Mini Fluid chAlleNge and End-expiratory Occlusion Test and to Assess flUid responsiVEness in opeRating Room

Study Overview
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Brief Summary
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End-expiratory occlusion test (EEOT) has been previously successfully tested in surgical patients, consisting of the interruption of the mechanical ventilation for 30 seconds, and in the evaluation of the changes in the SV. The mini fluid challenge test (mFC) aims at testing the increase in SV after the rapid administration of a small aliquot of the predefined FC. Both these test have been previously evaluated in small-sized studies and never compared each other.

Detailed Description
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Targeted fluid therapy has received increasing attention in the management of patients showing acute circulatory failure in both intensive care unit (ICU) and operating room (OR), aiming at preventing both inadequate tissue blood flow and fluid overload [1]. In fact, unnecessary fluid administration can increase morbidity and mortality and length of hospital stay of critically ill and surgical patients [2-10]. Since the only physiological reason to give a fluid challenge (FC) is to increase the stroke volume (SV) [11-13] and this effect is obtained only in about 50% of ICU and OR patients [14, 15], a vast literature investigated the possibility of predict this effect before FC administration, but the issue remains extremely challenging [1, 13, 16-18]. Bedside clinical signs and pressure and static volumetric static variables, do not predict fluid responsiveness [17]. Moreover, several physiological factors affect the reliability of the ventilator-induced dynamic changes in pulse pressure and stroke volume [pulse pressure variation (PPV) and stroke volume (SV) variation (SVV), respectively], and their echographic surrogates, in a significant number of ICU and OR patients [19-22]. To overcome these limitations, the functional hemodynamic assessment (i.e. the assessment of the dynamic interactions of hemodynamic variables in response to a defined perturbation), of fluid responsiveness has gained in popularity [17, 18, 23]. A functional hemodynamic test (FHT) consist in a manoeuvre determining a sudden change in cardiac function and/or heart lung interaction, affecting the hemodynamics of fluid responders and non-responders to a different extent [17, 18, 23]. The FHT called passive leg raising (PLR) has been successfully used for assessing the fluid responsiveness in ICU patients since 2009 [24] and its reliability has been confirmed by three large meta-analyses [25-27]. However, the PLR is not usually practicable in the OR. A lot of different FHTs have been proposed, as alternative to the PLR, in ICU and, more recently, OR. These tests could be basically subdivided in two groups. A subgroup of FHTs is based on sudden and brief variations of the mechanical ventilation to induce a change in right ventricle preload and/or after load and, as consequence, of left ventricle SV [24, 28]. Among these tests, the end-expiratory occlusion test (EEOT) has been previously successfully tested in surgical patients, consisting of the interruption of the mechanical ventilation for 30 seconds, and in the evaluation of the changes in the SV. A second subgroup aims at testing the increase in SV after the rapid administration of a small aliquot of the predefined FC [29, 30]. This test is called mini fluid challenge (mFC). Both these test have been previously evaluated in small-sized studies and never compared each other. The primary aim of the present study is to compare the reliability of EEOT and mFC in predicting fluid responsiveness in patients undergoing general surgery.

Official Title
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Mini Fluid chAlleNge and End-expiratory Occlusion Test and to Assess flUid responsiVEness in opeRating Room: an Open-label, Randomized Clinical Trial

Conditions
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Hemodynamic Instability, Anesthesia, Surgery

Intervention / Treatment
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* Diagnostic Test: End-expiratory occlusion test (EEOT)
* Other: mini fluid challenge (mFC)


Participation Criteria
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Eligibility Criteria
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All elective adults (age > 18 years) consecutive patients scheduled for elective abdominal surgery requiring invasive arterial monitoring and scheduled in those operating rooms equipped with ventilators having an expiratory-hold function. The preoperative exclusion criteria were 1) any recurrent cardiac arrhythmia; 2) known reduced left (ejection fraction < 30%) or right (systolic peak velocity of tricuspid annular motion < 0.17 m/s) ventricular systolic function; Body Mass Index > 35; 4) chronic obstructive pulmonary disease classified as GOLD ≥ 2. Once enrolled, the patient can be additionally excluded because of the occurrence of one of the following intraoperative conditions: 1) significant bleeding (more than 500 ml in ½ hour); 2) persistent and/or recurrent extrasystoles; 3) persistent low quality of the arterial signal despite optimization of the signal (see further).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: The study protocol was started during a period of intraoperative hemodynamic stability, as previously defined (i.e. change in mean arterial pressure of less than 10% during 5 minutes). The study protocol is was the following: 1) a set of measurements was recorded (T0) at a baseline ventilation of 7 ml/Kg and then the EEOT is performed by using the software function, expiratory hold, to interrupt mechanical ventilation; 2) after one minute a set of measurements was recorded (T1); 3) the mFC is then performed; 4) a FC of overall 4 mL/Kg of crystalloid solution is infused over 9 minutes (T2). The attending anesthetist is allowed to interrupt the protocol at any stage for either hemodynamic instability or any other adverse effects requiring urgent treatment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment - hemodynamic tests: EEOT and mFC<br>Interventions: all the enrolled patients will be tested using the EEOT and the mFC. | Diagnostic Test: End-expiratory occlusion test (EEOT)<br>* The EEOT is performed by interrupting the mechanical ventilation for 30 seconds, by using and end-expiratory hold on the ventilator.<br>Other: mini fluid challenge (mFC)<br>* The mFC is performed by injecting a first aliquot of 100 ml of crystalloid over 1 minute before completing the 4 ml/kg-FC over the residual 9 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ROC curve calculation | Calculation of the area under the ROC curve considering the response to the fluid challenge test (considered as gold standard). | 10 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ROC:Comparison of the areas under the ROC curve of each test (EEOT and mFC) | Comparison of the areas under the ROC curve of each test (EEOT and mFC) | 10 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mini Fluid Challenge, End-expiratory occlusion test, Fluid responsiveness, Functional Hemodynamic Test