Prophylactic Norepinephrine Infusion Combined With Colloid Coloading for Postspinal Anesthesia Hypotension

Study Overview
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Brief Summary
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The purpose of this study is to investigate the suitable infusion dose of prophylactic norepinephrine infusion combined with 6% Hydroxyethyl starch (130/0.4) coload for post-spinal anesthesia hypotension in patients undergoing cesarean section.

Detailed Description
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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. Vasopressor 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 with colloid coload is still unknown. The purpose of this study is to investigate the suitable infusion dose of prophylactic norepinephrine infusion combined with 6% Hydroxyethyl starch (130/0.4) coload for post-spinal anesthesia hypotension in patients undergoing cesarean section.

Official Title
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Prophylactic Norepinephrine Infusion Combined With 6% Hydroxyethyl Starch (130/0.4) Coload for Postspinal Anesthesia Hypotension in Patients Undergoing Cesarean Section: A Randomized, Controlled, Dose-finding Trial

Conditions
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Adverse Event

Intervention / Treatment
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* Drug: Normal saline
* Drug: Norepinephrine (0.025 μg/kg/min)
* Drug: Norepinephrine (0.05 μg/kg/min)
* Drug: Norepinephrine (0.075 μg/kg/min)
* Drug: Norepinephrine (0.1 μg/kg/min)


Participation Criteria
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Eligibility Criteria
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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 Coagulation or renal function disorders Known allergy to hydroxyethyl starch Fetal distress, or known fetal developmental anomaly

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>Simultaneous with spinal anesthesia, 500 mL 6% Hydroxyethyl starch (130/0.4) coload was given and a maintenance dose of normal saline by IV infusion. | Drug: Normal saline<br>* Simultaneous with spinal anesthesia, 500 mL 6% Hydroxyethyl starch (130/0.4) coload was given and a maintenance dose of normal saline by IV infusion.<br>* Other names: NS;|
| Experimental: 0.025 μg/kg/min group<br>Simultaneous with spinal anesthesia, 500 mL 6% Hydroxyethyl starch (130/0.4) coload was given and a maintenance dose of norepinephrine (0.025 μg/kg/min) by IV infusion. | Drug: Norepinephrine (0.025 μg/kg/min)<br>* Simultaneous with spinal anesthesia, 500 mL 6% Hydroxyethyl starch (130/0.4) coload was given and a different maintenance dose of norepinephrine by IV infusion.<br>* Other names: Vasopressor;|
| Experimental: 0.05 μg/kg/min group<br>Simultaneous with spinal anesthesia, 500 mL 6% Hydroxyethyl starch (130/0.4) coload was given and a maintenance dose of norepinephrine (0.05 μg/kg/min) by IV infusion. | Drug: Norepinephrine (0.05 μg/kg/min)<br>* Simultaneous with spinal anesthesia, 500 mL 6% Hydroxyethyl starch (130/0.4) coload was given and a different maintenance dose of norepinephrine by IV infusion.<br>* Other names: Vasopressor;|
| Experimental: 0.075 μg/kg/min group<br>Simultaneous with spinal anesthesia, 500 mL 6% Hydroxyethyl starch (130/0.4) coload was given and a maintenance dose of norepinephrine (0.075 μg/kg/min) by IV infusion. | Drug: Norepinephrine (0.075 μg/kg/min)<br>* Simultaneous with spinal anesthesia, 500 mL 6% Hydroxyethyl starch (130/0.4) coload was given and a different maintenance dose of norepinephrine by IV infusion.<br>* Other names: Vasopressor;|
| Experimental: 0.1μg/kg/min group<br>Simultaneous with spinal anesthesia, 500 mL 6% Hydroxyethyl starch (130/0.4) coload was given and a maintenance dose of norepinephrine (0.1μg/kg/min) by IV infusion. | Drug: Norepinephrine (0.1 μg/kg/min)<br>* Simultaneous with spinal anesthesia, 500 mL 6% Hydroxyethyl starch (130/0.4) coload was given and a different maintenance dose of norepinephrine by IV infusion.<br>* Other names: Vasopressor;|

What is the study measuring?
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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 | 
| 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 value | Analyse from umbilical arterial blood gases. | Immediately after fetal delivery | 
| Partial pressure of oxygen | Analyse from umbilical arterial blood gases. | Immediately after fetal delivery | 
| Concentration of base excess | Analyse from umbilical arterial blood gases. | Immediately after fetal delivery | 
| Apgar score (0-10; a higher score means a better outcome) | A= Appearance (0-2); P=Pulse (0-2); G=Grimace (0-2); A=Attitude (0-2); R=Respiration (0-2) | 5 min after fetal delivery | 
| Apgar score (0-10;a higher score means a better outcome) | A= Appearance (0-2); P=Pulse (0-2); G=Grimace (0-2); A=Attitude (0-2); R=Respiration (0-2) | 5 min after fetal delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Norepinephrine, Hydroxyethyl starch, Postspinal anesthesia hypotension, Coload, Cesarean section