CORVaso: Cardiac Output Response to Vasopressin Infusion In Abdominal Surgery Patients Under Mechanical Ventilation

Sponsor

University Hospital, Clermont-Ferrand (Other)

Overall Status

Recruiting

CT.gov ID

NCT04935814

Collaborator

(none)

Enrollment

Location

Arm

18.7

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In this study, the investigators propose to explore the hemodynamic variations induced by vasopressin and its influence on cardiac output, mean systemic pressure, and venous return resistance measured through cardiopulmonary interactions, according to the approach proposed by Guyton, in patients undergoing major abdominal surgeries.

Condition or Disease	Intervention/Treatment	Phase
Major Abdominal Surgery General Anesthesia Mechanical Ventilation Vasopressin Infusion	Drug: Vasopressin, Arginine	Phase 4

Detailed Description

Maintaining hemodynamic stability is one of the main objectives of the anesthesiologist or the intensivist, either in the ICU or the OR. This consists of optimizing cardiac output to ensure satisfactory systemic perfusion during the peri-operative period or the ICU stay. The occurrence of oxygen debt (mismatch between oxygen consumption and transport) and/or tissue hypoperfusion are key factors in the development of organ failure. Numerous studies have shown in recent years that individualized hemodynamic optimization (cardiac output and organ perfusion pressure) reduces the risk of postoperative and ICU morbidity and mortality.

Monitoring of cardiac output and stroke volume is a valuable and essential aid in determining the therapies to be used for this optimization, whether it involves volume expansion or the use of a vasopressor or even inotropic agent.

Several vasopressor therapies have been available to date. Norepinephrine is currently the reference in the treatment of vasoplegic shock states, but also in the operating room during major surgery or in fragile patients. Other molecules are currently available and are used in a disparate manner, according to the habits of each practitioner, sometimes outside regulatory rules, not following international recommendations concerning the pathology in question: adrenaline, dopamine, phenylephrine, terlipressin...

Vasopressin (D-arginine-D-vasopressin) is an endogenous hormone synthesized by the hypothalamus (peptide composed of 9 amino acids) which has an antidiuretic renal action through its V2 receptor but also a vasoconstriction activity through its V1a receptor, at the level of the smooth muscles of the vascular wall. It also participates in the stimulation of catecholamine secretion by the adrenal medulla. Vasopressin is commercially available under the name "argipressin". It is currently indicated as an adjunct to other vasopressors such as norepinephrine in refractory septic shock to maintain satisfactory hemodynamic stability.

However, its vasoconstrictive and hemodynamic effects, including its influence on cardiac output, have never been studied to date and to the knowledge of investigators. In particular, there are no studies showing the influence of this molecule on mean systemic pressure and venous return resistance, which are fundamental determinants of its impact on left heart function and thus on cardiac output.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

CORVaso is a pharmacological trial which aims to determine the variations of cardiac output during vasopressin infusion in major abdominal surgery patients.CORVaso is a pharmacological trial which aims to determine the variations of cardiac output during vasopressin infusion in major abdominal surgery patients.

Masking:

None (Open Label)

Masking Description:

Patients are under general anesthesia and outcomes assessor (statistician) will be blinded of patients positions orders. Sequential positions of patients will be randomized.

Primary Purpose:

Basic Science

Official Title:

Cardiac Output Response to Vasopressin Infusion In Abdominal Surgery Patients Under Mechanical Ventilation: A Clinical Pharmacodynamics Study

Actual Study Start Date :

Jun 9, 2021

Anticipated Primary Completion Date :

Dec 10, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Continuous vasopressin infusion After general anesthesia, patients will receive a continuous infusion of vasopressin in order to improve mean arterial pressure by 20 mmHg.	Drug: Vasopressin, Arginine Once vasopressin infusion started, patients positions will be randomized: Trendelenburg (-30°), anti Trendelenburg (+30°) and supine position (0°).

Arm

Intervention/Treatment

Experimental: Continuous vasopressin infusion

After general anesthesia, patients will receive a continuous infusion of vasopressin in order to improve mean arterial pressure by 20 mmHg.

Drug: Vasopressin, Arginine

Once vasopressin infusion started, patients positions will be randomized: Trendelenburg (-30°), anti Trendelenburg (+30°) and supine position (0°).

Outcome Measures

Primary Outcome Measures

Variation of cardiac output after an infusion of vasopressin at different levels of cardiac preload [15 minutes after position change]
Using a thermodilution method, cardiac output will be measured and recorded at different levels of cardiac preload obtained by changing patient's position (Trendelenburg, anti-Trendelenburg and supine position).

Secondary Outcome Measures

Variation of mean systemic filling pressure and venous return after an infusion of vasopressin at different levels of cardiac preload [15 minutes after position change]
Mean systemic filling pressure will be determined by plotting the venous return curve using the cardiopulmonary interaction described by Guyton, by changing patient's position (Trendelenburg, anti-Trendelenburg and supine position).
Variation of central venous pressure after an infusion of vasopressin at different levels of cardiac preload [15 minutes after position change]
Using a central venous catheter, the central venous pressure will be determined.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults above 18
Planned for a major abdominal surgery under general anesthesia
Under mechanical ventilation
Presence of a central venous and arterial lines allowing transpulmonary thermodilution cardiac output measurement
Patient's consent with a social insurance

Exclusion Criteria:

Do not consent to participate
History of heart attack, arteriopathy or aneurysm
Contraindication to use transpulmonary thermodilution to measure cardiac output :
coagulopathy
cardiac arrythmia
presence of pace-maker or defibrillator
severe valvulopathy
Patients with Acute Respiratory Distress Syndrome (according to Berlin criteria)
History of arterial hypertension (treated or not)
History of seizure, chronic headache, asthma or heart failure
Left Ventricular Ejection Fraction (LVEF) < 45% or right ventricular dysfunction
History of pulmonary lobectomy or surgery
History of restrictive or obstructive pulmonary disease
Body Mass Index (BMI) < 15 or > 40 kg/m²
Pregnancy
Known allergy to vasopressin
Patients under protection of justice (guardianship, curators...)