Abstract 13917: A Pro-Inflammatory, Hyperinsulin State, Not Hyperglycemia, is Associated With Adverse Outcomes After Pediatric Heart Surgery
Introduction: Hyperglycemia following CPB for congenital heart disease (CHD) may be associated with poor outcomes. This may be due to an insulin resistant, pro-inflammatory state and not directly to hyperglycemia, but this has not been studied.
Hypothesis: The combination of high insulin levels and a heightened inflammatory state is associated with impaired cardiac output and adverse clinical outcomes following CPB for CHD.
Methods: Children undergoing CPB for CHD were prospectively enrolled. Plasma hormone and cytokine levels were measured for up to 72 hours following surgery and results were log transformed for analysis. A subset of children in the ICU had cardiac index (CI) measured by respiratory mass spectrometry. Data on standard clinical outcomes were recorded.
Results: 157 children (mean age 3.6 years, IQR 0.33-4.44) were enrolled. 31% had peak glucose 180-270 mg/dL and 17% > 270 mg/dL. 22 subjects (14%) reached the composite adverse outcome consisting of shock, seizures, renal or hepatic dysfunction, infection, cardiac arrest, ECMO or death (n=3). Glucose > 270 mg/dL was associated with a combination of higher IL6 and insulin (p=0.05) and trended toward association with the composite outcome (p=0.09). Higher IL6, IL8 and IL10 were each associated with lower glucose/insulin ratios (EST: -1.8 (0.6), p=0.002; -1.8 (0.4), p<0.001 and -1.7 (0.6), p=0.01 respectively), an indirect marker of insulin resistance. This ratio was lower in those reaching the composite outcome (3.1 vs. 4.7, p=0.001). IL6, IL8 and IL10 were increased in those subjects who developed the composite outcome (EST: +0.6 (0.2), p=0.01; +1.0 (0.3), p=0.002 and +0.6 (0.3), p=0.05 respectively). Multivariable analysis including cytokines, insulin and glucose revealed that interaction between insulin and IL6 showed the strongest association with odds of reaching the composite outcome (OR: 1.02/IL6*insulin, p=0.02) and with lower CI (EST: -0.21 (0.08) ml/min/kg per IL6*insulin, p=0.01). Hyperglycemia was associated with neither outcome nor CI in this model.
Conclusion: It is the interaction of a pro-inflammatory state and high insulin, and not hyperglycemia, which is associated with outcome after CPB for CHD. This may be due to insulin resistance and mediated by adverse effects on CI.
- Insulin resistance
- Pediatric cardiac intensive care
- Congenital heart disease
- Congenital heart surgery
- © 2011 by American Heart Association, Inc.