Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04984603
Other study ID # RECHMPL19_0616
Secondary ID
Status Active, not recruiting
Phase
First received
Last updated
Start date February 1, 2020
Est. completion date June 1, 2022

Study information

Verified date November 2021
Source University Hospital, Montpellier
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Peripheral Veno-Arterial Extra Corporeal Membrane Oxygenation (VA ECMO) is a temporary assistance that provides a mechanical circulatory support in patients victim of cardiogenic shock (CS) or refractory cardiac arrest. During VA-ECMO support, hypotension may frequently occur due to deteriorated cardiac function, vasoplegia, or hypovolemia. Volume expansion is a common means to correct hypotension and improve systemic perfusion, but inappropriate fluid therapy is associated with adverse outcomes. As other intensive care unit (ICU) patients, VA-ECMO assisted patients have been shown to have higher mortality in case of large early fluid administration. Prediction of fluid responsiveness could achieve a lower fluid balance and improve outcomes of patients treated with VA-ECMO. Several dynamic hemodynamic parameters based on cardio-pulmonary interactions (stroke volume, pulse pressure or inferior vena cava variations induced by invasive ventilation cycles) have been described and validated for predicting fluid responsiveness in critically ill patients. Unfortunately, the VA-ECMO conditions (native cardiac circulation by-pass, low pulsatility, presence of drainage canulation in the inferior vena cava, the use of low tidal volume) make this parameters less reliable. Simulation of a fluid loading by shifting blood from the lower limbs and splanchnic compartment thanks to a revisable maneuver is another feasible approach to assess fluid responsiveness. Whereas the use of different maneuvers have been validated in the classical ICU population, very few data exist in the ECMO population and their application is questioning because blood transfer may be modified by the preload dependence of the ECMO. Recently, Luo et al showed that the variation of aortic Velocity Time Integral (VTI) measured using echocardiography induced by a Trendelenburg maneuver was predictive of fluid responsiveness during VA-ECMO support. However, their study excluded patients with low cardiac ejection (pulse pressure < 15 mmHg) so that their data may not be extrapolated to the acute phase of heart failure requiring full mechanical support. Moreover, aortic VTI measurement suffers from low reproducibility in case of low native cardiac output (NCO) and arrythmia; and can be time-consuming. The investigators previously demonstrated in an observational prospective study that End-tidal CO2 (EtCO2) and Pulse Pressure (PP) were strongly correlated to NCO during VA-ECMO when NCO < 2l/min. The investigators aim to study the variations of aortic VTI, EtCO2 and PP induced by Passive Leg Rising (PLR) and their ability to predict fluid responsiveness in patients under VA-ECMO.


Description:

Settings : This prospective non interventional study is conducted since february 2020 in the investigators' ICU and has been approved by their hospital's institutional review board. Informed consent is obtained from all patients or their surrogates. Patients : All patients who receive VA-ECMO support and mechanical ventilation for refractory cardiogenic shock or cardiac arrest of any etiology (acute myocardial infarction, end-stage dilated cardiomyopathy, heart surgery, fulminant myocarditis…) are screened. Patients conditioning : Patients are sedated by propofol/dexmedetomidine and sufentanyl and under invasive mechanical ventilation. Continuous blood pressure is monitored via a radial arterial catheter. PP is defined as systolic arterial pressure-diastolic arterial pressure. Central venous catheter is placed at the upper body for central venous oxygen saturation (ScVO2) monitoring. Lung ventilation is managed with low levels of respiratory rate (10-14 breaths/min) and tidal volume (4-6mL/ kg), and with a modest level of positive end- expiratory pressure (8-10 cmH2O) to ensure protective ventilation. EtCO2 is measured noninvasively from exhaled breath on a ventilator circuit and monitored using a ventilator CO2 analyzer (Maquet servo U, Drager Evita Infinity V500). ECMO circuit settings and patients management under ECMO : VA-ECMO consist of polyvinyl chloride tubing with a membrane oxygenator (PH.I.S.I.O and EOS; Sorin Group, Clamart, France), a centrifugal pump (Stockert; Sorin Group), and percutaneous or surgically inserted arterial and venous femoral cannulae (Fem-Flex and Fem-Track, Edwards Life- sciences, Guyancourt, France) with or without an additional 7 F cannula inserted distally into the femoral artery to prevent lower limb ischemia. An oxygen-air blender (Sechrist Industries, Anaheim, CA) ventilate the membrane oxygenator. Unfractionated heparin is administrated to maintain an anti-factor-Xa activity of between 0.2 and 0.3 IU/mL. In the initial phase of the circulatory assistance, VA-ECMO flow is set to provide adequate tissue perfusion (ScVO2 ≥ 65%) and to obtain correction of metabolic acidosis (serum lactate clearance). Thereafter, the VA-ECMO flow is set at the lowest rate necessary to ensure adequate tissue perfusion, while the highest NCO is wanted. Respiratory minute ventilation and ECMO sweep gas flow are adjusted to maintain baseline PaCO2 in a normal range, of around 40 mmHg. Protocol : Following data are recorded before inclusion : - Age, gender, weight. - VA-ECMO indication and reason to perform vascular expansion - Vasopressive support : noradrenaline mg/h, dobutamine mg/h; inhaled nitric oxyde. - Richmond agitation-Sedation scale (RASS) and Behavioral Pain Scale (BPS) levels. - Ventilatory settings : tidal volume, positive end-expiratory pressure. Protocol steps : The protocol include four sequential steps : 1. Baseline position: semirecumbent position (45°) 2. Supine position with a 0° angulation 3. Passive leg raising (after securing of VA ECMO tubing) : using an automatic bed elevation technique, the lower limbs are raised to a 45° angle while the patient's trunk is lowered in supine position 4. Return to baseline and realization of a fluid challenge (administration of 500 mL of isotonic saline serum over 15 min). Data collection : All following data are recorded after 1 minute of stabilization at step 1, 3 and at the end of step 4 : - Clinical data : heart rate, systolic, diastolic, mean and pulse arterial pressures, EtCO2. - Doppler echocardiography (transthoracic or trans-esophageal) data : E and A waves measured with mitral inflow Doppler (ratio E/A), Velocity Time Integral (VTI) at the level of the left ventricular outflow, using the 5-chamber apical view. Three consecutive measurements are recorded to calculate a mean VTI value. - ECMO data : pump outflow (PO, in mL/min), pump rotation speed (round/min). Left ventricular outflow tract (LVOT) diameter is measured by echocardiography at step 1 Central venous pressure is measured at step 2 and 3 Tele-expiratory inferior vena cava diameter is measured at step 1 and 3 Statistical analysis : Categorical variables (expressed as absolute value and percentage) will be compared using the chi-squared test. Continuous variables (expressed as median [25th-75th percentile]) will be compared with Student's t test or the Mann-Whitney U test, as appropriate according to the normality distribution assessed graphically. Fluid responsiveness will be defined by a 15% increase of aortic VTI (ΔVTI>15%) between step 1 (half sitting position) and the end of step 4 (after fluid expansion). Linear regression analysis will be used to demonstrate relationships between percent change of VTI (ΔVTI), PP (ΔPP), EtCO2 (ΔEtCO2) induced by PLR maneuver and fluid challenge. Receiver Operating Characteristic (ROC) curves will be generated to evaluate percent changes in VTI, PP and EtCO2 induced by the PLR maneuver to predicts fluid responsiveness. The area under ROC curve will be compared using the DeLong test. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and associated 95% confidence intervals (CI) will be calculated based on the cutoff value as determined by the Youden Index (specificity+sensitivity - 1). Statistical significance will be defined as p <0.05.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 60
Est. completion date June 1, 2022
Est. primary completion date September 1, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility All patients who receive VA-ECMO support and mechanical ventilation for refractory cardiogenic shock or cardiac arrest of any etiology (acute myocardial infarction, end-stage dilated cardiomyopathy, heart surgery, fulminant myocarditis…) are screened. Inclusion criteria are: Decision to perform volume expansion made by the attending physician for one of the following reasons: - Hypotension or attempt to reduce vasopressor dose - Hypoperfusion (oliguria, skin mottling, hyperlactatemia) - Suspected Low NCO Exclusion criteria are - Age less than 18 years - Evidence of significant hypovolemia such as kicking drainage cannula - Active hemorrhage - Concomitant left ventricle assist device (Impella/ LVAD) or Intra-aortic balloon pump (IABP) - Atrial or ventricular communication - Significant aortic insufficiency - Unsatisfactory cardiac echogenicity (an inability to correctly align the Doppler beam to generate reliable VTI measurements at the left ventricular outflow tract (LVOT)

Study Design


Related Conditions & MeSH terms


Intervention

Procedure:
PLR in patients under VA-ECMO
After securing the VA-ECMO tubing, PLR is realized using an automatic bed elevation technique. The lower limbs are raised to a 45° angle while the patient's trunk is lowered in supine position

Locations

Country Name City State
France Uhmontpellier Montpellier

Sponsors (1)

Lead Sponsor Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Correlation between VTI changes induced by PLR and VTI changes induced by fluid challenge VTI variations induced by PLR vs VTI variations induced by fluid challenge During VA-ECMO support (<28 days)
Secondary Correlation between EtCO2 changes induced by PLR and EtCO2 changes induced by fluid challenge EtCO2 variations induced by PLR vs EtCO2 variations induced by fluid challenge During VA-ECMO support (<28 days)
Secondary Correlation between PP changes induced by PLR and PP changes induced by fluid challenge PP variations induced by PLR vs PP variations induced by fluid challenge During VA-ECMO support (<28 days)
See also
  Status Clinical Trial Phase
Recruiting NCT03283995 - Hemodynamic Assessment in Cardiogenic Shock Regarding the Etiology
Active, not recruiting NCT04325035 - The Safety and Efficacy of Istaroxime for Pre-Cardiogenic Shock Phase 2
Active, not recruiting NCT05100836 - SURPASS Impella 5.5 Study
Not yet recruiting NCT05106491 - Efficacy and Safety of Synchronized Cardiac Support in Cardiogenic Shock Patients N/A
Completed NCT02301819 - ExtraCorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock N/A
Completed NCT01367743 - Study Comparing the Efficacy and Tolerability of Epinephrine and Norepinephrine in Cardiogenic Shock Phase 4
Recruiting NCT05728359 - Genomic Determinants of Outcome in Cardiogenic Shock
Recruiting NCT05699005 - Individualized or Conventional Transfusion Strategies During Peripheral VA-ECMO Phase 1
Not yet recruiting NCT06338345 - Pharmacokinetics and Modelling of Beta-Lactam in ECMO-VA Patients N/A
Completed NCT03436641 - Microcirculation in Cardiogenic Shock
Recruiting NCT03313687 - SafeTy and Outcome of contemPorary Treatment Strategies for Cardiogenic SHOCK
Recruiting NCT05506449 - The RECOVER IV Trial N/A
Completed NCT04144660 - "Treatment Use of ECMO In Pregnancy or Peripartum Patient."
Completed NCT04548739 - Cerebral Autoregulation in Pediatric ECMO (ECMOX 2)
Recruiting NCT04141410 - Global Longitudinal Strain Assessment in Cardiogenic Shock During Sepsis
Not yet recruiting NCT05879276 - Effect at 3 Months of Early Empagliflozin Initiation in Cardiogenic Shock Patients on Mortality, Rehospitalization, Left Ventricular Ejection Fraction and Renal Function. Phase 3
Enrolling by invitation NCT05570864 - Score TO Predict SHOCK - STOP SHOCK
Completed NCT02591771 - Study of Multistep Pharmacological and Invasive Management for Cardiogenic Shock Phase 2
Terminated NCT02279979 - Thoratec Corporation HeartMate PHP™ Cardiogenic Shock Trial N/A
Completed NCT01374867 - CardShock Study and Registry N/A