesthesia: A Prospective Dose-Finding Study
Frontiers in Pharmacology
cesarean delivery
anesthesia
spinal
norepinephrine
hypotension
title The ED50 and ED95 of Prophylactic Norepinephrine for Preventing Post-Spinal Hypotension During Cesarean Delivery Under Combined Spinal-Epidural Anesthesia: A Prospective Dose-Finding Study
title_full The ED50 and ED95 of Prophylactic Norepinephrine for Preventing Post-Spinal Hypotension During Cesarean Delivery Under Combined Spinal-Epidural Anesthesia: A Prospective Dose-Finding Study
title_fullStr The ED50 and ED95 of Prophylactic Norepinephrine for Preventing Post-Spinal Hypotension During Cesarean Delivery Under Combined Spinal-Epidural Anesthesia: A Prospective Dose-Finding Study
title_full_unstemmed The ED50 and ED95 of Prophylactic Norepinephrine for Preventing Post-Spinal Hypotension During Cesarean Delivery Under Combined Spinal-Epidural Anesthesia: A Prospective Dose-Finding Study
title_short The ED50 and ED95 of Prophylactic Norepinephrine for Preventing Post-Spinal Hypotension During Cesarean Delivery Under Combined Spinal-Epidural Anesthesia: A Prospective Dose-Finding Study
title_sort ed50 and ed95 of prophylactic norepinephrine for preventing post spinal hypotension during cesarean delivery under combined spinal epidural anesthesia a prospective dose finding study
topic cesarean delivery
anesthesia
spinal
norepinephrine
hypotension
url https://www.frontiersin.org/articles/10.3389/fphar.2021.691809/full
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