Original article
Pediatric cardiac
Tight Glycemic Control Protects the Myocardium and Reduces Inflammation in Neonatal Heart Surgery

https://doi.org/10.1016/j.athoracsur.2010.03.093Get rights and content

Background

Neonatal cardiac surgery evokes hyperglycemia and a systemic inflammatory response. Hyperglycemia is associated with intensified inflammation and adverse outcome in critically ill children and in pediatric cardiac surgery. Recently we demonstrated that tight glycemic control (TGC) reduced morbidity and mortality of critically ill children. Experimental data suggest that insulin protects the myocardium in the setting of ischemia-reperfusion injury, but this benefit could be blunted by coinciding hyperglycemia. We hypothesized that insulin-titrated TGC, initiated prior to myocardial ischemia and reperfusion, protects the myocardium and attenuates the inflammatory response after neonatal cardiac surgery.

Methods

This is a prospective randomized study at a university hospital. Fourteen neonates were randomized to intraoperative and postoperative conventional insulin therapy or TGC. Study endpoints were effects on myocardial damage and function; inflammation, endothelial activation, and clinical outcome parameters.

Results

Tight glycemic control significantly reduced circulating levels of cardiac troponin-I (p = 0.009), heart fatty acid-binding protein (p = 0.01), B-type natriuretic peptide (p = 0.002), and the need for vasoactive support (p = 0.008). The TGC suppressed the rise of the proinflammatory cytokines interleukin-6 (p = 0.02) and interleukin-8 (p = 0.05), and reduced the postoperative increase in C-reactive protein (p = 0.04). Myocardial concentrations of Akt, endothelial nitric-oxide synthase, and their phosphorylated forms were not different between groups.

Conclusions

In neonates undergoing cardiac surgery, intraoperative and postoperative TGC protects the myocardium and reduces the inflammatory response. This appears not to be mediated by an early, direct insulin signaling effect, but may rather be due to independent effects of preventing hyperglycemia during reperfusion.

Section snippets

Patients

This study comprised a predefined subgroup analysis as part of a prospective randomized controlled trial [6]. A subgroup of neonates with transposition of the great arteries (d-TGA) or truncus arteriosus, scheduled for surgical repair, was prospectively and randomly assigned to conventional insulin therapy (CIT) or TGC, initiated at induction of anesthesia and continued throughout surgery and stay in the pediatric (P) ICU. Allocation to treatment groups was done by sealed envelopes. The

Demography and Clinical Outcome

Fourteen neonates were included, 7 in each group. There were no differences between groups in baseline characteristics and CPB variables. Median time to extubation tended to be shorter in the TGC group. There were no significant differences in renal function and duration of stay in PICU and the hospital. There were no early or late deaths. The lower incidence of DSC (29% vs 0%) and need for PM (57% vs 14%) in the first 48 hours in the TGC group was not significant (Table 2).

Glucose and Insulin

In the TGC group BG

Comment

This study demonstrates that intraoperative and postoperative TGC in neonatal CHS protected the myocardium and attenuated the inflammatory response evoked by the surgical procedure, which may favorably affect clinical outcome. This did not appear to be mediated by direct insulin signaling effects, but to effects of preventing hyperglycemia during reperfusion.

Implementing TGC carries the risk of evoking biochemical hypoglycemia. We could not identify any deleterious symptoms of these

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