An observational study in Circulatory Failure, Critical Illness and Hypovolemia, sponsored by Izmir Katip Celebi University. Recruiting at 1 site in Turkey (Türkiye). Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-04.
Sponsored by Izmir Katip Celebi University · Observational
This prospective observational study evaluates whether monitoring changes in exhaled carbon dioxide (End-Tidal CO2 or EtCO2) during a "Passive Leg Raising" (PLR) test can reliably predict fluid responsiveness in critically ill patients.
In the Intensive Care Unit (ICU), fluid management is a critical balance; while fluid is necessary for tissue perfusion, overload can lead to severe complications. Traditional static measurements (like central venous pressure) are often unreliable for guiding therapy. Dynamic tests like PLR are preferred as they simulate a fluid bolus reversibly by shifting blood from the legs to the heart.
Researchers will observe mechanically ventilated patients planned for fluid resuscitation. The study compares the accuracy of non-invasive EtCO2 changes during PLR against a reference standard "Mini Fluid Challenge" (100 mL fluid administration). Fluid responsiveness will be confirmed using echocardiographic measurements (LVOT-VTI) or arterial pressure changes. The goal is to validate EtCO2 as a practical, real-time tool for safe fluid management.
Fluid management is the cornerstone of hemodynamic stabilization in ICU patients with circulatory failure. However, distinguishing between patients who will benefit from fluid (responders) and those who will not is vital to prevent the high mortality associated with inappropriate fluid administration.Static parameters (e.g., CVP, MAP) fail to reliably predict fluid responsiveness. Dynamic parameters are superior but have limitations, such as dependence on regular heart rhythm and specific ventilation settings. Consequently, interest has shifted toward non-invasive surrogates for cardiac output, such as End-Tidal CO2 (EtCO2), which tracks pulmonary blood flow changes under constant ventilation. This study investigates whether Delta EtCO2 during a PLR maneuver can accurately predict the response to a fluid challenge. The primary objective is to determine the diagnostic accuracy of Delta EtCO2 during PLR. Its predictive value will be validated against the hemodynamic response to a Mini Fluid Challenge (MFC), serving as the reference method. This prospective, single-center, observational cohort study includes adult patients in the ICU receiving mechanical ventilation who require fluid resuscitation.
Passive Leg Raising (PLR) Test: The patient starts in a semi-recumbent position (45°). They are then moved to a supine position with legs raised to 45° without manual handling to avoid sympathetic stimulation. This auto-transfuses blood from the lower body to the central circulation, increasing preload.
Mini Fluid Challenge (MFC): Following PLR, 100 mL of crystalloid fluid is infused intravenously over approximately 1 minute.
Definition of Fluid Responsiveness (Reference Standard): An increase in Left Ventricular Outflow Tract Velocity Time Integral (LVOT-VTI) of >10% on echocardiography. If cardiac output/VTI cannot be assessed, responsiveness is defined as a Systolic Arterial Pressure increase of > 4%, a Pulse Pressure variation decrease of > 2%, or a Mean Arterial Pressure increase of > 15%.
The sample size was calculated using G*Power 3.1 software based on a pilot study of 6 patients. In the pilot study, Delta EtCO2 values were found to be 3.5±2.1 mmHg in the fluid responder group and 2.1±1.1 mmHg in the non-responder group. Based on these findings, with an effect size (Cohen's d) of 0.72, an alpha error level of 0.05, and a targeted power (1-beta) of 0.80, the required sample size was calculated. Accounting for a potential 10% attrition rate, the study is planned to be conducted with a total of 68 patients.
487 studies on the registry are indexed under Shock; 107 are open to participants now.
This study's planned enrollment of 68 is below the median of 100 across 247 observational studies indexed under Shock.
Browse Shock studies →Izmir Katip Celebi University is the lead sponsor of 198 studies on the registry; 39 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The study population consists of adult patients (aged 18 years or older) admitted to the Intensive Care Unit (ICU) of a university hospital. Eligible participants are those who have been receiving mechanical ventilation support for at least 24 hours and have been identified by the primary intensive care team as requiring a fluid responsiveness assessment via a mini fluid challenge. The cohort includes patients with circulatory failure or suspected hypovolemia where fluid resuscitation is clinically indicated. Patients with contraindications to passive leg raising (e.g., intracranial hypertension, deep vein thrombosis), spontaneous breathing, or severe cardiac valve pathologies are excluded.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients who demonstrate a significant hemodynamic improvement following the Mini Fluid Challenge (MFC. Defined as an increase in Left Ventricular Outflow Tract Velocity Time Integral (LVOT-VTI) of \>10%. If VTI unavailable, increase in Systolic Arterial Pressure \> 4%, Pulse Pressure variation decrease \> 2%, or Mean Arterial Pressure increase \> 15%.
Patients who do not demonstrate a significant hemodynamic improvement following the Mini Fluid Challenge (MFC). Defined as an increase in LVOT-VTI of \< 10% (or failure to meet the alternative blood pressure criteria).
Change in End-Tidal Carbon Dioxide (Delta EtCO2) during Passive Leg Raising (PLR)
The absolute difference in End-Tidal CO2 (EtCO2) levels will be calculated between the baseline measurement (T0, patient semi-recumbent at 45°) and the measurement taken during the Passive Leg Raising test (T1, patient supine with legs raised to 45°). The diagnostic accuracy of this Delta EtCO2 will be evaluated by comparing it against the patient's fluid responsiveness status (Responder vs. Non-Responder) determined by the subsequent Mini Fluid Challenge.
Time frame: Measured between 60 to 90 seconds after the position change.
Change in Arterial Blood Pressures (SAP, DAP, MAP)
Systolic (SAP), Diastolic (DAP), and Mean Arterial Pressure (MAP) will be monitored at baseline (T0) and during the PLR maneuver (T1). The changes in these pressures will be compared between the fluid responder and non-responder groups.
Time frame: Measured between 60 to 90 seconds after the position change.
Change in Heart Rate (Delta HR)
Heart rate will be monitored at baseline (T0) and during the PLR maneuver (T1). The absolute change (Delta HR) will be compared between the fluid responder and non-responder groups.
Time frame: Measured between 60 to 90 seconds after the position change.
Change in Pulse Pressure Variation (Delta PPV)
Pulse Pressure Variation (PPV) will be monitored at baseline (T0) and during the PLR maneuver (T1). The change in PPV will be compared between the fluid responder and non-responder groups.
Time frame: Measured between 60 to 90 seconds after the position change.
Change in Oxygen Saturation (Delta SO2)
Oxygen Saturation (SO2) will be monitored at baseline (T0) and during the PLR maneuver (T1). The change will be compared between the fluid responder and non-responder groups.
Time frame: Measured between 60 to 90 seconds after the position change.
Change in Vena Cava Inferior (VCI) Distensibility Index
The VCI diameter will be measured using ultrasonography during inspiration and expiration at baseline (T0) and during the PLR maneuver (T1). The VCI distensibility index will be calculated and its change compared between the groups.
Time frame: Measured between 60 to 90 seconds after the position change.
Change in Left Ventricular Outflow Tract Velocity Time Integral (LVOT-VTI)
This is the reference standard used to classify patients. Following the Mini Fluid Challenge (100ml crystalloid over 1 min), the percentage change in LVOT-VTI is measured. An increase of \>10% defines the patient as a "Fluid Responder".
Time frame: Immediately following the 1-minute Mini Fluid Challenge.
Plan to share: Undecided — All data necessary to support the study protocol, including de-identified individual participant data (IPD) related to study protocol, and primary and secondary outcome measures, will be made available upon reasonable request from qualified researchers for academic purposes, in accordance with institutional and ethical guidelines.
No publications or documents are linked to this record.
Started Jan 2026 (actual). Primary completion is estimated for Jan 2027, 12 months after the start.
Of 120 non-industry observational studies under Shock, half reached primary completion within 26 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 52. This study's planned 12 months is below that.
Counting every sponsor, half of 127 studies reached it within 26 months; a quarter within 12 and three quarters within 52.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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