Dynamic Estimation of Cardiac Output in the Operating Room (TRIPLEFLOW)

Estimation of Cardiac Output in the Operating Room by Pulse Wave Analysis and Esophageal Doppler Blood Velocity: Comparison of the Two Methods

During major surgery, it is recommended to monitor invasive arterial blood pressure and cardiac output (CO) during hemodynamic interventions (fluid challenge or vasopressors). Esophageal Doppler is currently considered as the reference method for monitoring cardiac output in the operating room. The PRAM method (pressure recording analytical method) with the MostCareUp monitor (Vytech, Padova, Italy) and the LTIA method (long time interval analysis) allow cardiac output estimation derived from non-calibrated arterial pressure waveform analysis. Few studies have looked at relative changes in cardiac output during hemodynamic intervention with these two methods. The aim of this study is to compare the relative changes in cardiac output during hemodynamic interventions as measured using PRAM and LTIA methods, compared to esophageal Doppler.

Study Overview

• Status: Recruiting
• Conditions: Blood Pressure; Surgery; General Anesthesia; Intensive Care; Hemodynamic Instability; Cardiac Output; Interventional Radiology; Organ Failure
• Intervention / Treatment: Device: Trans-esophageal Doppler monitoring; Device: MostCareUP Haemodynamic Monitor; Device: Argos Cardiac Output (CO) Monitor

Detailed Description

Hemodynamic optimization is a major issue in the perioperative and intensive care settings. The titration of fluid in the operating room and in intensive care guided by the variations of the stroke volume (SV) and therefore of the cardiac output (CO) improves morbimortality. Esophageal Doppler is currently considered as the reference method for monitoring cardiac output in the operating room. However, when its use is not possible, there are devices that allow continuous estimation of cardiac output from the pulse wave contour (i.e. an invasive blood pressure signal). The PRAM method (pressure recording analytical method) with the MostCareUp monitor (Vytech, Padova, Italy) and the LTIA method (long time interval analysis) using an analog-to-digital converter connected to the patient's scope seem to be promising pulse wave analysis techniques. The majority of studies investigating these devices have focused on cardiac output values from a purely static perspective. Few studies have looked at changes in cardiac output during hemodynamic intervention (fluid challenge or use of vasopressors). However, in daily clinical practice, it is the dynamic information on CO that informs doctors on the effectiveness of therapeutic challenges. Thus, our hypothesis is to compare the variations in cardiac output estimated by PRAM et LTIA methods with those obtained using esophageal Doppler, during surgical procedures under general anesthesia.

The main goal of this study is to compare the relative changes in cardiac output obtained during hemodynamic interventions (fluid challenge or vasopressors) using PRAM and LTIA versus esophageal doppler. Parameters measured for the primary objective: 1. Continuous measurement and recording of the invasive blood pressure signal 2. Continuous and simultaneous measurement of cardiac output by MostCareUp (Vytech, Padova, Italy) and esophageal doppler. 3. Estimation of cardiac output from the arterial pressure signal by means of a digital analog converter using the LTIA algorithm connected to the patient's scope. For all patients, data from the cardiac output monitors are recorded throughout the procedure and the resuscitation stay. The secondary objective is to study the hemodynamic parameters of ventriculoarterial coupling calculated by the PRAM method and measured by esophageal doppler, other than CO and SV during therapeutic challenges. Parameters measured for the secondary objective: Global Afterload Angle (GALA), the value of the dicrote wave, dP/dtmax (myocardial contractility index), cardiac efficiency (CCE), arterial elastance, the total impedance of the system (Ztot).

Experimental design: this is a single-center, observational prospective study The study concerns adult patients benefiting from intraoperative hemodynamic optimization under general anesthesia, including routine monitoring of blood pressure and measurement of cardiac output by esophageal Doppler.

This study is "non-interventional" on adult patients undergoing interventional radiology, surgery under general anesthesia, or admitted to the ICU for postoperative organ failure. All measurements are obtained from standard monitoring including blood pressure and cardiac output measurement by transesophageal Doppler. Monitoring includes continuous electrocardiogram, SpO2, ventilatory parameters and depth of anesthesia by Bispectral Index. During the anaesthesia consultation, the patients will be given a letter of information on the objectives and the course of the study. Their non-opposition to participating in this study will be collected at the latest during the pre-anesthetic visit, the day before the operation. The protocol starts on the day of the operation. For all patients, the procedures will be performed under general anesthesia with an intravenous anesthesia protocol with a concentration objective (Orchestra® Base Primea - Fresenius Kabi France). The protocol does not interact with the care procedure. On the day of the procedure, the MostCareUp (Vytech, Padova, Italy) will be connected in series with the pressure head already in place. The blood pressure signals will be continuously recorded to allow estimation of the cardiac output by the LTIA method using an analog-to-digital converter. This calculation is made from the signal that has been transmitted to the multiparametric scope monitor and is therefore not directly connected to the patient. The acquisition of the analog signal is done via USB2.0 thanks to a Video Capture Card equipped with a converter. The software recalculates with its algorithm an estimation of the cardiac output from the data. The clinician in charge in the operating room will use only the hemodynamic data from the esophageal Doppler to guide his therapeutic strategy. Synchronization of the 2 devices. Recording of events during therapeutic tests if there is an indication for treatment. Usual protocol of the therapeutic challenges service: Patient receiving intraoperative vascular filling titration to optimize cardiac output (maximize SV/CO), patient with persistent arterial hypotension (MAP < 65 mmHg or < 80% of baseline) during the procedure despite adequate depth of anesthesia (BIS 40-50) and optimized cardiac output motivating vasopressor injection. For all patients, data from the 2 cardiac output monitors and hemodynamics will be collected during and after the therapeutic tests. Under no circumstances will a decision on therapeutic strategy be made based on PRAM or LTIA data. No additional complementary examination will be performed. The physician in charge of the study collecting the data does not intervene at any time in the management of the patient. The implementation of this type of intraoperative monitoring does not prolong the duration of anesthesia.

The measure of agreement the investigators will use is the intra-class correlation coefficient. To compare 3 measurement modalities, assuming that the intraclass correlation coefficient for the measurement of VES variations will be 0.85 with a confidence interval with width of 0.1 and a first-species risk of 0.05, 84 patients must be included. It is expected that the signals of 10% of the included patients will be of insufficient quality for their exploitation. Therefore, the calculated sample size is 92 patients.

Results will be expressed as mean (standard deviation) or median (interquartile range) depending on the normality of the data distribution. A Bland-Altman analysis for repeated measures will be used to evaluate the agreement between the cardiac output measured by esophageal Doppler and the cardiac output estimated by the two pulse wave monitors. It will be associated with a calculation of the bias and its 95% confidence interval, the upper/lower limits of agreement and their 95% confidence intervals, and the percentage error. A percentage of error less than or equal to 30% indicates the agreement of the technique with the reference method. The agreement of cardiac output variations measured by esophageal Doppler and pulse wave analysis will be evaluated by a Bland-Altman analysis. The percentage of agreement will be evaluated using a four-quadrant plot. Acceptable agreement is defined as greater than 90%. The analyses will be repeated in the filler and vasopressor subgroups. The ability of pulse wave monitors to detect responders to filling will be assessed and compared with esophageal doppler. Subjects will be defined as responders to volume expansion when the filling test increases the ESV by more than 10%.

• Study Type: Observational
• Enrollment (Anticipated): 92

Contacts and Locations

• Study Contact: Name: Alex HONG, MD; Phone Number: +33 (0)149958309; Email: alex.hong@aphp.fr
• Study Contact Backup: Name: Joaquim MATEO, MD; Phone Number: +33 (0)149958374; Email: joaquim.mateo@aphp.fr

Study Locations

• France
  • Paris, France, 75010
    • Recruiting
    • AP-HP, Lariboisière Hospital, Department of Anesthesiology and Intensive Care
    • Contact: Alex HONG, MD; Phone Number: +33 (0)149958309; Email: alex.hong@aphp.fr
    • Contact: Joaquim MATEO, MD; Phone Number: +33 (0)149958374; Email: joaquim.mateo@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients eligible for an interventional radiology procedure, surgery under general anesthesia, or admitted to intensive care unit for postoperative organ failure, benefiting from intraoperative and postoperative hemodynamic optimization in intensive care including routine blood pressure monitoring and measurement of cardiac output by esophageal Doppler.

Description

Inclusion Criteria:

• Major patients (≥ 18 years )
• Eligible for an interventional radiology procedure or surgery under general anesthesia
• Monitoring of invasive blood pressure and cardiac output by trans-esophageal Doppler.
• Patients informed and having expressed their non-opposition to participation in this research

Exclusion Criteria:

• Patients under 18 years old
• Atrial fibrillation
• Contraindication to trans-esophageal doppler
• Patient opposed to protocol participation
• Pregnant woman
• Patient under judicial protection
• Patient without affiliation to a social security scheme

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients undergoing general anesthesia and benefiting from intraoperative hemodynamic optimization; Patients undergoing general anesthesia and benefiting from intraoperative hemodynamic optimization, including routine monitoring of blood pressure and measurement of cardiac output by trans-esophageal Doppler.

Device: Trans-esophageal Doppler monitoring; Trans-esophageal Doppler monitoring (CARDIOQ-ODM; Deltex Medical, Chichester, UK) for monitoring of cardiac output; Device: MostCareUP Haemodynamic Monitor; MostCareUp (Vytech, Padova, Italy) waveform analysis cardiac output monitor; Device: Argos Cardiac Output (CO) Monitor; Argos monitor (Retia Medical, Valhalla, NY, USA) for cardiac output monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac output using the trans-esophageal Doppler technique	Measure of cardiac output with trans-esophageal doppler (CARDIOQ-ODM; Deltex Medical, Chichester, UK) in L/min (COTOD)	Duration of the surgery (maximum 1 day)
Cardiac output using the MostCareUp monitor	Measure of cardiac output with MostCareUp (Vytech, Padova, Italy) in L/min (COPRAM)	Duration of the surgery (maximum 1 day)
Cardiac output using the Argos monitor	Measure of cardiac output with Argos monitor (Retia Medical, Valhalla, NY, USA) in L/min (COLTIA)	Duration of the surgery (maximum 1 day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of the value of the dicrote wave with MostCareUp monitor	The value of the dicrote wave will be recorded with the MostCareUp monitor (Vytech, Padova, Italy) during the whole procedure	Duration of the surgery (maximum 1 day)
Measure of dP/dtmax (myocardial contractility index) with MostCareUp monitor	The dP/dtmax (myocardial contractility index) will be recorded with the MostCareUp monitor (Vytech, Padova, Italy) during the whole procedure	Duration of the surgery (maximum 1 day)
Measure of the cardiac efficiency (CCE) with MostCareUp monitor	The cardiac efficiency (CCE) will be recorded with the MostCareUp monitor (Vytech, Padova, Italy) during the whole procedure	Duration of the surgery (maximum 1 day)
Measure of arterial elastance with MostCareUp monitor	The arterial elastance will be recorded with the MostCareUp monitor (Vytech, Padova, Italy) during the whole procedure	Duration of the surgery (maximum 1 day)
Measure of the total impedance of the system (Ztot) with MostCareUp monitor	The total impedance of the system (Ztot) will be recorded with the MostCareUp monitor (Vytech, Padova, Italy) during the whole procedure	Duration of the surgery (maximum 1 day)
Measure of the Global Afterload Angle (GALA) using the trans-esophageal Doppler technique	The Global Afterload Angle (GALA) will be recorded with trans-esophageal Doppler (CARDIOQ-ODM; Deltex Medical, Chichester, UK) during the whole procedure	Duration of the surgery (maximum 1 day)
Measure of arterial elastance using the trans-esophageal Doppler technique	The the arterial elastance will be recorded with trans-esophageal Doppler (CARDIOQ-ODM; Deltex Medical, Chichester, UK) during the whole procedure	Duration of the surgery (maximum 1 day)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: INSERM UMR-942, Paris, France
• Investigators: Principal Investigator: Alex HONG, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: June 7, 2021
• First Submitted That Met QC Criteria: June 7, 2021
• First Posted (Actual): June 15, 2021

Study Record Updates

• Last Update Posted (Actual): October 18, 2021
• Last Update Submitted That Met QC Criteria: October 11, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Cardiac output monitoring; Pulse contour analysis; Vasopressors; Fluid challenge; Trans-esophageal doppler; Pressure recording analytical method; Long time interval analysis
• Other Study ID Numbers: APHP210311; 2021-A00088-33 (Other Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No