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Effect of Phenylephrine Versus Norepinephrine on Venous Return

Primary Purpose

Arterial Hypotension

Status
Unknown status
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Phenylephrine
Norepinephrine
Sponsored by
Algemeen Ziekenhuis Maria Middelares
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Arterial Hypotension focused on measuring cardiac output, pulse pressure variation, fluid responsiveness, hemodynamic monitoring

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • General Hospital Maria MiddelaresRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

phenylephrine

norepinephrine

Arm Description

starts at 15 µg/kg/h phenylephrine and titrated to main a minimal systolic blood pressure of 100 mmHg

starts at 1.5 µg/kg/h phenylephrine and titrated to main a minimal systolic blood pressure of 100 mmHg

Outcomes

Primary Outcome Measures

pulse pressure variation
the evolution of the pulse pressure variation in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration

Secondary Outcome Measures

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
cardiac output
the evolution of the cardiac output in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
stroke volume (variation)
the evolution of the stroke volume (variation) in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
heart rate
the evolution of the heart rate in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
ventilation frequency
the evolution of the ventilation frequency in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
end-tidal CO2
the evolution of the end-tidal CO2 in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
tidal volume
the evolution of the tidal volume in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
TAPSE
the evolution of the tricuspid annular plane systolic excursion in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration

Full Information

First Posted
March 11, 2019
Last Updated
October 9, 2019
Sponsor
Algemeen Ziekenhuis Maria Middelares
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1. Study Identification

Unique Protocol Identification Number
NCT03872570
Brief Title
Effect of Phenylephrine Versus Norepinephrine on Venous Return
Official Title
Comparison of the Hemodynamic Effects of Phenylephrine and Norepinephrine in Patients Undergoing Deep Inferior Epigastric Perforator (DIEP) Flap Surgery.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Unknown status
Study Start Date
June 1, 2019 (Actual)
Primary Completion Date
June 1, 2020 (Anticipated)
Study Completion Date
June 15, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Algemeen Ziekenhuis Maria Middelares

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arterial Hypotension
Keywords
cardiac output, pulse pressure variation, fluid responsiveness, hemodynamic monitoring

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
phenylephrine
Arm Type
Active Comparator
Arm Description
starts at 15 µg/kg/h phenylephrine and titrated to main a minimal systolic blood pressure of 100 mmHg
Arm Title
norepinephrine
Arm Type
Active Comparator
Arm Description
starts at 1.5 µg/kg/h phenylephrine and titrated to main a minimal systolic blood pressure of 100 mmHg
Intervention Type
Drug
Intervention Name(s)
Phenylephrine
Intervention Description
intravenous administration
Intervention Type
Drug
Intervention Name(s)
Norepinephrine
Intervention Description
intravenous administration
Primary Outcome Measure Information:
Title
pulse pressure variation
Description
the evolution of the pulse pressure variation in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Time Frame
perioperative
Secondary Outcome Measure Information:
Title
mean arterial blood pressure
Description
the evolution of the mean arterial blood pressure in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Time Frame
perioperative
Title
cardiac output
Description
the evolution of the cardiac output in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Time Frame
perioperative
Title
stroke volume (variation)
Description
the evolution of the stroke volume (variation) in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Time Frame
perioperative
Title
heart rate
Description
the evolution of the heart rate in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Time Frame
perioperative
Title
ventilation frequency
Description
the evolution of the ventilation frequency in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Time Frame
perioperative
Title
end-tidal CO2
Description
the evolution of the end-tidal CO2 in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Time Frame
perioperative
Title
tidal volume
Description
the evolution of the tidal volume in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Time Frame
perioperative
Title
TAPSE
Description
the evolution of the tricuspid annular plane systolic excursion in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration
Time Frame
perioperative

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alain F Kalmar, MD, PhD
Phone
+32 246 17 29
Email
alain.kalmar@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Silvie Allaert, MD, PhD
Phone
+32 246 17 28
Email
silvie.allaert@azmmsj.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alain F Kalmar, MD, PhD
Organizational Affiliation
Maria Middelares Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
General Hospital Maria Middelares
City
Ghent
State/Province
Oost-Vlaanderen
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alain F Kalmar, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
29569112
Citation
Kalmar AF, Allaert S, Pletinckx P, Maes JW, Heerman J, Vos JJ, Struys MMRF, Scheeren TWL. Phenylephrine increases cardiac output by raising cardiac preload in patients with anesthesia induced hypotension. J Clin Monit Comput. 2018 Dec;32(6):969-976. doi: 10.1007/s10877-018-0126-3. Epub 2018 Mar 22.
Results Reference
background
PubMed Identifier
24368739
Citation
O'Connell TD, Jensen BC, Baker AJ, Simpson PC. Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol Rev. 2013 Dec 24;66(1):308-33. doi: 10.1124/pr.112.007203. Print 2014.
Results Reference
background
PubMed Identifier
16227334
Citation
Beloeil H, Mazoit JX, Benhamou D, Duranteau J. Norepinephrine kinetics and dynamics in septic shock and trauma patients. Br J Anaesth. 2005 Dec;95(6):782-8. doi: 10.1093/bja/aei259. Epub 2005 Oct 14.
Results Reference
background
PubMed Identifier
7056280
Citation
Hengstmann JH, Goronzy J. Pharmacokinetics of 3H-phenylephrine in man. Eur J Clin Pharmacol. 1982;21(4):335-41. doi: 10.1007/BF00637623.
Results Reference
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Effect of Phenylephrine Versus Norepinephrine on Venous Return

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