Effect of peri-operative transfusion of blood products on pulmonary leakage measured with the pulmonary leakage index in a cohort of cardiac surgery patients.

Cardiac surgery patients post operatively often have a compromised oxygenation.
Many causes are suggested, e.g. atelectasis, pulmonary edema and acute lung
injury (ALI) or its more severe form acute respiratory distress syndrome
(ARDS). A possible important factor may be peri-operative blood transfusions
causing transfusion related acute lung injury (TRALI). TRALI is thought to be a
two hit entity. The *first hit* is lung endothelial activation with priming of
the neutrophils in the lung, caused by e.g. an operation, trauma or an
infection. The *second hit* is caused by the bloodtransfusion, resulting in
neutrophil activation and finally pulmonary leakage. Either antibodies present
in donor blood or bio-active lipids which accumulate during storage of blood
account for the second hit. For several reasons, cardiac surgery patients may
form a group of patients at high risk for TRALI. During the intra-thoracic
surgical procedure the lungs are usually left deflated and non-ventilated for
several hours, which may cause injury to the lung vasculature (the *primary
hit*). Secondly, these patients often receive transfusion of blood products.
The distinction between hydrostatic pulmonary edema and ALI is difficult
because of the low specificity of clinical diagnostic criteria. Furthermore,
these entities may not be mutually exclusive. The Pulmonary Leak Index (PLI)
can be used as a measure of microvascular permeabiltity and has been shown to
be an early marker of acute lung injury in critically ill patients. The PLI is
typically elevated more than three- to four- fold in ARDS.

1) to determine whether blood transfusion leads to pulmonary leakage measured
by PLI

2)to determine if pulmonary leakage is correlated with:
- the type of transfusion (erythrocytes, plasma or platelets)
- the amount of transfusion
- type of donor
- duration of storage of blood products
- the presence of HLA/HNA antibodies in donorblood
- the presence of bio-active lipid concentration in donorblood
- the presence of inflammation markers in the broncho alveolair fluid

In a prospective cohort study we will measure the pulmonary leakage index in 50
post operative cardiac surgery patients after multiple blood transfusions.
Furthermore a mini lavage ot the lungs will be done. This is done as standard
patient care on our ICU

PLI measurement will be done by labeling Transferrin in vivo, after i.v.
injection of 67Gallium (Ga)-citrate, 4 MBq (physical half-life 78 h;
Mallinckrodt Diagnostica, Petten, The Netherlands) as written before in studies
from our research group. Demographic data from patients will be obtained out of
the clinical files. Data about transfusions, donors and storage duration will
be obtained via Sanquin. HLA/HNA analysis will be performed by Sanquin. Bio
active lipids will be measured by thin plate chromatography.

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