Passive Leg Raising for Predicting Fluid Responsiveness in VA-ECMO Assisted Patients

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.