title: Fresh and stored red blood cell transfusion equivalently induce subclinical pulmonary gas exchange deficit in normal humans.
abstract: 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 On study days, 2 U of blood were withdrawn while maintaining isovolemia, followed by transfusion with either the volunteer's autologous fresh red blood cells (RBCs) removed 2 hours earlier or their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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesia & Perioperative Care, University of California, San Francisco, Box 0648, San Francisco, CA 94143-0648, USA. weiskopf@anesthesia.ucsf.edu
authors.forename: Richard B
authors.initials: RB
authors.lastname: Weiskopf
authors.forename: John
authors.initials: J
authors.lastname: Feiner
authors.forename: Pearl
authors.initials: P
authors.lastname: Toy
authors.forename: Jenifer
authors.initials: J
authors.lastname: Twiford
authors.forename: David
authors.initials: D
authors.lastname: Shimabukuro
authors.forename: Jeremy
authors.initials: J
authors.lastname: Lieberman
authors.forename: Mark R
authors.initials: MR
authors.lastname: Looney
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Lowell
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gropper
mesh_terms: D000328:Adult; D001793:Blood Preservation / Q000592:standards; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D011659:Pulmonary Gas Exchange / Q000502:physiology*; D055815:Young Adult