A Comparison of Intermittent Intravenous Boluses of Phenylephrine and Norepinephrine to Prevent Spinal-induced Hypotension in Cesarean Deliveries

A Comparison of Intermittent Intravenous Boluses of Phenylephrine and Norepinephrine to Prevent Spinal-induced Hypotension in Cesarean Deliveries: a Randomized Controlled Study

Hypotension is a very common complication of spinal anesthesia for cesarean delivery, and can have unwanted side effects on both mother and fetus if not treated promptly. Phenylephrine has been the drug of choice to treat this spinal-induced hypotension. Although phenylephrine is safe to use for this indication, it has been associated with reflex bradycardia and a reduction in cardiac output.

Norepinephrine is a potent vasopressor used to treat hypotension in the critical care setting. Recent studies have looked at norepinephrine's use in the obstetric setting, and have shown that it can be used safely and also has favourable hemodynamic properties when compared to phenylephrine, with less bradycardia and less depression of cardiac output.

The investigators recently conducted a study to determine the ED90 of norepinephrine, and now plan to compare bolus doses of phenylephrine to norepinephrine for treating hypotension following spinal anesthesia for cesarean section.

The investigators hypothesize that norepinephrine, when given as a bolus to prevent post spinal hypotension, will result in around 70% relative decrease in the rate of bradycardia when compared to phenylephrine in patients undergoing elective cesarean delivery under spinal anesthesia.

Study Overview

• Status: Completed
• Conditions: Hypotension
• Intervention / Treatment: Drug: Norepinephrine; Drug: Phenylephrine

Detailed Description

Norepinephrine is a potent vasopressor used to treat hypotension in the critical care setting. Recent studies have looked at norepinephrine's use in the obstetric setting, and have shown that it can be used safely and also has favourable hemodynamic properties when compared to phenylephrine, with less bradycardia and less depression of cardiac output. These studies have been limited to using norepinephrine as an infusion and there is limited data with it being used as a bolus to prevent hypotension. A recent study was undertaken at Mount Sinai hospital to determine the ED90 of norepinephrine to treat post spinal hypotension. Secondary outcome data from this trial showed that the incidence of bradycardia associated with this treatment is approximately 7.5%, several times less when compared to the reported 30% with phenylephrine. It would therefore be prudent at this stage to undertake a randomized trial comparing the hemodynamic profile of phenylephrine (our standard practice) and norepinephrine used as intermittent boluses to prevent hypotension and avoid decrease in heart rate during cesarean delivery.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X5
      • Mount Sinai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Informed consent
• Elective CS under spinal anesthesia
• Normal singleton pregnancy beyond 36 weeks gestation
• ASA physical status 2-3
• Current (pregnant) weight 50-100 kg, height 150-180 cm
• Age over 18 years

Exclusion Criteria:

• Patient refusal
• Inability to communicate in English
• Allergy or hypersensitivity to phenylephrine
• Preexisting or pregnancy-induced hypertension
• Cardiovascular or cerebrovascular disease
• Fetal abnormalities
• History of diabetes, excluding gestational diabetes
• Contra-indications for spinal anesthesia
• Allergy or hypersensitivity to sulfite
• Use of monoamine oxidase inhibitors, triptyline or imipramine antidepressants
• Untreated hyperthyroid patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: norepinephrine 6mcg; norepinephrine, given as 1mL IV boluses, to treat post-spinal hypotension	Drug: Norepinephrine; Norepinephrine diluted in 5% dextrose solution to a concentration of 6mcg/mL; Other Names: Norepinephrine bitartrate
Active Comparator: phenylephrine 100mcg; phenylephrine, given as 1mL IV boluses, to treat post-spinal hypotension	Drug: Phenylephrine; Phenylephrine diluted in 0.9% normal saline solution to a concentration of 100mcg/mL; Other Names: Phenylephrine Hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bradycardia: Heart rate less than 50 bpm	Heart rate less than 50 bpm, from induction of spinal anesthesia	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of vomiting	Presence of vomiting in patients from induction of spinal anesthesia to delivery of the fetus.	30 minutes
Hypotension: Systolic blood pressure less than 80% of baseline	Systolic blood pressure below 80% of baseline, from induction of spinal anesthesia to delivery of the fetus.	30 minutes
Number of hypotensive episodes	The number of times the systolic blood pressure measures below 80% of baseline, from induction of spinal anesthesia to delivery of the fetus.	30 minutes
Hypertension: Systolic blood pressure at or above 120% of baseline	Systolic blood pressure at or above 120% of baseline, from induction of spinal anesthesia to delivery of the fetus.	30 minutes
Tachycardia: Heart rate greater than 30% of baseline	Heart rate greater than 30%, from induction of spinal anesthesia to delivery of the fetus.	30 minutes
Presence of nausea	Presence of nausea in patients from induction of spinal anesthesia to delivery of the fetus.	30 minutes
Number of episodes of nausea	The number of episodes of nausea experienced by patients from induction of spinal anesthesia to delivery of the fetus.	30 minutes
Number of episodes of vomiting	The number of episodes of vomiting experienced by patients from induction of spinal anesthesia to delivery of the fetus.	30 minutes
Total dose of study drug given	Total dose of study drug given from induction of spinal anesthesia to delivery of the fetus.	30 minutes
Apgar scores	The Apgar scores of the infant at 1 and 5 minutes post delivery.	1 minute and 5 minutes
Umbilical artery pH	Umbilical artery pH	24 hours
Umbilical artery partial pressure of carbon dioxide	Umbilical artery partial pressure of carbon dioxide	24 hours
Umbilical artery partial pressure of oxygen	Umbilical artery partial pressure of oxygen	24 hours
Umbilical artery bicarbonate (mmol/L)	Umbilical artery bicarbonate	24 hours
Umbilical artery base excess (mmol/L)	Umbilical artery base excess	24 hours
Umbilical vein pH	Umbilical vein pH	24 hours
Umbilical vein partial pressure of carbon dioxide	Umbilical vein partial pressure of carbon dioxide	24 hours
Umbilical vein partial pressure of oxygen	Umbilical vein partial pressure of oxygen	24 hours
Umbilical vein bicarbonate (mmol/L)	Umbilical vein bicarbonate	24 hours
Umbilical vein base excess (mmol/L)	Umbilical vein base excess	24 hours

Collaborators and Investigators

• Sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: November 7, 2016
• First Submitted That Met QC Criteria: November 9, 2016
• First Posted (Estimate): November 15, 2016

Study Record Updates

• Last Update Posted (Actual): May 24, 2017
• Last Update Submitted That Met QC Criteria: May 23, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: cesarean section; blood pressure; spinal anesthesia; vasopressor
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Norepinephrine; Phenylephrine; Oxymetazoline
• Other Study ID Numbers: 16-07

Plan for Individual participant data (IPD)

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