Anemia, Cardiogenic Shock, Extracorporeal Membrane Oxygenation, Oxygen Delivery, Transfusion Related Complication
Conditions
Keywords
ECMO, ECLS, Refractory cardiogenic shock, Transfusion, ScVO2, Outcome
Brief summary
This multicenter randomized controlled trial compare two transfusion strategies of red blood cells transfusion in patients supported by veno-arterial extracorporeal membrane oxygenation for refractory cardiogenic shock. An individualized transfusion strategy based on ScVO2 level, is compared to a conventionnal strategy based on predefined hemoglobin threshold. The primary endpoint is the consumption of packed red blod cells, secondary endpoints are subgroup analysis, mortality, morbidity, and cost-effectiveness
Detailed description
Peripheral VA-ECMO is the mainstay of mechanical circulatory support in refractory cardiogenic shock. This treatment is associated with a high consumption of packed red blood cells (PRBCs), which can reach 1 to 3 units of PRBCs per day of support. The main reasons for such a high consumption of PRBCs are the very frequent hemorrhagic complications and the prevalence of anemias not directly related to the hemorrhagic episodes. These anemias are frequent during VA-ECMO support owing to hemolysis, hemodilution, previous bleeding episodes, thrombosis, etc. In order to restore, maintain, or increase oxygen delivery (DO2) to peripheral organs, RGCs are often performed when anemia is observed. Several studies have reported an association between transfusion of these PRBCs with morbidity and mortality in this ECMO setting. There is no appropriate strategy to reduce PRBC consumption, taking into account other determinants of DO2. In addition, there is currently no validated or consensus hemoglobin threshold to guide transfusion in this specific population. Furthermore, this predefined threshold-based approach may be inappropriate in the setting of VA-ECMO due to differences in DO2 requirements between patients based on their etiology, disease severity, and ECMO modality. In addition, large variations in DO2 can be observed in the same patient and between ECMO settings. Therefore, a more individualized strategy guided by a DO2 surrogate, ScVO2, may be more appropriate in this population. This ScVO2 approach has recently been shown to be associated with reduced PRBCs in two randomized controlled trials in cardiac surgery patients. The objective of this multicenter randomized controlled trial is to compare two red cell transfusion strategies in patients receiving extracorporeal veno-arterial membrane oxygenation for refractory cardiogenic shock. An individualized transfusion strategy based on ScVO2 level is compared with a conventional strategy based on a predefined hemoglobin threshold. The primary endpoint is red blood cell consumption, the secondary endpoints are subgroup analysis, mortality, morbidity, and cost-effectiveness.
Interventions
DRUGPacked Red Blood Cells (PRBCs)
Patient will recieve PRBCs transfusion only in case of ScVO2 level\<65% after assessment of patient for optimisation of SaO2 targeting 100%, volume status, ECMO flow (increase to 20% in relevant), pain, anxiety and fever (body temperature \>38°3). In both groups transfusion may be performed in case massive bleeding according to local protocols, STEMI, Hyperlactatemia \>4 that can be related to oxygen demand and supply DO2/VO2 ratio impairement, in all groups, transfusion should be performed in case of hemolobin level \<7g/dL or worsening of neurological condition (Increase in Neurological SOFA component of 1 and more) related to DO2/VO2 impairement.
Sponsors
University Hospital, Lille
Amiens University Hospital
University Hospital, Caen
University Hospital, Rouen
Centre Hospitalier Universitaire Dijon
Centre Hospitalier de Lens
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Patients and datamanagement responsible for statistical analysis will be blinded of the patient allocation group until the study completion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age of 18 and older, * supported by peripheral VA-ECMO * for cardiogenic shock * Life expentency \>90 days * Central venous line available ScVO2 measurement
Exclusion criteria
* Pregnancy, * Lack of health insurance, * Opposition to blood transfusion, * Known congenital hemoglobin disease or disorder, * Metabolic alcaloosis with pH\>7.8, * eCPR, * Legally incapacitated adults
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of PRBCs transfused per VA-ECMO day of support | From randomisation until VA-ECMO weanning assessed up to 28 days | Total number of PRBCs transfused during support adjusted for VA- ECMO duration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of PRBCs transfused per VA-ECMO day of support in postcardiotomy patients | From randomisation until VA-ECMO weanning assessed up to 28 days | Total number of PRBCs transfused during support adjusted for VA- ECMO duration in patients that underwent cardiac surgery |
| Total number of PRBCs transfused during the 28-day following cannulation | From randomisation until 28 days | Total number of PRBCs transfused during the 28-day following cannulation |
| Changes in hemoglobin levels during VA-ECMO support | From randomisation until VA-ECMO weanning assessed up to 28 days | daily hemoglobin levels |
| Changes in ScVO2 levels during VA-ECMO support | From randomisation until VA-ECMO weanning assessed up to 28 days | daily ScVO2 levels |
| Changes in vosoactive index score levels during VA-ECMO support | From randomisation until VA-ECMO weanning assessed up to 28 days | daily vasoactive index score levels |
| Mortality under ECMO support | From randomisation until VA-ECMO weanning assessed up to 28 days | All cause mortality before ECMO weaning |
| 90-day Mortality | 90 days from cannulation | All cause mortality from cannulation untill 90 days |
| ECMO removal modalities | From randomisation until VA-ECMO weanning assessed up to 28 days | Proportion of patients that according to each reason for removal ( Recovery, heart transplantation, Left ventricle or biventricle assist device or death under support) |
| Duration of mechanical ventilation | 28 days from cannulation | Duration of mechnanical ventilation from cannulation untill 28 days |
| Proportion of patient that received a renal replacement therapy and its duration | 28 days from cannulation | Number of patient that underwent a renal replacement therapy and duration of renal replacement therapy from cannulation untill 28 days |
| Duration of vasoactive support | 28 days from cannulation | Duration of vasoactive drug support from cannulation untill 28 days |
| Hospital lenght of stay | 28 days from cannulation | Length of stay from cannulation censored at 90 day |
| HLA immuno-sensitisation | 28 and 90 days from cannulation | Proportion of HLA immunosensitisation occuring after cannulation |
| Proportion of patient with Transfusion related immunologic ( non HLA-related) complications | From randomisation until 28 days | Transfusion related acute lung injury, hemolytic anemia, irregular antibodies |
| Proportion of patients with nex onset of sepsis | From randomisation until 28 days | Sepsis is defined according to Surviving Sepsis Campaign guideline |
| Proportion of patients with a new onset of acute kidney injury | From randomisation until 28 days | Acute kidney injury is define according to KDIGO classification |
| Proportion of patients with liver failure | From randomisation until 28 days | Liver failure is defined as Hepatic component of SOFA score, Transaminasis Levels |
| Ischemic stroke | From randomisation until 28 days | Ischemic stroke is defined as clinical symptoms confirmed by aCT Scan of MRI imaging |
| Myocardial infarction | From randomisation until 28 days | According to the Universal definition of myocardial infarction, ESC guidelines |
| Pulmonary oedema | From randomisation until 28 days | Dignose by the attending physician based on (Dyspnae, Thoracic X-rays), bowel ischemia ( Abdominal CT or endoscopy proven) |
| Anaphylactic complications | From randomisation until 28 days | Anaphylaxis defined according to Ring and Messer Classification |
| Bowel Ischemia | From randomisation until 28 days | Proven by Abdominal CT or endoscopy |
| Cost effectiveness analysis | 28 days, 90 days and 5 years from randomisation | Actual costs at 28 and 90 days and modelisation for 5 years |
Countries
France
Contacts
CONTACTMouhamed MOUSSA, MD
PRINCIPAL_INVESTIGATORMouhamed MOUSSA, MD
University Hospital, Lille
Outcome results
None listed