Oxygen Extraction-guided Transfusion

Study Overview
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Brief Summary
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In critically ill patients, optimized strategies for red blood cells transfusion (RBCT) are still controversial. Most recent guidelines suggest that clinical practice in ICU setting should follow a restrictive approach to RBCT (i.e., hemoglonim level < 7.0 g/dL).In our previous study, oxygen extraction ratio (O2ER) has shown good performance as a marker to identify the correct timing for RBCT, potentially affecting 90-day mortality in non-bleeding, critically ill patients [11]. Moreover, our data suggested that an individualized strategy for RBCT may reduce the incidence of acute kidney injury (AKI), which is possibly related to a better delivery of oxygen and organ perfusion.

Official Title
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Oxygen Extraction-guided Transfusion Strategy in Critically Ill Patients. A Randomized Controlled Trial.

Conditions
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Blood Transfusion

Intervention / Treatment
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* Other: Individualized red blood cell transfusion strategy
* Other: European guidelines red blood cell transfusion strategy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence of Hb levels ≤ 9.0 g/dL (as confirmed through a blood test and/or through blood gas analysis); Presence of a central venous line (either jugular or subclavear), with confirmed correct position of the catheter tip at the atriocaval junction (allowing correct estimation of mixed venous saturation, SvO2). Exclusion Criteria: Age < 18 years; Female patients during pregnancy; Clinical evidence of acute ongoing/persistent bleeding; Diagnosis of hematological malignancy; Diagnosis of sickle cell disease, or other diseases exposing the patient to chronic RCBTs; Acquired or congenital disorders of coagulation; Patients with ongoing AKI and/or known chronic kidney disease (CKD).

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individualized RBCT<br>Requires daily assessment of hemoglobin (Hb) levels. Prescription of RCBT is restricted to patients who present Hb ≤ 9.0 g/dL and O2ER ≥ 30%. If O2ER < 30%, transfusion will take place only when Hb falls below 7.0 g/dL. Further O2ER measurements during the day in this group are allowed, and the clinician should not be blinded of the results. To tolerate Hb levels below 7.0 g/dL with O2ER < 30% remains a clinical decision, documented in the CRF. Transfusion with Hb below 6.0 g/dL is mandatory | Other: Individualized red blood cell transfusion strategy<br>* Prescription of RCBT is restricted to patients who present Hb ≤ 9.0 g/dL and O2ER ≥ 30%.<br>|
| Active Comparator: Control group<br>Requires daily assessment of hemoglobin levels. Prescription of RCBT is restricted to patients who present Hb ≤ 7.0 g/dL, despite of O2ER values. Indeed, O2ER calculation takes place at least once daily in this group but does not interfere with clinical decision to prescribe RBCT. A liberal transfusion threshold (i.e. 9.0 g/dL) is still possible in critically ill adults with acute coronary syndromes, as indicated by the European current guidelines | Other: European guidelines red blood cell transfusion strategy<br>* RBCT according to ESICM guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Kidney Injury (AKI) | Primary outcome will be the incidence of AKI, according to KDIGO latest definitions | 7-day after study inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90-day mortality |  | 90-day after study inclusion | 
| proportion of patients undergoing RBCT, despite adequate/low O2ER | Patients receiving RBCT with O2ER<30% | 28 days | 
| SOFA score variations | SOFA score at study inclusion-SOFA score at day 5 | 5 days | 
| variations in myocardial-specific troponin | variations in myocardial-specific troponin | 24 hours after study inclusion | 
| days on vasopressors | number of days on vasopressor therapy | 28 days | 
| Major Adverse Kidney Events by 90 days (MAKE90) | composite of death, new renal replacement therapy, or persistent renal dysfunction | 90 days | 
| ICU mortality | ICU mortality | through study completion, an average of 180 days | 
| In-hospital mortality | In-hospital mortality | through study completion, an average of 180 days |