Norepinephrine Prophylaxis for Postspinal Anesthesia Hypotension

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the suitable infusion dose of norepinephrine for prophylaxis against post-spinal anesthesia hypotension.

Detailed Description
-----------------
Post-spinal anesthesia hypotension is a frequent complication during spinal anesthesia for cesarean section. The incidence of post-spinal anesthesia hypotension is as high as 62.1-89.7% if prophylactic measures are not taken. Vasopressors has been highly recommended for routine prevention and/or treatment of post-spinal anesthesia hypotension. As a potential substitute drug for phenylephrine, norepinephrine has gradually been used in parturients undergoing cesarean section. There's some evidence that prophylactic infusion of norepinephrine could effectively reduce the incidence of post-spinal anesthesia hypotension in parturients undergoing cesarean section. But the ideal infusion dose of norepinephrine is still unknown. The purpose of this study is to investigate the suitable infusion dose of norepinephrine for prophylaxis against post-spinal anesthesia hypotension.

Official Title
-----------------
Norepinephrine Prophylaxis for Postspinal Anesthesia Hypotension in Parturients Undergoing Cesarean Section: a Randomized, Placebo-controlled Dose-finding Trial

Conditions
-----------------
Adverse Effect

Intervention / Treatment
-----------------
* Drug: Norepinephrine
* Drug: Normal saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-40 years Primipara or multipara Singleton pregnancy ≥37 weeks American Society of Anesthesiologists physical status classification I to II Scheduled for elective cesarean section under spinal anesthesia Exclusion Criteria: Body height < 150 cm Body weight > 100 kg or body mass index (BMI) ≥ 40 kg/m2 Eclampsia or chronic hypertension or baseline blood pressure ≥ 160mmHg Hemoglobin < 7g/dl Fetal distress, or known fetal developmental anomaly

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Control group<br>Simultaneous with subarachnoid block, a bolus of 1ml normal saline was given followed by normal saline infusion | Drug: Normal saline<br>* Simultaneous with subarachnoid block, a bolus of 1ml normal saline was given followed by normal saline infusion<br>* Other names: NS;|
| Experimental: 0.025 μg/kg/min group<br>Simultaneous with subarachnoid block, a bolus of 6μg norepinephrine was given followed by a maintenance dose of norepinephrine (0.025 μg/kg/min). | Drug: Norepinephrine<br>* Simultaneous with subarachnoid block, a bolus of 6μg norepinephrine was given followed by different infusion dose of norepinephrine.<br>* Other names: Vasopressors;|
| Experimental: 0.05 μg/kg/min group<br>Simultaneous with subarachnoid block, a bolus of 6μg norepinephrine was given followed by a maintenance dose of norepinephrine (0.05 μg/kg/min). | Drug: Norepinephrine<br>* Simultaneous with subarachnoid block, a bolus of 6μg norepinephrine was given followed by different infusion dose of norepinephrine.<br>* Other names: Vasopressors;|
| Experimental: 0.075 μg/kg/min group<br>Simultaneous with subarachnoid block, a bolus of 6μg norepinephrine was given followed by a maintenance dose of norepinephrine (0.075 μg/kg/min). | Drug: Norepinephrine<br>* Simultaneous with subarachnoid block, a bolus of 6μg norepinephrine was given followed by different infusion dose of norepinephrine.<br>* Other names: Vasopressors;|
| Experimental: 0.1 μg/kg/min group<br>Simultaneous with subarachnoid block, a bolus of 6μg norepinephrine was given followed by a maintenance dose of norepinephrine (0.1 μg/kg/min). | Drug: Norepinephrine<br>* Simultaneous with subarachnoid block, a bolus of 6μg norepinephrine was given followed by different infusion dose of norepinephrine.<br>* Other names: Vasopressors;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of post-spinal anesthesia hypotension | Systolic blood pressure (SBP) < 80% of the baseline | 1-15 minutes after spinal anesthesia. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall stability of systolic blood pressure control versus baseline | Evaluated by performance error (PE). | 1-15 minutes after spinal anesthesia. | 
| Overall stability of heart rate control versus baseline | Evaluated by performance error (PE). | 1-15 minutes after spinal anesthesia. | 
| The incidence of severe post-spinal anesthesia hypotension. | Systolic blood pressure (SBP) < 60% of the baseline. | 1-15 minutes after spinal anesthesia. | 
| The incidence of nausea and vomiting. | Presence of nausea and vomiting in patients after spinal anesthesia | 1-15 minutes after spinal anesthesia. | 
| The incidence of bradycardia. | Heart rate < 55 beats/min. | 1-15 minutes after spinal anesthesia. | 
| The incidence of hypertension. | Systolic blood pressure (SBP) >120% of the baseline. | 1-15 minutes after spinal anesthesia. | 
| pH | From umbilical arterial blood gases. | Immediately after delivery. | 
| Partial pressure of oxygen | From umbilical arterial blood gases. | Immediately after delivery. | 
| Base excess | From umbilical arterial blood gases. | Immediately after delivery. | 
| APGAR score | A= Appearance P=Pulse G=Grimace A=Attitude R=Respiration | 1min after delivery | 
| APGAR score | A= Appearance P=Pulse G=Grimace A=Attitude R=Respiration | 5min after delivery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Norepinephrine, Hypotension, Cesarean section, Dose-finding