Cerebral edema is an uncommon but devastating complication of diabetic ketoacidosis in children. Risk factors for this complication have not been clearly defined. In this multicenter study, we identified 61 children who had been hospitalized for diabetic ketoacidosis within a 15-year period and in whom cerebral edema had developed. Two additional groups of children with diabetic ketoacidosis but without cerebral edema were also identified: 181 randomly selected children and 174 children matched to those in the cerebral-edema group with respect to age at presentation, onset of diabetes (established vs. newly diagnosed disease), initial serum glucose concentration, and initial venous pH. Using logistic regression, we compared the three groups with respect to demographic characteristics and biochemical variables at presentation and compared the matched groups with respect to therapeutic interventions and changes in biochemical values during treatment. A comparison of the children in the cerebral-edema group with those in the random control group showed that cerebral edema was significantly associated with lower initial partial pressures of arterial carbon dioxide (relative risk of cerebral edema for each decrease of 7.8 mm Hg [representing 1 SD], 3.4; 95 percent confidence interval, 1.9 to 6.3; P<0.001) and higher initial serum urea nitrogen concentrations (relative risk of cerebral edema for each increase of 9 mg per deciliter [3.2 mmol per liter] [representing 1 SD], 1.7; 95 percent confidence interval, 1.2 to 2.5; P=0.003). A comparison of the children with cerebral edema with those in the matched control group also showed that cerebral edema was associated with lower partial pressures of arterial carbon dioxide and higher serum urea nitrogen concentrations. Of the therapeutic variables, only treatment with bicarbonate was associated with cerebral edema, after adjustment for other covariates (relative risk, 4.2; 95 percent confidence interval, 1.5 to 12.1; P=0.008). Children with diabetic ketoacidosis who have low partial pressures of arterial carbon dioxide and high serum urea nitrogen concentrations at presentation and who are treated with bicarbonate are at increased risk for cerebral edema.

Diabetic ketoacidosis in children may cause brain injuries ranging from mild to severe. Whether intravenous fluids contribute to these injuries has been debated for decades. We conducted a 13-center, randomized, controlled trial that examined the effects of the rate of administration and the sodium chloride content of intravenous fluids on neurologic outcomes in children with diabetic ketoacidosis. Children were randomly assigned to one of four treatment groups in a 2-by-2 factorial design (0.9% or 0.45% sodium chloride content and rapid or slow rate of administration). The primary outcome was a decline in mental status (two consecutive Glasgow Coma Scale scores of <14, on a scale ranging from 3 to 15, with lower scores indicating worse mental status) during treatment for diabetic ketoacidosis. Secondary outcomes included clinically apparent brain injury during treatment for diabetic ketoacidosis, short-term memory during treatment for diabetic ketoacidosis, and memory and IQ 2 to 6 months after recovery from diabetic ketoacidosis. A total of 1389 episodes of diabetic ketoacidosis were reported in 1255 children. The Glasgow Coma Scale score declined to less than 14 in 48 episodes (3.5%), and clinically apparent brain injury occurred in 12 episodes (0.9%). No significant differences among the treatment groups were observed with respect to the percentage of episodes in which the Glasgow Coma Scale score declined to below 14, the magnitude of decline in the Glasgow Coma Scale score, or the duration of time in which the Glasgow Coma Scale score was less than 14; with respect to the results of the tests of short-term memory; or with respect to the incidence of clinically apparent brain injury during treatment for diabetic ketoacidosis. Memory and IQ scores obtained after the children’s recovery from diabetic ketoacidosis also did not differ significantly among the groups. Serious adverse events other than altered mental status were rare and occurred with similar frequency in all treatment groups. Neither the rate of administration nor the sodium chloride content of intravenous fluids significantly influenced neurologic outcomes in children with diabetic ketoacidosis. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration; PECARN DKA FLUID ClinicalTrials.gov number, NCT00629707.)

Symptomatic cerebral edema occurs in approximately 1% of children with diabetic ketoacidosis (DKA). However, asymptomatic or subclinical cerebral edema is thought to occur more frequently. Some small studies have found narrowing of the cerebral ventricles indicating cerebral edema in most or all children with DKA, but other studies have not detected narrowing in ventricle size. In this study, we measured the intercaudate width of the frontal horns of the lateral ventricles using magnetic resonance imaging (MRI) in children with DKA during treatment and after recovery from the DKA episode. We determined the frequency of ventricular narrowing and compared clinical and biochemical data for children with and without ventricular narrowing. Forty‐one children completed the study protocol. The lateral ventricles were significantly smaller during DKA treatment (mean width, 9.3 ± 0.3 vs. 10.2 ± 0.3 mm after recovery from DKA, p < 0.001). Children with ventricular narrowing during DKA treatment (22 children, 54%) were more likely to have mental status abnormalities than those without narrowing [12/22 vs. 4/19 with Glasgow Coma Scale (GCS) scores below 15 during therapy, p = 0.03]. Multiple logistic regression analysis revealed that a lower initial PCO₂ level was significantly associated with ventricular narrowing [odds ratio (OR) = 0.88, 95% confidence interval (95% CI) = 0.78–0.99, p = 0.047). No other variables analyzed were associated with ventricular narrowing in the multivariate analysis. We conclude that narrowing of the lateral ventricles is evident in just over half of children being treated for DKA. Although children with ventricular narrowing did not exhibit neurological abnormalities sufficient for a diagnosis of ‘symptomatic cerebral edema’, mild mental status abnormalities occurred frequently, suggesting that clinical evidence of cerebral edema in children with DKA may be more common than previously reported.

OBJECTIVE. The optimal treatment for Graves’ disease in children is controversial. Antithyroid medications are often used initially, but many children eventually require alternative therapies. We evaluated predictors of remission after 2 years of antithyroid medication use. METHODS. We prospectively studied children who had Graves’ disease and were treated with antithyroid medications. We compared children who achieved remission after 2 years with those who had persistent disease to determine which variables were associated with remission; multiple logistic regression and binary recursive partitioning analyses were used to evaluate interactions among predictive variables. RESULTS. Of 51 children who completed the study, 15 (29%) achieved remission. Children who achieved remission had lower thyroid hormone concentrations at presentation than those with persistent disease (free thyroxine: 6.17 ± 3.10 vs 9.86 ± 7.54 ng/dL; total triiodothyronine: 431 ± 175 vs 561 ± 225 ng/dL). Children who achieved remission were also more likely to be euthyroid within 3 months of initiating propylthiouracil (82% vs 29%). Binary recursive partitioning analysis identified rapid achievement of euthyroid status after initiation of propylthiouracil, lower initial triiodothyronine, and older age as significant predictors of remission. CONCLUSIONS. Thyroid hormone concentrations at diagnosis, age, and initial response to propylthiouracil can be used to stratify patients according to the likelihood of remission after 2 years of antithyroid medication use. These data provide a useful guide for clinical decision-making regarding Graves’ disease in children.