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.