Prevention of Hypotension During Cesarean Section

Study Overview
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Brief Summary
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The aim of this double-blind randomized study will be to compare a fixed-rate prophylactic noradrenaline infusion to a fixed-rate prophylactic phenylephrine infusion during elective cesarean section under combined spinal-epidural anesthesia

Detailed Description
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Spinal anesthesia is the anesthetic technique of choice for elective cesarean section. Spinal anesthesia can be complicated by hypotension, with incidence exceeding 80% occasionally. Hypotension can lead to nausea, emesis and a subjective feeling of discomfort due to cerebral hypoperfusion. If left untreated, severe or sustained hypotension can lead to decreased uteroplacental flow and fetal distress of premature or compromised fetuses while severe complications to the parturient might ensue, such as loss of consciousness, aspiration, apnea or cardiac arrest One of the standard techniques to avoid maternal hypotension is the administration of a continuous phenylephrine infusion while studies have demonstrated its superiority as compared to rescue bolus phenylephrine administration. Additionally, as compared to ephedrine, phenylephrine is associated with less neonatal acidosis and better maintenance of uteroplacental blood flow. However, phenylephrine can lead to baroreceptor-mediated reflex bradycardia, with untoward consequences for maternal cardiac output. Recently, noradrenaline has been shown to be effective in maintaining blood pressure in obstetric patients. Noradrenaline is a strong-alpha agonist with weak beta-action, too. Therefore, it might prove superior in maintaining cardiac output as compared to phenylephrine. There have been a few studies examining the use of noradrenaline as a continuous infusion in this context but the optimal dose and safety and efficacy profile of noradrenaline continuous infusion in obstetrics is yet to be determined In all parturients, standard hemodynamic monitoring will be applied. Baseline systolic arterial pressure will be considered the average of three consecutive measurements that will not differ more than 10% among them. All parturients will have a peripheral intravenous catheter placed in the upper extremity after baseline hemodynamic measurements are recorded and will be infused 5 mL/kg of hydroxyethylstarch (pre-loading) before the regional procedure. Study group allocation will taker place according to a computer-generated sequence of random numbers. A standard spinal anesthetic consisting of ropivacaine 0.75% 1.8 mL plus fentanyl 10 μg will be administered in the left lateraL position at the L3-4 or L4-5 vertebral interspace. The study infusion medication (either phenylephrine or norepinephrine, depending on group allocation) will be started at the same time cerebrospinal fluid is obtained, immediately before injection of spinal medications. After the intrathecal injection, patients will placed in the supine position with a left lateral tilt of the table to provide left uterine displacement and to prevent aortocaval compression. The spinal sensory level will be tested bilaterally by pinprick to ensure a T4 dermatomal level before surgical incision. Hemodynamic parameters (systolic arterial blood pressure, diastolic arterial blood pressure, mean arterial blood pressure and heart rate) will be measured and recorded at discrete timepoints throughout the operation (baseline, start of vasoactive agent administration, parturient at supine position, sympathetic block at T4, knife-to-skin, neonatal delivery, start of oxytocin administration, start of skin closure, end of operation. During the operation, a rescue dose of phenylephrine 50 μg will be administered when systolic arterial pressure drops below 80% of baseline in combination with heart rate>80 bpm. Ephedrine 5 mg will be administered when there is hypotension (systolic arterial pressure <80% of baseline) in combination with heart rate less than 80 bpm. Hypertensive episodes (systolic blood pressure >120% of baseline) will be treated with halving the infusion while when systolic arterial pressure increases above 130% of baseline the infusion will be discontinued and will be restarted when systolic blood pressure decreases below the upper limit of the target range (120% of baseline value).

Official Title
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Comparison of Continuous Infusion of Noradrenaline Versus Phenylephrine During Cesarean Section Under Spinal Anesthesia. A Randomized Controlled Trial

Conditions
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Hypotension Symptomatic, Obstetric Anesthesia Problems, Cesarean Section Complications, Vasoconstriction

Intervention / Treatment
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* Procedure: phenylephrine infusion
* Procedure: norepinephrine infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult parturients, American Society of Anesthesiologists (ASA) I-II, singleton gestation>37 weeks elective cesarean section Exclusion Criteria: Body Mass Index (BMI) >40 kg/m2 Body weight <50 kg Body weight>100 kg height<150 cm height>180 cm multiple gestation fetal abnormality fetal distress active labor cardiac disease pregnancy-induced hypertension thrombocytopenia coagulation abnormalities use of antihypertensive medication during pregnancy communication or language barriers lack of informed consent contraindication for regional anesthesia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 48 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: phenylephrine infusion<br>phenylephrine infusion (30 mL/h corresponding to 50 μg/min) | Procedure: phenylephrine infusion<br>* In parturients allocated to the phenylephrine group, a phenylephrine infusion will be initiated as soon as spinal anesthesia is established<br>|
| Active Comparator: norepinephrine infusion<br>norepinephrine infusion (30 mL/h corresponding to 4 μg/min) | Procedure: norepinephrine infusion<br>* In parturients allocated to the norepinephrine group group, a phenylephrine infusion will be initiated as soon as spinal anesthesia is established<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of bradycardia | any incidence of heart rate<60/min will be recorded | intraoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| need for vasoconstrictor | parturient needed or not vasoconstrictor during the operation | intraoperative | 
| type of vasoconstrictor administered | phenylephrine verus ephedrine | intraoperative | 
| number of bolus doses of vasoconstrictor administered | number of provided interventions to maintain systolic blood pressure within the set limits will be recorded | intraoperative | 
| total dose of vasoconstrictor administered | total dose in mg for ephedrine or μg for phenylephrine | intraoperative | 
| incidence of hypotension | any occurrence of hypotension throughout the operation will be recorded (systolic arterial pressure<80% of baseline throughout the operation) | intraoperative | 
| incidence of hypertension | any incidence of systolic blood pressure >120% of baseline will be recorded | intraoperative | 
| incidence of nausea/vomiting | incidence of nausea and vomiting throughout the operation | intraoperative | 
| neonatal Apgar score at 1 min | neonatal Apgar score will be recorded at 1 min after delivery. The Apgar score is determined by evaluating the newborn baby on five simple criteria on a scale from zero to two, then summing up the five values thus obtained. The resulting Apgar score ranges from zero to 10. Scores 7 and above are generally normal; 4 to 6, fairly low; and 3 and below are generally regarded as critically low and cause for immediate resuscitative efforts. | 1 min post delivery | 
| neonatal Apgar score at 5 min | neonatal Apgar score will be recorded at 5 min after delivery. The Apgar score is determined by evaluating the newborn baby on five simple criteria on a scale from zero to two, then summing up the five values thus obtained. The resulting Apgar score ranges from zero to 10. Scores 7 and above are generally normal; 4 to 6, fairly low; and 3 and below are generally regarded as critically low and cause for immediate resuscitative efforts. | 5 min post delivery | 
| neonatal blood gases | fetal cord blood analysis will be performed immediately post-delivery | 1 min post delivery | 
| glucose in neonatal blood | glucose will be measured in the cord blood gas sample taken immediately post-delivery | 1 min post delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypotension, phenylephrine, noradrenaline, cardiac output, fetal, maternal hemodynamics, cesarean section