title: Preload responsiveness is associated with increased interleukin-6 and lower organ yield from brain-dead donors.
abstract: OBJECTIVE
  Brain death induces dramatic changes in hemodynamics. Ischemic injury and inflammation resulting from inadequate resuscitation might influence organ yield for transplantation. Using functional hemodynamic monitoring in brain-dead organ donors, we test the hypothesis that donor preload (fluid) responsiveness is associated with increased inflammatory response and lower organ yield for transplantation.
  
  
  METHODS
  Prospective, observational, pilot study.
  
  
  METHODS
  A large intensive care unit of a university hospital in the United States.
  
  
  METHODS
  Twenty-one brain-dead organ donors between July 2006 and April 2007.
  
  
  METHODS
  None.
  
  
  RESULTS
  Following declaration of brain death, we collected data on donor demographics, mechanism of brain death, and number of organs procured and transplanted. Functional hemodynamics were monitored using pulse contour analysis technique. Plasma tumor necrosis factor, interleukin-6, and interleukin-10 concentrations were measured at study enrollment, after 4 hrs, and immediately before organ procurement for transplantation. Preload responsiveness (pulse pressure variation >13%) was observed in 48% of donors (mean +/- sd pulse pressure variation, 19.2% +/- 4.8%). Plasma interleukin-6 and tumor necrosis factor concentrations at study enrollment were greater in preload responsive donors: mean concentrations of interleukin-6 in preload responsive vs. unresponsive donors were 5420 +/- 9102 vs. 378 +/- 631 pg/mL (p = .009), and mean concentrations of tumor necrosis factor were 60.5 +/- 103.6 vs. 15.7 +/- 10.1 pg/mL (p = .048). Preload responsive compared with unresponsive donors had significantly increased interleukin-6 (p = .013) and tumor necrosis factor (p = .044) concentrations over time. Fewer organs were transplanted from preload responsive donors: mean organs transplanted from preload responsive vs. unresponsive donors were 1.8 +/- 0.9 vs. 3.7 +/- 2.5 (p = .034). In multivariable regression, older donor age (p = .028) and increased plasma interleukin-6 concentration (p = .035) were significantly associated with lower number of organs transplanted.
  
  
  CONCLUSIONS
  Preload responsiveness is common in brain-dead organ donors and is associated with higher inflammatory response and lower organ yield. A controlled trial of preload optimization is warranted in brain-dead donors.
authors.affiliation: CRISMA Laboratory, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Raghavan
authors.initials: R
authors.lastname: Murugan
authors.forename: Ramesh
authors.initials: R
authors.lastname: Venkataraman
authors.forename: Abdus S
authors.initials: AS
authors.lastname: Wahed
authors.forename: Michele
authors.initials: M
authors.lastname: Elder
authors.forename: Melinda
authors.initials: M
authors.lastname: Carter
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Madden
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D005260:Female; D005440:Fluid Therapy; D006439:Hemodynamics; D006801:Humans; D020896:Hypovolemia / Q000097:blood / Q000175:diagnosis*; D015850:Interleukin-6 / Q000097:blood*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016377:Organ Transplantation; D010865:Pilot Projects; D011446:Prospective Studies; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000517:prevention & control*; D020858:Tissue and Organ Harvesting
chemical_list: D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6