Role of End-Tidal CO2 During Passive Leg Raising to Predict Fluid Responsiveness in ICU

The Role of End-Tidal Carbon Dioxide Changes During Passive Leg Raising in Predicting Fluid Responsiveness for Mechanically Ventilated Patients in the Intensive Care Unit: A Prospective Observational Study

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.

Inclusion Criteria:

• Patients aged 18 years or older.
• Patients who have been followed in the intensive care unit (ICU) with mechanical ventilation support for at least 24 hours.
• Patients for whom a mini fluid challenge (MFC) is clinically planned by the intensive care team.
• Patients for whom informed consent has been obtained from first-degree relatives or a legal representative.

Exclusion Criteria:

• Patients younger than 18 years of age.
• Pregnant patients.
• Patients without consent from first-degree relatives or a legal representative.
• Patients with known deep vein thrombosis (DVT) in the leg veins (risk of embolism during leg raising).
• Patients with pathologies that may cause increased intracranial pressure (e.g., intracranial mass, hemorrhage).
• Patients with uncontrolled hypertension.
• Patients with severe cardiac disease (e.g., right heart failure, pulmonary hypertension, advanced valvular pathology).
• Patients with carbon dioxide (CO2) retention.
• Patients who have undergone hip surgery or hip replacement surgery where Passive Leg Raising (PLR) cannot be performed.
• Patients with spontaneous breathing.
• Patients with a probability of high intra-abdominal pressure.
• Patients who cannot lie in a supine position.
• Patients with current peripheral oxygen saturation (SpO2) < 88%.
• Patients on mechanical ventilation requiring pressure support > 16 mmHg or PEEP > 10 mmHg.