A Clinical Trial to Detect Subclinical Transfusion-induced Lung Injury during Surgery.

BACKGROUND: Transfusion-related acute lung injury incidence remains the leading cause of posttransfusion mortality. The etiology may be related to leukocyte antibodies or biologically active compounds in transfused plasma, injuring susceptible recipient's lungs. The authors have hypothesized that transfusion could have less severe effects that are not always appreciated clinically and have shown subtly decreased pulmonary oxygen gas transfer in healthy volunteers after transfusion of fresh and 21-day stored erythrocytes. In this study, the authors tested the same hypothesis in surgical patients. METHODS: Ninety-one patients undergoing elective major spine surgery with anticipated need for erythrocyte transfusion were randomly allocated to receive their first transfusion of erythrocytes as cell salvage (CS), washed stored, or unwashed stored. Clinicians were not blinded to group assignment. Pulmonary gas transfer and mechanics were measured 5 min before and 30 min after erythrocyte transfusion. RESULTS: The primary outcome variable, gas transfer, as assessed by change of PaO2/FIO2, with erythrocyte transfusion was not significant in any group (mean ± SD; CS: 9 ± 59; washed: 10 ± 26; and unwashed: 15 ± 1) and did not differ among groups (P = 0.92). Pulmonary dead space (VD/VT) decreased with CS transfusion (-0.01 ± 0.04; P = 0.034) but did not change with other erythrocytes; the change from before to after erythrocyte transfusion did not differ among groups (-0.01 to +0.01; P = 0.28). CONCLUSIONS: The authors did not find impaired gas exchange as assessed by PaO2/FIO2 with transfused erythrocytes that did or did not contain nonautologous plasma. This clinical trial did not support the hypothesis of erythrocyte transfusion-induced gas exchange deficit that had been found in healthy volunteers.

Fresh and stored red blood cell transfusion equivalently induce subclinical pulmonary gas exchange deficit in normal humans.

BACKGROUND: Transfusion can cause severe acute lung injury, although most transfusions do not seem to induce complications. We tested the hypothesis that transfusion can cause mild pulmonary dysfunction that has not been noticed clinically and is not sufficiently severe to fit the definition of transfusion-related acute lung injury. METHODS: We studied 35 healthy, normal volunteers who donated 1 U of blood 4 weeks and another 3 weeks before 2 study days separated by 1 week. On study days, 2 U of blood were withdrawn while maintaining isovolemia, followed by transfusion with either the volunteer's autologous fresh red blood cells (RBCs) removed 2 hours earlier or their autologous stored RBCs (random order). The following week, each volunteer was studied again, transfused with the RBCs of the other storage duration. The primary outcome variable was the change in alveolar to arterial difference in oxygen partial pressure (AaDo(2)) from before to 60 minutes after transfusion with fresh or older RBCs. RESULTS: Fresh RBCs and RBCs stored for 24.5 days equally (P = 0.85) caused an increase of AaDo(2) (fresh: 2.8 mm Hg [95% confidence interval: 0.8-4.8; P = 0.007]; stored: 3.0 mm Hg [1.4-4.7; P = 0.0006]). Concentrations of all measured cytokines, except for interleukin-10 (P = 0.15), were less in stored leukoreduced (LR) than stored non-LR packed RBCs; however, vascular endothelial growth factor was the only measured in vivo cytokine that increased more after transfusion with LR than non-LR stored packed RBCs. Vascular endothelial growth factor was the only cytokine tested with in vivo concentrations that correlated with AaDo(2). CONCLUSION: RBC transfusion causes subtle pulmonary dysfunction, as evidenced by impaired gas exchange for oxygen, supporting our hypothesis that lung impairment after transfusion includes a wide spectrum of physiologic derangements and may not require an existing state of altered physiology. These data do not support the hypothesis that transfusion of RBCs stored for >21 days is more injurious than that of fresh RBCs.