title: Blood transfusion during cardiac surgery is associated with inflammation and coagulation in the lung: a case control study.
abstract: BACKGROUND
  Blood transfusion is associated with increased morbidity and mortality in cardiac surgery patients, but cause-and-effect relations remain unknown. We hypothesized that blood transfusion is associated with changes in pulmonary and systemic inflammation and coagulation occurring in patients who do not meet the clinical diagnosis of transfusion-related acute lung injury (TRALI).
  
  
  METHODS
  We performed a case control study in a mixed medical-surgical intensive care unit of a university hospital in the Netherlands. Cardiac surgery patients (n = 45) were grouped as follows: those who received no transfusion, those who received a restrictive transfusion (one two units of blood) or those who received multiple transfusions (at least five units of blood). Nondirected bronchoalveolar lavage fluid (BALF) and blood were obtained within 3 hours postoperatively. Normal distributed data were analyzed using analysis of variance and Dunnett's post hoc test. Nonparametric data were analyzed using the Kruskal-Wallis and Mann-Whitney U tests.
  
  
  RESULTS
  Restrictive transfusion increased BALF levels of interleukin (IL)-1β and D-dimer compared to nontransfused controls (P < 0.05 for all), and IL-1β levels were further enhanced by multiple transfusions (P < 0.01). BALF levels of IL-8, tumor necrosis factor α (TNFα) and thrombin-antithrombin complex (TATc) were increased after multiple transfusions (P < 0.01, P < 0.001 and P < 0.01, respectively) compared to nontransfused controls, but not after restrictive transfusions. Restrictive transfusions were associated with increased pulmonary levels of plasminogen activator inhibitor 1 compared to nontransfused controls with a further increase after multiple transfusions (P < 0.001). Concomitantly, levels of plasminogen activator activity (PAA%) were lower (P < 0.001), indicating impaired fibrinolysis. In the systemic compartment, transfusion was associated with a significant increase in levels of TNFα, TATc and PAA% (P < 0.05).
  
  
  CONCLUSIONS
  Transfusion during cardiac surgery is associated with activation of inflammation and coagulation in the pulmonary compartment of patients who do not meet TRALI criteria, an effect that was partly dose-dependent, suggesting transfusion as a mediator of acute lung injury. These pulmonary changes were accompanied by systemic derangement of coagulation.
authors.affiliation: Department of Intensive Care Medicine and Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, Meibergdreef 9, Amsterdam NL-1105 AZ, The Netherlands. p.r.tuinman@amc.uva.nl
authors.forename: Pieter R
authors.initials: PR
authors.lastname: Tuinman
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Vlaar
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Cornet
authors.forename: Jorrit J
authors.initials: JJ
authors.lastname: Hofstra
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: Albertus
authors.initials: A
authors.lastname: Beishuizen
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: Ab Johan
authors.initials: AJ
authors.lastname: Groeneveld
authors.forename: Nicole P
authors.initials: NP
authors.lastname: Juffermans
mesh_terms: D055371:Acute Lung Injury / Q000097:blood; D000368:Aged; D001777:Blood Coagulation; D006348:Cardiac Surgical Procedures; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology*; D007430:Intraoperative Care / Q000009:adverse effects*; D008171:Lung Diseases / Q000097:blood / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D065227:Transfusion Reaction; D016896:Treatment Outcome