Clinical trial NCT02654847: Norepinephrine To Prevent Hypotension After Spinal Anesthesia For Cesarean Delivery: A Dose Finding Study
Official title: Norepinephrine To Prevent Hypotension After Spinal Anesthesia For Cesarean Delivery: A Dose Finding 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: 2016-01-13
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Spinal anesthesia is the most common anesthetic technique for elective Cesarean delivery (CD), but the most frequent unwanted side effect is hypotension, which can cause nausea and vomiting, as well as effects on the fetus. Prevention and treatment of maternal hypotension includes intravenous fluids and vasopressors. Phenylephrine is the most common vasopressor used for this purpose. However, it has been shown to reduce maternal heart rate and cardiac output, which may be a concern in an already compromised fetus. Norepinephrine is commonly used in high concentrations in intensive care and recent studies have suggested that in low concentrations it may be a better alternative to phenylephrine in elective CD, as it does not reduce the maternal heart rate or cardiac output. The optimum bolus dose of norepinephrine to prevent hypotension after spinal anesthesia in elective CD has not been elucidated. The investigators propose this study to determine the dose that would be effective in 90% of patients (ED90).

A previous study by Ngan Kee et al, using continuous infusion of norepinephrine to prevent hypotension in elective CD, suggested a potency ratio for norepinephrine to phenylephrine of approximately 16:1. Hence, the investigators hypothesise that the ED90 will be approximately 6 µg, given that the current phenylephrine bolus dose at the investigators' institution is approximately 100 µg.

Detailed description: The use of norepinephrine to prevent and treat hypotension during cesarean delivery (CD) is new and data in the literature are scarce. A recent randomised controlled trial by Ngan Kee et al compared continuous infusions of norepinephrine and phenylephrine to prevent hypotension during CD. They showed that norepinephrine was effective at maintaining blood pressure, with a greater cardiac output and heart rate compared to phenylephrine. However, the effective bolus dose of norepinephrine needed to prevent maternal hypotension was not determined, and since this is a relatively new arena, no dose-response studies are available in the literature either. Therefore, it would be logical to establish the effective bolus dose of norepinephrine TO PREVENT HYPOTENSION during elective CD.

Eligibility criteria: Inclusion Criteria:

* Elective CD under spinal anesthesia
* Normal singleton pregnancy beyond 36 weeks gestation
* ASA physical status II/III
* Weight 50-100 kg, height 150-180 cm
* Age over 18 years
* Informed consent

Exclusion Criteria:

* Patient refusal
* Allergy or hypersensitivity to norepinephrine or sulfite
* Preexisting or pregnancy-induced hypertension
* Cardiovascular or cerebrovascular disease
* Fetal abnormalities
* History of diabetes, excluding gestational diabetes
* Use of monoamine oxidase inhibitors, triptyline or imipramine antidepressants

Primary outcomes:
measure: Systolic blood pressure
timeFrame: 30 minutes
Secondary outcomes:
measure: Presence of Nausea
timeFrame: 30 minutes
measure: Presence of Vomiting
timeFrame: 30 minutes
measure: Hypertension: Systolic blood pressure at or above 120% of baseline
timeFrame: 30 minutes
measure: Bradycardia: Heart rate less than 50 bpm
timeFrame: 30 minutes
measure: Upper sensory level of anesthetic block, assessed by pinprick upon delivery
timeFrame: 30 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
timeFrame: 24 hours
measure: Umbilical artery base excess
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
timeFrame: 24 hours
measure: Umbilical vein base excess
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, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Onwochei DN, Ngan Kee WD, Fung L, Downey K, Ye XY, Carvalho JCA. Norepinephrine Intermittent Intravenous Boluses to Prevent Hypotension During Spinal Anesthesia for Cesarean Delivery: A Sequential Allocation Dose-Finding Study. Anesth Analg. 2017 Jul;125(1):212-218. doi: 10.1213/ANE.0000000000001846.