Preventive Intramuscular Phenylephrine in Elective Cesarean Section Under Spinal Anesthesia

Preventive Intramuscular Phenylephrine in Elective Cesarean Section Under Spinal Anesthesia: A Randomized Controlled Tiral

Spinal anesthesia is the preferred anesthesia method in cesarean section to provide satisfactory analgesia and muscle relaxant with less impact on respiratory system. However, hypotension often occurred due to the block of sympathetic nerve, causing maternal decline of frontal lobe oxygenation, nausea vomit and the decrease of uteroplacental perfusion. Several measures are used to prevent or treat hypotension caused by spinal anesthesia: prehydration, limb compression, left lateral tilt of operation tables or usage of vasopressors. In the past decade, the most recommended vasopressor to prevent or treat hypotension in spinal anesthesia in cesarean section was phenylephrine, an α-adrenergic receptor, maintaining maternal blood pressure and fetal acid-base state. In clinical work, there are two ways to use phenylephrine : intravenous method with less onset time (several seconds and duration (several minutes) and intramuscular method with longer onset time (10-15 minutes) and duration (1 hour). Many trials demonstrated the protective effect of preventive intravenous phenylephrine on maternal hemodynamics and neonatal acid-base status. However, few trials reported the effect of preventive intramuscular phenylephrine on cesarean section under spinal anesthesia.

Study Overview

• Status: Completed
• Conditions: Spinal Anesthesia; Elective Cesarean Section
• Intervention / Treatment: Drug: Phenylephrine; Drug: Normal saline; Drug: Bupivacaine

Detailed Description

Hypotension often occurred in parturients undergoing cesarean section in spinal anesthesia. This study aims to determine whether preventive intramuscular phenylephrine can better the fetal acid-base state and maternal hemodynamics.

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • The Affiliated Hospital of Xuzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Age 18 years to 40 years.
2. Elective cesarean section
3. American Society of Anesthesiologists (ASA) grade from I to Ⅱ, height from 150 cm to 180 cm, BMI<40kg/m2
4. Singleton pregnancy
5. Without pregnancy complications

Exclusion Criteria:

1. Multiple pregnancy
2. Preoperative bradycardia
3. Coagulation dysfunction
4. Parturients with hypertension, diabetes, eclampsia and other pregnancy complications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intramuscular phenylephrine group; Patients in intramuscular phenylephrine group will receive spinal anesthesia with bupivacaine. 5 mg (1ml) phenylephrine intramuscular injection will be given into the gluteus maximus muscle before anesthesia.1ml of 0.9% normal saline intravenous injection will be given after the subarachnoid injection is completed.	Drug: Phenylephrine; 5 mg (1ml) phenylephrine intramuscular injection will be given into the gluteus maximus muscle before anesthesia.100ug (1ml) phenylephrine intravenous injection will be given after the subarachnoid injection is completed .; Other Names: Metasympatol; Drug: Normal saline; 1ml 0.9% normal saline intramuscular injection will be given into the gluteus maximus muscle before anesthesia and after the subarachnoid injection is completed.; Other Names: Physiological saline; Drug: Bupivacaine; All patients will receive spinal anesthesia with bupivacaine.; Other Names: Marcaine
Active Comparator: Intravenous phenylephrine group; Patients in intravenous phenylephrine group will receive spinal anesthesia with bupivacaine. 1ml of 0.9% normal saline intramuscular injection will be given into the gluteus maximus muscle before anesthesia.100ug (1ml) phenylephrine intravenous injection will be given after the subarachnoid injection is completed.	Drug: Phenylephrine; 5 mg (1ml) phenylephrine intramuscular injection will be given into the gluteus maximus muscle before anesthesia.100ug (1ml) phenylephrine intravenous injection will be given after the subarachnoid injection is completed .; Other Names: Metasympatol; Drug: Normal saline; 1ml 0.9% normal saline intramuscular injection will be given into the gluteus maximus muscle before anesthesia and after the subarachnoid injection is completed.; Other Names: Physiological saline; Drug: Bupivacaine; All patients will receive spinal anesthesia with bupivacaine.; Other Names: Marcaine
Placebo Comparator: Placebo group; Patients in intravenous phenylephrine group will receive spinal anesthesia with bupivacaine. 1ml of 0.9% normal saline intramuscular injection will be given into the gluteus maximus muscle before anesthesia. 1ml of 0.9% normal saline intravenous injection will be given after the subarachnoid injection is completed.	Drug: Phenylephrine; 5 mg (1ml) phenylephrine intramuscular injection will be given into the gluteus maximus muscle before anesthesia.100ug (1ml) phenylephrine intravenous injection will be given after the subarachnoid injection is completed .; Other Names: Metasympatol; Drug: Normal saline; 1ml 0.9% normal saline intramuscular injection will be given into the gluteus maximus muscle before anesthesia and after the subarachnoid injection is completed.; Other Names: Physiological saline; Drug: Bupivacaine; All patients will receive spinal anesthesia with bupivacaine.; Other Names: Marcaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Umbilical artery potential of hydrogen (pH)	detected by a blood gase analyzer	after the baby is delivered

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Umbilical venous potential of hydrogen (pH)	detected by a blood gase analyzer	after the baby is delivered
Umbilical artery base excess	detected by a blood gase analyzer	after the baby is delivered
Umbilical venous base excess	detected by a blood gase analyzer	after the baby is delivered
Umbilical artery partial pressure of oxygen (PaO2)	detected by a blood gase analyzer	after the baby is delivered
Umbilical venous partial pressure of oxygen (PaO2)	detected by a blood gase analyzer	after the baby is delivered
Umbilical artery partial pressure of carbon dioxide (PaCO2)	detected by a blood gase analyzer	after the baby is delivered
Umbilical venous partial pressure of carbon dioxide (PaCO2)	detected by a blood gase analyzer	after the baby is delivered
Umbilical artery lactate	detected by a blood gase analyzer	after the baby is delivered
Umbilical venous lactate	detected by a blood gase analyzer	after the baby is delivered
Umbilical artery glucose	detected by a blood gase analyzer	after the baby is delivered
Umbilical venous glucose	detected by a blood gase analyzer	after the baby is delivered
Incidence of fetal acidosis	Umbilical artery pH value<7.20	after the baby is delivered
Incidence of hypotension	decrease of systolic blood pressure>20% baseline values	intraoperative
Incidence of hypertension	increase of systolic blood pressure>20% baseline values	intraoperative
Incidence of bradycardia	heart rate <50 bpm	intraoperative
Incidence of nausea or vomit	observed by the anesthesiologist	intraoperative

Collaborators and Investigators

• Sponsor: Xuzhou Medical University
• Investigators: Principal Investigator: Chao Xu, M.D., The Affiliated Hospital of Xuzhou Medical University

Publications and helpful links

General Publications

• Foss VT, Christensen R, Rokamp KZ, Nissen P, Secher NH, Nielsen HB. Effect of phenylephrine vs. ephedrine on frontal lobe oxygenation during caesarean section with spinal anesthesia: an open label randomized controlled trial. Front Physiol. 2014 Mar 3;5:81. doi: 10.3389/fphys.2014.00081. eCollection 2014.
• Macarthur A, Riley ET. Obstetric anesthesia controversies: vasopressor choice for postspinal hypotension during cesarean delivery. Int Anesthesiol Clin. 2007 Winter;45(1):115-32. doi: 10.1097/AIA.0b013e31802b8d53. No abstract available.
• Mon W, Stewart A, Fernando R, Ashpole K, El-Wahab N, MacDonald S, Tamilselvan P, Columb M, Liu YM. Cardiac output changes with phenylephrine and ephedrine infusions during spinal anesthesia for cesarean section: A randomized, double-blind trial. J Clin Anesth. 2017 Feb;37:43-48. doi: 10.1016/j.jclinane.2016.11.001. Epub 2016 Dec 26.
• Thomas DG, Robson SC, Redfern N, Hughes D, Boys RJ. Randomized trial of bolus phenylephrine or ephedrine for maintenance of arterial pressure during spinal anaesthesia for Caesarean section. Br J Anaesth. 1996 Jan;76(1):61-5. doi: 10.1093/bja/76.1.61.
• Lin FQ, Qiu MT, Ding XX, Fu SK, Li Q. Ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean section: an updated meta-analysis. CNS Neurosci Ther. 2012 Jul;18(7):591-7. doi: 10.1111/j.1755-5949.2012.00345.x.
• Mohta M, Aggarwal M, Sethi AK, Harisinghani P, Guleria K. Randomized double-blind comparison of ephedrine and phenylephrine for management of post-spinal hypotension in potential fetal compromise. Int J Obstet Anesth. 2016 Aug;27:32-40. doi: 10.1016/j.ijoa.2016.02.004. Epub 2016 Feb 21.
• Saravanan S, Kocarev M, Wilson RC, Watkins E, Columb MO, Lyons G. Equivalent dose of ephedrine and phenylephrine in the prevention of post-spinal hypotension in Caesarean section. Br J Anaesth. 2006 Jan;96(1):95-9. doi: 10.1093/bja/aei265. Epub 2005 Nov 25.
• Magalhaes E, Goveia CS, de Araujo Ladeira LC, Nascimento BG, Kluthcouski SM. Ephedrine versus phenylephrine: prevention of hypotension during spinal block for cesarean section and effects on the fetus. Rev Bras Anestesiol. 2009 Jan-Feb;59(1):11-20. doi: 10.1590/s0034-70942009000100003. English, Portuguese.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Actual): August 31, 2018
• Study Completion (Actual): August 31, 2018

Study Registration Dates

• First Submitted: April 7, 2018
• First Submitted That Met QC Criteria: April 13, 2018
• First Posted (Actual): April 25, 2018

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 2, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Phenylephrine; Intramuscular
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Anesthetics, Local; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Bupivacaine; Phenylephrine; Oxymetazoline
• Other Study ID Numbers: XYFY2018-KL010-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No