Pyuria in Children with Diabetic Ketoacidosis.

Acute kidney injury occurs frequently during pediatric diabetic ketoacidosis (DKA). We reviewed urinalyses from 561 children with DKA; pyuria was detected in 19% overall and in 40% of children with more comprehensive urine testing (≥3 urinalyses) during DKA.

Clinical Characteristics of Children with Cerebral Injury preceding Treatment of Diabetic Ketoacidosis.

Previous studies have identified more severe acidosis and higher blood urea nitrogen (BUN) as risk factors for cerebral injury during treatment of diabetic ketoacidosis (DKA) in children; however, cerebral injury also can occur before DKA treatment. We found that lower pH and higher BUN levels also were associated with cerebral injury at presentation.

Hypertension during Diabetic Ketoacidosis in Children.

OBJECTIVES: To characterize hemodynamic alterations occurring during diabetic ketoacidosis (DKA) in a large cohort of children and to identify clinical and biochemical factors associated with hypertension. STUDY DESIGN: This was a planned secondary analysis of data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in DKA Study, a randomized clinical trial of fluid resuscitation protocols for children in DKA. Hemodynamic data (heart rate, blood pressure) from children with DKA were assessed in comparison with normal values for age and sex. Multivariable statistical modeling was used to explore clinical and laboratory predictors of hypertension. RESULTS: Among 1258 DKA episodes, hypertension was documented at presentation in 154 (12.2%) and developed during DKA treatment in an additional 196 (15.6%), resulting in a total of 350 DKA episodes (27.8%) in which hypertension occurred at some time. Factors associated with hypertension at presentation included more severe acidosis, (lower pH and lower pCO2), and stage 2 or 3 acute kidney injury. More severe acidosis and lower Glasgow Coma Scale scores were associated with hypertension occurring at any time during DKA treatment. CONCLUSIONS: Despite dehydration, hypertension occurs in a substantial number of children with DKA. Factors associated with hypertension include greater severity of acidosis, lower pCO2, and lower Glasgow Coma Scale scores during DKA treatment, suggesting that hypertension might be centrally mediated.

Regional Brain Water Content and Distribution During Diabetic Ketoacidosis.

OBJECTIVE: To characterize regional differences in brain water distribution and content during diabetic ketoacidosis (DKA) in children and determine whether these differences correlate with regional vascular supply. STUDY DESIGN: We compared changes in brain water distribution and water content in different brain regions during DKA by analyzing magnetic resonance diffusion weighted imaging data collected during DKA and after recovery in 45 children (<18 years of age). We measured the apparent diffusion coefficient (ADC) of water in the frontal and occipital cortex, basal ganglia, thalamus, hippocampus, and medulla. Brain water content was also measured in a subset of patients. RESULTS: ADC values were elevated (suggesting vasogenic cerebral edema) in the frontal cortex, basal ganglia, thalamus, and hippocampus during DKA. In contrast, ADC values in the medulla and the occipital cortex were not increased during DKA, and ADC changes in the medulla tended to be negatively correlated with other regions. Regions supplied by the anterior/middle cerebral artery circulation had greater elevations in both ADC and brain water content during DKA compared with regions supplied by the posterior cerebral artery circulation. CONCLUSIONS: ADC changes during DKA in the brainstem contrast with those of other brain regions, and changes in both ADC and brain water content during DKA vary according to regional vascular supply. These data suggest that brainstem blood flow might possibly be reduced during DKA concurrent with hyperemia in other brain regions.

Cerebral hyperemia measured with near infrared spectroscopy during treatment of diabetic ketoacidosis in children.

OBJECTIVE: To use near infrared spectroscopy (NIRS) to evaluate the timing of onset and duration of cerebral hyperemia during diabetic ketoacidosis (DKA) treatment in children, and to investigate the relationship of cerebral hyperemia to intravenous fluid treatment. STUDY DESIGN: We randomized children aged 8-18 years with DKA to either more rapid or slower intravenous fluid treatment (19 total DKA episodes). NIRS was used to measure rSo2 during DKA treatment. NIRS monitoring began as soon as informed consent was obtained and continued until the patient was transferred out of the critical care unit. RESULTS: rSo2 values above the normal range (>80%) were detected in 17 of 19 DKA episodes (mean rSo2 during initial 8 hours of DKA treatment: 86% ± 7%, range 65%-95%). Elevated rSo2 values were detected as early as the second hour of DKA treatment and persisted for as long as 27 hours. Hourly mean rSo2 levels during treatment did not differ significantly by fluid treatment group. CONCLUSIONS: During DKA treatment, children have elevated rSo2 values consistent with cerebral hyperemia. Hyperemia occurs as early as the second hour of DKA treatment and may persist for ≥ 27 hours. Cerebral rSo2 levels during treatment did not differ significantly in patients treated with slower versus more rapid intravenous rehydration.

Diabetic ketoacidosis and memory dysfunction in children with type 1 diabetes.

OBJECTIVE: We tested the hypothesis that diabetic ketoacidosis (DKA) results in memory deficits typical of hypoxic/ischemic injury because recent studies suggest that cerebral metabolic changes similar to those observed in hypoxic/ischemic cerebral injury are observed in children with DKA, even without symptoms suggesting cerebral injury. STUDY DESIGN: Thirty-three children with type 1 diabetes mellitus (T1DM) and a history of DKA and 29 children with T1DM without a history of DKA were enrolled from an academic hospital pediatric endocrinology clinic. These groups were comparable on demographic and disease-related variables. These groups' ability to recall events in association with specific details, the memory function most directly affected by mild hypoxia/ischemia, was compared on 2 tasks (ie, event-color associations and event-spatial position associations). RESULTS: In multivariate analyses controlling for other critical variables, children with DKA history had significantly lower rates of accurate memory on both tasks (mean, 0.34 +/- 0.13 on the color task and 0.57 +/- 0.15 on the spatial task) than did children without DKA history (mean, 0.44 +/- 0.11 and 0.65 +/- 0.18, P < .01). CONCLUSIONS: DKA disrupts memory function, underscoring the importance of DKA prevention when T1DM is known and prompt diagnosis of children with new onset of T1DM.

Correlation of clinical and biochemical findings with diabetic ketoacidosis-related cerebral edema in children using magnetic resonance diffusion-weighted imaging.

OBJECTIVE: To determine clinical and biochemical factors influencing cerebral edema formation during diabetic ketoacidosis (DKA) in children. STUDY DESIGN: We used magnetic resonance diffusion-weighted imaging to quantify edema formation. We measured the apparent diffusion coefficient (ADC) of brain water during and after DKA treatment in 26 children and correlated ADC changes with clinical and biochemical variables. RESULTS: Mean ADC values were elevated during DKA treatment compared with baseline (8.13 +/- 0.47 vs 7.74 +/- 0.49 x 10(-4) mm(2)/sec, difference in means 0.40, 95% CI: 0.25 to 0.55, P < .001). Children with altered mental status during DKA had greater elevation in ADC. ADC elevation during DKA was positively correlated with initial serum urea nitrogen concentration (correlation coefficient 0.41, P = .03) and initial respiratory rate (correlation coefficient 0.61, P < .001). ADC elevation was not significantly correlated with initial serum glucose, sodium or effective osmolality, nor with changes in glucose, sodium or osmolality during treatment. Multivariable analyses identified the initial urea nitrogen concentration and respiratory rate as independently associated with ADC elevation. CONCLUSIONS: The degree of edema formation during DKA in children is correlated with the degree of dehydration and hyperventilation at presentation, but not with factors related to initial osmolality or osmotic changes during treatment. These data support the hypothesis that CE is related to cerebral hypoperfusion during DKA, and that osmotic fluctuations during DKA treatment do not play a primary causal role.

Mechanism of cerebral edema in children with diabetic ketoacidosis.

OBJECTIVES: Cerebral edema during diabetic ketoacidosis (DKA) has been attributed to osmotic cellular swelling during treatment. We evaluated cerebral water distribution and cerebral perfusion during DKA treatment in children. STUDY DESIGN: We imaged 14 children during DKA treatment and after recovery, using both diffusion and perfusion weighted magnetic resonance imaging (MRI). We assessed the apparent diffusion coefficients (ADCs) and measures reflecting cerebral perfusion. RESULTS: The ADC was significantly elevated during DKA treatment (indicating increased water diffusion) in all regions except the occipital gray matter. Mean reductions in the ADC from initial to postrecovery MRI were: basal ganglia 4.7 +/- 2.5 x 10(-5) mm(2)/s (P=.002), thalamus 3.7 +/- 2.8 x 10(-5) mm(2)/s, (P=.002), periaqueductal gray matter 4.3 +/- 5.1 x 10(-5) mm(2)/s (P=.03), and frontal white matter 2.0 +/- 3.1 x 10(-5) mm(2)/s (P=.03). In contrast, the ADC in the occipital gray matter increased significantly from the initial to postrecovery MRI (mean increase 3.9 +/- 3.9 x 10(-5) mm(2)/s, P=.004). Perfusion MRI during DKA treatment revealed significantly shorter mean transit times (MTTs) and higher peak tracer concentrations, possibly indicating increased cerebral blood flow (CBF). CONCLUSIONS: Elevated ADC values during DKA treatment suggests a vasogenic process as the predominant mechanism of edema formation rather than osmotic cellular swelling.