Critical illness hyperglycemia: is failure of the beta-cell to meet extreme insulin demand indicative of dysfunction?

In the recent study by Preissig and Rigby in Critical Care, the authors argue that critical illness hyperglycemia in children with both respiratory failure and cardiovascular failure is due to a primary failure of the beta-cell. However, alternative explanations that the failure is secondary to an increase in insulin resistance leading to beta-cell exhaustion, or a negative impact of exogenous glucocorticoid therapy, may be equally likely

Tight Glycemic Control After Pediatric Cardiac Surgery in High-Risk Patient Populations

Background—Our previous randomized, clinical trial showed that postoperative tight glycemic control (TGC) for children undergoing cardiac surgery did not reduce the rate of health care–associated infections compared with standard care (STD). Heterogeneity of treatment effect may exist within this population. Methods and Results—We performed a post hoc exploratory analysis of 980 children from birth to 36 months of age at the time of cardiac surgery who were randomized to postoperative TGC or STD in the intensive care unit. Significant interactions were observed between treatment group and both neonate (age ≤30 days; P=0.03) and intraoperative glucocorticoid exposure (P=0.03) on the risk of infection. The rate and incidence of infections in subjects ≤60 days old were significantly increased in the TGC compared with the STD group (rate: 13.5 versus 3.7 infections per 1000 cardiac intensive care unit days, P=0.01; incidence: 13% versus 4%, P=0.02), whereas infections among those \u3e60 days of age were significantly reduced in the TGC compared with the STD group (rate: 5.0 versus 14.1 infections per 1000 cardiac intensive care unit days, P=0.02; incidence: 2% versus 5%, P=0.03); the interaction of treatment group by age subgroup was highly significant (P=0.001). Multivariable logistic regression controlling for the main effects revealed that previous cardiac surgery, chromosomal anomaly, and delayed sternal closure were independently associated with increased risk of infection. Conclusions—This exploratory analysis demonstrated that TGC may lower the risk of infection in children \u3e60 days of age at the time of cardiac surgery compared with children receiving STD. Meta-analyses of past and ongoing clinical trials are necessary to confirm these findings before clinical practice is altered

Design and Rationale of Safe Pediatric Euglycemia After Cardiac Surgery (SPECS): A Randomized Controlled Trial of Tight Glycemic Control After Pediatric Cardiac Surgery

Objectives: To describe the design of a clinical trial testing the hypothesis that children randomized to tight glycemic control with intensive insulin therapy after cardiac surgery will have improved clinical outcomes compared to children randomized to conventional blood glucose management. Design: Two-center, randomized controlled trial. Setting: Cardiac ICUs at two large academic pediatric centers. Patients: Children from birth to those aged 36 months recovering in the cardiac ICU after surgery with cardiopulmonary bypass. Interventions: Subjects in the tight glycemic control (intervention) group receive an intravenous insulin infusion titrated to achieve normoglycemia (target blood glucose range of 80–110 mg/dL; 4.4–6.1 mmol/L). The intervention begins at admission to the cardiac ICU from the operating room and terminates when the patient is ready for discharge from the ICU. Continuous glucose monitoring is performed during insulin infusion to minimize the risks of hypoglycemia. The standard care group has no target blood glucose range. Measurements and Main Results: The primary outcome is the development of any nosocomial infection (bloodstream, urinary tract, and surgical site infection or nosocomial pneumonia). Secondary outcomes include mortality, measures of cardiorespiratory function and recovery, laboratory indices of nutritional balance, immunologic, endocrinologic, and neurologic function, cardiac ICU and hospital length of stay, and neurodevelopmental outcome at 1 and 3 yrs of age. A total of 980 subjects will be enrolled (490 in each treatment arm) for sufficient power to show a 50% reduction in the prevalence of the primary outcome. Conclusions: Pediatric cardiac surgery patients may recognize great benefit from tight glycemic control in the postoperative period, particularly with regard to reduction of nosocomial infections. The Safe Pediatric Euglycemia after Cardiac Surgery trial is designed to provide an unbiased answer to the question of whether this therapy is indeed beneficial and to define the associated risks of therapy

Tight glycemic control in the ICU - is the earth flat?

Tight glycemic control in the ICU has been shown to reduce mortality in some but not all prospective randomized control trials. Confounding the interpretation of these studies are differences in how the control was achieved and underlying incidence of hypoglycemia, which can be expected to be affected by the introduction of continuous glucose monitoring (CGM). In this issue of Critical Care, a consensus panel provides a list of the research priorities they believe are needed for CGM to become routine practice in the ICU. We reflect on these recommendations and consider the implications for using CGM today