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Fresh and Stored Red Blood Cell Transfusion Equivalently Induce Subclinical Pulmonary Gas Exchange Deficit in Normal Humans

Weiskopf, Richard B. MD*; Feiner, John MD*; Toy, Pearl MD*; Twiford, Jenifer BSN*; Shimabukuro, David MD*; Lieberman, Jeremy MD*; Looney, Mark R. MD; Lowell, Clifford A. MD, PhD; Gropper, Michael A. MD, PhD*

doi: 10.1213/ANE.0b013e318241fcd5
Cardiovascular Anesthesiology
Chinese Language Editions

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 On study days, 2 U of blood were withdrawn while maintaining isovolemia, followed by transfusion with either the volunteer's autologous fresh red blood cells (RBCs) removed 2 hours earlier or their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 (AaDO2) 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 AaDO2 (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 AaDO2.

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.

Published ahead of print January 19, 2012 Supplemental Digital Content is available in the text.

From the Departments of *Anesthesia & Perioperative Care, †Medicine, and ‡Laboratory Medicine, University of California, San Francisco, San Francisco, California.

Supported by a Public Health Service Award from the National Heart, Lung, and Blood Institute, National Institutes of Health, grant 1 P50 HL54476.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Richard B. Weiskopf, MD, Department of Anesthesia & Perioperative Care, University of California, San Francisco, Box 0648, San Francisco, CA 94143-0648. Address e-mail to or

Accepted November 7, 2011

Published ahead of print January 19, 2012

© 2012 International Anesthesia Research Society
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