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

2021

2021 Jun 29

1935-5548

<p><strong>OBJECTIVE: </strong>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.</p>

<p><strong>RESEARCH DESIGN AND METHODS: </strong>The current analysis involved moderate or severe DKA episodes ( = 714) in children age &lt;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).</p>

<p><strong>RESULTS: </strong>The rate of change of pH did not differ by treatment arm, but Pco 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%).</p>

<p><strong>CONCLUSIONS: </strong>In children treated for DKA, faster fluid administration rates led to a more rapid normalization of anion gap and Pco than slower fluid infusion rates but were associated with an increased frequency of hyperchloremic acidosis.</p>

10.2337/dc20-3113

Diabetes Care

34187840

Frequency and Risk Factors of Acute Kidney Injury During Diabetic Ketoacidosis in Children and Association With Neurocognitive Outcomes.

2020

e2025481

2020 Dec 01

2574-3805

<p><strong>Importance: </strong>Acute kidney injury (AKI) occurs commonly during diabetic ketoacidosis (DKA) in children, but the underlying mechanisms and associations are unclear.</p>

<p><strong>Objective: </strong>To investigate risk factors for AKI and its association with neurocognitive outcomes in pediatric DKA.</p>

<p><strong>Design, Setting, and Participants: </strong>This 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.</p>

<p><strong>Exposures: </strong>DKA requiring intravenous insulin therapy.</p>

<p><strong>Main Outcomes and Measures: </strong>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.</p>

<p><strong>Results: </strong>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 &lt; .001), higher heart rate (AOR for 1-SD increase in z-score, 1.20; 95% CI, 1.09-1.32; P &lt; .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 &lt; .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.</p>

<p><strong>Conclusions and Relevance: </strong>These findings suggest that AKI may occur more frequently in children with greater acidosis and circulatory volume depletion during DKA and may be part of a pattern of multiple organ injury involving the kidneys and brain.</p>

10.1001/jamanetworkopen.2020.25481

JAMA Netw Open

33275152

Cognitive Function Following Diabetic Ketoacidosis in Children With New-Onset or Previously Diagnosed Type 1 Diabetes.

2020

2020 Sep 22

1935-5548

<p><strong>OBJECTIVE: </strong>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.</p>

<p><strong>RESEARCH DESIGN AND METHODS: </strong>We 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.</p>

<p><strong>RESULTS: </strong>Among all patients, moderate/severe DKA was associated with lower intelligence quotient (IQ) (β = -0.12, &lt; 0.001), item-color recall (β = -0.08, = 0.010), and forward digit span (β = -0.06, = 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (β = -0.08, = 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA were independently associated with lower IQ (β = -0.10 and β = -0.09, respectively, &lt; 0.01) and higher HbA was associated with lower item-color recall (β = -0.10, = 0.007) after hypoglycemia, diabetes duration, and socioeconomic status were accounted for.</p>

<p><strong>CONCLUSIONS: </strong>A 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.</p>

10.2337/dc20-0187

Diabetes Care

32962981

Hypertension During Diabetic Ketoacidosis in Children.

2020

2020 May 06

1097-6833

<p><strong>OBJECTIVES: </strong>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.</p>

<p><strong>STUDY DESIGN: </strong>This was a planned secondary analysis of data from the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) 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.</p>

<p><strong>RESULTS: </strong>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 PCO), and stage 2 or 3 Acute Kidney Injury (AKI). More severe acidosis and lower Glasgow Coma Scale (GCS) scores were associated with hypertension occurring at any time during DKA treatment.</p>

<p><strong>CONCLUSIONS: </strong>Despite dehydration, hypertension occurs in a substantial number of children with DKA. Factors associated with hypertension include greater severity of acidosis, lower PCO and lower GCS scores during DKA treatment, suggesting that hypertension might be centrally mediated.</p>

10.1016/j.jpeds.2020.04.066

J. Pediatr.

32387716

Implementation of a Clinical Decision Support System for Children With Minor Blunt Head Trauma Who Are at Nonnegligible Risk for Traumatic Brain Injuries.

2018

2018 Dec 22

1097-6760

<p><strong>STUDY OBJECTIVE: </strong>To determine the effect of providing risk estimates of clinically important traumatic brain injuries and management recommendations on emergency department (ED) outcomes for children with isolated intermediate Pediatric Emergency Care Applied Research Network clinically important traumatic brain injury risk factors.</p>

<p><strong>METHODS: </strong>This was a secondary analysis of a nonrandomized clinical trial with concurrent controls, conducted at 5 pediatric and 8 general EDs between November 2011 and June 2014, enrolling patients younger than 18 years who had minor blunt head trauma. After a baseline period, intervention sites received electronic clinical decision support providing patient-level clinically important traumatic brain injury risk estimates and management recommendations. The following primary outcomes in patients with one intermediate Pediatric Emergency Care Applied Research Network risk factor were compared before and after clinical decision support: proportion of ED computed tomography (CT) scans, adjusted for age, time trend, and site; and prevalence of clinically important traumatic brain injuries.</p>

<p><strong>RESULTS: </strong>The risk of clinically important traumatic brain injuries was known for 3,859 children with isolated findings (1,711 at intervention sites before clinical decision support, 1,702 at intervention sites after clinical decision support, and 446 at control sites). In this group, pooled CT proportion decreased from 24.2% to 21.6% after clinical decision support (odds ratio 0.86; 95% confidence interval 0.73 to 1.01). Decreases in CT use were noted across intervention EDs, but not in controls. The pooled adjusted odds ratio for CT use after clinical decision support was 0.73 (95% confidence interval 0.60 to 0.88). Among the entire cohort, clinically important traumatic brain injury was diagnosed at the index ED visit for 37 of 37 (100%) patients before clinical decision support and 32 of 33 patients (97.0%) after clinical decision support.</p>

<p><strong>CONCLUSION: </strong>Providing specific risks of clinically important traumatic brain injury through electronic clinical decision support was associated with a modest and safe decrease in ED CT use for children at nonnegligible risk of clinically important traumatic brain injuries.</p>

10.1016/j.annemergmed.2018.11.011

Ann Emerg Med

30583957

Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): study protocol for a pilot randomized controlled trial.

2018

593

2018 Oct 30

1745-6215

<p><strong>BACKGROUND: </strong>Trauma is the leading cause of morbidity and mortality in children in the United States. The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage, however, the drug has not been evaluated in a clinical trial in severely injured children. We designed the Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC) trial to evaluate the feasibility of conducting a confirmatory clinical trial that evaluates the effects of TXA in children with severe trauma and hemorrhagic injuries.</p>

<p><strong>METHODS: </strong>Children with severe trauma and evidence of hemorrhagic torso or brain injuries will be randomized to one of three arms: (1) TXA dose A (15&nbsp;mg/kg bolus dose over 20&nbsp;min, followed by 2&nbsp;mg/kg/hr infusion over 8&nbsp;h), (2) TXA dose B (30&nbsp;mg/kg bolus dose over 20&nbsp;min, followed by 4&nbsp;mg/kg/hr infusion over 8&nbsp;h), or (3) placebo. We will use permuted-block randomization by injury type: hemorrhagic brain injury, hemorrhagic torso injury, and combined hemorrhagic brain and torso injury. The trial will be conducted at four pediatric Level I trauma centers. We will collect the following outcome measures: global functioning as measured by the Pediatric Quality of Life (PedsQL) and Pediatric Glasgow Outcome Scale Extended (GOS-E Peds), working memory (digit span test), total amount of blood products transfused in the initial 48&nbsp;h, intracranial hemorrhage progression at 24&nbsp;h, coagulation biomarkers, and adverse events (specifically thromboembolic events and seizures).</p>

<p><strong>DISCUSSION: </strong>This multicenter trial will provide important preliminary data and assess the feasibility of conducting a confirmatory clinical trial that evaluates the benefits of TXA in children with severe trauma and hemorrhagic injuries to the torso and/or brain.</p>

<p><strong>TRIAL REGISTRATION: </strong>ClinicalTrials.gov registration number: NCT02840097 . Registered on 14 July 2016.</p>

10.1186/s13063-018-2974-z

Trials

30376893

Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis.

2018

2275-2287

2018 06 14

1533-4406

<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>METHODS: </strong>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 &lt;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.</p>

<p><strong>RESULTS: </strong>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.</p>

<p><strong>CONCLUSIONS: </strong>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 .).</p>

10.1056/NEJMoa1716816

N. Engl. J. Med.

29897851

Use of Traumatic Brain Injury Prediction Rules With Clinical Decision Support.

2017

2017 Mar 24

1098-4275

<p><strong>OBJECTIVES: </strong>We determined whether implementing the Pediatric Emergency Care Applied Research Network (PECARN) traumatic brain injury (TBI) prediction rules and providing risks of clinically important TBIs (ciTBIs) with computerized clinical decision support (CDS) reduces computed tomography (CT) use for children with minor head trauma.</p>

<p><strong>METHODS: </strong>Nonrandomized trial with concurrent controls at 5 pediatric emergency departments (PEDs) and 8 general EDs (GEDs) between November 2011 and June 2014. Patients were &lt;18 years old with minor blunt head trauma. Intervention sites received CDS with CT recommendations and risks of ciTBI, both for patients at very low risk of ciTBI (no Pediatric Emergency Care Applied Research Network rule factors) and those not at very low risk. The primary outcome was the rate of CT, analyzed by site, controlling for time trend.</p>

<p><strong>RESULTS: </strong>We analyzed 16 635 intervention and 2394 control patients. Adjusted for time trends, CT rates decreased significantly (P &lt; .05) but modestly (2.3%-3.7%) at 2 of 4 intervention PEDs for children at very low risk. The other 2 PEDs had small (0.8%-1.5%) nonsignificant decreases. CT rates did not decrease consistently at the intervention GEDs, with low baseline CT rates (2.1%-4.0%) in those at very low risk. The control PED had little change in CT use in similar children (from 1.6% to 2.9%); the control GED showed a decrease in the CT rate (from 7.1% to 2.6%). For all children with minor head trauma, intervention sites had small decreases in CT rates (1.7%-6.2%).</p>

<p><strong>CONCLUSIONS: </strong>The implementation of TBI prediction rules and provision of risks of ciTBIs by using CDS was associated with modest, safe, but variable decreases in CT use. However, some secular trends were also noted.</p>

10.1542/peds.2016-2709

Pediatrics

28341799

Development, Evaluation and Implementation of Chief Complaint Groupings to Activate Data Collection: A Multi-Center Study of Clinical Decision Support for Children with Head Trauma.

2015

521-35

2015

1869-0327

<p><strong>BACKGROUND: </strong>Overuse of cranial computed tomography scans in children with blunt head trauma unnecessarily exposes them to radiation. The Pediatric Emergency Care Applied Research Network (PECARN) blunt head trauma prediction rules identify children who do not require a computed tomography scan. Electronic health record (EHR) based clinical decision support (CDS) may effectively implement these rules but must only be provided for appropriate patients in order to minimize excessive alerts.</p>

<p><strong>OBJECTIVES: </strong>To develop, implement and evaluate site-specific groupings of chief complaints (CC) that accurately identify children with head trauma, in order to activate data collection in an EHR.</p>

<p><strong>METHODS: </strong>As part of a 13 site clinical trial comparing cranial computed tomography use before and after implementation of CDS, four PECARN sites centrally developed and locally implemented CC groupings to trigger a clinical trial alert (CTA) to facilitate the completion of an emergency department head trauma data collection template. We tested and chose CC groupings to attain high sensitivity while maintaining at least moderate specificity.</p>

<p><strong>RESULTS: </strong>Due to variability in CCs available, identical groupings across sites were not possible. We noted substantial variability in the sensitivity and specificity of seemingly similar CC groupings between sites. The implemented CC groupings had sensitivities greater than 90% with specificities between 75-89%. During the trial, formal testing and provider feedback led to tailoring of the CC groupings at some sites.</p>

<p><strong>CONCLUSIONS: </strong>CC groupings can be successfully developed and implemented across multiple sites to accurately identify patients who should have a CTA triggered to facilitate EHR data collection. However, CC groupings will necessarily vary in order to attain high sensitivity and moderate-to-high specificity. In future trials, the balance between sensitivity and specificity should be considered based on the nature of the clinical condition, including prevalence and morbidity, in addition to the goals of the intervention being considered.</p>

10.4338/ACI-2015-02-RA-0019

Appl Clin Inform

26448796