Comparison of Two Norepinephrine Bolus Doses for Management of Post-spinal Hypotension During Cesarean Delivery

Study Overview
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Brief Summary
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In this study the investigators will compare two doses of norepinephrine bolus (6 mcg and 10 mcg) in management of maternal hypotensive episode after subarachnoid block during Cesarean delivery.

Detailed Description
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Maternal hypotension after subarachnoid block is a frequent and deleterious complication during cesarean delivery. Although prophylaxis against hypotension using vasopressors had become a standard recommendation; the incidence of hypotension is still ∼ 20% . Thus; management of maternal hypotension using vasopressor boluses is usually needed . The commonly used vasopressors during cesarean delivery are ephedrine, phenylephrine, and recently norepinephrine. The use of ephedrine is usually accompanied with maternal tachycardia and fetal acidosis. Phenylephrine had been the first line for prevention and management of maternal hypotension; however, its use might result in bradycardia and decreased maternal cardiac output . Norepinephrine is an alpha adrenergic agonist with weak beta adrenergic agonistic activity; thus, it does not cause significant cardiac depression as phenylephrine does. Norepinephrine was introduced for use during cesarean delivery with promising results . Few previous studies investigated the efficacy of Norepinephrine infusion for prevention of maternal hypotension. A dose-response study had investigated the best dose of Norepinephrine for prevention of maternal hypotension. In the aforementioned dose-response study, a dose of 6 mcg was reported as the best dose for prophylaxis against maternal hypotension. No studies had investigated the best bolus dose of norepinephrine for management of a maternal hypotensive episode. In this study the investigators will investigate the efficacy and side effects of two doses of norepinephrine bolus doses (6 mcg and 10 mcg) in management of maternal hypotensive episode after subarachnoid block during cesarean delivery.

Official Title
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Norepinephrine for Management of Post-spinal Anesthesia Hypotension During Cesarean Delivery: a Comparison of Two Bolus Doses

Conditions
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Cesarean Section Complications, Spinal Anesthetic Toxicity

Intervention / Treatment
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* Drug: Norepinephrine 6 mcg
* Drug: Norepinephrine 10 mcg
* Drug: Norepinephrine infusion
* Drug: Bupivacaine hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women Scheduled for cesarean delivery Exclusion Criteria: Patients with severe cardiac dysfunction Patients with low blood pressure Patients with ante-partum bleeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Experimental: Norepinephrine 6 mcg<br>Mothers in this group will receive a bolus of Norepinephrine 6 mcg for management of hypotensive episode after spinal anesthesia using Bupivacaine hydrochloride under prophylactic Norepinephrine infusion | Drug: Norepinephrine 6 mcg<br>* An intravenous bolus of norepinephrine 6 mcg will be administered for management of maternal hypotension.<br>* Other names: Levophed;Drug: Norepinephrine infusion<br>* Prophylactic norepinephrine infusion will be started after subarachnoid block.<br>* Other names: Levophed;Drug: Bupivacaine hydrochloride<br>* Subarachnoid block will be performed using Bupivacaine hydrochloride (2.2 mL) in addition to fentanyl 25 mcg.<br>* Other names: marcaine;|
| Active Comparator: Norepinephrine 10 mcg<br>Mothers in this group will receive a bolus of Norepinephrine 10 mcg for management of hypotensive episode after spinal anesthesia using Bupivacaine hydrochloride under prophylactic Norepinephrine infusion. | Drug: Norepinephrine 10 mcg<br>* An intravenous bolus of norepinephrine 10 mcg will be administered for management of maternal hypotension.<br>* Other names: Levophed;Drug: Norepinephrine infusion<br>* Prophylactic norepinephrine infusion will be started after subarachnoid block.<br>* Other names: Levophed;Drug: Bupivacaine hydrochloride<br>* Subarachnoid block will be performed using Bupivacaine hydrochloride (2.2 mL) in addition to fentanyl 25 mcg.<br>* Other names: marcaine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of successful management of maternal hypotension | number of patients with successful management of maternal hypotensive episode (defined as return of systolic blood pressure to be ≥ 80% of the baseline reading in the next reading 2 minutes after administration of norepinephrine bolus). | 30 minutes after spinal anesthesia | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of successful management of severe maternal hypotension. | number of patients with successful management of maternal severe hypotensive episode (defined as systolic blood pressure lower than 60% of the baseline reading in the next reading 2 minutes after administration of norepinephrine bolus). | 30 minutes after spinal anesthesia | 
| Incidence of reactive hypertension | number of patients with reactive hypertension (defined as systolic blood pressure ≥120% from the baseline reading after administration of norepinephrine bolus). | 30 minutes after spinal anesthesia | 
| Systolic blood pressure. | Systolic blood pressure measured in mmHg. | 2 hours after subarachnoid block | 
| Heart rate | Number of heart beats per minute. | 2 hours after subarachnoid block | 
| Apgar score for evaluation of the activity of the fetus | the Apgar score of the fetus which range from 0 to 10. Th minimum value is 0 and the maximum value is 10. The worst value is 0 and the best value is 10. | 10 minutes | 
| Umbilical blood acidity | the measure of acidity or alkalinity of any solution on a logarithmic scale on which 7 is neutral, lower values are more acid and higher values more alkaline. | 10 minutes after delivery | 
| The frequency of vomiting. | The number of patients with vomiting. | 2 hours after subarachnoid block | 
| Incidence of bradycardia | number of patients with bradycardia (defined as heart rate less than 55 beat per minute after administration of norepinephrine bolus). | 2 hours after subarachnoid block |