Hemodynamic Monitoring and Fluid Responsiveness in Venoarterial Extracorporeal Membrane Oxygenation (VA ECMO) - "HemodynamECMOnitoring-VA Study"

Validation of Techniques for Hemodynamic Monitoring and Prediction of Fluid Responsiveness in Patients Undergoing Venoarterial Extracorporeal Membrane Oxygenation - A Prospective Diagnostic Accuracy Study ("HemodynamECMOnitoring-VA Study")

In extracorporeal membrane oxygenation (ECMO), blood is drawn out of the body via tubes, oxygenated in an artificial lung; and then pumped back into the blood vessels. This allows the supply of oxygen-rich blood to the organs (brain, heart, lungs, kidneys, liver, intestines, etc.) to be maintained. Continuous monitoring of cardiac function and circulatory status (blood pressure, blood flow to organs) is very important in intensive care medicine in order to control the administration of circulation-supporting medication and infusions. Various devices are routinely used for this task. However, in the specific situation of ECMO treatment, the measurements of these devices could be affected due to the artificial circulation; outside the body. The purpose of this study is therefore to test the accuracy of different methods of circulation monitoring during ECMO treatment.

Study Overview

• Status: Recruiting
• Conditions: Pneumonia; Hemodynamic Monitoring; ARDS; Intensive Care; Fluid Responsiveness; ECMO Treatment
• Intervention / Treatment: Device: Transthoracic Echocardiography; Device: Uncalibrated Pulse Contour Analysis; Device: Transpulmonary Thermodilution/Calibrated Pulse Contour Analysis; Device: Esophageal Doppler; Device: Bioreactance; Diagnostic test: Passive Leg Raising; Diagnostic test: Vena Cava Ultrasound; Diagnostic test: End-expiratory /-inspiratory occlusion test; Drug: Fluid bolus

Detailed Description

Hemodynamic monitoring and tests for fluid responsiveness are cornerstones of intensive care medicine. Generally, hemodynamic measurements can be obtained, for instance, with the following methods: pulmonary artery catheter, transthoracic echocardiography (TTE), esophageal doppler, transpulmonary thermodilution, pulse contour analysis and bioreactance, amongst others. Maneuvers for assessing volume responsiveness include passive leg raising (PLR), respiratory pulse pressure variation (PPV), stroke volume variation (SVV), inferior vena cava ultrasound (IVC), and end-inspiratory or end-expiratory occlusion tests. While these commonly used methods of hemodynamic assessment have been validated in various clinical scenarios, data are lacking in the setting of venoarterial extracorporeal membrane oxygenation (VA ECMO). VA ECMO is commonly used for circulatory support in patients with severe hemodynamic failure or cardiac arrest. Blood is most commonly drained from a femoral vein, pumped through an oxygenator, where it is oxygenated and decarboxylated, and thereafter reinfused into the patient via an arterial, most commonly femoral, return cannula. Theoretically, the artificial circulation with its blood drainage and return flows may interfere with common hemodynamic monitoring techniques and lead to erroneous measurements. The aim of this study therefore is to validate select techniques of hemodynamic monitoring and assessment of fluid responsiveness in patients on VA ECMO. In the context of this study, the performance of different hemodynamic monitoring tools and techniques for predicting fluid responsiveness will be compared.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bernhard Nagler, MD; Phone Number: +4314040044920; Email: bernhard.nagler@meduniwien.ac.at
• Study Contact Backup: Name: Thomas Staudinger, MD; Phone Number: +4314040044920; Email: thomas.staudinger@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Bernhard Nagler, MD; Phone Number: +4314040044920; Email: bernhard.nagler@meduniwien.ac.at
    • Contact: Thomas Staudinger, MD; Phone Number: +4314040044920; Email: thomas.staudinger@meduniwien.ac.at
    • Sub-Investigator: Bernhard Nagler, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient receiving VA ECMO support
• Age 18 - 75 years

Exclusion Criteria:

• Pregnancy
• Conditions not allowing for passive leg raising maneuvers, e.g. "open abdomen", known or suspected elevation of intracranial pressure, recent leg or spinal trauma or orthopedic conditions not permitting leg raising
• Known ischemic or hemorrhagic stroke within 3 months prior to study enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Entire Study Population; The entire study population will undergo serial hemodynamic assessments throughout the course of ECMO therapy. Hemodynamic variables are obtained using transthoracic echocardiography, uncalibrated pulse contour analysis, and optionally - depending on device availability - transpulmonary thermodilution, bioreactance and esophageal doppler. Maneuvers for assessing volume responsiveness include passive leg raising (PLR), respiratory pulse pressure variation (PPV), stroke volume variation (SVV), inferior vena cava ultrasound (IVC), and end-inspiratory or end-expiratory occlusion tests.

Device: Transthoracic Echocardiography; Transthoracic echocardiography (TTE) is used for intermittent non-invasive stroke volume (SV) measurements. It is calculated by multiplication of left ventricular out flow tract (LVOT) and LVOT velocity time integral (VTI), obtained in a parasternal long axis view and apical five chamber view, respectively.; Device: Uncalibrated Pulse Contour Analysis; Pulse Contour Analysis allows an automated and continuous measurement of stroke volume (SV). Its underlying principle is that the integral of the systolic arterial pressure curve directly correlates with stroke volume.; Device: Transpulmonary Thermodilution/Calibrated Pulse Contour Analysis; Transpulmonary thermodilution (TPTD) involves the administration of a cold saline bolus into a central venous catheter. A special thermistor catheter placed in the femoral or brachial artery detects the successive changes in blood temperature. The resulting heat dissipation curve is analyzed to estimate stroke volume, cardiac output and other hemodynamic variables such as intrathoracic thermal volume (ITTV), pulmonary thermal volume (PTV), global end-diastolic volume (GEDV), intrathoracic blood volume (ITBV) and extravascular lung water (EVLW). Intermittent TPTD-derived cardiac output measurements (typically performed 1-3x/d) are used to calibrate pulse contour analysis.; Device: Esophageal Doppler; In esophageal Doppler, a thin ultrasound probe, coated with aqueous ultrasound gel, is orally or nasally inserted into the esophagus and orientated towards the aorta. By emission and detection of continuous wave Doppler signals, real time spectral waveforms of red blood cell velocity in the aorta are obtained, from which cardiac indices can be derived.; Device: Bioreactance; Bioreactance is a noninvasive hemodynamic monitoring technique, in which four double electrode sensors are placed on the skin of the chest. A high frequency sine wave is transmitted across the thorax. Pulsatile flow in the aorta causes phase shifts and amplitude changes of this signal, which are measured across the different electrodes and used to compute cardiac output.; Diagnostic test: Passive Leg Raising; Passive Leg Raising (PLR) is a maneuver that mimics a fluid challenge by shifting about 300 ml of venous blood from the lower body to the heart. Thereby, it can help to predict fluid responsiveness without actual fluid infusion. To start with, the patient is placed in a semi-recumbent position. Then, the bed is adjusted so that the patient's torso is moved to a horizontal position and the lower limbs are raised to an angle of 45°. Hemodynamic effects occur and can be measured within one minute.; Diagnostic test: Vena Cava Ultrasound; Inferior Vena Cava (IVC) Ultrasound has become a popular technique for assessing volume status. IVC diameter is measured in a subcostal long-axis IVC view 1-2 cm from the junction with the right atrium. The magnitude of distensibility during mechanical ventilation cycles or collapsibility during spontaneous breathing has been proposed to correlate with fluid responsiveness; Diagnostic test: End-expiratory /-inspiratory occlusion test; In preload-dependent patients, mechanical ventilation induces periodic changes in cardiac output. Standardized maneuvers of end-expiratory or end-inspiratory interruption over 15 seconds may increase or decrease stroke volume, respectively, which is a valid predictor of fluid responsiveness; Drug: Fluid bolus; To verify fluid responsiveness, 500 ml of balanced crystalloids will be infused over a time of 15-20 min (25-33.33 ml/min) after completion of passive leg raising and restoration of baseline patient positioning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Agreement of receiver operating characteristic (ROC) curves for predicting fluid responsiveness using the passive leg-raising test between different cardiac output measurement techniques (echocardiography, pulse contour analysis, thermodilution).	Cardiac Output (L/min) will be measured using transthoracic echocardiography, uncalibrated pulse contour analysis, and thermodilution before, during, and after a passive leg-raising test, as well as after administration of a fluid bolus of 500 ml balanced crystalloids over 15-20 min. A cardiac output increase of > 15% will be the cut-off for defining fluid responsiveness. Receiver operating characteristic (ROC) curves will be generated for each cardiac output measurement technique and compared using the Hanley-McNeil method. The agreement between the ROC curves (Hanley-McNeil test statistic) will serve as the primary outcome.	Repeated measurements throughout ECMO therapy (duration ranging from a few days to up to 24 weeks) and within up to 7 days after ECMO removal. Separate analysis for controlled and assisted mechanical ventilation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic performance (receiver operating characteristic (ROC) area under the curve) of an inspiratory and expiratory occlusion test in conjunction with pulse contour analysis for the prediction of fluid responsiveness during ECMO.	Cardiac Output (L/min) will be measured using calibrated and uncalibrated pulse contour analysis before, during, and after an end-inspiratory and end-expiratory occlusion test (15 s), as well as after administration of a fluid bolus of 500 ml balanced crystalloids over 15-20 min. A cardiac output increase of > 15% after fluid infusion will be the cut-off for defining fluid responsiveness. Receiver operating characteristic (ROC) curves will be generated to assess the performance of the end-inspiratory and end-expiratory occlusion tests and the best threshold for predicting fluid responsiveness during ECMO.	Repeated measurements throughout ECMO therapy (duration ranging from a few days to several weeks) and within a few days after ECMO removal. Separate analysis for controlled and assisted mechanical ventilation.
Changes of cardiac output (L/min) over the course of ECMO therapy	Cardiac output (L/min) will be measured at different time points (at least at the beginning of ECMO therapy and after ECMO removal) throughout ECMO therapy using transthoracic echocardiography, uncalibrated pulse contour analysis, and thermodilution.	Repeated measurements throughout ECMO therapy (duration ranging from a few days to up to 24 weeks) and within up to 7 days after ECMO removal.
Changes of tricuspid annular plane systolic excursion (TAPSE, mm) over the course of ECMO therapy	Tricuspid annular plane systolic excursion (TAPSE, mm) will be measured at different time points (at least at the beginning of ECMO therapy and after ECMO removal) throughout ECMO therapy using transthoracic echocardiography.	Repeated measurements throughout ECMO therapy (duration ranging from a few days to up to 24 weeks) and within up to 7 days after ECMO removal.
Changes of tissue doppler imaging tricuspid annular velocity (cm/s) over the course of ECMO therapy	Tissue doppler imaging tricuspid annular velocity (cm/s) will be measured at different time points (at least at the beginning of ECMO therapy and after ECMO removal) throughout ECMO therapy using transthoracic echocardiography.	Repeated measurements throughout ECMO therapy (duration ranging from a few days to up to 24 weeks) and within up to 7 days after ECMO removal.
Changes in cardiac output (L/min, measured by transthoracic echocardiography, uncalibrated pulse contour analysis, thermodilution) at different ECMO blood flow rates	During the first days of VA ECMO therapy, cardiac output (L/min) will be measured repeatedly at different ECMO blood flow rates (baseline blood flow, blood flow reduced by 1 l/min, return to baseline blood flow, blood flow increased by 1 l/min) using transthoracic echocardiography, uncalibrated pulse contour analysis, and thermodilution.	During the first (up to 7) days of VA ECMO therapy.

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: May 3, 2024
• First Submitted That Met QC Criteria: September 10, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: ARDS; Stroke Volume; Cardiac Output; Extracorporeal Membrane Oxygenation; Fluid Responsiveness; Critical Care Medicine; Hemodynamic Monitoring; Pulse Pressure Variation; Intensive Care Medicine; Transpulmonary Thermodilution; Pulse Contour Analysis; VV ECMO; Passive Leg Raising; Bioreactance; End-expiratory Occlusion Test; End-inspiratory Occlusion Test; LVOT VTI; Vena Cava Ultrasound
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Imaging; Diagnostic Techniques, Cardiovascular; Heart Function Tests; Cardiac Imaging Techniques; Ultrasonography; Echocardiography
• Other Study ID Numbers: 1613/2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data that underlie results in a publication may be provided to qualified researchers with academic interest in hemodynamic monitoring. Data or samples shared will be coded, with no PHI included.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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