Effect of Phenylephrine Versus Norepinephrine on Venous Return

Arterial Hypotension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03872570
• Other study ID #: MMS.2019.008
• Status: Recruiting
• Phase: Phase 4
• Start date: June 1, 2019
• Est. completion date: June 15, 2020

Study information

• Verified date: October 2019
• Source: Algemeen Ziekenhuis Maria Middelares
• Contact: Alain F Kalmar, MD, PhD
• Phone: +32 246 17 29
• Email: alain.kalmar[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: June 15, 2020
• Est. primary completion date: June 1, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Arterial Hypotension
• Hypotension

Intervention

Drug:
• Phenylephrine
intravenous administration
• Norepinephrine
intravenous administration

Locations

Country	Name	City	State
Belgium	General Hospital Maria Middelares	Ghent	Oost-Vlaanderen

Sponsors (1)

Lead Sponsor	Collaborator
Algemeen Ziekenhuis Maria Middelares

Country where clinical trial is conducted

Belgium, 

References & Publications (4)

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	cardiac output	the evolution of the cardiac output in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration	perioperative
Secondary	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
Secondary	heart rate	the evolution of the heart rate in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration	perioperative
Secondary	ventilation frequency	the evolution of the ventilation frequency in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration	perioperative
Secondary	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
Secondary	tidal volume	the evolution of the tidal volume in a time course of 20 minutes after the start of phenylephrine/norepinephrine administration	perioperative
Secondary	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