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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Hypotension

Intervention / Treatment
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* Drug: Norepinephrine
* Drug: Phenylephrine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| Presence of vomiting | Presence of vomiting in 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vasopressor, blood pressure, cesarean section, spinal anesthesia