Tight glycemic control protects the myocardium and reduces inflammation in neonatal heart surgery.
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.
Vlasselaers
Dirk
D
Department of Intensive Care Medicine, Katholieke Universiteit Leuven, Belgium. dirk.vlasselaers@uzleuven.be
Mesotten
Dieter
D
Langouche
Lies
L
Vanhorebeek
Ilse
I
van den Heuvel
Ingeborg
I
Milants
Ilse
I
Wouters
Pieter
P
Wouters
Patrick
P
Meyns
Bart
B
Bjerre
Mette
M
Hansen
Troels Krarup
TK
Van den Berghe
Greet
G
D001786:Blood Glucose / Q000378:metabolism*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D016638:Critical Illness / Q000628:therapy; D006330:Heart Defects, Congenital / Q000097:blood / Q000601:surgery; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007231:Infant, Newborn; D007328:Insulin / Q000008:administration & dosage; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D011446:Prospective Studies; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin