International Journal of Infectious Diseases 15 (2011) e504
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Letter to the Editor Meningococcal septic shock: is insulin lifesaving in children? Meningococcal septic shock (MSS) is a fulminant form of sepsis characterized by an overwhelming production of pro- and antiinflammatory cytokines, together with metabolic derangement.1 Hyperglycemia is associated with a significantly worse outcome in children affected by meningococcal sepsis.2 In critically ill adult patients in general, and in patients with sepsis in particular, hyperglycemia and insulin resistance are long universal findings.3 In contrast, in critically ill children with MSS, hyperglycemia correlated with hypoinsulinemia rather than insulin resistance has been described.1 Intensive insulin therapy has already been recommended for the management of hyperglycemia in severe sepsis and septic shock in some adult populations, but there is a paucity of data for the pediatric intensive care setting.1,3 Evidence is growing that strictly maintaining normoglycemia improves the outcome in critical illness, decreasing both morbidity and mortality.2,3 However the risk of hypoglycemia has raised concerns about insulin supplementation, even if its clinical relevance remains to be defined.1,3 Whether intensive insulin therapy per se or lowered glucose levels by intensive insulin therapy is the main mechanism in the beneficial effect of tight glycemic control has yet to be determined.2,3It has recently been reported that anti-inflammatory effects of insulin may contribute to the protective benefits against organ injury/dysfunction caused by extensive systemic inflammation, independently of any effect on blood glucose.3,4 Insulin has been shown to reduce the catabolic response, as well as to control hyperglycemia and limit apoptosis damage.3,4 It seems to have the ability to suppress the production of proinflammatory cytokines and acute phase proteins with a direct effect on the transcriptional nuclear factor-kappa B (NF-kB) that modulates the proinflammatory cytokines, adhesion molecules and chemokines.4–6 Insulin has been described to suppress the production of tumor necrosis factor-alpha (TNF-a), interleukin-1 (IL-1), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), and reactive oxygen species (ROS).5,6 In addition, this hormone has been described to increase the production of antiinflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) and the synthesis of endothelial nitric oxide (eNO).4–6
With respect to the above, we hypothesize that children suffering from MSS with insulin deficiency may derive clinical benefits from insulin replacement, because this approach may be considered as supplementing a deficient vital hormone. Insulin may be lifesaving by suppressing systemic inflammation independently of controlling hyperglycemia. Randomized controlled trials are needed in order to introduce intensive insulin therapy into the treatment guidelines for this group of patients. Conflict of interest: No conflict of interest to declare. References 1. van Waardenburg DA, Jansen TC, Vos GD, Buurman WA. Hyperglycemia in children with meningococcal sepsis and septic shock: the relation between plasma levels of insulin and inflammatory mediators. J Clin Endocrinol Metab 2006;91:3916–21. 2. Day KM, Haub N, Betts H, Inwald DP. Hyperglycemia is associated with morbidity in critically ill children with meningococcal sepsis. Pediatr Crit Care Med 2008;9:636–40. 3. Hirasawa H, Oda S, Nakamura M. Blood glucose control in patients with severe sepsis and septic shock. World J Gastroenterol 2009;15:4132–6. 4. Das UN. Insulin in the critically ill with focus on cytokines, reactive oxygen species, HLA-DR expression. J Assoc Physicians India 2007;55(Suppl):56–65. 5. Dugo L, Collin M, Allen Da, Murch O, Foster SJ, Yaqoob MM, et al. Insulin reduces the multiple organ injury and dysfunction caused by coadministration of lipopolysaccharide and peptidoglycan independently of blood glucose: role of glycogen synthase kinase-3beta inhibition. Crit Care Med 2006;34:1489–96. 6. Kidd LB, Schabbauer GA, Luyeudyk JP, Holscher TD, Tilley RE, Tencati M, et al. Insulin activation of the phosphatidylinositol 3-kinase/protein kinase B (Akt) pathway reduces lipopolysaccharide-induced inflammation in mice. J Pharmacol Exp Ther 2008;326:348–53.
Raffaella Mormilea, *, Mario De Micheleb Division of Pediatrics, Moscati Hospital, Via A. Gramsci, 81031 Aversa, Italy b Division of Cardiology, Moscati Hospital, Aversa, Italy
a
Corresponding Editor: William Cameron, Ottawa, Canada *Corresponding author. Tel.: +39 081 5001503 E-mail addresses:
[email protected] [email protected] (R. Mormile).
1201-9712/$36.00 – see front matter ß 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2011.03.012
3 February 2011
