Individualized Hemodynamic Optimization by Indirect Measurement of the Respiratory Quotient in Major Surgery: Prospective Randomized Multicentre Open-Label Study (OPHIQUE) Individualized Optimization by Indirect Measurement of the Respiratory Quotient

Study Overview
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Brief Summary
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The measurement of the inspired / expired fractions in O2 and CO2 is part of the daily monitoring of the intubated-ventilated patient in the operating theater. The ratio of VCO2 to VO2 (respiratory quotient (RQ)) is a non-invasive indirect measure of anaerobic metabolism of the patient, and an indirect reflection of tissue perfusion. We hypothesize that a hemodynamic optimization in major surgery individualized by non-invasive continuous measurement of the RQ would optimize TaO2 more specifically by informing us about the installation of a VO2 dependence, and therefore of an anaerobic metabolism. Patients are randomized in 2 groups : Control group: hemodynamic management of patients is done according to usual practices by maintenance of blood pressure by norepinephrine as well as optimization of Systolic Voume (SV) by vascular filling and use of dobutamine if necessary. Experimental group: perioperative hemodynamic management is based on an algorithm that includes RQ measurement and includes volume expansion, norepinephrine, FiO2 enhancement, RBC transfusion and dobutamine. Primary and secondary outcomes are recorded 1,2,7 and 30 days after the surgery.

Detailed Description
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• Background : The measurement of the inspired / expired fractions in O2 and CO2 is part of the daily monitoring of the intubated-ventilated patient in the operating theater. Changes in EtCO2 may reflect changes in metabolic CO2 production (VCO2), and oxygen extraction from the body (SvO2). The inspired / exhaled oxygen difference is an indirect reflection of the oxygen consumption (VO2). The ratio of VCO2 to VO2 (respiratory quotient (RQ)) is a non-invasive indirect measure of anaerobic metabolism of the patient, and an indirect reflection of tissue perfusion. Some studies, including a recent one carried out by our center, showed that the RQ was linked to the appearance of anaerobic metabolism and to the postoperative evolution of the patient. The RQ was correlated with arterial lactate levels and predicted the occurrence of postoperative complications. Thus, the RQ can be a reliable, continuous, non-invasive marker of anaerobic metabolism in the operating room and therefore of the adequacy of arterial oxygen Transport (TaO2) with respect to the VO2 of the patient Purpose : Th investigators hypothesize that a hemodynamic optimization in major surgery individualized by non-invasive continuous measurement of the RQ would optimize TaO2 more specifically by informing us about the installation of a VO2 dependence, and therefore of an anaerobic metabolism. Brief summary: The measurement of the inspired / expired fractions in O2 and CO2 is part of the daily monitoring of the intubated-ventilated patient in the operating theater. The ratio of VCO2 to VO2 (respiratory quotient (RQ)) is a non-invasive indirect measure of anaerobic metabolism of the patient, and an indirect reflection of tissue perfusion. We hypothesize that a hemodynamic optimization in major surgery individualized by non-invasive continuous measurement of the RQ would optimize TaO2 more specifically by informing us about the installation of a VO2 dependence, and therefore of an anaerobic metabolism. Patients are randomized in 2 groups : Control group: hemodynamic management of patients is done according to usual practices by maintenance of blood pressure by norepinephrine as well as optimization of Systolic Voume (SV) by vascular filling and use of dobutamine if necessary. Experimental group: perioperative hemodynamic management is based on an algorithm that includes RQ measurement and includes volume expansion, norepinephrine, FiO2 enhancement, RBC transfusion and dobutamine. Primary and secondary outcomes are recorded 1,2,7 and 30 days after the surgery. Number of groups and description of groups : 2 groups Control group: hemodynamic management of patients is done according to usual practices by maintenance of blood pressure by norepinephrine as well as optimization of SV by vascular filling and use of dobutamine if necessary. Experimental group: perioperative hemodynamic management is based on an algorithm that includes RQ measurement and includes volume expansion, norepinephrine, FiO2 enhancement, RBC transfusion and dobutamine. • Interventions : Control group: hemodynamic management of patients is done according to usual practices by maintenance of blood pressure by norepinephrine as well as optimization of SV by vascular filling and use of dobutamine if necessary. Experimental group: perioperative hemodynamic management is based on an algorithm that includes RQ measurement and includes volume expansion, norepinephrine, FiO2 enhancement, RBC transfusion and dobutamine. The primary outcome is defined by at least one organ failure within 7 days postoperatively. The duration of participation of each patient is 30 days and total research term is 49 months Number of subjects : 350 Statistical analysis : The null hypothesis will be rejected in favor of the alternative hypothesis (there is a difference) using a test of χ2 or a Fisher test according to the frequency of the complications with a risk of the first bilateral species of 5%. Key-words : respiratory quotient, post opérative complications, anaerobic metabolism.

Official Title
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Individualized Hemodynamic Optimization by Indirect Measurement of the Respiratory Quotient in Major Surgery: Prospective Randomized Multicentre Open-Label Study (OPHIQUE) Individualized Optimization by Indirect Measurement of the Respiratory Quotient

Conditions
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Post-Op Complication, Respiratory Complication

Intervention / Treatment
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* Procedure: : hemodynamic management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Abdominal, orthopedic or vascular surgery with general anesthesia ASA score ≥ II Estimated duration of surgery> 2 hours Consent signed. Affiliation to a social security scheme Exclusion Criteria: Untreated or unbalanced severe hypertension under treatment. Preoperative renal failure dialyzed. Acute heart failure. Acute coronary insufficiency. Vascular surgery with kidney plasty. Cardiac surgery. Permanent laparoscopy. Preoperative shock state. Refusal of patient's participation Pregnant woman, parturient or breastfeeding. Patient under guardianship or trusteeship, under the protection of justice or private public law. Anesthesia with loco-regional anesthesia (spinal anesthesia and epidural). Acute respiratory distress syndrome (PaO2 / FiO2 ratio <300). Chronic Respiratory Failure with Home Oxygen Therapy. Patient already included in another therapeutic trial with an experimental molecule. Emergency anesthesia

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>hemodynamic management of patients is done according to usual practices by maintenance of blood pressure by norepinephrine as well as optimization of SV by vascular filling and use of dobutamine if necessary. | Procedure: : hemodynamic management<br>* Control group: hemodynamic management of patients is done according to usual practices by maintenance of blood pressure by norepinephrine as well as optimization of SV by vascular filling and use of dobutamine if necessary. Experimental group: perioperative hemodynamic management is based on an algorithm that includes RQ measurement and includes volume expansion, norepinephrine, FiO2 enhancement, RBC transfusion and dobutamine.<br>|
| Experimental: Experimental group<br>perioperative hemodynamic management is based on an algorithm that includes RQ measurement and includes volume expansion, norepinephrine, FiO2 enhancement, RBC transfusion and dobutamine. | Procedure: : hemodynamic management<br>* Control group: hemodynamic management of patients is done according to usual practices by maintenance of blood pressure by norepinephrine as well as optimization of SV by vascular filling and use of dobutamine if necessary. Experimental group: perioperative hemodynamic management is based on an algorithm that includes RQ measurement and includes volume expansion, norepinephrine, FiO2 enhancement, RBC transfusion and dobutamine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| organ failure | at least one organ failure within 7 days postoperatively. • Organ failure is defined according to the recommendations of the European Anesthesia Society (ESA) and the European Resuscitation Society (ESICM). | 7 days postoperatively | 
| mortality rate at day 30 |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the length of stay in the hospital |  | 30 days | 
| the SOFA score at day1 | The sequential organ failure assessment score (SOFA score), previously known as the sepsis-related organ failure assessment score, is used to track a person's status during the stay in an intensive care unit (ICU) to determine the extent of a person's organ function or rate of failure. The SOFA scoring system is useful in predicting the clinical outcomes of critically ill patients.According to an observational study at an Intensive Care Unit (ICU) in Belgium, the mortality rate is at least 50% when the score is increased, regardless of initial score, in the first 96 hours of admission, 27% to 35% if the score remains unchanged, and less than 27% if the score is reduced. Score ranges from 0 (best) to 24 (worst) points. | 1 day | 
| the SOFA score at day2 | The sequential organ failure assessment score (SOFA score), previously known as the sepsis-related organ failure assessment score, is used to track a person's status during the stay in an intensive care unit (ICU) to determine the extent of a person's organ function or rate of failure. The SOFA scoring system is useful in predicting the clinical outcomes of critically ill patients.According to an observational study at an Intensive Care Unit (ICU) in Belgium, the mortality rate is at least 50% when the score is increased, regardless of initial score, in the first 96 hours of admission, 27% to 35% if the score remains unchanged, and less than 27% if the score is reduced. Score ranges from 0 (best) to 24 (worst) points. | 2 days | 
| the SOFA score at day7 | The sequential organ failure assessment score (SOFA score), previously known as the sepsis-related organ failure assessment score, is used to track a person's status during the stay in an intensive care unit (ICU) to determine the extent of a person's organ function or rate of failure. The SOFA scoring system is useful in predicting the clinical outcomes of critically ill patients.According to an observational study at an Intensive Care Unit (ICU) in Belgium, the mortality rate is at least 50% when the score is increased, regardless of initial score, in the first 96 hours of admission, 27% to 35% if the score remains unchanged, and less than 27% if the score is reduced. Score ranges from 0 (best) to 24 (worst) points. | 7 days | 
| total volume of fluid intraoperatively |  | 30 days | 
| Plasma creatinine measured on day 0, day 1, day 2 and day 7 postoperatively |  | 7 days | 
| Plasma lactate measured on day 1, day 2 and day 7 postoperatively |  | 7 days | 
| C Reactive protein measured on day1, day2 and day7 postoperative |  | 7 days | 
| Troponin Tc measured on day1, day2 and day7 postoperatively |  | 7 days | 
| (NT pro) Brain Natriuretic Peptide ((NT pro) BNP) measured at day1, day2 and day7 postoperative |  | 7 days | 
| the incidence of each complication |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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respiratory quotient, post operative complications, anaerobic metabolism