Brain injury in children with diabetic ketoacidosis: Review of the literature and a proposed pathophysiologic pathway for the development of cerebral edema.
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SUBMITTER: Azova S
PROVIDER: S-EPMC10127934 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
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Brain injury in children with diabetic ketoacidosis: Review of the literature and a proposed pathophysiologic pathway for the development of cerebral edema.
Azova Svetlana S Rapaport Robert R Wolfsdorf Joseph J
Pediatric diabetes 20201203 2
Cerebral edema (CE) is a potentially devastating complication of diabetic ketoacidosis (DKA) that almost exclusively occurs in children. Since its first description in 1936, numerous risk factors have been identified; however, there continues to be uncertainty concerning the mechanisms that lead to its development. Currently, the most widely accepted hypothesis posits that CE occurs as a result of ischemia-reperfusion injury, with inflammation and impaired cerebrovascular autoregulation contribu ...[more]
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Project description:ObjectivePrevious studies show that vasogenic cerebral edema (CE) occurs during diabetic ketoacidosis (DKA) treatment in children, but the role of intravenous fluids in contributing to CE is unclear. We used magnetic resonance diffusion weighted imaging to quantify subclinical CE in children with DKA randomized to 2 intravenous fluid regimens.MethodsChildren with DKA were randomized to receive fluids at a more rapid rate (n = 8) or a slower rate (n = 10), with all other aspects of DKA treatment kept identical. Children underwent diffusion weighted imaging 3 to 6 hours and 9 to 12 hours after beginning DKA treatment and after recovery from DKA (≥ 72 hours after beginning treatment). We calculated brain apparent diffusion coefficient (ADC) values as the average of measurements in the basal ganglia, thalamus, frontal white matter, and hippocampus and determined the mean brain ADC value during DKA treatment by averaging data from the 3- to 6-hour and 9- to 12-hour measurements. The difference in mean brain ADC between DKA treatment and postrecovery was used as an index of the severity of CE during DKA treatment.ResultsMean brain ADC values during DKA treatment were significantly higher than postrecovery values, consistent with vasogenic CE (842 ± 38 vs 800 ± 41 × 10(-6) mm(2)/second, P = .002). We did not detect significant differences in ADC elevation in children treated with more rapid versus slower rehydration (β coefficient 0.11 for 1 SD change in ADC, 95% confidence interval: -0.91 to 1.13).ConclusionsADC changes during DKA treatment (reflective of vasogenic CE) do not appear to be substantially affected by the rate of intravenous fluid administration.
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Project description:Cerebral edema is a devastating complication of DKA which is extremely rare in adults but is the leading cause of diabetes-related death in the pediatric population. Newly diagnosed diabetes, younger age, first episode of DKA, severity of DKA at presentation, and administration of bicarbonate are predictive of cerebral edema in DKA. We present a case of a young adult with DKA as the presenting symptom of diabetes, whose clinical course was complicated by renal failure, refractory shock, and cerebral edema. This case addresses the controversy surrounding bicarbonate therapy in DKA and its possible role in the development of a rare fatal complication of DKA.
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Project description:OBJECTIVES:Neurologic deterioration associated with cerebral edema in diabetic ketoacidosis is typically sudden in onset, progresses rapidly, and requires emergent treatment. The utility of brain imaging by head CT in decisions to treat for cerebral edema has not been previously studied. The objective of this study was to describe the characteristics of pediatric patients with diabetic ketoacidosis who develop altered mental status and evaluate the role of head CT in this cohort. DESIGN:Retrospective analysis of clinical, biochemical, and radiologic data. SETTING:Tertiary care children's hospital (2004-2010). PATIENTS:Six hundred eighty-six admissions of patients (< 26 yr) with diabetic ketoacidosis. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Altered mental status was documented during 96 of 686 diabetic ketoacidosis admissions (14%). Compared with alert patients, those with altered mental status were younger (median, 12.0 vs 13.1 yr; p = 0.007) and more acidotic (pH, 7.04 vs 7.19; p < 0.001), with higher serum osmolality (328 vs 315 mOsm/kg; p < 0.001) and longer hospital length of stay (4.5 vs 3 d; p = 0.002). Head CT was performed during 60 of 96 diabetic ketoacidosis admissions with altered mental status (63%), 16 (27%) of which had abnormal results. Hyperosmolar therapy for cerebral edema was given during 23 of the 60 admissions (38%), during which 12 (52%) had normal head CT results, eight of these 12 (67%) after cerebral edema treatment and four (33%) before. Of the 11 admissions with abnormal head CT results that received hyperosmolar therapy, four head CT scan (36%) occurred after hyperosmolar treatment and seven (64%) before. For the 11 admissions with head CT before cerebral edema treatment, there was a median 2-hour delay between head CT and hyperosmolar therapy. CONCLUSIONS:In this single-center retrospective study, there was no evidence that decisions about treatment of patients with diabetic ketoacidosis and suspected cerebral edema were enhanced by head CT, and head CT may have led to a significant delay in hyperosmolar therapy.
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Project description:ObjectivesTo 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 designThis 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.ResultsAmong 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.ConclusionsDespite 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.
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Project description:BackgroundCerebral malaria, defined as otherwise unexplained coma in a patient with circulating parasitemia, is a common disease in the developing world. The clinical diagnosis lacks specificity and children with other underlying causes of coma might be misdiagnosed as having cerebral malaria. The presence of malarial retinopathy can be used to differentiate children whose comas are caused by Plasmodium falciparum and its attendant pathophysiologies from those with other reasons for their abnormal mental status. Children with cerebral malaria who lack malarial retinopathy have not previously been described.MethodsAll patients admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi, during a 12-month period with a clinical diagnosis of cerebral malaria were evaluated for the presence of malarial retinopathy. Thirty-two patients lacked retinopathy findings. Clinical, laboratory, and radiologic information data were collected.ResultsThirty-two cases of retinopathy-negative cerebral malaria are presented.ConclusionsChildren with retinopathy-negative cerebral malaria share a common clinical phenotype with lower rates of mortality compared with those who have malarial retinopathy. There are at least 4 possible pathophysiologic explanations for this common condition.
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Project description:BackgroundThe second-generation antipsychotics (SGAs) are associated with metabolic disturbances. Diabetic ketoacidosis (DKA) is a rare, but potentially fatal sign of acute glucose metabolism dysregulation, which may be associated with the use of SGAs. This study aims to review published reports of patients with schizophrenia and antipsychotic drug-associated DKA, focusing on the effective management of both conditions.MethodsUsing a predefined search strategy, we searched PubMed and EMBASE from their inception to July 2016. The search terms were related to "diabetic ketoacidosis" and "antipsychotic medication." Case reports, case series, and reviews of case series written in English language were included in the review.ResultsSixty-five reports were analyzed. In most patients who developed antipsychotic-associated DKA, 1 or more suspected antipsychotic medications were discontinued. In 5 cases, a rechallenge test was trialed, and in only 1 case, it resulted in the elevation of blood glucose. The majority was subsequently treated with a different SGA in combination with insulin/oral hypoglycemic agents; although approximately a third of patients had a complete resolution of symptoms or could control diabetes with diet only at the point of discharge.ConclusionsPatients taking antipsychotic medications should be regularly screened for insulin resistance and educated about potential complications of antipsychotic medications. This will allow clinicians to individualize treatment decisions and reduce iatrogenic contribution to morbidity and mortality. To achieve best treatment outcomes, antipsychotic-induced DKA should be treated jointly by psychiatry and endocrinology teams.
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Project description:ObjectiveGlomerular injury is a recognized complication of diabetic ketoacidosis (DKA), yet the tubular lesions are poorly understood. The aim of this prospective study was to evaluate the presence and reversibility of tubular injury during DKA in children with type 1 diabetes (T1D).Research design and methodsBlood and urine samples were collected from 40 children with DKA (52% boys, mean age 11 ± 4 years, venous pH 7.2 ± 0.1, glucose 451 ± 163 mg/dL) at three timepoints: 0-8 and 12-24 h after starting insulin, and 3 months after discharge. Mixed-effects models evaluated the changes in tubular injury markers over time (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule 1 [KIM-1], and interleukin 18 [IL-18]). We also evaluated the relationships among the tubular injury biomarkers, copeptin, a vasopressin surrogate, and serum uric acid (SUA).ResultsSerum NGAL, KIM-1, and IL-18 were highest at 0-8 h (306.5 ± 45.9 ng/mL, 128.9 ± 10.1 pg/mL, and 564.3 ± 39.2 pg/mL, respectively) and significantly decreased over 3 months (p = 0.03, p = 0.01, and p < 0.001, respectively). There were strong relationships among increases in copeptin and SUA and rises in tubular injury biomarkers. At 0-8 h, participants with acute kidney injury (AKI) [17%] showed significantly higher concentrations of tubular injury markers, copeptin, and SUA.ConclusionsDKA was characterized by tubular injury, and the degree of injury associated with elevated copeptin and SUA. Tubular injury biomarkers, copeptin and SUA may be able to predict AKI in DKA.
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Project description:ImportanceAcute kidney injury (AKI) occurs commonly during diabetic ketoacidosis (DKA) in children, but the underlying mechanisms and associations are unclear.ObjectiveTo 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.ExposuresDKA requiring intravenous insulin therapy.Main outcomes and measuresAKI 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.ResultsAmong 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.Conclusions and relevanceThese 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.
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