Clinical and Laboratory Predictors of Dehydration Severity in Children With Diabetic Ketoacidosis.

STUDY OBJECTIVE: Our primary objective was to characterize the degree of dehydration in children with diabetic ketoacidosis (DKA) and identify physical examination and biochemical factors associated with dehydration severity. Secondary objectives included describing relationships between dehydration severity and other clinical outcomes. METHODS: In this cohort study, we analyzed data from 753 children with 811 episodes of DKA in the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation Study, a randomized clinical trial of fluid resuscitation protocols for children with DKA. We used multivariable regression analyses to identify physical examination and biochemical factors associated with dehydration severity, and we described associations between dehydration severity and DKA outcomes. RESULTS: Mean dehydration was 5.7% (SD 3.6%). Mild (0 to <5%), moderate (5 to <10%), and severe (≥10%) dehydration were observed in 47% (N=379), 42% (N=343), and 11% (N=89) of episodes, respectively. In multivariable analyses, more severe dehydration was associated with new onset of diabetes, higher blood urea nitrogen, lower pH, higher anion gap, and diastolic hypertension. However, there was substantial overlap in these variables between dehydration groups. The mean length of hospital stay was longer for patients with moderate and severe dehydration, both in new onset and established diabetes. CONCLUSION: Most children with DKA have mild-to-moderate dehydration. Although biochemical measures were more closely associated with the severity of dehydration than clinical assessments, neither were sufficiently predictive to inform rehydration practice.

Effects of Fluid Rehydration Strategy on Correction of Acidosis and Electrolyte Abnormalities in Children With Diabetic Ketoacidosis.

OBJECTIVE: Fluid replacement to correct dehydration, acidosis, and electrolyte abnormalities is the cornerstone of treatment for diabetic ketoacidosis (DKA), but little is known about optimal fluid infusion rates and electrolyte content. The objective of this study was to evaluate whether different fluid protocols affect the rate of normalization of biochemical derangements during DKA treatment. RESEARCH DESIGN AND METHODS: The current analysis involved moderate or severe DKA episodes (n = 714) in children age <18 years enrolled in the Fluid Therapies Under Investigation in DKA (FLUID) Trial. Children were assigned to one of four treatment groups using a 2 × 2 factorial design (0.90% or 0.45% saline and fast or slow rate of administration). RESULTS: The rate of change of pH did not differ by treatment arm, but Pco2 increased more rapidly in the fast versus slow fluid infusion arms during the initial 4 h of treatment. The anion gap also decreased more rapidly in the fast versus slow infusion arms during the initial 4 and 8 h. Glucose-corrected sodium levels remained stable in patients assigned to 0.90% saline but decreased in those assigned to 0.45% saline at 4 and 8 h. Potassium levels decreased, while chloride levels increased more rapidly with 0.90% versus 0.45% saline. Hyperchloremic acidosis occurred more frequently in patients in the fast arms (46.1%) versus the slow arms (35.2%). CONCLUSIONS: In children treated for DKA, faster fluid administration rates led to a more rapid normalization of anion gap and Pco2 than slower fluid infusion rates but were associated with an increased frequency of hyperchloremic acidosis.

Circulating matrix metalloproteinases in children with diabetic ketoacidosis.

BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMPs) mediate blood-brain barrier dysfunction in inflammatory disease states. Our objective was to compare circulating MMPs in children with diabetic ketoacidosis (DKA) to children with type 1 diabetes mellitus without DKA. RESEARCH DESIGN AND METHODS: This was a prospective study performed at five tertiary-care pediatric hospitals. We measured plasma MMP-2, MMP-3, and MMP-9 early during DKA (time 1; within 2 h of beginning intravenous fluids) and during therapy (time 2; median 8 h; range: 4-16 h). The primary outcome was MMP levels in 34 children with DKA vs. 23 children with type 1 diabetes without DKA. Secondary outcomes included correlations between MMPs and measures of DKA severity. RESULTS: In children with DKA compared with diabetes controls, circulating MMP-2 levels were lower (mean 77 vs. 244 ng/mL, p < 0.001), MMP-3 levels were similar (mean 5 vs. 4 ng/mL, p = 0.57), and MMP-9 levels were higher (mean 67 vs. 25 ng/mL, p = 0.002) early in DKA treatment. MMP-2 levels were correlated with pH at time 1 (r = 0.45, p = 0.018) and time 2 (r = 0.47, p = 0.015) and with initial serum bicarbonate at time 2 (r = 0.5, p = 0.008). MMP-9 levels correlated with hemoglobin A1c in DKA and diabetes controls, but remained significantly elevated in DKA after controlling for hemoglobin A1c (ß = -31.3, p = 0.04). CONCLUSIONS: Circulating MMP-2 levels are lower and MMP-9 levels are higher in children during DKA compared with levels in children with diabetes without DKA. Alterations in MMP expression could mediate BBB dysfunction occurring during DKA.

Risk of traumatic brain injuries in children younger than 24 months with isolated scalp hematomas.

STUDY OBJECTIVE: We aimed to determine the association between scalp hematoma characteristics and traumatic brain injuries in young children with blunt head trauma who have no other symptoms or signs suggestive of traumatic brain injuries (defined as "isolated scalp hematomas"). METHODS: This was a secondary analysis of children younger than 24 months with minor blunt head trauma from a prospective cohort study in 25 Pediatric Emergency Care Applied Research Network emergency departments. Treating clinicians completed a structured data form. For children with isolated scalp hematomas, we determined the prevalence of and association between scalp hematoma characteristics and (1) clinically important traumatic brain injury (death, neurosurgery for traumatic brain injury, intubation >24 hours for traumatic brain injury, or positive computed tomography (CT) scan in association with hospitalization ≥2 nights for traumatic brain injury); and (2) traumatic brain injury on CT. RESULTS: Of 10,659 patients younger than 24 months were enrolled, 2,998 of 10,463 (28.7%) with complete data had isolated scalp hematomas. Clinically important traumatic brain injuries occurred in 12 patients (0.4%; 95% confidence interval [CI] 0.2% to 0.7%); none underwent neurosurgery (95% CI 0% to 0.1%). Of 570 patients (19.0%) for whom CTs were obtained, 50 (8.8%; 95% CI 6.6% to 11.4%) had traumatic brain injuries on CT. Younger age, non-frontal scalp hematoma location, increased scalp hematoma size, and severe injury mechanism were independently associated with traumatic brain injury on CT. CONCLUSION: In patients younger than 24 months with isolated scalp hematomas, a minority received CTs. Despite the occasional presence of traumatic brain injuries on CT, the prevalence of clinically important traumatic brain injuries was very low, with no patient requiring neurosurgery. Clinicians should use patient age, scalp hematoma location and size, and injury mechanism to help determine which otherwise asymptomatic children should undergo neuroimaging after minor head trauma.