Effect of Phenylephrine Versus Norepinephrine on Venous Return

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ClinicalTrials.gov Identifier: NCT03872570

Recruitment Status : Unknown

Verified October 2019 by Dr. Alain Kalmar, MD, PhD, Algemeen Ziekenhuis Maria Middelares.
Recruitment status was: Recruiting

First Posted : March 13, 2019

Last Update Posted : October 11, 2019

Sponsor:

Information provided by (Responsible Party):

Dr. Alain Kalmar, MD, PhD, Algemeen Ziekenhuis Maria Middelares

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.

Condition or disease	Intervention/treatment	Phase
Arterial Hypotension	Drug: Phenylephrine Drug: Norepinephrine	Phase 4

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	40 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose:	Supportive Care
Official Title:	Comparison of the Hemodynamic Effects of Phenylephrine and Norepinephrine in Patients Undergoing Deep Inferior Epigastric Perforator (DIEP) Flap Surgery.
Actual Study Start Date :	June 1, 2019
Estimated Primary Completion Date :	June 1, 2020
Estimated Study Completion Date :	June 15, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Low Blood Pressure

Drug Information available for: Norepinephrine Phenylephrine Phenylephrine hydrochloride Oxymetazoline Oxymetazoline hydrochloride

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: phenylephrine starts at 15 µg/kg/h phenylephrine and titrated to main a minimal systolic blood pressure of 100 mmHg	Drug: Phenylephrine intravenous administration
Active Comparator: norepinephrine starts at 1.5 µg/kg/h phenylephrine and titrated to main a minimal systolic blood pressure of 100 mmHg	Drug: Norepinephrine intravenous administration

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 85 Years (Adult, Older Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03872570

Contacts

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Contact: Alain F Kalmar, MD, PhD	+32 246 17 29	alain.kalmar@gmail.com
Contact: Silvie Allaert, MD, PhD	+32 246 17 28	silvie.allaert@azmmsj.be

Locations

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Belgium
General Hospital Maria Middelares	Recruiting
Ghent, Oost-Vlaanderen, Belgium, 9000
Contact: Alain F Kalmar, MD, PhD

Sponsors and Collaborators

Algemeen Ziekenhuis Maria Middelares

Investigators

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Principal Investigator:	Alain F Kalmar, MD, PhD	Maria Middelares Hospital

More Information

Publications:

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.

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. Review.

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. Epub 2005 Oct 14.

Hengstmann JH, Goronzy J. Pharmacokinetics of 3H-phenylephrine in man. Eur J Clin Pharmacol. 1982;21(4):335-41.

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Responsible Party:	Dr. Alain Kalmar, MD, PhD, Staff Anesthesist, Algemeen Ziekenhuis Maria Middelares
ClinicalTrials.gov Identifier:	NCT03872570
Other Study ID Numbers:	MMS.2019.008
First Posted:	March 13, 2019 Key Record Dates
Last Update Posted:	October 11, 2019
Last Verified:	October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Dr. Alain Kalmar, MD, PhD, Algemeen Ziekenhuis Maria Middelares:


cardiac output pulse pressure variation fluid responsiveness hemodynamic monitoring

Additional relevant MeSH terms:

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Hypotension Vascular Diseases Cardiovascular Diseases Phenylephrine Oxymetazoline Norepinephrine Cardiotonic Agents Mydriatics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs	Sympathomimetics Vasoconstrictor Agents Nasal Decongestants Respiratory System Agents Adrenergic alpha-1 Receptor Agonists Adrenergic alpha-Agonists Adrenergic Agonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Protective Agents

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