title: Inflammatory response after neonatal cardiac surgery and its relationship to clinical outcomes.
abstract: BACKGROUND
  Cardiac surgery in infants results in a profound inflammatory response secondary to cardiopulmonary bypass (CPB) and the need for blood products. It is not clear how this inflammatory response modulates postoperative course or whether quantification of proinflammatory cytokines can aid with risk stratification. In this study, we prospectively assessed a panel of candidate markers to determine the time course for inflammation and the association of specific markers with clinical outcomes defined as intensive care unit length of stay (LOS).
  
  
  METHODS
  We obtained preoperative blood samples from 92 neonates undergoing surgery with CPB and then serially for 5 days after surgery. Numerous interleukins were assayed along with tumor necrosis factor (TNF)-alpha and interferon (INF)-gamma. The most common surgical procedures were arterial switch procedure (n = 35) and Norwood operation (n = 34). Multivariate analysis was performed to determine if inflammatory mediators could independently predict prolonged intensive care unit LOS.
  
  
  RESULTS
  Compared with the presurgery level, there were statistically significant increases (p < 0.005) for 8 out of 11 inflammatory markers: INF-gamma, interleukin (IL)-10, IL-13, IL-2, IL-5, IL-8, TNF-alpha, and IL-6 after surgery. The only cytokine on the first postoperative day that was independently associated with prolonged length of stay was IL-8 (p = 0.002). Cytokine values measured on postoperative day 3 were most valuable in predicting prolonged LOS. A model that included use of circulatory arrest, and day 3 measures of IL-6 and IL-8 yielded an area under of the curve of 0.88 (95% confidence interval 0.79 to 0.96) for predicting a prolonged LOS.
  
  
  CONCLUSIONS
  In summary, neonatal heart surgery for complex lesions elicits a broad inflammatory response. This early inflammatory response appears nonspecific and did not predict clinical course. Persistence of specific inflammatory mediators on the third day after surgery, however, provided important prognostic information. As such, select cytokines may serve as valuable biomarkers in this population. Whether strategies targeting specific cytokines can alter clinical course is not known.
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia. Electronic address: wmahle@emory.edu.
authors.forename: William T
authors.initials: WT
authors.lastname: Mahle
authors.affiliation: Rollins School of Public Health, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Emilia
authors.initials: E
authors.lastname: Matthews
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Kanter
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Kogon
authors.affiliation: Division of Neonatology, Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Shannon E G
authors.initials: SE
authors.lastname: Hamrick
authors.affiliation: Rollins School of Public Health, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Strickland
mesh_terms: D015415:Biomarkers / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000097:blood* / Q000209:etiology*; D007902:Length of Stay; D008297:Male; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016207:Cytokines