Healthy Adult, Cardiac Output, Hemodynamic, Passive Leg Raising
Conditions
Keywords
Passive leg raising, Cardiac Ouptut, Thoracic Bioreactance, Noninvasive Ventilation
Brief summary
Passive leg raising (PLR) transiently increases venous return and cardiac preload and is commonly used to predict fluid responsiveness in critically ill patients. Repeated fluid boluses contribute to fluid overload in septic shock, whereas PLR may provide similar hemodynamic effects without fluid administration. Before evaluating repeated PLR in septic shock patients, it is necessary to determine whether the cardiac output response to PLR remains present during repeated PLR maneuvers. SYSLE-1 is a prospective interventional physiological crossover study conducted in healthy volunteers. Participants will undergo six consecutive passive leg raising sessions performed either during spontaneous breathing or non-invasive ventilation, in randomized order. The study aims to determine whether the increase in cardiac output induced by the first PLR maneuver persists during repeated PLR sessions.
Detailed description
The passive leg raising maneuver induces a reversible transfer of venous blood from the lower extremities toward the thoracic compartment, thereby increasing cardiac preload. In preload-dependent individuals, PLR increases stroke volume and cardiac output without administration of intravenous fluids. In septic shock, repeated fluid challenges remain common during the first days of management but may contribute to positive fluid balance, tissue edema, organ dysfunction, and increased mortality. Since the hemodynamic effects of PLR resemble those of a fluid challenge while avoiding fluid administration, repeated PLR maneuvers could represent an alternative strategy for improving preload and cardiac output. The SYSLE-1 study is designed as the first phase of a broader research program aimed at evaluating repeated PLR in septic shock patients. The present study investigates whether the cardiac output response to PLR remains preserved during six repeated PLR sessions in healthy volunteers. Participants will complete two study days in randomized order: one under spontaneous breathing and one under non-invasive ventilation. During each study day, six PLR sessions lasting 10 minutes each will be performed and separated by 50-minute recovery periods in a semi-recumbent position. Cardiac output measured by thoracic bioreactance is the primary endpoint. Additional physiological measurements include arterial pressure, heart rate variability, brachial artery diameter, cardiac output measured using pulse contour analysis and echocardiography, end-tidal carbon dioxide, comfort assessments, and safety outcomes.
Interventions
PROCEDUREPassive Leg Raising
Passive leg raising is performed using an electrically operated hospital bed to move participants from a semi-recumbent position (30° trunk elevation) to a position with the trunk horizontal and legs elevated at 45°. Each maneuver lasts 10 minutes and is repeated six times at hourly intervals.
PROCEDURENon-Invasive Ventilation
Non-invasive ventilation is delivered via an oronasal mask using a critical care ventilator. NIV is applied for 5 minutes before passive leg raising, throughout the 10-minute maneuver, and for 5 minutes after return to the semi-recumbent position, resulting in six repeated 20-minute NIV periods during the study day. Ventilator settings: FiO2 21%, initial PEEP 5 cmH2O (adjustable down to 2 cmH2O for tolerance), and pressure support 0-5 cmH2O, titrated to avoid a tidal volume \>15 mL/kg predicted body weight (target 8-12 mL/kg).
Sponsors
Centre Hospitalier Régional d'Orléans
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Participants will undergo two study periods in randomized order. During one study day, passive leg raising sessions will be performed during spontaneous breathing. During the other study day, the same sessions will be performed under non-invasive ventilation. A washout period of at least 24 hours and up to 10 days separates study days.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female participant. * Age 18 years or older. * Healthy volunteer without known acute or chronic disease. * No significant cardiovascular or respiratory disease. * No medication use within 10 days before the first study day (except oral contraceptives). * Intact upper and lower limbs. * Written informed consent.
Exclusion criteria
* Body mass index greater than 35 kg/m². * Use of illicit psychoactive substances within the previous 3 months. * Congenital or acquired absence of part or all of an upper or lower limb. * Known allergy to hydrocolloid dressings. * Pregnant or breastfeeding women. * Under guardianship, curatorship, or legal protection. * Deprived of liberty. * Not affiliated with a health insurance system. * Participation in another drug study during an exclusion period. * Member of the Lieu de Recherches Interventionnelles sur la Personne Humaine (LRIPH) or Intensive Care Unit staff. * Refusal to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in cardiac output during the sixth passive leg raising session compared with the first passive leg raising session, for each day of study procedure | During study procedures on Days 1 and 2 (up to 10 days apart). From enrollment to the end of study (day 2) at 3 months maximum. | Cardiac output measured every minute using thoracic bioreactance. The study will assess whether the increase in cardiac output during the sixth PLR session is non-inferior to 30% of the increase observed during the first PLR session. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in cardiac output response across PLR sessions 1 to 6. | During each study day, across six passive leg raising sessions performed over approximately 6 hours. From enrollment to the end of study (day 2) at 3 months maximum. | Change in cardiac output measured by thoracic bioreactance during each passive leg raising session. Cardiac output changes observed during sessions 1 through 6 will be described and compared. |
| Effect of ventilation mode on cardiac output response to passive leg raising | During the two study days (up to 10 days apart). From enrollment to the end of study (day 2) at 3 months maximum. | Comparison of the increase in cardiac output induced by passive leg raising between spontaneous breathing sessions and non-invasive ventilation sessions using thoracic bioreactance measurements. |
| Cardiac output evolution during passive leg raising | During each 10-minute passive leg raising session. From enrollment to the end of study (day 2) at 3 months maximum | Minute-by-minute cardiac output measured by thoracic bioreactance during passive leg raising to characterize the temporal profile of the hemodynamic response. |
| Effect of ventilation mode on cardiac output evolution during passive leg raising | During each 10-minute passive leg raising session on both study days. From enrollment to the end of study (day 2) at 3 months maximum. | Comparison of cardiac output trajectories measured during passive leg raising under spontaneous breathing and non-invasive ventilation. |
| Cardiac output recovery after passive leg raising | During the 50-minute recovery period following each passive leg raising session. From enrollment to the end of study (day 2) at 3 months maximum. | Evolution of cardiac output after returning from passive leg raising to the semi-recumbent position, assessed using thoracic bioreactance. |
| LF/HF ratio derived from heart rate variability. | During each study day, across six passive leg raising sessions (approximately 6 hours). From enrollment to the end of study (day 2) at 3 months maximum. | Changes in the low-frequency to high-frequency (LF/HF) ratio derived from heart rate variability analysis as an indicator of autonomic nervous system activity during repeated passive leg raising sessions |
| Change in brachial artery diameter measured by ultrasound. | Measured before, during, and near the end of each passive leg raising session during both study days. From enrollment to the end of study (day 2) at 3 months maximum. | Brachial artery diameter assessed by ultrasound to characterize vasomotor responses associated with passive leg raising. |
| Agreement between cardiac output measurement methods (bioreactance, Clearsight®, echocardiography). | During each study day, across all passive leg raising sessions. From enrollment to the end of study (day 2) at 3 months maximum. | Comparison of cardiac output measurements obtained by thoracic bioreactance, pulse contour analysis (Clearsight®), and transthoracic echocardiography. |
| Agreement between blood pressure measurement methods (oscillometry and Clearsight®). | During each study day, across all passive leg raising sessions. From enrollment to the end of study (day 2) at 3 months maximum. | Comparison of systolic, diastolic, and mean arterial pressure measurements obtained by automated oscillometry and the Clearsight® system |
| Correlation between end-tidal carbon dioxide and cardiac output during non-invasive ventilation | During the non-invasive ventilation study day (approximately 6 hours). From enrollment to the end of study (day 2) at 3 months maximum. | Correlation between minute-by-minute end-tidal carbon dioxide values and cardiac output measured by thoracic bioreactance during passive leg raising sessions performed under non-invasive ventilation |
| Participant-reported discomfort,. | Assessed during and after each passive leg raising session on both study days (approximately 6 hours / study day). From enrollment to the end of study (day 2) at 3 months maximum. Scale from 0 to 10: 0 no discomfort and 10 worst imaginable discomfort. | Participant ratings of discomfort using an 11-point numerical rating scale during study procedures and non-invasive ventilation exposure. |
| Participant-reported respiratory difficulty. | Assessed during and after each passive leg raising session on both study days (approximately 6 hours per study day). From enrollment to the end of study (day 2) at 3 months maximum. Scale from 0 to 10: 0 no difficulty and 10 worst imaginable difficulty. | Participant ratings of breathing difficulty using an 11-point numerical rating scale during study procedures and non-invasive ventilation exposure. |
| Participant-reported pain. | Assessed during and after each passive leg raising session on both study days (approximately 6 hours per study day). From enrollment to the end of study (day 2) at 3 months maximum. Scale from 0 to 10: 0 no pain and 10 worst imaginable pain. | Participant ratings of pain using an 11-point numerical rating scale during study procedures and non-invasive ventilation exposure. |
Countries
France
Contacts
CONTACTMai-Anh PhD NAY, Physician
CONTACTFanny LOUAT
PRINCIPAL_INVESTIGATORMai-Anh PhD NAY, Physician
Centre Hospitalier Régional d'Orléans
Outcome results
None listed