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Hemodynamic instability remains one of the leading causes of morbidity and mortality among critically ill patients in intensive care units. One major contributor to this instability is intravascular fluid deficit. Although fluid administration is often preferred as an initial intervention, inaccurate estimation of fluid requirements carries significant risks. Inadequate resuscitation may lead to tissue hypoperfusion and organ dysfunction, whereas excessive fluid loading is associated with pulmonary edema, increased intra-abdominal pressure, multi-organ dysfunction, and increased mortality. Consequently, reliable prediction of fluid responsiveness is considered a critical determinant in modern intensive care management.
The limited reliability of static parameters in predicting fluid responsiveness and the fact that PPV retains its validity only under specific clinical conditions highlight the need for more effective methods. In recent years, hemodynamic changes assessed during the passive leg raising (PLR) maneuver have gained prominence; particularly, left ventricular outflow tract velocity time integral (LVOT VTI)-based cardiac output measurements have been identified as a strong parameter for predicting fluid responsiveness . Moreover, changes in pulse pressure variation (PPV) during PLR have also been reported as a potential predictor; however, the number of studies prospectively comparing PPV variation and LVOT VTI-based cardiac output change within the same patient population remains limited . Therefore, the proposed study aims to fill this gap in the literature and contribute to fluid management in the intensive care setting.
The aim of this study is to compare the performance of PPV variation and LVOT VTI-based cardiac output change after the PLR maneuver in predicting fluid responsiveness among mechanically ventilated critically ill patients, and to determine the diagnostic value of both methods. The findings of the present study are expected to support more reliable decision-making in fluid therapy and provide clinical evidence toward the individualization of fluid management in intensive care practice.
This study is designed as a prospective observational trial. No additional intervention, procedure, or treatment beyond standard clinical practice will be performed. All data will be obtained during routine clinical management in our intensive care unit.
In mechanically ventilated patients with suspected fluid deficit, the passive leg raising (PLR) maneuver is applied as part of standard practice, during which changes in pulse pressure variation (PPV) are recorded by invasive arterial monitoring.
In this observational study, transthoracic echocardiographic (TTE) measurements of LVOT VTI will be performed by an experienced operator in addition to routine practice. Using pulse wave Doppler (PW), LVOT VTI will be recorded, and stroke volume (SV) and cardiac output (CO) will be calculated by multiplying the LVOT VTI value by the LVOT diameter. Consequently, changes in PPV and LVOT VTI-based CO during PLR will be compared.
Following TTE measurements of LVOT VTI and LVOT diameter in both the semi-recumbent position (45°) and immediately after PLR, SV and CO will be calculated. Based on these measurements, patients will be allocated into two groups:
After grouping patients accordingly, PPV changes during PLR will be compared between the two groups. This will allow evaluation of the predictive performance of PPV variation relative to LVOT VTI-based CO change in determining fluid responsiveness. All measurements will be performed by an experienced clinician without disrupting standard patient care. No additional fluid loading, invasive procedures, or therapeutic interventions will be undertaken throughout the study.
The primary aim is to compare the diagnostic performance of PPV variation and LVOT VTI-based cardiac output changes following a PLR maneuver in predicting fluid responsiveness. The study seeks to determine the diagnostic value of both methods to support more individualised fluid management.
The recorded data will include:
Informed consent will be obtained from all participating patients or their legally authorized representatives.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fluid Responders | Defined as an increase in LVOT VTI-based Cardiac Output (CO) of ≥ 10% from baseline. | ||
| Fluid Non-Responders | Defined as an increase in LVOT VTI-based Cardiac Output (CO) of < 10% from baseline. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in Pulse Pressure Variation (Delta PPV) | Pulse Pressure Variation (PPV) is recorded via invasive arterial monitoring at baseline (T0, semi-sitting) and during the Passive Leg Raising maneuver (T1). | Baseline (T0) and between 60 seconds after the PLR maneuver. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change in Cardiac Output (Delta CO) | Cardiac Output (CO) is calculated using the Left Ventricular Outflow Tract Velocity Time Integral (LVOT VTI) and the LVOT diameter measured via transthoracic echocardiography. | Baseline (T0) and between 60 seconds after the PLR maneuver. |
| Correlation between Delta PPV and Delta CO |
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Inclusion Criteria:
Exclusion Criteria:
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The study population consists of adult critically ill patients admitted to the Intensive Care Unit (ICU) who are receiving mechanical ventilation support. Eligible participants are those identified by the intensive care team as having a suspected intravascular fluid deficit, for whom a fluid responsiveness assessment is clinically indicated. The cohort specifically targets patients undergoing the Passive Leg Raising (PLR) maneuver as part of routine standard practice, where invasive arterial monitoring is available to record Pulse Pressure Variation (PPV).
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Murat Aksun, M.D. | Contact | +90 552 363 16 14 | murataksun@yahoo.com | |
| Ahmet Salih Tüzen, M.D. | Contact | +90 535 391 55 77 | astuzen@icloud.com |
| Name | Affiliation | Role |
|---|---|---|
| Murat Aksun | Izmir Katip Celebi University Atatürk Training and Research Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Izmir Katip Celebi University Atatürk Training and Research Hospital İzmir, , Turkey | Izmir | Turkey (Türkiye) |
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.
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| ID | Term |
|---|---|
| D020896 | Hypovolemia |
| D016638 | Critical Illness |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020969 | Disease Attributes |
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Correlation Coefficient (r) between PPV Change and Cardiac Output Change |
| Baseline (T0) and between 60 seconds after the PLR maneuver. |
| Hemodynamic Parameter Changes (MAP, HR) | Measurement of changes in mean arterial pressure and heart rate before and after PLR and comparison between groups. | Baseline (T0) and between 60 seconds after the PLR maneuver. |
| Diagnostic Accuracy (ROC-AUC, Sensitivity, Specificity, Cut-off) | Evaluation of diagnostic performance of ΔPPV and ΔCO using receiver operating characteristic (ROC) analysis, including AUC, optimal cut-off value, sensitivity, and specificity for predicting fluid responsiveness. | Baseline (T0) and between 60 seconds after the PLR maneuver. |