Applied nutritional investigationBaseline insulin/glucose ratio as a marker for the clinical course of hyperglycemic critically ill children treated with insulin
Introduction
Critical illness is associated with many endocrine, metabolic, and immunologic changes [1]. One of these is hyperglycemia, which is caused by a complex interaction of endogenous and exogenous factors. Hepatic insulin resistance, the resulting excessive gluconeogenesis, and impaired glucose use in peripheral tissues are considered to be the driving forces behind stress hyperglycemia in critically ill adults [2], [3]. Studies in critically ill children have reported an association between hyperglycemia and morbidity (e.g., longer length of stay [LOS] in the intensive care unit [ICU], duration of ventilator use, and an adverse neurologic outcome) [1].
The underlying mechanisms of hyperglycemia and risk factors in critically ill children have been little studied and only in small groups of patients [4], [5]. Van Waardenburg et al. [4] proposed that hyperglycemia associated with hypoinsulinemia rather than insulin resistance may be the normal pathophysiologic response, at least in children with meningococcal septic shock. Preissig and Rigby [5] reported a different etiology of hyperglycemia in critically ill children that is dependent on the presence of respiratory and/or cardiovascular failure. Insulin resistance, as defined by an increased C-peptide/glucose ratio, was the prominent cause of hyperglycemia in children with respiratory failure only versus primary β-cell dysfunction in children with respiratory and cardiovascular failures [5].
Intensive insulin therapy in critically ill children (targeting blood glucose concentrations 2.8–4.4 mmol/L [50–80 mg/dL] in infants and 3.9–5.5 mmol/L [70–100 mg/dL] in older children) resulted in shorter ICU LOS and fewer secondary infections [6]. We have successfully implemented a nurse-driven glucose control protocol for critically ill children of all ages with hyperglycemia (defined as blood glucose level >8 mmol/L [>145 mg/dL]) at any time during admission. This resulted in normoglycemia within 12 h for 94% of the children involved without episodes of hypoglycemia (≤2.2 mmol/L) [7].
The focus of our research was to investigate the relations of baseline insulin/glucose ratio to the clinical course of critically ill children. Such information will provide insight into the pathophysiologic mechanisms leading to hyperglycemia and will optimize preventive and therapeutic measures for hyperglycemia in critically ill children.
Better insight into the pathophysiologic mechanisms leading to hyperglycemia will enable the implementation of optimal preventive and therapeutic measures concerning hyperglycemia in critically ill children. We related the endogenous insulin response to hormonal parameters (insulin and cortisol), metabolic parameters (free fatty acids, triacylglycerols, cholesterol, and lactate) and immunologic parameters (C-reactive protein and white blood cell count) just before the start of insulin therapy.
Because insulin therapy increases the risk of hypoglycemia with its adverse effects, it seemed essential to define the categories of critically ill children who might benefit from insulin therapy. Therefore, we also looked at specific laboratory and clinical markers that might predict a beneficial effect from insulin therapy.
Section snippets
Setting
The pediatric ICU (PICU) of the university children’s hospital is a tertiary 34-bed multidisciplinary unit providing for high acute medical and surgical conditions in children up to 18 y old.
Design
This was a prospective evaluation of critically ill children 2 wk to 18 y of age consecutively admitted to the PICU of the Erasmus MC–Sophia Children’s Hospital from January 2006 through July 2009 and showing hyperglycemia (defined as blood glucose level >8 mmol/L [>145 mg/dL]) that met the criteria for
Baseline characteristics
The study group consisted of 64 children (24 girls, median age 7.0 y, range 0.3–16.9 y) with various diagnoses. Fifty-one had respiratory or cardiovascular failure, for which they received mechanical ventilation or inotropic support. There were no children with severe hepatic failure. One child was admitted with acute renal insufficiency requiring dialysis therapy. Eleven children (17%) died during PICU admission. Five of them died during insulin therapy. Patients’ characteristics just before
Discussion
In this study, children with a hyperinsulinemic response were more often mechanically ventilated and had significant longer durations of insulin therapy, mechanical ventilation, and PICU LOS than children with a hypoinsulinemic response. The duration of hospital stay, mortality, and other clinical outcome parameters did not differ between the two groups. A recent study in critically ill adults found no differences in morbidity or mortality between patients with an overt insulin resistance and
Conclusions
Hyper- and hypoinsulinemic responses play a role in the occurrence of hyperglycemia in critically ill children. A hyperinsulinemic response was associated with longer durations of insulin therapy, mechanical ventilation, and PICU LOS compared with a hypoinsulinemic response. Most children without respiratory failure showed relatively low insulin levels and insulin/glucose ratios, and they received insulin therapy only briefly. Therefore, the insulin/glucose ratio in combination with type of
Acknowledgments
The authors acknowledge K. Hagoort for his careful editing and Prof. Dr. D. Tibboel for critically reviewing the report.
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