BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.)

IMPORTANCEAcute kidney injury (AKI) occurs commonly during diabetic ketoacidosis (DKA) in children, but the underlying mechanisms and associations are unclear. OBJECTIVE To investigate risk factors for AKI and its association with neurocognitive outcomes in pediatric DKA. DESIGN, SETTING, AND PARTICIPANTSThis cohort study was a secondary analysis of data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in DKA Study, a prospective, multicenter, randomized clinical trial comparing fluid protocols for pediatric DKA in 13 US hospitals. Included DKA episodes occurred among children age younger than 18 years with blood glucose 300 mg/dL or greater and venous pH less than 7.25 or serum bicarbonate level less than 15 mEq/L. EXPOSURES DKA requiring intravenous insulin therapy. MAIN OUTCOMES AND MEASURES AKI occurrence and stage were assessed using serum creatinine measurements using Kidney Disease: Improving Global Outcomes criteria. DKA episodes with and without AKI were compared using univariable and multivariable methods, exploring associated factors. RESULTS Among 1359 DKA episodes (mean [SD] patient age, 11.6 [4.1] years; 727 [53.5%] girls; 651 patients [47.9%] with new-onset diabetes), AKI occurred in 584 episodes (43%; 95% CI, 40%-46%).A total of 252 AKI events (43%; 95% CI, 39%-47%) were stage 2 or 3. Multivariable analyses identified older age (adjusted odds ratio [AOR] per 1 year, 1.05; 95% CI, 1.00-1.09; P = .03), higher initial serum urea nitrogen (AOR per 1 mg/dL increase, 1.14; 95% CI, 1.11-1.18; P < .001), higher heart rate (AOR for 1-SD increase in z-score, 1.20; 95% CI, 1.09-1.32; P < .001), higher glucose-corrected sodium (AOR per 1 mEq/L increase, 1.03; 95% CI, 1.00-1.06; P = .001) and glucose concentrations (AOR per 100 mg/dL increase, 1.19; 95% CI, 1.07-1.32; P = .001), and lower pH (AOR per 0.1 increase, 0.63; 95% CI, 0.51-0.78; P < .001) as variables associated with AKI. Children with AKI, compared with those without, had lower scores on tests of short-term memory during DKA (mean [SD] digit span recall: 6.8 [2.4] vs 7.6 [2.2]; P = .02) and lower mean (SD) IQ scores 3 to 6 months after recovery from DKA (100.0 [12.2] vs 103.5 [13.2]; P = .005). Differences persisted after adjusting for DKA severity and demographic factors, including socioeconomic status. (continued) Key Points Question What are the mechanisms, risk factors, and outcomes associated with acute kidney injury (AKI) during pediatric diabetic ketoacidosis (DKA)? Findings In this cohort study using data from 1359 DKA episodes in a large, multicenter, prospective study of fluid treatment during DKA, AKI occurred in 43% of episodes and was associated with greater acidosis and greater circulatory volume depletion. Children who had AKI were more likely to have subtle cognitive impairment during DKA and lower IQ at longer-term follow-up. Meaning These findings suggest that AKI is frequent in pediatric DKA and there is a pattern of multiorgan dysfunction during childhood DKA with the possibility of c...

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This study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes and whether the same is true in children who had previously been diagnosed after accounting for variations in glycemic control and other relevant factors. RESEARCH DESIGN AND METHODSWe prospectively enrolled 758 children, 6-18 years old, who presented with DKA in a randomized multisite clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. A total of 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2-6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled. RESULTSAmong all patients, moderate/severe DKA was associated with lower intelligence quotient (IQ) (b 5 20.12, P < 0.001), item-color recall (b 5 20.08, P 5 0.010), and forward digit span (b 5 20.06, P 5 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (b 5 20.08, P 5 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA 1c were independently associated with lower IQ (b 5 20.10 and b 5 20.09, respectively, P < 0.01) and higher HbA 1c was associated with lower item-color recall (b 5 20.10, P 5 0.007) after hypoglycemia, diabetes duration, and socioeconomic status were accounted for. CONCLUSIONSA single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia.Diabetic ketoacidosis (DKA) is a common complication of type 1 diabetes (1). Of children with new onset of type 1 diabetes, 25-40% present with DKA (2). In established patients, DKA may be the consequence of poor adherence to insulin regimens, illness, or malfunction of diabetes care equipment (e.g., insulin pumps) (2). Brain injury has long been recognized as an uncommon, but serious, complication of