Inflammatory Response After Neonatal Cardiac Surgery and Its Relationship to Clinical Outcomes

Abstract

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). 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. 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. 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.