Glucose Dysregulation and Neurological Injury Biomarkers in Critically Ill Children

Abstract

Targeting normoglycemia with intensive insulin therapy (IIT) improved short-term outcome of pediatric intensive care unit (PICU) patients but increased the incidence of hypoglycemia. Both hyperglycemia and hypoglycemia may adversely affect the developing brain. We studied the impact of targeting normoglycemia with IIT on brain injury markers. This is a preplanned analysis of PICU patients included in a randomized controlled study. The study was conducted at a university hospital PICU. Seven hundred PICU patients participated. Patients were assigned to IIT targeting normal-for-age fasting blood glucose levels or insulin infusion only to prevent excessive hyperglycemia. Serum S100B and neuron-specific enolase (NSE), biomarkers of astrocytic and neuronal damage, respectively, were measured on fixed days (n = 700) and in a nested case-control design before and after hypoglycemia (n = 126). Admission levels of S100B and NSE differed according to diagnosis and illness severity (P < 0.0001). IIT did not affect the time course of these markers. Patients experiencing hypoglycemia in PICU had higher S100B and NSE from admission onward than those without hypoglycemia. In the nested case-control study, both markers decreased after hypoglycemia (P = 0.001 and P = 0.009), unlike in the controls on matched days. IIT in PICU did not evoke neurological damage detectable by circulating S100B and NSE, despite increased incidence of hypoglycemia. Elevated markers in patients with hypoglycemia were not caused by hypoglycemia itself but rather reflect an increased incidence of hypoglycemia in the most severely ill. This hypoglycemia risk appears difficult to capture by classical illness severity scores.