Estimated Oxygen Extraction Versus Dynamic Parameters for Perioperative Hemodynamic Optimization

Study Overview
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Brief Summary
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The aim of the study is to evaluate the complications rate of high risk patients undergoing non-cardiac surgery that receive two different protocols of hemodynamic optimization. A group of patients receive a protocol based on dynamic parameters of fluid responsiveness; the other group of patients receive a protocol based of the optimization of oxygen extraction. The hypothesis is that a perioperative hemodynamic optimization protocol based on oxygen extraction is not inferior to a protocol based on dynamic parameters of fluid responsiveness considering the complication rate developed postoperatively.

Detailed Description
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Any surgical intervention is a trauma for the organism and a stress response is activated to cope the external insult. This stress response is responsible of an increase in oxygen consumption. If patient is not able to overcome the deficit in oxygen consumption (VO2) during the first hours postoperatively, he/she will go toward complications (in case of delay to meet metabolic demand) or death (in case of persistent VO2 deficit). Therefore, several protocols have been developed to optimise haemodynamic parameters with the aim to reduce tissue hypoperfusion coming from maldistribution or inadequate perfusion and meet the increased metabolic need as soon as possible. Every patient that probably will not be able to face the surgical stress himself might benefit from modulation of haemodynamic parameters. Actually, goal directed therapy (GDT) is able to improve survival only in high-risk surgical patients. Instead, the reduction of complications rate has been shown also in intermediate-risk population. Originally, hemodynamic optimisation protocols were developed to reach supranormal value for cardiac output (CO), oxygen delivery (DO2) and VO2. Based on the concept that oxygen extraction rate (O2ER) reflects the balance between DO2 and VO2, a GDT protocol based on O2ER estimation (O2ERe) calculated as (SaO2-ScvO2)/SaO2 has been proposed showing a significantly lower number of organ failure postoperatively compared with control group. The major determinants of DO2 are cardiac output (CO), haemoglobin level (Hb) and arterial oxygen saturation (SaO2). An inadequate CO may be optimised using fluids as first line therapy and then inotropes. In mechanically ventilated patients, heart-lung interaction is useful to recognise in which portion of the Frank-Starling curve the heart of the patient is working and then if CO is able to rise after fluid administration aimed to increase preload. Several parameters based on mini-invasive monitor systems are available to assess fluid responsiveness such as pulse pressure variation (PPV) and stroke volume variation (SVV).

Official Title
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Estimated Oxygen Extraction Versus Dynamic Parameters for Perioperative Hemodynamic Optimization of Patients Undergoing Non-cardiac Surgery: a Non-inferiority Randomized Controlled Trial

Conditions
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Perioperative/Postoperative Complications, Morality

Intervention / Treatment
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* Diagnostic Test: Dynamic parameters of fluid responsiveness protocol
* Diagnostic Test: Estimated oxygen extraction protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients undergoing general anesthesia and mechanical ventilation for elective major open abdominal surgery (gastrointestinal, urologic, gynecologic and vascular surgery) expected duration of surgical procedure higher than 120 minutes ASA II-III-IV planned postoperative ICU/HDU admission Exclusion Criteria: <18 years old pregnancy arrhythmia arterial curve alteration (resonance, damping) not solvable palliative surgical procedures denial of consent

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Estimated Oxygen Extraction<br> | Diagnostic Test: Estimated oxygen extraction protocol<br>* Oxygen extraction is estimated by the difference of arterial oxygen saturation and central venous oxygen saturation divided by arterial oxygen saturation. A cutoff of 27% is used as a marker of inadequate tissue perfusion requiring hemodynamic optimization.<br>|
| Active Comparator: Dynamic Parameters<br> | Diagnostic Test: Dynamic parameters of fluid responsiveness protocol<br>* Dynamic parameter of fluid responsiveness (pulse pressure variation/stroke volume variation) are used to optimize hemodynamics intraoperatively and during the first 6 hours postoperatively when appropriate. A cutoff of 12% is used to predict an increase of stroke volume >10% after fluid administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complications rate | Evaluate the difference of postoperative complications rate between the two groups | From date of randomization until the date of hospital discharge assessed up to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluid administered | Evaluate the difference of total amount of fluids administered during the perioperative period between the two groups | Immediately after the surgery, 6 hours postoperatively and at the date of ICU/HDU discharge assessed up to 90 days | 
| Fluid balance | Evaluate the difference of fluid balance (difference between fluid administered and fluid loss) during postoperative period between the two groups | Immediately after the surgery, 6 hours postoperatively and at the date of ICU/HDU discharge assessed up to 90 days | 
| Vasopressor/inopropic drugs | Evaluate the difference in needs of vasopressor/inotropic drugs (reporting mean dosage used) between the two groups | Immediately after the, 6 hours postoperatively and at the date of ICU/HDU discharge assessed up to 90 days | 
| Hospital length of stay | Evaluate the difference of total number of days of hospital stay between the two groups | From date of randomization until the date of hospital discharge or death from any cause assessed up to 90 days | 
| Mortality at day 28 | Evaluate the difference of mortality rate at day 28 between the two groups | Day 28 from randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peri-operative goal-directed therapy, Hemodynamic optimization, Postoperative complications, Mortality