Age of Blood Evaluation, resuscitation in the critically ill

Donated red cells in the Netherlands can be stored up to 35 days. However some
laboratory and clinical data suggest that giving older units could be less
effective and detrimental. Loss of deformability and 2,3 DGP, the release of
cytokines and the release of other mediators are reported.
Anemia is a common problem on the ICU. 95% of all American ICU patients
develops anemia in the first 3 days of admittance; 40-45% of all ICU patients
receives at least one red cell transfusion during the ICU admittance.
An extended RCT evaluating the consequences of red cell storage time has never
been done. In the ABLE study we wish to compare the effect of red cells younger
then 8 days with red cells tranfused according to standard procedure.


Substudie in het VUmc: the role of storage time of transfused red blood cells
on microcirculation and tissue oxygenation in critically ill patients:

In literature side-effects of red blood cell (RBC) transfusions are widely
described. It is thought that there might be an important role for the
microcirculation in detrimental effects on clinical outcome after RBC
transfusion. During storage RBC undergo biochemical changes which lead to the
deformation of red cells and which can cause impairing of the microcirculation
because the RBC have to migrate through the smallest capillairies. Various
studies intended to evaluate the direct impact of RBC transfusion on
microcirculation, but they don't show unequivocal results. Therefore we ould
like to determine the effects of storage time of RBC's on microcirculation
using SDF imaging.
Futhermore we question whether the objectiveof RBC transfusion, to maintain
adequate tissue hemoglobin oxygenation is accomplished independent of the
storage time of RBC's. Therefore we will evaluate the tissue hemoglobin
oxygenation after transfusion of standard or fresh RBCs using near infrared
spectometry (NIRS).

ABLE study:
To determine whether red cells stored less than 8 days reduce the 90-day
all-cause mortality with 5% in critically ill ICU patients in need of a red
cell transfusion compared to ICU patients who receive "older" red cells stored
2 to 35 days.


Substudy in the VUmc: the role of storage time of transfused red blood cells on
microcirculation and tissue oxygenation in critically ill patients:
The aim is to gain more insight in the effect of storage time of RBCs on
microcirculation and tissue hemoglobin oxygenation in critically ill patients.

The ABLE study is a double-blind, multicenter, randomized clinical trial. The
study will run in Canada, France, Great Britain and the Netherlands. We have
chosen to study a heterogeneous group of critically ill patients who receive at
least one red cell unit throughout the critical care phase of their illness
using pre-storage leuko-reduced cells. Patients will be randomized to receive
either 1) standard issue red cells (storage: 2 to 35 days) or 2) red cells
stored 2 to 7 days. We plan to compare 90-day all-cause mortality, other
mortality rates (28-day, ICU, hospital and 6-month mortality), rates and
severity of organ failure, rates of serious nosocomial infections, length of
time receiving organ support such as mechanical ventilation, and length of ICU
and hospital stay.


Substudy in the VUmc: the role of storage time of transfused red blood cells on
microcirculation and tissue oxygenation in critically ill patients:
Sublingual and microcirculatory density and perfusion will be monitored using
non-invasive Side Stream Dark Field (SDF) imaging in 40 patients who are
included in the ABLE study on 5 different time points (before transfusion of a
RBC unit, immediately following transfusion, 1 hour after transfusion, 6 hours
after transfusion, 24 hours after transfusion)

To determine the relation between tissue hemoglobin oxygenation and storage
time of RBCs tissue hemoglobin oxygenation will be measured using near-infrared
spectroscopy (NIRS) using the Equanox-7600. Tissue hemoglobin oxygenation will
be measured simultaneously with the SDF measurements, by placing an adhesive
strip as a sensor on the patient's forehead.

The intervention of our interest is the transfusion of red cells with a reduced
maximal storage time. We will randomize between transfusing red cells stored 2
to 7 days and red cells stored according to standard procedure; 2 - 35 days.

To our knowledge, the standard care in regards to red cell transfusion used in
this study does not involve any additional risk. Our experimental arm receives
*fresher* red blood cells (2- 8 days) while the control arm receives standard
care (red cells from 2 -35 days of age). So our *experimental* intervention is
in fact a subscribed limitation within the standard practice. Red cells in the
"fresher" arm are processed and checked for pathogens according to the standard
protocol. There is no known direct benefit in participating in this study.
Participants receiving younger blood may respond better to the red cell
transfusion.

VuMC substudy:
The burden associated with participation in this study is limited. Patients
will be subjected to non-invasive SDF imaging under the tongue together with
NIRS measurements on the forehead at five different time points.