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Original Articles: Pediatric Cardiac

Invited Commentary

Division of Cardiothoracic Surgery, Rhode Island Hospital, Warren Alpert School of Medicine, Brown University, 1 Hoppin St, Room S.230, Providence, RI 02903

(Email: jfeng{at}lifespan.org).

Hyperglycemia is associated with increased severity of illness and subsequent morbidity and mortality. Evidence suggests that even a short period of hyperglycemia leads to the long lasting up-regulation of gene expression that is associated with activation of inflammatory factors. A recent prospective, randomized controlled trial demonstrated that tight glycemic control (TGC) reduces morbidity and mortality of critically ill children undergoing congenital heart operations [1].

In this article, Vlasselaers and colleagues extend their previous studies regarding intensive insulin therapy in pediatric patients to selected neonates in intensive care who underwent congenital heart operations [2]. There are three important, novel findings in this study:

1 Intraoperative and postoperative TGC in neonates significantly reduced circulating levels of cardiac troponin-I, heart fatty acid-binding protein, and B-type natriuretic peptide, suggesting that TGC protects the reperfused myocardium.

2 TGC suppressed the release of proinflammatory cytokines and C-reactive protein, indicating that TGC reduces the inflammatory response, which may also contribute to protecting the reperfused myocardium.

3 Intensive insulin therapy failed to increase myocardial levels of several prosurvival and insulin-related protein kinases compared with the control group, demonstrating that TGC-mediated benefits are mediated by preventing hyperglycemia rather than by directly affecting the insulin-signaling pathway.

The short-term benefits offered by TGC in the present study may affect the long-term clinical outcomes in the TGC infants. Thus, the article of Vlasselaers and colleagues not only provides new evidence for the significance of tightly controlling glycemia in congenital heart patients but also paves the way for understanding the mechanism responsible for TGC-induced myocardial protection.

This interesting and preliminary study, with a relatively small sample size of 14 patients, has left a number of issues to be further addressed regarding TGC-related myocardial protection and antiinflammation. Did TGC affect proapoptosis signaling, such as B-cell lymphoma 2 (Bcl-2) family-protein expression, cytochrome C release, caspases activity, and cells positive for terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling in the reperfused myocardium? Did TGC prevent the activation or release of inflammatory factors of the myocardium?

Hypoglycemia can also be very detrimental to critically ill patients. Recently, investigators and pediatric intensivists have questioned how—or if—they should apply intensive glycemic control to their patients [3–6]. The debate is focusing on the issues of the optimal target range of blood glucose and the safety of intensive glycemic control [3–6]. Specifically, in the present study, four episodes of risk hypoglycemia developed in 2 of 7 patients.

Although no deleterious symptoms of hypoglycemic events have been identified, little is known about the long-term consequences of hypoglycemia in critically ill neonates. Overall, this work is a substantial contribution to the current knowledge of glycemic control in critically ill infants undergoing congenital heart operations and intensive care, suggesting opportunities for future study in a randomized, blinded, large-sample-size, and multicenter fashion. In addition, new techniques, such as more accurate systems for blood glucose measurement, combined with algorithm-driven treatment protocols during TGC, need to be developed to minimize the risk of iatrogenic hypoglycemia.

	References

Top References

 

1. Vlasselaers D, Milants I, Desmet L, et al. Intensive insulin therapy for patients in pediatric intensive care: a prospective, randomized controlled study Lancet 2009;373:547-556.[Medline]
2. Vlasselaers D, Mesotten D, Langouche L, et al. Tight glycemic control protects the myocardium and reduces inflammation in neonatal heart surgery Ann Thorac Surg 2010;90:22-30.[Abstract/Free Full Text]
3. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU N Engl J Med 2006;354:449-461.[Medline]
4. NICE-SUGAR Study Investigators Intensive versus conventional insulin therapy in critically ill patients N Engl J Med 2009;360:1283-1297.[Medline]
5. Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis JAMA 2008;300:933-944.[Abstract/Free Full Text]
6. Egi M, Bellomo R, Stachowski E, et al. Hypoglycemia and outcome in critically ill patients Mayo Clin Proc 2010;85:217-224.[Abstract/Free Full Text]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Jun Feng Frank W. Sellke Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Feng, J. Articles by Sellke, F. W. Search for Related Content PubMed PubMed Citation Articles by Feng, J. Articles by Sellke, F. W. Related Collections Cardiac - pharmacology Congenital - cyanotic Related Article