title: Transfusion of 35-Day Stored RBCs in the Presence of Endotoxemia Does Not Result in Lung Injury in Humans.
abstract: OBJECTIVE
  Transfusion-related acute lung injury is the leading cause of transfusion-related mortality. Preclinical studies have shown that aged RBCs can induce transfusion-related acute lung injury in the presence of a "first hit" (e.g., sepsis). Clinical studies, however, show conflicting results on this matter. We tested whether maximally stored RBCs are able to induce lung injury in the presence of a "first hit" in humans (Dutch Trial Register: NTR4455).
  
  
  METHODS
  Open-label, randomized controlled trial.
  
  
  METHODS
  Healthy male volunteers.
  
  
  METHODS
  Eighteen healthy male volunteers donated one unit of autologous RBCs 2 or 35 days before the experiment. The experiment was started by infusion of 2 ng/kg lipopolysaccharide ("first hit"). After 2 hours, volunteers received normal saline (n = 6), 2-day stored transfusion (n = 6), or 35-day stored transfusion (n = 6) ("second hit"). Blood was sampled hourly. Six hours after transfusion, the diffusion capacity of the lungs for carbon monoxide was tested and volunteers underwent spirometry, chest x-ray study, and a bronchoalveolar lavage.
  
  
  RESULTS
  All volunteers fulfilled sepsis criteria after lipopolysaccharide injection. The stored blood transfusion did not result in significant changes in either hemodynamic or respiratory variables compared with the control groups. Furthermore, chest x-rays, lung function, and PaO2/FIO2 ratios did not differ between groups. Transfusion of stored autologous RBCs did not result in an increased level of protein in the lungs or neutrophil influx.
  
  
  CONCLUSIONS
  Transfusion of 35-day stored autologous RBCs in the presence of endotoxemia does not result in lung injury in humans.
authors.affiliation: 1Laboratory of Experimental Intensive Care and Anesthesia, Academic Medical Centre, Amsterdam, The Netherlands. 2Department of Intensive Care, Academic Medical Centre, Amsterdam, The Netherlands. 3Department of Blood Cell Research, Sanquin Blood Supply, Amsterdam, The Netherlands. 4Department of Pediatric Intensive Care, Academic Medical Centre, Amsterdam, The Netherlands. 5Department Product and Process Development, Sanquin Blood Supply, Amsterdam, The Netherlands. 6Department of Respiratory Medicine, Academic Medical Centre, Amsterdam, The Netherlands. 7Department of Haematology, Academic Medical Centre, Amsterdam. The Netherlands. 8Department of Immunopathology, Sanquin Research, Plesmanlaan, Amsterdam, The Netherlands. 9Department of Experimental Immunology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Peters
authors.forename: Maike E
authors.initials: ME
authors.lastname: van Hezel
authors.forename: Bart
authors.initials: B
authors.lastname: Cortjens
authors.forename: Anita M
authors.initials: AM
authors.lastname: Tuip-de Boer
authors.forename: Robin
authors.initials: R
authors.lastname: van Bruggen
authors.forename: Dirk
authors.initials: D
authors.lastname: de Korte
authors.forename: René E
authors.initials: RE
authors.lastname: Jonkers
authors.forename: Peter I
authors.initials: PI
authors.lastname: Bonta
authors.forename: Sacha S
authors.initials: SS
authors.lastname: Zeerleder
authors.forename: Rene
authors.initials: R
authors.lastname: Lutter
authors.forename: Nicole P
authors.initials: NP
authors.lastname: Juffermans
authors.forename: Alexander P J
authors.initials: AP
authors.lastname: Vlaar
mesh_terms: D055371:Acute Lung Injury / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology*; D000328:Adult; D001793:Blood Preservation / Q000592:standards; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002248:Carbon Monoxide; D019446:Endotoxemia / Q000139:chemically induced; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D004912:Erythrocytes; D064368:Healthy Volunteers; D006801:Humans; D008070:Lipopolysaccharides; D008297:Male; D009504:Neutrophils; D010100:Oxygen; D010313:Partial Pressure; D011506:Proteins / Q000032:analysis; D011653:Pulmonary Diffusing Capacity; D013902:Radiography, Thoracic; D013147:Spirometry; D055815:Young Adult
chemical_list: D008070:Lipopolysaccharides; D011506:Proteins; D002248:Carbon Monoxide; D010100:Oxygen