Comparison of the effectiveness and safety of two insulin infusion protocols in the management of hyperglycemia in critically ill children.

OBJECTIVES: To compare the effectiveness and safety of a paper-based and a computerized algorithm used for tight glycemic control. SETTING: Academic pediatric intensive care unit. DESIGN: Retrospective cohort study. PATIENTS: Two groups of nondiabetic critically ill children with persistent hyperglycemia (blood glucose ≥140 mg/dL [ ≥7.8 mmol/L] for at least 2 hrs) were included. INTERVENTION: One group of patients' blood glucose was controlled at 90-119 mg/dL (5.0-6.6 mmol/L) using the Yale Insulin Infusion Protocol (YIIP), a paper-based protocol. Another group of patients' blood glucose was controlled at 80-110 mg/dL (4.4-6.1 mmol/L) with eProtocol insulin (ePi), a computerized decision support tool. MEASUREMENTS AND MAIN RESULTS: The effectiveness of the protocols was compared using percentages of blood glucose values within target range and glucose variability index. A safety comparison was made using hypoglycemia rates at ≤40 mg/dL (≤2.2 mmol/L), ≤50 mg/dL (≤2.8 mmol/L), and ≤60 mg/dL (≤3.3 mmol/L). Forty-two patients and 12 patients were included in the YIIP and ePi groups, respectively. The percent of values in range was lower in the YIIP group (33%) compared with the ePi group (41%) (p < .001). Mean glucose variability index was comparable in the two groups (18.7 ± 8.9 mg/dL/hr [1.0 ± 0.5 mmol/L/hr] for the YIIP group and 14.4 ± 7.6 mg/dL/hr [0.8 ± 0.4 mmol/L/hr] for the ePi group; p = .111). Hypoglycemia rates were statistically similar in both groups. In the YIIP group, 10% of patients and in the ePi group, 25% of patients had blood glucose ≤40 mg/dL (≤2.2 mmol/L) (p = .168). CONCLUSION: YIIP is less effective but is as safe as ePi in achieving tight glycemic control. We are awaiting the results of two multicenter trials designed to determine the survival benefit of tight glycemic control in children. Further studies are needed to determine the clinical significance of the different glucose metrics in critically ill patients.

Decompensated hyperglycemic hyperosmolarity without significant ketoacidosis in the adolescent and young adult population.

AIM: To identify patients aged 10-30 years with probable hyperglycemic hyperosmolar syndrome (HHS), to describe demographic and clinical profiles, and to attempt to assess risk factors for poor outcomes. STUDY DESIGN: Retrospective cohort study (medical records review). SETTING: A 944-bed tertiary care teaching and research hospital and a 425-bed affiliated facility. PATIENTS: 10-30 year-old patients with a primary or secondary discharge diagnosis of HHS or diabetic ketoacidosis (DKA). Patients with a serum glucose >600 mg/dl in the absence of significant ketoacidosis (possible HHS) were profiled. Further stratification based on measured or calculated serum osmolarity >320 mOsm/kg (probable HHS) was undertaken. INTERVENTIONS: Patients received treatment for hyperglycemic crises, consisting primarily of fluids, electrolyte replacement and insulin. MEASUREMENTS AND MAIN RESULTS: Of the 629 admissions, 10 with a diagnosis of HHS and 33 with a diagnosis of DKA met the initial study criteria for HHS. 60% were African Americans and 89% were new-onset diabetics. From this group, 20 admissions had serum osmolarity > or =320 mOsm/kg. Fisher's exact test and Pearson coefficients were used to examine associations between risk factor and poor outcomes and correlations between admission data and length of hospital stay, respectively. Serious complications occurred in four patients (including two deaths, 10% mortality) and were limited to those with unreversed shock over the first 24 hours of admission and who received <40 ml/kg of intravenous fluids over the first 6 hours of treatment. CONCLUSIONS: HHS was underdiagnosed in this population and occurred disproportionately in African Americans. Serious complications occurred exclusively in those with unreversed shock and inadequate fluid resuscitation.

Pediatric fatality following ingestion of dinitrophenol: postmortem identification of a "dietary supplement".

Dinitrophenol, a chemical currently used as an insecticide, is known to uncouple mitochondrial oxidative phosphorylation. A component of explosives, it has also been used in the past as a food coloring and clothing dye. In the 1930s, physicians prescribed it for weight loss, but this practice was discontinued when reports of cataracts, deaths, and other adverse outcomes came to light. We describe in our report the overdose and fatality of a teenager who purchased the product as a weight loss dietary supplement by mail order. We also describe a laboratory method that allowed postmortem determination of the dinitrophenol concentration in the victim's serum. Her death, despite prompt medical treatment, underscores the danger of dinitrophenol. The easy accessibility and apparent resurgent interest in dinitrophenol as a weight loss agent is extremely timely and troubling.

A critical role of neural-specific JNK3 for ischemic apoptosis.

c-Jun N-terminal kinase (JNK) signaling is an important contributor to stress-induced apoptosis, but it is unclear whether JNK and its isoforms (JNK1, JNK2, and JNK3) have distinct roles in cerebral ischemia. Here we show that JNK1 is the major isoform responsible for the high level of basal JNK activity in the brain. In contrast, targeted deletion of Jnk3 not only reduces the stress-induced JNK activity, but also protects mice from brain injury after cerebral ischemia-hypoxia. The downstream mechanism of JNK3-mediated apoptosis may include the induction of Bim and Fas and the mitochondrial release of cytochrome c. These results suggest that JNK3 is a potential target for neuroprotection therapies in stroke.

Brain death in children.

In 1981, the Report of the Medical Consultants on the Diagnosis of Death established guidelines for the diagnosis of brain death and, in 1995, the American Academy of Neurology published practice parameters to standardize determination of brain death. In 1987, the American Academy of Pediatrics established guidelines for determining brain death in children. Despite the establishment of these guidelines, the declaration of "death" based on the cessation of brain function remains complex and controversial. In this review are discussed the current guiding principles and the controversies in the diagnosis of brain death in children.