Cardiac Output Changes in Cesarean Section

Comparison of Norepinephrine and Phenylephrine in Cesarean Section by Transesophageal Ultrasound

Since 2011, phenylephrine was recommended as the preferred drug to maintain blood pressure in obstetric anesthesia.Phenylephrine, an α adrenoceptor agonist, can induce peripheral vasoconstriction to maintain blood pressure, while reflexly decrease heart rate and result in cardiac output (CO) reduction.Norepinephrine acts not only as an α adrenoceptor receptor agonist, but also as a weaker β adrenergic receptor agonist. It can elevate blood pressure the same asphenylephrine, meanwhile produce positive inotropic effect including increasing heart rate.Thus, the administration of norepinephrine can maintain blood pressue and avoid the decline of CO. The purpose of this study is to evaluate the effect of norepinephrine and phenylephrine on maternal CO in cesarean section by transesophageal echocardiography.

Study Overview

• Status: Unknown
• Conditions: Hemodynamic Instability; Obstetrical Complication of Anesthesia; Cardiac Output,Low
• Intervention / Treatment: Drug: Phenylephrine; Drug: Norepinephrine

Detailed Description

Combined spinal epidural anesthesia (CSEA) is a commonly used anesthetic methods in cesarean section. The main problem of CSEA is hypotension, which will cause maternal nausea and vomiting, reduced uteroplacental blood flow and fetal acidosis. One of the important methods for prevention and treatment of hypotension after CSEA is to give vasoactive drugs.

Since 2011, phenylephrine was recommended as the preferred drug to maintain blood pressure in obstetric anesthesia.Phenylephrine, an α adrenoceptor agonist, can induce peripheral vasoconstriction to maintain blood pressure, while reflexly decrease heart rate and result in cardiac output (CO) reduction.Dyer et al. used bioimpedance technique to analyze the hemodynamic changes in normal pregnant women. A bolus of 80 ug phenylephrine was administrated when maternal mean arterial pressure decreased 20% after CSEA. It was found that cardiac output (CO) decreased significantly (14%) after phenylephrine administrationcompared with the baseline.And the decrease of CO induced by phenylephrine was in a dose dependent.All the studies referred above recruitednormal pregnant women, and the decreased CO did not have an adverse effect on neonatal birth. However, as we all know, the decrease of CO will influence uteroplacental blood, which may lead to adverse results in existed intrauterine distress fetal. All authors of those studies stressed that the decrease of CO induced by phenylephrine may increase the risks of fetal distress or other adverse consequences. So, it is crucial for obstetric anesthesiologist to choose a suitable vasoactive drugs, which can maintain both maternal blood pressure and uteroplacental perfusion in order to keep intrauterine environment steady.

Norepinephrine acts not only as an α adrenoceptor receptor agonist, but also as a weaker β adrenergic receptor agonist. It can elevate blood pressure the same asphenylephrine, meanwhile produce positive inotropic effect including increasing heart rate.Thus, the administration of norepinephrine can maintain blood pressue and avoid the decline of CO. And norepinephrine is superior to phenylephrine in the respect of organ perfusion.

There is little research about the administration of norepinephrine in obstetric anesthesia.Ngan Kee et al.compared phenylephrine (0.57μg/kg/min) with norepinephrine (0.035μg/kg/min) in the treatment of hypotension in obstetric anesthesia. CO monitored by a suprasternal Doppler ultrasound every 5 minutes. CO and heart rate was significantly higher in norepinephrine group than that in phenylephrine group, while peripheral vascular resistance was significantly lower in norepinephrine group than that in phenylephrine group. And the oxygen content in umbilical venous was significantly higher in norepinephrine group, which may be related to the norepinephrine induced lower peripheral vascular resistance and high cardiac output.Monitoring of CO can give a comprehensive understanding of hemodynamics in the pregnant. It enables obstetric anesthesiologist to use liquid expansion rationally and administrate vasoactive agents properly.Although the accuracy of suprasternal Doppler ultrasound was high in that study, the interval of 5min to monitor CO may miss the rapid changes in hemodynamics of pregnant women.In the present study, we will monitor CO continuously by a small diameter (6 mm) transesophageal echocardiography, which can be retained in the patient's esophagus.

The purpose of this study is to evaluate the effect of norepinephrine and phenylephrine on maternal CO in cesarean section by transesophageal echocardiography.Fetal umbilical cord blood, neonatal 1min Apgar score, 5 min Apgar scores and neonatal plasma catecholamine concentrations will be collected to understand the effects of norepinephrine and phenylephrine on fetal.

• Study Type: Interventional
• Enrollment (Anticipated): 106
• Phase: Early Phase 1

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. age >=18 years,<=40 years;
2. height 150-180 cm;
3. weight 55-80 kg;
4. full-term gestation (>36 wk and <41 wk)
5. singleton pregnancy undergoing elective cesarean section under CSEA

Exclusion Criteria:

1. contraindications to spinal anesthesia;
2. patients with any complicated pregnancy;
3. fetal compromise;
4. need of emergency;
5. in labor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: phenylephrine; phenylejphrine (one bolus for 40 ug/ml)	Drug: Phenylephrine; Hypotension (systolic BP <80% of baseline) will be treated with intravenous boluses of phenylephrine 40 μg.
Experimental: norepinephrine; norepinephrine (one bolus for 2 ug/ml)	Drug: Norepinephrine; Hypotension (systolic BP <80% of baseline) will be treated with intravenous boluses of norepinephrine 2 μg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
cardiac output	from baseline (before spinal injection) until 10 minutes after spinal injection

Secondary Outcome Measures

Outcome Measure	Time Frame
systolic blood pressure	from baseline (before spinal injection) until 10 minutes after spinal injection
heart rate	from baseline (before spinal injection) until 10 minutes after spinal injection
Apgar score	1 min and 5 min after delivery
Umbilical cord arterial blood pH/BE/Lac	time at delivery
umbilical plasma catecholamine concentration	time at delivery

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Study Chair: Zhenzhou He, MD, Deparment of Anesthesia,South Campus,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai,China

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Anticipated): June 1, 2016
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: April 29, 2016
• First Submitted That Met QC Criteria: May 2, 2016
• First Posted (Estimate): May 3, 2016

Study Record Updates

• Last Update Posted (Estimate): May 3, 2016
• Last Update Submitted That Met QC Criteria: May 2, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: cesarean section; cardiac output; norepinephrin
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Cardiac Output, Low; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Norepinephrine; Phenylephrine; Oxymetazoline
• Other Study ID Numbers: Renji-2016035k

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No