Effect of Phenylephrine Versus Norepinephrine on Venous Return

Study Overview
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Brief Summary
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Induction of general anesthesia often induces a decrease in the mean arterial blood pressure (MAP) caused by arterial and venous dilatation. Fluid administration is conventionally used to increase the patient's total blood volume, but is often associated with multiple adverse events such as postoperative edema. Arterial hypotension can also be treated by vasopressor agents such as norepinephrine and phenylephrine which mainly increase the blood pressure by arterial vasoconstriction. Compared to phenylephrine, norepinephrine has a shorter half-life (2 - 3 minutes) and improves the MAP by increase in cardiac contractility. In a recent study at our department it was demonstrated that besides arterial vasoconstriction, phenylephrine also improves venous return and cardiac output by venous vasoconstriction. The aim of this study is to compare the hemodynamic effects of both vasopressor agents in patients undergoing deep inferior epigastric perforators (DIEP) flap surgery. If significant differences between both agents are demonstrated, these findings can provide an important basis for future recommendations.

Detailed Description
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In consecutive patients scheduled for DIEP flap surgery, all hemodynamic and respiratory variables are recorded electronically for subsequent off line analysis. A systolic blood pressure of minimal 100 mmHg will be maintained during surgery by optimization of the cardiac preload and titrated norepinephrine (1.5 µg/kg/h) or phenylephrine (15 µg/kg/h) administration. Cardiac preload optimization will be based on pulse pressure variation (PPV) measurement, which is calculated by pulse contour analysis of the radial arterial pressure curve. Following the international goal-directed fluid therapy guidelines, plasmalyte will be administrated if the PPV>11%. The tricuspid annular plane systolic excursion (TAPSE) will be measured by transthoracic echocardiography (TTE) to evaluate the inotropic effect of norepinephrine and phenylephrine. In addition, TTE will be used to measure the cardiac output to calibrate the PPV measurements.

Official Title
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Comparison of the Hemodynamic Effects of Phenylephrine and Norepinephrine in Patients Undergoing Deep Inferior Epigastric Perforator (DIEP) Flap Surgery.

Conditions
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Arterial Hypotension

Intervention / Treatment
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* Drug: Phenylephrine
* Drug: Norepinephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients scheduled for DIEP flap surgery Exclusion Criteria: unwilling or unable to grant written informed consent contra-indications for phenylephrine or norepinephrine cardiac arrhythmia no necessity for pharmacological blood pressure management

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: phenylephrine<br>starts at 15 µg/kg/h phenylephrine and titrated to main a minimal systolic blood pressure of 100 mmHg | Drug: Phenylephrine<br>* intravenous administration<br>|
| Active Comparator: norepinephrine<br>starts at 1.5 µg/kg/h phenylephrine and titrated to main a minimal systolic blood pressure of 100 mmHg | Drug: Norepinephrine<br>* intravenous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pulse pressure variation | the evolution of the pulse pressure variation in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration | perioperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean arterial blood pressure | the evolution of the mean arterial blood pressure in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration | perioperative | 
| cardiac output | the evolution of the cardiac output in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration | perioperative | 
| stroke volume (variation) | the evolution of the stroke volume (variation) in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration | perioperative | 
| heart rate | the evolution of the heart rate in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration | perioperative | 
| ventilation frequency | the evolution of the ventilation frequency in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration | perioperative | 
| end-tidal CO2 | the evolution of the end-tidal CO2 in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration | perioperative | 
| tidal volume | the evolution of the tidal volume in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration | perioperative | 
| TAPSE | the evolution of the tricuspid annular plane systolic excursion in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration | perioperative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiac output, pulse pressure variation, fluid responsiveness, hemodynamic monitoring