Clinical trial NCT02962986: A Comparison of Intermittent Intravenous Boluses of Phenylephrine and Norepinephrine to Prevent Spinal-induced Hypotension in Cesarean Deliveries
Official title: A Comparison of Intermittent Intravenous Boluses of Phenylephrine and Norepinephrine to Prevent Spinal-induced Hypotension in Cesarean Deliveries: a Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypotension
Keywords: vasopressor
blood pressure
cesarean section
spinal anesthesia
Lead sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Sponsor class: OTHER
First posted: 2016-11-15
Enrollment: 112
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Bradycardia: Heart rate less than 50 bpm
timeFrame: 30 minutes
Secondary outcomes:
measure: Hypotension: Systolic blood pressure less than 80% of baseline
timeFrame: 30 minutes
measure: Number of hypotensive episodes
timeFrame: 30 minutes
measure: Hypertension: Systolic blood pressure at or above 120% of baseline
timeFrame: 30 minutes
measure: Tachycardia: Heart rate greater than 30% of baseline
timeFrame: 30 minutes
measure: Presence of nausea
timeFrame: 30 minutes
measure: Number of episodes of nausea
timeFrame: 30 minutes
measure: Presence of vomiting
timeFrame: 30 minutes
measure: Number of episodes of vomiting
timeFrame: 30 minutes
measure: Total dose of study drug given
timeFrame: 30 minutes
measure: Apgar scores
timeFrame: 1 minute and 5 minutes
measure: Umbilical artery pH
timeFrame: 24 hours
measure: Umbilical artery partial pressure of carbon dioxide
timeFrame: 24 hours
measure: Umbilical artery partial pressure of oxygen
timeFrame: 24 hours
measure: Umbilical artery bicarbonate (mmol/L)
timeFrame: 24 hours
measure: Umbilical artery base excess (mmol/L)
timeFrame: 24 hours
measure: Umbilical vein pH
timeFrame: 24 hours
measure: Umbilical vein partial pressure of carbon dioxide
timeFrame: 24 hours
measure: Umbilical vein partial pressure of oxygen
timeFrame: 24 hours
measure: Umbilical vein bicarbonate (mmol/L)
timeFrame: 24 hours
measure: Umbilical vein base excess (mmol/L)
timeFrame: 24 hours
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
Study officials:
affiliation: MOUNT SINAI HOSPITAL
name: Jose CA Carvalho, MD
role: PRINCIPAL_INVESTIGATOR
References: