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Prophylactic Phenylephrine Increases the Dose Requirement of Oxytocin to Treat Uterine Atony During Cesarean Delivery: A Double-Blinded, Single-Center, Randomized and Placebo-Controlled Trial

Purpose: Studies involving mouse models and human uterine smooth muscle cells have shown that phenylephrine inhibits uterine contractions in non-pregnant mice and human in vitro cell via cyclic adenosine monophosphate (cAMP) signaling. However, there has been no limited exploration to date of the ef...

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Autores principales: Shen, Yao-Hua, Yang, Fan, Jin, Li-Dan, Qian, Yu-Jia, Xing, Li, Huang, Ya-Li, Lin, Su-Feng, Xiao, Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563700/
https://www.ncbi.nlm.nih.gov/pubmed/34744714
http://dx.doi.org/10.3389/fphar.2021.720906
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author Shen, Yao-Hua
Yang, Fan
Jin, Li-Dan
Qian, Yu-Jia
Xing, Li
Huang, Ya-Li
Lin, Su-Feng
Xiao, Fei
author_facet Shen, Yao-Hua
Yang, Fan
Jin, Li-Dan
Qian, Yu-Jia
Xing, Li
Huang, Ya-Li
Lin, Su-Feng
Xiao, Fei
author_sort Shen, Yao-Hua
collection PubMed
description Purpose: Studies involving mouse models and human uterine smooth muscle cells have shown that phenylephrine inhibits uterine contractions in non-pregnant mice and human in vitro cell via cyclic adenosine monophosphate (cAMP) signaling. However, there has been no limited exploration to date of the effect of phenylephrine on uterine contractions in clinical practice. This study aimed to compare the dose requirement of oxytocin with or without the infusion of prophylactic phenylephrine to prevent post spinal hypotension during cesarean delivery under combined spinal and epidural anesthesia. Methods: This was a double-blinded, single-center, randomized, control study. One hundred and sixty pregnant patients provided informed consent and were randomly allocated to the phenylephrine (phenylephrine infusion) and control (saline infusion) groups. Patients randomized to the phenylephrine group received an intravenous prophylactic phenylephrine infusion at a fixed rate of 0.5 μg/kg/min. The control group received a saline placebo at the same rate and used the same apparatus for delivery. After neonatal delivery and clamping of the umbilical cord, patients received a standard institutional oxytocin protocol. The primary outcome measure was the total dose of oxytocin administered during CD. Secondary outcomes including the proportion (%) of patients requiring a secondary uterotonic agent and estimated blood loss (EBL) in the first 24 h after surgery. Results: The median oxytocin dose administered was significantly higher in the phenylephrine group than in the control group [6.9 ± 2.5 international standardized units (IU) vs. 5.4 ± 2.4 IU, p = 0.0004]. The number of patients that required a secondary uterotonic agent was significantly higher in the phenylephrine group than in the control group (24.2% vs. 9.1%; p = 0.034). The EBL in the first 24-h postoperatively was similar between the two groups (467 ± 47 ml vs. 392 ± 38 ml; p = 0.22). Conclusions: Prophylactic infusion of phenylephrine used to prevent post-spinal hypotension during CD was associated with a higher dose of oxytocin. This has important clinical implications, as the suboptimal use of oxytocin is associated with an increased risk of postpartum hemorrhage and increased maternal morbidity and mortality. Further studies are now needed to confirm these findings.
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spelling pubmed-85637002021-11-04 Prophylactic Phenylephrine Increases the Dose Requirement of Oxytocin to Treat Uterine Atony During Cesarean Delivery: A Double-Blinded, Single-Center, Randomized and Placebo-Controlled Trial Shen, Yao-Hua Yang, Fan Jin, Li-Dan Qian, Yu-Jia Xing, Li Huang, Ya-Li Lin, Su-Feng Xiao, Fei Front Pharmacol Pharmacology Purpose: Studies involving mouse models and human uterine smooth muscle cells have shown that phenylephrine inhibits uterine contractions in non-pregnant mice and human in vitro cell via cyclic adenosine monophosphate (cAMP) signaling. However, there has been no limited exploration to date of the effect of phenylephrine on uterine contractions in clinical practice. This study aimed to compare the dose requirement of oxytocin with or without the infusion of prophylactic phenylephrine to prevent post spinal hypotension during cesarean delivery under combined spinal and epidural anesthesia. Methods: This was a double-blinded, single-center, randomized, control study. One hundred and sixty pregnant patients provided informed consent and were randomly allocated to the phenylephrine (phenylephrine infusion) and control (saline infusion) groups. Patients randomized to the phenylephrine group received an intravenous prophylactic phenylephrine infusion at a fixed rate of 0.5 μg/kg/min. The control group received a saline placebo at the same rate and used the same apparatus for delivery. After neonatal delivery and clamping of the umbilical cord, patients received a standard institutional oxytocin protocol. The primary outcome measure was the total dose of oxytocin administered during CD. Secondary outcomes including the proportion (%) of patients requiring a secondary uterotonic agent and estimated blood loss (EBL) in the first 24 h after surgery. Results: The median oxytocin dose administered was significantly higher in the phenylephrine group than in the control group [6.9 ± 2.5 international standardized units (IU) vs. 5.4 ± 2.4 IU, p = 0.0004]. The number of patients that required a secondary uterotonic agent was significantly higher in the phenylephrine group than in the control group (24.2% vs. 9.1%; p = 0.034). The EBL in the first 24-h postoperatively was similar between the two groups (467 ± 47 ml vs. 392 ± 38 ml; p = 0.22). Conclusions: Prophylactic infusion of phenylephrine used to prevent post-spinal hypotension during CD was associated with a higher dose of oxytocin. This has important clinical implications, as the suboptimal use of oxytocin is associated with an increased risk of postpartum hemorrhage and increased maternal morbidity and mortality. Further studies are now needed to confirm these findings. Frontiers Media S.A. 2021-10-20 /pmc/articles/PMC8563700/ /pubmed/34744714 http://dx.doi.org/10.3389/fphar.2021.720906 Text en Copyright © 2021 Shen, Yang, Jin, Qian, Xing, Huang, Lin and Xiao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Shen, Yao-Hua
Yang, Fan
Jin, Li-Dan
Qian, Yu-Jia
Xing, Li
Huang, Ya-Li
Lin, Su-Feng
Xiao, Fei
Prophylactic Phenylephrine Increases the Dose Requirement of Oxytocin to Treat Uterine Atony During Cesarean Delivery: A Double-Blinded, Single-Center, Randomized and Placebo-Controlled Trial
title Prophylactic Phenylephrine Increases the Dose Requirement of Oxytocin to Treat Uterine Atony During Cesarean Delivery: A Double-Blinded, Single-Center, Randomized and Placebo-Controlled Trial
title_full Prophylactic Phenylephrine Increases the Dose Requirement of Oxytocin to Treat Uterine Atony During Cesarean Delivery: A Double-Blinded, Single-Center, Randomized and Placebo-Controlled Trial
title_fullStr Prophylactic Phenylephrine Increases the Dose Requirement of Oxytocin to Treat Uterine Atony During Cesarean Delivery: A Double-Blinded, Single-Center, Randomized and Placebo-Controlled Trial
title_full_unstemmed Prophylactic Phenylephrine Increases the Dose Requirement of Oxytocin to Treat Uterine Atony During Cesarean Delivery: A Double-Blinded, Single-Center, Randomized and Placebo-Controlled Trial
title_short Prophylactic Phenylephrine Increases the Dose Requirement of Oxytocin to Treat Uterine Atony During Cesarean Delivery: A Double-Blinded, Single-Center, Randomized and Placebo-Controlled Trial
title_sort prophylactic phenylephrine increases the dose requirement of oxytocin to treat uterine atony during cesarean delivery: a double-blinded, single-center, randomized and placebo-controlled trial
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563700/
https://www.ncbi.nlm.nih.gov/pubmed/34744714
http://dx.doi.org/10.3389/fphar.2021.720906
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