Ludwigshafen Am Main, Germany

Restrictive Versus Liberal Thresholds for RBC Transfusion in ECMO

Extracorporeal membrane oxygenation (ECMO) is used as a supportive method in case of temporary and potentially reversible cardiac or respiratory failure, refractory to conventional therapies. Over the past decades, application of ECMO has been increasing worldwide. As ECMO is generally used as a 'last resort' therapy, the population is vulnerable, and many complications can occur. Anemia occurs in >90% of the patients on ECMO, caused by many different patient-related, disease-related, and ECMO-related factors. Nevertheless, rationale for the recommended hemoglobin (Hb) thresholds for red blood cell (RBC) transfusion in this patient population is limited. This was recently confirmed by the members of the European Society of Intensive Care Medicine (ESICM), who concluded in their clinical practice guideline that no recommendation on transfusion thresholds can be made, since solid evidence is missing. The panel stated that this area is a research priority. This lack of evidence-based guidelines may explain the high variance in Hb thresholds applied, as well as the thresholds in use being relatively liberal. As a result, transfusion of RBC is very common. Observational studies describe that almost 9 out of 10 patients receiving ECMO receive at least one RBC transfusion, and the total amount is very high. These numbers are even more remarkable when comparing to other patient populations in the Intensive Care Unit (ICU), in which 1 out of 4 patients receives RBC with way lesser amounts. One of the main arguments for using a liberal transfusion threshold in ECMO is the hypothesis that in patients receiving ECMO, tissue hypoxemia can develop due to decreased pulmonary oxygen intake (e.g., in pneumonia as indication for veno-venous [VV] ECMO), or decreased cardiac output (e.g., in myocardial infarction as indication for veno-arterial [VA] ECMO). By providing a larger Hb buffer, it is assumed that the oxygen delivery (DO2) will be preserved and the incidence of tissue hypoxemia will be reduced. However, evidence to either confirm or refute this hypothesis is lacking. Since ECMO ensures oxygenation and can provide a blood flow of up to 7 L/min, it can be assumed that ECMO fully compensates for the possible decrease in DO2. Although RBC transfusion can be lifesaving, it is also a risk-bearing intervention with substantial risk for morbidity and mortality in this critically ill population. In similar patient populations without ECMO, maintaining a restrictive RBC transfusion strategy (Hb 7.0 g/dL) has been proven non-inferior to a more liberal practice (Hb 9.0 g/dL). This includes randomized controlled trials (RCTs) in septic shock patients (comparable to patients on VV ECMO), cardiothoracic surgery patients, and even patients suffering from acute myocardial infarction and anemia (comparable to patients on VA ECMO). Although these conclusions are promising, they cannot directly be translated to patients supported by ECMO, although underlying conditions are similar. Moreover, RBC transfusions are expensive and donors are becoming more scarce. In this vulnerable critically ill patient population with an enhanced risk for transfusion related complications, it is of utmost importance to only administer a RBC transfusion when the benefits outweigh the risks. As both anemia and transfusion are associated with poor outcomes, observational studies cannot answer the question whether a restrictive Hb threshold is non-inferior to a liberal strategy. There is a need to define general thresholds to improve the efficiency of indications for RBC transfusion in ECMO. Since one of the most commonly used triggers for RBC transfusion is Hb concentration, this forms the basis for our study to investigate whether it is non-inferior to maintain a restrictive transfusion threshold (intervention group: Hb 7 g/dL) compared to the current standard of 9 g/dL in patients on ECMO, independent of the mode. This study is funded by ZonMW (Zorgonderzoek Medische Wetenschappen), part of the NWO (Nederlandse Organisatie voor Wetenschappelijk Onderzoek; the Dutch Organization for Scientific Research, Den Haag, the Netherlands), reference number 10390032310031.

Red Blood Cell Transfusion in ECMO - a Feasibility Trial

A recent Cochrane analysis recommended a transfusion strategy that minimises the use of RBC transfusions in critically ill patients (by tolerating anaemia to avoid the adverse effects of an RBC transfusion). However, the analysis acknowledges that the degree of anaemia which can be tolerated by such patients is unknown, especially in patients suffering from conditions that limit oxygen delivery to the organs (like cardiac disease). As a result, the Australian Blood Authority's guidelines recommend an RBC transfusion to a patient at an Hb concentration of less than 70 g/L, while a transfusion at a Hb between 70 and 90 g/L should be based on the need to relieve clinical signs and symptoms of anaemia. However, this range is broad, and many studies in the general critically ill cohort have shown lower transfusion triggers are non-inferior to higher transfusion triggers. No studies have been completed directly evaluating transfusion triggers in the ECMO patient cohort. ECMO patients differ to the general critically ill cohort as they have different physiological requirements, are at higher-risk for poor outcomes, and have an increased requirement for transfusions. Hb is a key driver of oxygen delivery (DO2), and critically ill ECMO patients are more commonly exposed to low DO2 due to low cardiac output and borderline oxygenation. Therefore, studies must be done to evaluate the optimal transfusion trigger/s (as determined by Hb concentration) that optimise mortality and long-term outcomes of ECMO patients. Should the ROSSETTA Pilot results indicate adequate separation of at least 10g/L between the two study groups, and that patient safety has not been adversely affected by the trial methods, feasibility will be deemed confirmed and the protocol not in need of modification prior to full trial commencement. At this point the ROSETTA Pilot will be transitioned into the Red Blood Cell Transfusion Domain, within RECOMMEND Platform Trial. The Primary and Secondary outcomes of the trial at large, will be answered during this stage.

Trial of Indication-Based Transfusion of Red Blood Cells in ECMO

Observational studies of children on ECMO have shown an association between large-volume RBC transfusion and mortality. However, the hematocrit (or hemoglobin) level at which optimal tissue oxygen delivery occurs is unknown. TITRE - Trial of Indication-based Transfusion of Red Blood Cells in ECMO, is a prospective, randomized clinical trial to be conducted at 18-20 study sites. The overarching goal of TITRE is to determine whether restricting RBC transfusion according to an indication-based strategy for those with bleeding and/or deficit of tissue oxygen delivery, compared with transfusion based on center-specific hemoglobin or hematocrit thresholds, can reduce organ dysfunction and improve later neurodevelopment in critically ill children receiving ECMO support. Aim 1: To test whether children < 6 years of age on ECMO support who are randomized to a strategy of indication-based versus center-specific threshold-based RBC transfusion will have greater improvement in organ function. Aim 2: To test whether survivors among children age < 6 years on ECMO support who are randomized to indication-based compared to center-specific threshold-based RBC transfusion will have better neurodevelopmental outcomes and health-related QOL at one year post-randomization. Key design features include: Randomization stratified by patient age (neonate: =< 28d vs. non-neonate) and by diagnosis (CHD vs. other diagnosis); and a target sample size of 228 patients. Endpoints will be evaluated during ECMO, at hospital discharge, and at 3, 6, 9, and 12 months. To ensure trial integrity, the primary outcome (pSOFA: Pediatric Sequential Organ Failure Assessment score) will be adjudicated by an independent committee and neurodevelopmental assessments will be blinded.

Liberal Transfusion Strategy in Elderly Patients

Oxygen Extraction-guided Transfusion

Packed Red Blood Cell Transfusion During Cardiac Arrest

Comparison of Hemanext ONE® System and Conventional Red Blood Cell Transfusion

The primary objective is to evaluate whether the total number of hypoxically stored red blood cell (RBCs) units per unit of time transfused in patients with haematologic malignancies, requiring chronic blood transfusion therapy, is non-inferior to the total number of units of conventionally stored RBCs per unit of time transfused. Secondary objectives include the following: 1. Analysis of volume of blood transfused 2. Analysis of number of transfusion events throughout the study period 3. Key laboratory assessments (hemoglobin and hematocrit) and average hemoglobin increment after transfusions of hypoxically stored RBCs compared to that with conventionally stored RBCs 4. Evaluation of Quality of Life (QoL) 5. Change in serum ferritin 6. Safety assessment

Variation of Echocardiographic Parameters After Red Blood Cell Transfusion in Emergency Department Anemic Patients