Norepinephrine To Prevent Hypotension After Spinal Anesthesia For Cesarean Delivery: A Dose Finding Study

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Status: Completed

Conditions: Hypotension

Treatments: Drug: Normal Saline; Drug: Norepinephrine

Study type: Interventional

Funder types: Other

Identifiers

NCT02654847

16-02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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40 participants in 6 patient groups

Norepinephrine 3 micrograms/mL

Active Comparator group

Description:

1mL of a solution of norepinephrine, containing 3 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline.

Treatment:

Drug: Norepinephrine

Drug: Normal Saline

Norepinephrine 4 micrograms/mL

Active Comparator group

Description:

1mL of a solution of norepinephrine, containing 4 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline.

Treatment:

Drug: Norepinephrine

Drug: Normal Saline

Norepinephrine 5 micrograms/mL

Active Comparator group

Description:

1mL of a solution of norepinephrine, containing 5 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline.

Treatment:

Drug: Norepinephrine

Drug: Normal Saline

Norepinephrine 6 micrograms/mL

Active Comparator group

Description:

1mL of a solution of norepinephrine, containing 6 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline.

Treatment:

Drug: Norepinephrine

Drug: Normal Saline

Norepinephrine 7 micrograms/mL

Active Comparator group

Description:

1mL of a solution of norepinephrine, containing 7 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline.

Treatment:

Drug: Norepinephrine

Drug: Normal Saline

Norepinephrine 8 micrograms/mL

Active Comparator group

Description:

1mL of a solution of norepinephrine, containing 8 micrograms/mL in normal saline, will be given intravenously to a patient if her blood pressure decreases from baseline.

Treatment:

Drug: Norepinephrine

Drug: Normal Saline