Transfusion Savings in Heart Surgery: Impact of Individual Strategy by Erythropoietin and Metabolic Adjustment (ScvO2)

Study Overview
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Brief Summary
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Preoperative anemia, bleeding and transfusions have been recognized as a Deadly triad in cardiac surgery associated with an increased morbidity,mortality, and costs related. Thus strategies to reduce unnecessary RBC transfusions and to optimize preoperative anemia must be developed .The study evaluate an individual blood conservation strategy based on patient blood management bundles in cardiac surgery patients: optimisation perioperative hemoglobin level by erythropoietin and ferric carboxymaltose (Ferinject) associated with the use of ScV02 to guide perioperative erythrocyte transfusion.

Detailed Description
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Preoperative anemia is the most common haematological abnormalities in cardiac surgery affecting 20 to 40% of patients and is becoming increasingly prevalent due to an ageing population with more chronic diseases.Preoperative anemia is independently associated with increased risk of adverse outcome following cardiac surgery but also implies blood transfusions which, associated with anemia, increase significantly perioperative cardiac morbidity and mortality. Therefore, strategies of blood conservation to optimize anemia and to minimize transfusion have been developped in the concept of the Blood Patient Management (BPM). To correct anemia, intravenous iron has been shown to be an effective treatment with increase hemoglobin (Hb) level in the perioperative period. It is now established that intravenous iron, as ferric carboxymaltose (Ferinject) is better tolerated compared to oral supplementation with better stimulation of erythropoiesis and,consequently, higher Hb levels. Based on promising results in the orthopedic surgery patients, the use of recombinant human erythropoietin (EPO) has also been proposed in cardiac surgery. Secondly, because even one red blood cells products (RBC) compromises postoperative outcome, guidelines suggest to adopt restrictive threshold of Hb levels to decide RBC transfusion. However, beyond the fact that RBC transfusion correct Hb level, the final goal of blood transfusion is to improve oxygen delivery to hypoxemic tissue. In this respect, the relevance of the use of a Hb threshold to guide transfusion have been questioned. Venous oxygen saturation (SvO2) and ScvO2 (central oxygen venous saturation), global parameters of tissue oxygenation, in stable hemodynamic and respiratory conditions, may be an relevant marker of anemia tolerance. Recently, the investigators demonstrated the lack of benefit in terms of ScvO2 increase during erythrocyte transfusion if ScvO2 was > 65%. In order to reduce exposure to transfusion, the management of anemia with EPO and perioperative intravenous FCM associated with the use of ScvO2 could be interesting to both improve Hb levels and reduce RBC transfusion.

Official Title
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Patient Blood Management in Cardiac Surgery by Erythropoietin, Ferric Carboxymaltose and Metabolic Adjustment (ScvO2): A Randomized Controlled Study

Conditions
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Cardiac Surgery, Transfusion, Perioperative Anemia

Intervention / Treatment
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* Drug: EPO (600UI/Kg, sub-cutaneous) and Ferric Carboxymaltose (FCM) (20 mg/kg in 250 mL of saline solution 0.9% over 15 min)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled Cardiac surgery for more than 24 hours High risk of perioperative transfusion defined by a TRUST Score ≥ 3 Veno-Venous catheter in Superior vena cava territory Patient Affiliate or beneficiary of social security Collection on free, informed and written consent Exclusion Criteria: EPO and FCM contraindication Patients already treated by EPO at the time of inclusion Non controlled Infectious endocarditis defined by ESC guidelines 2015 Patients including in an other research Patients whose physical and/or psychological health is severely impaired and who, according to the investigator, may affect the participant's compliance with the study. Patients deprived from his rights (guardianship or tutelage measure) Patients who refuses to sign the consent pregnant or lactating woman

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STOP Group<br>EPO (600UI/Kg, sub-cutaneous) and Ferric Carboxymaltose (FCM) (20 mg/kg in 250 mL of saline solution 0.9% over 15 min) will be administered if Hb < 13g/dL the day before surgery Hb ≥ 7g/dL AND ScvO2 > 65% in postoperative ICU stay Postoperative Transfusion will be guided by ScvO2 values : if Hb ≤ 8 g/dL AND ScvO2 ≤ 65% or if Hb < 7g/dL independently of ScVO2 value | Drug: EPO (600UI/Kg, sub-cutaneous) and Ferric Carboxymaltose (FCM) (20 mg/kg in 250 mL of saline solution 0.9% over 15 min)<br>* EPO (600UI/Kg, sub-cutaneous) and Ferric Carboxymaltose (FCM) (20 mg/kg in 250 mL of saline solution 0.9% over 15 min) will be administered if Hb < 13g/dL the day before surgery Hb ≥ 7g/dL AND ScvO2 > 65% in postoperative ICU stay Postoperative Transfusion will be guided by ScvO2 values : if Hb ≤ 8 g/dL AND ScvO2 ≤ 65% or if Hb < 7g/dL independently of ScVO2 value<br>|
| No Intervention: Control Group<br>Only postoperative anemia will be managed: RBC transfusion will be performed if Hb ≤ 8 g/dL (2017 EACTS/EACTA guidelines) Iron sucrose administration if Hb > 8g/dL : 2 injections of 200 mg according to Height (+/- 70 Kg) in 250 mL of saline solution 0.9% over 1h30 into 48 h intervals without exceeding a total dose of 15mg/kg. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transfusion incidence at hospital discharge | Number of patients transfused of blood units | up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU transfusion incidence | Number of blood units transfused during ICU stay | at ICU discharge or up to Day 28 | 
| total of blood units transfused | number of blood units administered per patient | up to day 28 | 
| Hemoglobin level at surgery discharge and Hemoglobin level at 1 month after discharge from hospital | the last hemoglobin value at surgery discharge and the hemoglobin value at 1 month after discharge from hospital | at surgery discharge (or at Day 28) and at 1 month after discharge from hospital | 
| The total duration of mechanical ventilation | The total duration of mechanical ventilation in ICU | at ICU discharge or up to Day 28 | 
| length of stay in ICU | numbers of days in ICU | up to day 28 | 
| Length of hospital stay | Length of stay during hospitalization (Between 1 and 28 day) | at day 28 | 
| Incidence of Mortality | Incidence of 28-day mortality | at day 28 | 
| Incidence of postoperative events in ICU | AKI (KDIGO criteria), Cardiac dysfunction (acute heart failure requiring inotrope or extracorporeal life support (ECLS), arrythmia), vascular dysfunction (norepinephrine support without sepsis), respiratory dysfunction (non invasive ventilation devices, secondary intubation,mechanical ventilation more than 12 hours), septic complications (sepsis/septic shock) | at day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Perioperative Erythropoietin, Perioperative Iron, ScVO2, Patient blood Management, Blood Transfusion