Norepinephrine Versus Phenylephrine Continuous Variable Infusion in Cesarean Delivery

Study Overview
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Brief Summary
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Comparison will be conducted between continuous variable infusions of Phenylephrine with starting dose of 0.75 mcg/Kg/min and Norepinephrine Bitartrate with starting dose of 0.1 mcg/Kg/min (with norepinephrine base of 0.05 mcg/Kg/min) for prophylaxis against Post-spinal hypotension during cesarean delivery

Detailed Description
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Maternal hypotension is a common complication after spinal anesthesia for cesarean delivery (CD). Many vasopressors have been used for prevention of post-spinal hypotension (PSH) during CD; however, the optimum protocol for prophylaxis is not established yet. Phenylephrine (PE) is a popular vasopressor used in obstetric anesthesia; however, its use is limited by its marked cardiac depressant nature. Norepinephrine (NE) is a potent vasopressor characterized by both α adrenergic agonistic activity in addition to a weak β adrenergic agonistic activity; thus, NE is considered a vasopressor with minimal cardiac depressant effect; these pharmacological properties would make NE an attractive alternative to PE. In this study, the investigators will compare continuous variable infusion of both drugs (PE and NE) with doses of 0.75 mcg/Kg/min and 0.05 mcg/Kg/min respectively for prophylaxis against PSH during CD. We used Norepinephrine Bitartrate 8 mg ampules which contains norepinephrine base of 4 mg.

Official Title
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Norepinephrine Versus Phenylephrine Continuous Variable Infusion for Prevention of Post-spinal Hypotension During Cesarean Delivery: A Randomized Controlled Double-blinded Trial

Conditions
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Cesarean Section Complications, Spinal Anesthesia

Intervention / Treatment
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* Drug: Phenylephrine
* Drug: Norepinephrine
* Drug: Bupivacaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Full term Pregnant women Scheduled for cesarean section Exclusion Criteria: Pre-eclampsia Eclampsia Bleeding Cardiac dysfunction

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Phenylephrine<br>Will receive spinal anesthesia using Bupivacaine. Then, phenylephrine infusion by a starting rate of 0.75 mcg/Kg/min. The rate will be then adjusted according to the patient blood pressure. The infusion will stop in case of reactive hypertension. The infusion will start again when blood pressure returns to normal reading. Infusion will be increased by 20% if hypotension occurred. | Drug: Phenylephrine<br>* Phenylephrine variable infusion with a starting rate of 0.75 mcg/Kg/min.<br>Drug: Bupivacaine<br>* Bupivacaine will be injected in the subarachnoid space with a dose of 10 mg.<br>* Other names: Marcaine;|
| Experimental: Norepinephrine<br>Will receive spinal anesthesia using Bupivacaine. Then, norepinephrine bitartrate infusion by a starting rate of 0.1 mcg/Kg/min (equivalent to norepinephrine base of 0.05 mcg/Kg/min). The rate will be then adjusted according to the patient blood pressure. The infusion will stop in case of reactive hypertension. The infusion will start again when blood pressure returns to normal reading. Infusion will be increased by 20% if hypotension occurred. | Drug: Norepinephrine<br>* Norepinephrine bitartrate variable infusion with a starting rate of 0.1 mcg/Kg/min (equivalent to norepinephrine base of 0.05 mcg/Kg/min).<br>* Other names: Levophed;Drug: Bupivacaine<br>* Bupivacaine will be injected in the subarachnoid space with a dose of 10 mg.<br>* Other names: Marcaine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of post-spinal anesthesia hypotension. | Defined as the percentage of patients with decreased systolic blood pressure less than 80% of the baseline reading | 30 minutes after spinal anesthesia | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of severe post-spinal anesthesia hypotension | Defined as the percentage of patients with decreased systolic blood pressure less than 60% of the baseline reading | 30 minutes after spinal anesthesia | 
| Incidence of severe delivery hypotension | Defined as the percentage of patients with decreased systolic blood pressure less than 80% of the baseline reading | 10 minutes after delivery | 
| 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 assessment of the general state of the fetus | APGAR score of the fetus ranging from 0 to 10. the higher the value, the better he score | 10 minutes after delivery | 
| Incidence of reactive hypertension | Defined as the percentage of patients with increased systolic blood pressure more than 80% of the baseline reading | 2 hours after spinal anesthesia | 
| Umbilical arterial potential hydrogen (PH) | PH in the blood sample obtained from umbilical artery scaled from 1 to 14 | 10 minutes after delivery | 
| Umbilical arterial Partial pressure of Carbon dioxide | in the blood sample obtained from umbilical artery measured in mmHg | 10 minutes after delivery | 
| incidence of nausea | The percentage of patients with nausea | 2 hours | 
| Incidence of vomiting | The percentage of patients with nausea | 2 hours | 
| Total phenylephrine consumption | the total dose of phenylephrine consumed during the operation | 2 hours | 
| Total norepinephrine consumption | the total dose of norepinephrine consumed during the operation | 2 hours | 
| Total ephedrine consumption | the total dose of ephedrine consumed during the operation | 2 hours |