title: Magnitude of the inflammatory response to cardiopulmonary bypass and its relation to adverse clinical outcomes.
abstract: BACKGROUND
  Cardiopulmonary bypass (CPB) induces an inflammatory response believed to contribute to postoperative morbidity. We hypothesized that the magnitude of the inflammatory response following CPB would be associated with adverse clinical outcomes.
  
  
  METHODS
  Twenty-nine patients had plasma TNF, IL-6, IL-8, elastase, histamine, complement C5a, and complement C3a measured by ELISA before, during, and after cardiac operations employing CPB. Inflammatory mediator levels were analyzed with respect to outcomes.
  
  
  RESULTS
  Mediator levels peaked at 4 h post-CPB and either returned to baseline or substantially decreased by 24 h. Patients with peak mediator levels above the median for the group as a whole were classified as 'hyper-responders'; those with levels below the median were classified as 'normal responders'. While IL-8, C3a, and IL-6 levels were independently associated with adverse outcomes, TNF, histamine, and C5a levels were not. Elastase levels trended towards adverse outcomes. IL-8 'hyper-responders' experienced significantly greater postoperative weight gain and had higher IL-8 levels at 24 h (p<0.05), with trends towards renal impairment and protracted supplemental oxygen requirements. C3a 'hyper-responders' strongly trended towards increased bleeding, delayed extubation, greater postoperative weight gain, and decreased levels of independent functioning at discharge (p < or = 0.10). IL-6 'hyper-responders' experienced significantly more postoperative bleeding, delayed extubation, and higher IL-6 levels at 24 h compared to 'normal responders' (p < 0.05). They strongly trended towards greater postoperative weight gain and decreased levels of independent functioning at discharge (p < or = 0.10).
  
  
  CONCLUSIONS
  Patients who have an exaggerated inflammatory response to CPB tend to bleed more, require more respiratory support, demonstrate greater capillary leak via weight gain, and display a decline in independent functioning relative to normal responders. Thus, it appears that the magnitude of the inflammatory response to CPB adversely influences clinical outcomes.
authors.affiliation: Department of General Surgery, Virginia Mason Medical Center, Seattle, WA, USA. jhholmes@u.washington.edu
authors.forename: J H
authors.initials: JH
authors.lastname: Holmes
authors.forename: N C
authors.initials: NC
authors.lastname: Connolly
authors.forename: D L
authors.initials: DL
authors.lastname: Paull
authors.forename: M E
authors.initials: ME
authors.lastname: Hill
authors.forename: S W
authors.initials: SW
authors.lastname: Guyton
authors.forename: S F
authors.initials: SF
authors.lastname: Ziegler
authors.forename: R A
authors.initials: RA
authors.lastname: Hall
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D015926:Complement C3a / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006331:Heart Diseases / Q000209:etiology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000473:pathology*; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010196:Pancreatic Elastase / Q000097:blood; D011183:Postoperative Complications / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D015926:Complement C3a; D010196:Pancreatic Elastase