Original Article
Risk Factors for Cerebral Edema in Children with Diabetic Ketoacidosis
N Engl J Med 2001; 344:264-269January 25, 2001
- Abstract
Background
Cerebral edema is an uncommon but devastating complication of diabetic ketoacidosis in children. Risk factors for this complication have not been clearly defined.
Methods
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.
Results
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).
Conclusions
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.
Media in This Article
Figure 1
Time between the Initiation of Therapy and Neurologic Deterioration in Children with Diabetic Ketoacidosis and Cerebral Edema.Table 1
Characteristics of the Children at the Time of Presentation.Article Activity
- Article
Diabetic ketoacidosis occurs in 25 to 40 percent of children with newly diagnosed type 1 diabetes mellitus1,2 and may later recur in association with illness or noncompliance with treatment. Clinically apparent cerebral edema occurs in approximately 1 percent of episodes of diabetic ketoacidosis in children and is associated with a mortality rate of 40 to 90 percent.3-6 Cerebral edema is responsible for 50 to 60 percent of diabetes-related deaths in children.7,8
The pathophysiologic mechanism underlying the cerebral edema associated with diabetic ketoacidosis is controversial. Clinical studies to date, most of which have been small, have provided little information about predictive factors. In this case–control study of children with diabetic ketoacidosis, we evaluated the associations between cerebral edema and the following factors: demographic characteristics and initial biochemical characteristics, therapeutic interventions, and changes in biochemical values during treatment.
Methods
Study Subjects
Cerebral-Edema Group
We identified all the children (persons ≤18 years of age) in whom cerebral edema related to diabetic ketoacidosis developed between 1982 and 1997 at any of 10 pediatric centers. To identify these children, we reviewed the records of all the children who had been admitted because of diabetic ketoacidosis and whose records indicated that they had had cerebral edema, cerebral infarction, coma, seizures, or death, or that they had undergone computed tomographic scanning, magnetic resonance imaging, intubation, or treatment with mannitol. The records of all children who died (with or without type 1 diabetes) at these 10 centers during the study period were also reviewed to ensure that no cases of cerebral edema related to diabetic ketoacidosis had been missed.
To be included in the study, children identified as having cerebral edema were required to meet all the following criteria: the presence of diabetic ketoacidosis (defined as a serum glucose concentration >300 mg per deciliter [16.7 mmol per liter], a venous pH <7.25 or a serum bicarbonate concentration <15 mmol per liter, and the presence of ketones [acetoacetate] in the urine); alteration in mental status (obtundation or disorientation); and either radiographically or pathologically confirmed cerebral edema or specific treatment for cerebral edema (hyperosmolar therapy or controlled hyperventilation) that was followed by clinical improvement.
Because cerebral infarction may occur as a consequence of cerebral edema or impending herniation,9,10 radiographic studies of children with cerebral infarction were also reviewed by a neuropathologist. Six patients whose radiographs revealed patterns of infarction consistent with the consequences of cerebral edema were included in the cerebral-edema group.9
Control Groups
For each child with cerebral edema, we identified six other children who were designated as controls, three in each of two control groups. One control group (the “random controls”) consisted of children with diabetic ketoacidosis (as defined above) who were randomly selected with use of a computer-generated list of numbers from among all the children admitted for diabetic ketoacidosis at each center during the study period. The second control group (the matched controls) consisted of children with diabetic ketoacidosis (as defined above) who were matched with the children with cerebral edema according to age (within two years), onset of diabetes (established vs. newly diagnosed disease), venous pH at presentation (within 0.1), and serum glucose concentration at presentation (within 200 mg per deciliter [11.1 mmol per liter]). If pH values were not available, children were matched according to serum bicarbonate concentration (within 3 mmol per liter). If more than three matched controls could be identified for a child with cerebral edema, the controls whose dates of admission most closely approximated that of the child with cerebral edema were chosen.
Data Collection
The following data from the record of each child were recorded by one investigator at each center: demographic characteristics, initial biochemical values, treatment regimen, and changes in laboratory values during treatment. We calculated other variables according to the following formulas11-14: corrected serum sodium concentration = measured serum sodium concentration + ([(serum glucose concentration – 100) ÷ 100] × 1.6), with the serum glucose concentration expressed in milligrams per deciliter; osmo-lality = (2 × serum sodium concentration) + (serum glucose concentration ÷ 18) + (serum urea nitrogen concentration ÷ 2.8), with the serum sodium concentration expressed in millimoles per liter and the serum glucose and serum urea nitrogen concentrations in milligrams per deciliter; arterial pH = venous pH + 0.05; and the partial pressure of arterial carbon dioxide = the partial pressure of venous carbon dioxide – 6. Information from nursing records about treatments given during each hour was used to calculate the rates of administration of fluid, sodium, and insulin. In the cerebral-edema group, these rates and changes in biochemical variables during treatment were calculated for the interval between the initiation of therapy (defined as the first intravenous administration of fluids or insulin) and the onset of symptomatic cerebral edema; in the control groups, these values were calculated for the same interval.
To assess interrater agreement in the recording of data, 10 percent of the records were randomly selected and reexamined by a single investigator. Interrater agreement with respect to eight variables (the initial serum glucose and sodium concentrations, the initial venous pH value, the use or nonuse of a bolus dose of insulin, the rates of insulin and fluid administration during the first hour of treatment, the use or nonuse of bicarbonate therapy, and the dose of bicarbonate, if used) was evaluated with use of the weighted kappa statistic. The consistency of the recording of data among investigators was excellent, with a median kappa statistic of 0.9 (range, 0.6 to 1.0).
The study was approved by the institutional review board of each participating institution.
Statistical Analysis
We compared data from the cerebral-edema group with data from both of the control groups by one-way analysis of variance for continuous variables and the chi-square test for categorical variables. The Kruskal–Wallis test was used when variances were unequal among the groups. The Scheffé15 and Bonferroni16 procedures were used to adjust for multiple comparisons in the analyses of variance and chi-square tests, respectively.
We compared the cerebral-edema group with the random control group by means of a logistic-regression analysis that included the demographic variables and initial biochemical variables. We compared the cerebral-edema group with the matched control group by means of a conditional logistic-regression analysis that included the demographic variables and initial biochemical variables as well as the therapeutic variables and changes in biochemical variables during therapy. Because the odds ratio approximates the relative risk of diseases with a low incidence, we computed the odds ratio to estimate the relative risk. If two or more variables were collinear, only the variable that was measured most frequently was included in the multivariate analysis. For continuous data, missing values (12 percent of the continuous data points) were imputed.17
Using bootstrap methods, we performed 1000 iterations of the multivariate analyses to assess their stability.18,19 We considered the association of a variable with cerebral edema to be validated if a significant association with cerebral edema was found in more than 50 percent of the 1000 repeated analyses.19 All the statistical computations were two-tailed and were performed with Stata statistical software20 (version 6.0, Stata, College Station, Tex.).
Results
Incidence of Cerebral Edema
Clinically apparent cerebral edema occurred in 61 of 6977 hospitalizations for diabetic ketoacidosis during the study period (0.9 percent; 95 percent confidence interval, 0.7 to 1.1 percent). The diagnosis of cerebral edema was based on deterioration in mental status accompanied by radiographic evidence in 32 of the 61 children (52 percent), by changes in mental status that improved after therapy for suspected cerebral edema in 27 children (44 percent), and by postmortem findings in 2 children (3 percent). Neurologic deterioration occurred a median of 7 hours (range, 0 to 25) after the initiation of therapy for diabetic ketoacidosis (Figure 1Figure 1
Time between the Initiation of Therapy and Neurologic Deterioration in Children with Diabetic Ketoacidosis and Cerebral Edema.), but in three of the children (5 percent), all of whom had radiographically apparent cerebral edema, it occurred before the initiation of therapy.Of the 61 children with cerebral edema, 35 (57 percent) recovered without sequelae, 13 (21 percent) survived with permanent neurologic dysfunction, and 13 (21 percent) died. During the study period, only two other children died as a result of diabetic ketoacidosis, both owing to cardiac arrest associated with hypokalemia and hypocalcemia.
Demographic and Initial Biochemical Variables
The 61 children in whom cerebral edema occurred were younger, more likely to be white, and more likely to have newly diagnosed diabetes than the 181 children in the randomly selected control group (Table 1Table 1
Characteristics of the Children at the Time of Presentation.). The children with cerebral edema also had more severe acidosis and hypocapnia and higher serum glucose, urea nitrogen, and creatinine concentrations at the time of presentation than the randomly selected controls.The 61 patients in the cerebral-edema group and the 174 children in the matched control group were well matched: there were no significant differences between these groups with respect to age, the proportion with newly diagnosed diabetes, serum glucose concentrations, and arterial pH values at the time of presentation (Table 1). However, the children with cerebral edema had significantly higher serum urea nitrogen concentrations and significantly lower partial pressures of arterial carbon dioxide than the matched controls. Eighty-five percent of the children in the cerebral-edema group had initial partial pressures of arterial carbon dioxide of less than 18 mm Hg, as compared with 54 percent of the random control group and 69 percent of the matched control group.
Comparison of the Children with Cerebral Edema and the Random Controls
In the multiple logistic-regression analysis, the only variables that were associated with cerebral edema, after adjustment for other covariates, were the serum urea nitrogen concentration and partial pressure of arterial carbon dioxide at the time of presentation (Table 2Table 2
Multivariate Analysis of Risk Factors for Cerebral Edema in the Children with Cerebral Edema as Compared with the Random Control Group.).Because both arterial pH values and serum bicarbonate concentrations are measures of the degree of acidosis and thus are collinear, we included only the latter in the main multivariate analysis. Likewise, we excluded the initial serum osmolality values from the multivariate analysis because of collinearity. When serum osmolality was substituted for the serum sodium, glucose, and urea nitrogen concentration in a subanalysis, it was not a significant predictor of the risk of cerebral edema. However, the initial partial pressure of arterial carbon dioxide continued to be a significant predictor of the risk of cerebral edema (data not shown).
Comparison of the Children with Cerebral Edema and the Matched Controls
In the conditional logistic-regression analysis, both a higher serum urea nitrogen concentration and a lower partial pressure of arterial carbon dioxide were independently associated with cerebral edema (Table 3Table 3
Multivariate Analysis of Risk Factors for Cerebral Edema in the Children with Cerebral Edema as Compared with the Matched Control Group.). A smaller increase in the serum sodium concentration during therapy and treatment with bicarbonate were also significantly associated with cerebral edema.We evaluated the timing of bicarbonate administration in relation to the onset of symptoms of cerebral edema in order to investigate the possibility of bias in bicarbonate administration. We sought to ensure that physicians were not administering bicarbonate in response to deteriorating mental status, thus creating a misleading association between this intervention and cerebral edema. Of the 23 children in the cerebral-edema group who were treated with bicarbonate, only 3 (13 percent) received the first dose within two hours before the onset of neurologic deterioration. By comparison, of the 43 children in the matched control group who were treated with bicarbonate, 4 (9 percent) received their first dose during this interval (P= 0.69). Thus, no bias in the use of bicarbonate was detected.
Validation of Multivariate Analyses
With bootstrap analysis, the results of the multivariate regression analyses were validated. All the variables that were found to be associated with cerebral edema in the original analyses were significantly associated with cerebral edema in more than 75 percent of the 1000 iterations of the multivariate analyses.
Discussion
In this study, the children with diabetic ketoacidosis who had higher serum urea nitrogen concentrations and more severe hypocapnia at presentation than other children with diabetic ketoacidosis were at increased risk for cerebral edema. Smaller increases in the serum sodium concentration during therapy also indicated a greater likelihood of cerebral edema. Of the therapeutic factors analyzed, only treatment with bicarbonate was associated with cerebral edema. Neither the initial serum glucose concentration nor the rate of change in the serum glucose concentration during therapy was associated with the development of cerebral edema, after adjustment for other covariates; the same was true of the rates of fluid, sodium, and insulin administration.
In the current study, symptomatic cerebral edema occurred in approximately 1 percent of the episodes of diabetic ketoacidosis. Asymptomatic cerebral swelling, however, is thought to occur more frequently.4,21 Whether these conditions represent a spectrum of disease presentation or whether they are manifestations of different pathophysiologic processes is unknown. Equally controversial is whether specific therapies contribute to the development of cerebral edema. In the current study as well as several previous investigations,8,22,23 symptomatic cerebral edema developed in a few children with diabetic ketoacidosis before the initiation of therapy. This observation suggests that although variations in treatment may exacerbate an ongoing pathologic process, cerebral edema is not necessarily caused by therapeutic interventions.
Previous investigations of cerebral edema in children with diabetic ketoacidosis cited younger age, a new diagnosis of diabetes, and the rate of fluid administration as factors associated with cerebral edema.5,6 In these studies, however, children with cerebral edema were not compared with controls, and there was no adjustment for possible confounding factors. In the current study, the differences associated with these three variables were not significant after adjustment for other covariates. The results of our study agree with those of a recent study in which the initial partial pressure of arterial carbon dioxide was found to be an important predictor of the risk of cerebral edema.24
We found that smaller increases in the serum sodium concentration during therapy were associated with cerebral edema, in agreement with previous studies.3,5,25,26 The rates of fluid or sodium administration, however, were not associated with the risk of cerebral edema, after adjustment for other covariates. In children with cerebral edema, failure of the serum sodium concentration to rise during therapy may not be the result of excess administration of free water. Physiologic responses to cerebral injury, such as cerebral salt wasting, may alter sodium homeostasis in these children.27,28
It has been hypothesized that cerebral edema in children with diabetic ketoacidosis may be caused by the accumulation of osmolytes in brain cells exposed to hyperosmolar conditions. A rapid decrease in extracellular osmolality during treatment would then result in osmotically mediated swelling of the brain.25,29-31 The current data do not fully support this theory, since none of the relevant variables — the serum glucose concentration at presentation, the change in serum glucose concentration during therapy, or the rate of fluid or sodium administration — were associated with the risk of cerebral edema.
Although osmotic factors and other mechanisms may play a part in the development of cerebral edema, our data lend support to the hypothesis that cerebral edema in children with diabetic ketoacidosis is related to brain ischemia.24,32 Both hypocapnia, which causes cerebral vasoconstriction, and extreme dehydration would be expected to decrease perfusion of the brain. In addition, bicarbonate therapy causes central nervous system hypoxia in laboratory animals with diabetic ketoacidosis.33 Hyperglycemia superimposed on an ischemic insult increases the extent of neurologic damage, blood–brain barrier dysfunction, and edema formation.34,35 This interaction might help to explain the occurrence of neurologic damage in association with minor degrees of cerebral hypoperfusion. Blood–brain barrier dysfunction and vasogenic edema may occur several hours after an ischemic insult as a result of the release of vasoactive substances and mediators of inflammation.34,35 The occurrence of cerebral edema several hours after the initiation of therapy thus correlates well with the hypothesis that the basis of this complication is ischemia. Finally, the more frequent occurrence of cerebral edema in children than in adults may be explained in part by the fact that children's brains have higher oxygen requirements than adults' brains and are thus more susceptible to ischemia.10,36
Although large in comparison with previous studies, our study was nonetheless limited in its ability to detect associations of smaller magnitude; in addition, within the 95 percent confidence intervals for the risks associated with several variables were values that indicated associations that were potentially relevant clinically. We therefore cannot definitively conclude that variables that were not associated with cerebral edema in this study are in fact unimportant in its pathogenesis. In addition, several children in the cerebral-edema group who met the clinical criteria for cerebral edema did not have radiographic or postmortem documentation of its presence. We cannot be certain that the observed neurologic decompensation in the latter children was due to cerebral edema; however, other causes of their neurologic abnormalities could not be identified, and the results of initial radiographic studies in children with cerebral edema may be normal, despite profound neurologic depression.6,10 Because data were not available for every variable of potential interest, we also cannot exclude the possibility that confounding factors that were not analyzed may have influenced the detected associations, particularly those related to the use of bicarbonate treatment.
We conclude that children with diabetic ketoacidosis who present with high initial serum urea nitrogen concentrations and low partial pressures of arterial carbon dioxide are at increased risk for cerebral edema. In addition, the lack of an increase in the serum sodium concentration during therapy is associated with an increased probability of cerebral edema. Children with these biochemical features should be monitored extensively for signs of neurologic deterioration, and hyperosmolar therapy should be available for immediate use in case early signs of cerebral edema occur. Finally, treatment with bicarbonate is associated with an increased risk of cerebral edema and should be avoided in most circumstances.
Supported by grants from the Children's Miracle Network and the Ambulatory Pediatrics Association.
We are indebted to Wes Johnson, Ph.D., and Mitch Watnik, Ph.D., for their assistance with the statistical analysis of this study; to Maria Medina, B.S., for her meticulous data entry; to William Ellis, M.D., for his review of cases of intracranial infarction; and to Joseph Wolfsdorf, M.D., for his critical review of the manuscript.
Source Information
From the Department of Pediatrics (N.G., N.K.) and the Division of Emergency Medicine, Department of Internal Medicine (N.K.), University of California, Davis, School of Medicine, Davis; the Division of Emergency Medicine, Royal Children's Hospital, Melbourne, Australia (P.B.); the Division of Emergency Medicine, Children's Hospital and Health Center, San Diego, Calif. (I.M.); the Department of Pediatrics, Brown University School of Medicine, Providence, R.I. (D.N.); the Division of Emergency Medicine, Children's Memorial Hospital, Chicago (J.T.); the Division of Emergency Medicine, Children's Hospital of Philadelphia, Philadelphia (J.L.); the Department of Pediatrics, University of Southern California School of Medicine, Los Angeles (F.K.); the Department of Pediatrics, Washington University School of Medicine, St. Louis (K.Q.); the Department of Pediatrics, University of Colorado Health Sciences Center, Denver (M.R.); and the Department of Pediatrics, Harvard Medical School, Boston (R.M.). Presented in part at the annual meetings of the Society for Pediatric Research, Boston, May 14, 2000, and the Society for Academic Emergency Medicine, San Francisco, May 25, 2000.
Address reprint requests to Dr. Glaser at the Division of Pediatric Endocrinology, University of California, Davis, Medical Center, 2516 Stockton Blvd., Sacramento, CA 95817, or at nsglaser@ucdavis.edu.
- References
References
1
Pinkney JH ,Bingley PJ ,Sawtell PA ,Dunger DB ,Gale EA . Presentation and progress of childhood diabetes mellitus: a prospective population-based study. Diabetologia 1994;37:70-74
CrossRef | Web of Science | Medline2
Faich GA ,Fishbein HA ,Ellis SE . The epidemiology of diabetic acidosis: a population-based study. Am J Epidemiol 1983;117:551-558
Web of Science | Medline3
Bello FA ,Sotos JF . Cerebral oedema in diabetic ketoacidosis in children. Lancet 1990;336:64-64
CrossRef | Web of Science | Medline4
Krane EJ ,Rockoff MA ,Wallman JK ,Wolfsdorf JI . Subclinical brain swelling in children during treatment of diabetic ketoacidosis. N Engl J Med 1985;312:1147-1151
Full Text | Web of Science | Medline5
Duck SC ,Wyatt DT . Factors associated with brain herniation in the treatment of diabetic ketoacidosis. J Pediatr 1988;113:10-14
CrossRef | Web of Science | Medline6
Rosenbloom A . Intracerebral crises during treatment of diabetic ketoacidosis. Diabetes Care 1990;13:22-33
CrossRef | Web of Science | Medline7
Scibilia J ,Finegold D ,Dorman J ,Becker D ,Drash A . Why do children with diabetes die? Acta Endocrinol Suppl (Copenh) 1986;279:326-333
Medline8
Edge JA ,Ford-Adams ME ,Dunger DB . Causes of death in children with insulin dependent diabetes 1990-96. Arch Dis Child 1999;81:318-323
CrossRef | Web of Science | Medline9
Bingaman WE ,Frank JI . Malignant cerebral edema and intracranial hypertension. Neurol Clin 1995;13:479-509
Web of Science | Medline10
Muir A . Cerebral edema in diabetic ketoacidosis: a look beyond rehydration. J Clin Endocrinol Metab 2000;85:509-513
CrossRef | Web of Science11
Katz MA . Hyperglycemia-induced hyponatremia -- calculation of expected serum sodium depression. N Engl J Med 1973;289:843-844
Full Text | Web of Science | Medline12
Choukair MK. Fluids and electrolytes. In: Siberry GK, Iannone R, eds. The Harriet Lane handbook: a manual for pediatric house officers. St. Louis: Mosby, 2000:229-50.
13
Alpers JB. Clinical laboratories handbook. 6th ed., 1988-89. Stow, Ohio: Lexi-Comp, 1988.
14
Gioia FR, Stephenson RL, Alterwitz SA. Principles of respiratory support and mechanical ventilation. In: Rogers MC, ed. Textbook of pediatric intensive care. Vol. 1. Baltimore: Williams & Wilkins, 1987:113-69.
15
Scheffe H . A method for judging all contrasts in the analysis of variance. Biometrika 1953;40:87-104
Web of Science16
Kleinbaum DG, Kupper LL, Muller KE. Applied regression analysis and other multivariable methods. 2nd ed. Boston: PWS–KENT Publishing, 1988.
17
Little RJA, Rubin DB. Statistical analysis with missing data. New York: John Wiley, 1987:44-7.
18
Efron B ,Gong G . A leisurely look at the bootstrap, the jackknife, and cross-validation. Am Stat 1983;37:36-48
CrossRef | Web of Science19
Chen CH ,George SL . The bootstrap and identification of prognostic factors via Cox's proportional hazards regression model. Stat Med 1985;4:39-46
CrossRef | Web of Science | Medline20
Stata statistical software: release 6.0. College Station, Tex.: Stata, 1999.
21
Hoffman WH ,Steinhart CM ,el Gammal T ,Steele S ,Cuadrado AR ,Morse PK . Cranial CT in children and adolescents with diabetic ketoacidosis. AJNR Am J Neuroradiol 1988;9:733-739
Web of Science | Medline22
Glasgow AM . Devastating cerebral edema in diabetic ketoacidosis before therapy. Diabetes Care 1991;14:77-78
Web of Science | Medline23
Couch RM ,Acott PD ,Wong GW . Early onset of fatal cerebral edema in diabetic ketoacidosis. Diabetes Care 1991;14:78-79
Web of Science | Medline24
Mahoney CP ,Vlcek BW ,DelAguila M . Risk factors for developing brain herniation during diabetic ketoacidosis. Pediatr Neurol 1999;21:721-727
CrossRef | Web of Science | Medline25
Harris G ,Fiordalisi I ,Finberg L . Safe management of diabetic ketoacidemia. J Pediatr 1988;113:65-68
CrossRef | Web of Science | Medline26
Harris GD ,Fiordalisi I ,Harris WL ,Mosovich LL ,Finberg L . Minimizing the risk of brain herniation during treatment of diabetic ketoacidemia: a retrospective and prospective study. J Pediatr 1990;117:22-31[Erratum, J Pediatr 1991;118:166-7.]
CrossRef | Web of Science | Medline27
Ganong CA ,Kappy MS . Cerebral salt wasting in children: the need for recognition and treatment. Am J Dis Child 1993;147:167-169[Erratum, Am J Dis Child 1993;147:369.]
Web of Science | Medline28
Isotani E ,Suzuki R ,Tomita K , et al. Alterations in plasma concentrations of natriuretic peptides and antidiuretic hormone after subarachnoid hemorrhage. Stroke 1994;25:2198-2203
CrossRef | Web of Science | Medline29
Arieff AI ,Kleeman CR . Cerebral edema in diabetic comas. II. Effects of hyperosmolality, hyperglycemia and insulin in diabetic rabbits. J Clin Endocrinol Metab 1974;38:1057-1067
CrossRef | Web of Science | Medline30
Silver SM ,Clark EC ,Schroeder BM ,Sterns RH . Pathogenesis of cerebral edema after treatment of diabetic ketoacidosis. Kidney Int 1997;51:1237-1244[Erratum, Kidney Int 1997;51:1662.]
CrossRef | Web of Science | Medline31
Prockop LD . Hyperglycemia, polyol accumulation, and increased intracranial pressure. Arch Neurol 1971;25:126-140
Web of Science | Medline32
Hammond P ,Wallis S . Cerebral oedema in diabetic ketoacidosis. BMJ 1992;305:203-204
CrossRef | Web of Science | Medline33
Bureau MA ,Begin R ,Berthiaume Y ,Shapcott D ,Khoury K ,Gagnon N . Cerebral hypoxia from bicarbonate infusion in diabetic acidosis. J Pediatr 1980;96:968-973
CrossRef | Web of Science | Medline34
Lin B ,Ginsberg MD ,Busto R ,Li L . Hyperglycemia triggers massive neutrophil deposition in brain following transient ischemia in rats. Neurosci Lett 2000;278:1-4
CrossRef | Web of Science | Medline35
Dietrich WD. Inflammatory factors regulating the blood-brain barrier. In: Feuerstein GZ, ed. Inflammatory cells and mediators in CNS disease. Amsterdam: Harwood Academic, 1999:137-55.
36
Jones MD Jr . Energy metabolism in the developing brain. Semin Perinatol 1979;3:121-129
Web of Science | Medline
- Citing Articles (142)
Citing Articles
1
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CrossRef2
Brian P. Walcott, Kristopher T. Kahle, J. Marc Simard. (2011) Novel Treatment Targets for Cerebral Edema. Neurotherapeutics
CrossRef3
Hoi-Ying Elsie Yu, Michael Agus, Mark D Kellogg. (2011) Clinical utility of Abbott Precision Xceed Pro® ketone meter in diabetic patients. Pediatric Diabetes 12:7, 649-655
CrossRef4
Monica S. Vavilala, Ken I. Marro, Todd L. Richards, Joan S. Roberts, Parichat Curry, Catherine Pihoker, Heidi Bradford, Dennis Shaw. (2011) Change in mean transit time, apparent diffusion coefficient, and cerebral blood volume during pediatric diabetic ketoacidosis treatment*. Pediatric Critical Care Medicine 12:6, e344-e349
CrossRef5
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CrossRef7
Radha Devi, Geetha Selvakumar, Lisa Clark, Carol Downer, Susan S Braithwaite. (2011) A dose-defining insulin algorithm for attainment and maintenance of glycemic targets during therapy of hyperglycemic crises. Diabetes Management 1:4, 397-412
CrossRef8
Kristina H Deeter, Joan S Roberts, Heidi Bradford, Todd Richards, Dennis Shaw, Kenneth Marro, Harvey Chiu, Catherine Pihoker, Anne Lynn, Monica S Vavilala. (2011) Hypertension despite dehydration during severe pediatric diabetic ketoacidosis. Pediatric Diabetes 12:4pt1, 295-301
CrossRef9
Sindhu Sivanandan, Aditi Sinha, Vandana Jain, Rakesh Lodha. (2011) Management of Diabetic Ketoacidosis. The Indian Journal of Pediatrics 78:5, 576-584
CrossRef10
M. W. Savage, K. K. Dhatariya, A. Kilvert, G. Rayman, J. A. E. Rees, C. H. Courtney, L. Hilton, P. H. Dyer, M. S. Hamersley, . (2011) Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis. Diabetic Medicine 28:5, 508-515
CrossRef11
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CrossRef12
James P. Marcin, Nathan Kuppermann, Daniel J. Tancredi, Nicole S. Glaser. (2011) Insulin administration for treatment of pediatric diabetic ketoacidosis: Are lower rates of infusion beneficial?*. Pediatric Critical Care Medicine 12:2, 217-219
CrossRef13
Said Al Hanshi, Frank Shann. (2011) Insulin infused at 0.05 versus 0.1 units/kg/hr in children admitted to intensive care with diabetic ketoacidosis*. Pediatric Critical Care Medicine 12:2, 137-140
CrossRef14
Horng Chua, Antoine Schneider, Rinaldo Bellomo. (2011) Bicarbonate in diabetic ketoacidosis - a systematic review. Annals of Intensive Care 1:1, 23
CrossRef15
N. Bouhours-Nouet, R. Coutant. (2011) Aspectos clínicos y diagnósticos de la diabetes infantil. EMC - Pediatría 46:4, 1-20
CrossRef16
Catherine Pihoker, Ildiko H. Koves, Nicole S. Glaser. 2011. Diabetic Ketoacidosis. , 1124-1130.
CrossRef17
Arlan L. Rosenbloom. (2010) The management of diabetic ketoacidosis in children. Diabetes Therapy 1:2, 103-120
CrossRef18
Martin N. Montoro. 2010. Pregnancy in Women with Complicated Diabetes Mellitus. , 717-728.
CrossRef19
M Abdul-Rasoul, M Al-Mahdi, H Al-Qattan, N Al-Tarkait, M Alkhouly, R Al-Safi, F Al-Shawaf, H Mahmoud. (2010) Ketoacidosis at presentation of type 1 diabetes in children in Kuwait: frequency and clinical characteristics. Pediatric Diabetes 11:5, 351-356
CrossRef20
Terry P. Klassen, Jason Acworth, Liza Bialy, Karen Black, James M. Chamberlain, Nicholas Cheng, Stuart Dalziel, Ricardo M. Fernandes, Eleanor Fitzpatrick, David W. Johnson, Nathan Kuppermann, Charles G. Macias, Mandi Newton, Martin H. Osmond, Amy Plint, Paolo Valerio, Yehezkel Waisman. (2010) Pediatric Emergency Research Networks. Pediatric Emergency Care 26:8, 541-543
CrossRef21
Terry P. Klassen, Jason Acworth, Liza Bialy, Karen Black, James M. Chamberlain, Nicholas Cheng, Stuart Dalziel, Ricardo M. Fernandes, Eleanor Fitzpatrick, David W. Johnson, Nathan Kuppermann, Charles G. Macias, Mandi Newton, Martin H. Osmond, Amy Plint, Paolo Valerio, Yehezkel Waisman. (2010) Pediatric Emergency Research Networks: a global initiative in pediatric emergency medicine. European Journal of Emergency Medicine 17:4, 224-227
CrossRef22
William H. Hoffman, Anuska V. Andjelkovic, Weixian Zhang, Gregory G. Passmore, Anders A.F. Sima. (2010) Insulin and IGF-1 receptors, nitrotyrosin and cerebral neuronal deficits in two young patients with diabetic ketoacidosis and fatal brain edema. Brain Research 1343, 168-177
CrossRef23
Michael L. Moritz, Juan Carlos Ayus. (2010) New aspects in the pathogenesis, prevention, and treatment of hyponatremic encephalopathy in children. Pediatric Nephrology 25:7, 1225-1238
CrossRef24
Desmond Bohn. (2010) Understanding the pathophysiology of cerebral edema in diabetic ketoacidosis: Another brick in the wall?*. Pediatric Critical Care Medicine 11:3, 421-423
CrossRef25
Jeffrey A. Kraut, Nicolaos E. Madias. (2010) Metabolic acidosis: pathophysiology, diagnosis and management. Nature Reviews Nephrology 6:5, 274-285
CrossRef26
R. Puttha, D. Cooke, A. Subbarayan, E. Odeka, I. Ariyawansa, M. Bone, I. Doughty, L. Patel, R. Amin, . (2010) Low dose (0.05 units/kg/h) is comparable with standard dose (0.1 units/kg/h) intravenous insulin infusion for the initial treatment of diabetic ketoacidosis in children with type 1 diabetes-an observational study. Pediatric Diabetes 11:1, 12-17
CrossRef27
Srinivas Murthy, Rana Sharara-Chami. (2010) Aggressive Fluid Resuscitation in Severe Pediatric Hyperglycemic Hyperosmolar Syndrome: A Case Report. International Journal of Pediatric Endocrinology 2010:1, 379063
CrossRef28
Srinivas Murthy, Rana Sharara-Chami. (2010) Aggressive Fluid Resuscitation in Severe Pediatric Hyperglycemic Hyperosmolar Syndrome: A Case Report. International Journal of Pediatric Endocrinology 2010, 1-4
CrossRef29
Simona Ghetti, Joshua K. Lee, Clare E. Sims, Dana M. DeMaster, Nicole S. Glaser. (2010) Diabetic Ketoacidosis and Memory Dysfunction in Children with Type 1 Diabetes. The Journal of Pediatrics 156:1, 109-114
CrossRef30
2010. Suggested Readings. , 575-581.
CrossRef31
Brendan D. Higgins, Joseph Costello, Maya Contreras, Patrick Hassett, Daniel Oʼ Toole, John G. Laffey. (2009) Differential Effects of Buffered Hypercapnia versus Hypercapnic Acidosis on Shock and Lung Injury Induced by Systemic Sepsis. Anesthesiology 111:6, 1317-1326
CrossRef32
Nicole Glaser. (2009) Cerebral injury and cerebral edema in children with diabetic ketoacidosis: could cerebral ischemia and reperfusion injury be involved?. Pediatric Diabetes 10:8, 534-541
CrossRef33
Ana PCP Carlotti, C St George-Hyslop, A-M Guerguerian, D Bohn, KS Kamel, ML Halperin. (2009) Occult risk factor for the development of cerebral edema in children with diabetic ketoacidosis: possible role for stomach emptying. Pediatric Diabetes 10:8, 522-533
CrossRef34
S. Steel, S. M. Tibby. (2009) Paediatric diabetic ketoacidosis. Continuing Education in Anaesthesia, Critical Care & Pain 9:6, 194-199
CrossRef35
T. Neuenfeldt, H.B. Hopf. (2009) Erfolgreiche Behandlung einer extremen metabolischen Acidose mit ausgeprägter Hypothermie. Der Anaesthesist 58:11, 1113-1118
CrossRef36
Alistair D. Nichol, Donall F. OʼCronin, Katherine Howell, Finola Naughton, Sorca OʼBrien, John Boylan, Clare OʼConnor, Daniel OʼToole, John G. Laffey, Paul McLoughlin. (2009) Infection-induced lung injury is worsened after renal buffering of hypercapnic acidosis. Critical Care Medicine 37:11, 2953-2961
CrossRef37
Monica S. Vavilala, Todd L. Richards, Joan S. Roberts, Harvey Chiu, Catherine Pihoker, Heidi Bradford, Kristina Deeter, Ken I. Marro, Dennis Shaw. (2009) Change in blood–brain barrier permeability during pediatric diabetic ketoacidosis treatment*. Pediatric Critical Care Medicine1
CrossRef38
Joseph Wolfsdorf, Maria E. Craig, Denis Daneman, David Dunger, Julie Edge, Warren Lee, Arlan Rosenbloom, Mark Sperling, Ragnar Hanas. (2009) Diabetic ketoacidosis in children and adolescents with diabetes. Pediatric Diabetes 10, 118-133
CrossRef39
Andrew W. Norris, Joseph I. Wolfsdorf. 2009. Diabetes Mellitus. , 458-504.
CrossRef40
Juan Diego Toledo, Vicente Modesto, Magdalena Peinador, Pablo Álvarez, José Luis López-Prats, Ramón Sanchis, Máximo Vento. (2009) Sodium Concentration in Rehydration Fluids for Children with Ketoacidotic Diabetes: Effect on Serum Sodium Concentration. The Journal of Pediatrics 154:6, 895-900
CrossRef41
&NA;. (2009) Treating diabetic ketoacidosis in children requires careful management of fluid, electrolytes and insulin. Drugs & Therapy Perspectives 25:3, 14-17
CrossRef42
Timothy Hanson, Wesley Johnson, Purushottam Laud. (2009) Semiparametric inference for survival models with step process covariates. Canadian Journal of Statistics 37:1, 60-79
CrossRef43
Alba E Morales, Kerri A Daniels. (2009) Cerebral edema before onset of therapy in newly diagnosed type 2 diabetes. Pediatric Diabetes 10:2, 155-157
CrossRef44
William H. Hoffman, Svetlana M. Stamatovic, Anuska V. Andjelkovic. (2009) Inflammatory mediators and blood brain barrier disruption in fatal brain edema of diabetic ketoacidosis. Brain Research 1254, 138-148
CrossRef45
Juan P. Hernández-Fonseca, Jaimar Rincón, Adriana Pedreañez, Ninoska Viera, José L. Arcaya, Edgardo Carrizo, Jesús Mosquera. (2009) Structural and Ultrastructural Analysis of Cerebral Cortex, Cerebellum, and Hypothalamus from Diabetic Rats. Experimental Diabetes Research 2009, 1-12
CrossRef46
M. Polak, J.-J. Robert. (2009) Control de la diabetes mellitus en el ni??o. EMC - Pediatr??a 44:3, 1-8
CrossRef47
Yuko Okutomi, Hisami Minayoshi, Sayaka Akiyama, Hirokazu Aihara, Kazumasa Tazawa, Kaoru Koyama, Hideki Miyao. (2009) Nihon Shuchu Chiryo Igakukai zasshi 16:1, 87-88
CrossRef48
D. W. Cooke, L. Plotnick. (2008) Management of Diabetic Ketoacidosis in Children and Adolescents. Pediatrics in Review 29:12, 431-436
CrossRef49
Paul Bradley, Joseph D Tobias. (2008) An Evaluation of the Outside Therapy of Diabetic Ketoacidosis in Pediatric Patients. American Journal of Therapeutics 15:6, 516-519
CrossRef50
Lisa M Swartz, Lori M Laffel. (2008) A teenage girl with cystic fibrosis-related diabetes, diabetic ketoacidosis, and cerebral edema. Pediatric Diabetes 9:4pt2, 426-430
CrossRef51
J Antonio Quiros, James P. Marcin, Nathan Kuppermann, Farid Nasrollahzadeh, Arleta Rewers, Joseph DiCarlo, E Kirk Neely, Nicole Glaser. (2008) Elevated serum amylase and lipase in pediatric diabetic ketoacidosis*. Pediatric Critical Care Medicine 9:4, 418-422
CrossRef52
Jeffrey Hom, Richard Sinert. (2008) Is Fluid Therapy Associated With Cerebral Edema in Children With Diabetic Ketoacidosis?. Annals of Emergency Medicine 52:1, 69-75.e1
CrossRef53
James P. Orlowski, Cheryl L. Cramer, Mariano R. Fiallos. (2008) Diabetic Ketoacidosis in the Pediatric ICU. Pediatric Clinics of North America 55:3, 577-587
CrossRef54
Daniel L. Levin. (2008) Cerebral edema in diabetic ketoacidosis. Pediatric Critical Care Medicine 9:3, 320-329
CrossRef55
MARK A. SPERLING, STUART A. WEINZIMER, WILLIAM V. TAMBORLANE. 2008. Diabetes Mellitus. , 374-421.
CrossRef56
Arlan L. Rosenbloom. (2008) Treatment of diabetic ketoacidosis and the risk of cerebral edema. The Journal of Pediatrics 152:1, 146-147
CrossRef57
Ewout Jasper Hoorn, Ana P.C.P. Carlotti, Mitchell L. Halperin, Desmond Bohn. (2008) Reply. The Journal of Pediatrics 152:1, 147-149
CrossRef58
Nicole Glaser, Nathan Kuppermann. (2008) DKA-related cerebral edema and intravenous fluid therapy: Potential pitfalls of uncontrolled retrospective studies. The Journal of Pediatrics 152:1, 145
CrossRef59
Kenneth T. Kwon, Virginia W. Tsai. (2007) Metabolic Emergencies. Emergency Medicine Clinics of North America 25:4, 1041-1060
CrossRef60
Elise Bismuth, Lori Laffel. (2007) Can we prevent diabetic ketoacidosis in children?. Pediatric Diabetes 8:s6, 24-33
CrossRef61
R. Hanas, F. Lindgren, B. Lindblad. (2007) Diabetic ketoacidosis and cerebral oedema in Sweden?a 2-year paediatric population study. Diabetic Medicine 24:10, 1080-1085
CrossRef62
Yuri Gilhotra, Paul Porter. (2007) Predicting diabetic ketoacidosis in children by measuring end-tidal CO 2 via non-invasive nasal capnography. Journal of Paediatrics and Child Health 43:10, 677-680
CrossRef63
Sandra L. Wootton-Gorges, Nicole S. Glaser. (2007) Imaging of the brain in children with type I diabetes mellitus. Pediatric Radiology 37:9, 863-869
CrossRef64
Marc H. Gorelick, Stacey Knight, Evaline A. Alessandrini, Rachel M. Stanley, James M. Chamberlain, Nathan Kuppermann, Elizabeth R. Alpern. (2007) Lack of Agreement in Pediatric Emergency Department Discharge Diagnoses from Clinical and Administrative Data Sources. Academic Emergency Medicine 14:7, 646-652
CrossRef65
Venkat Shankar, Anwarul Haque, Kevin B. Churchwell, William Russell. (2007) Insulin glargine supplementation during early management phase of diabetic ketoacidosis in children. Intensive Care Medicine 33:7, 1173-1178
CrossRef66
Irma Fiordalisi, William E Novotny, Donald Holbert, Laurence Finberg, Glenn D Harris, . (2007) An 18-yr prospective study of pediatric diabetic ketoacidosis: an approach to minimizing the risk of brain herniation during treatment. Pediatric Diabetes 8:3, 142-149
CrossRef67
JUNJI TAKAYA, REIKO OHASHI, YOSHIAKI HARADA, FUMIKO YAMATO, HIROHIKO HIGASHINO, YOHNOSUKE KOBAYASHI, KAZUNARI KANEKO. (2007) Cerebral edema in a child with diabetic ketoacidosis before initial treatment. Pediatrics International 49:3, 395-396
CrossRef68
R. R. Jahagirdar, V. V. Khadilkar, A. V. Khadilkar, S. K. Lalwani. (2007) Management of diabetic ketoacidosis in PICU. The Indian Journal of Pediatrics 74:6, 551-554
CrossRef69
SC Mcgeoch, SD Hutcheon, SM Vaughan, K John, NP O'Neill, DWM Pearson, SM Macrury. (2007) Development of a national Scottish diabetic ketoacidosis protocol. Practical Diabetes International 24:5, 257-261
CrossRef70
Paul Bradley, Joseph D Tobias. (2007) Serum Glucose Changes During Insulin Therapy in Pediatric Patients With Diabetic Ketoacidosis. American Journal of Therapeutics 14:3, 265-268
CrossRef71
Aaron L. Friedman. (2007) Choosing the Right Fluid and Electrolytes Prescription in Diabetic Ketoacidosis. The Journal of Pediatrics 150:5, 455-456
CrossRef72
Ewout J. Hoorn, Ana P.C.P. Carlotti, Leila A.A. Costa, Beth MacMahon, Gareth Bohn, Robert Zietse, Mitchell L. Halperin, Desmond Bohn. (2007) Preventing a Drop in Effective Plasma Osmolality to Minimize the Likelihood of Cerebral Edema During Treatment of Children with Diabetic Ketoacidosis. The Journal of Pediatrics 150:5, 467-473
CrossRef73
Aman Sharma, Susheel Kumar, Navneet Sharma, Sanjay Jain, Subhash Varma. (2007) Bilateral parietal lobe hemorrhage in a patient with diabetic ketoacidosis. Diabetes Research and Clinical Practice 75:3, 379-380
CrossRef74
Rebecca Steinmann. (2007) Pediatric Diabetic Ketoacidosis. AJN, American Journal of Nursing 107:3, 72CC-72KK
CrossRef75
KEELEY L. ROSE, CHRISTOPHER L. PIN, RENNIAN WANG, DOUGLAS D. FRASER. (2007) Combined Insulin and Bicarbonate Therapy Elicits Cerebral Edema in a Juvenile Mouse Model of Diabetic Ketoacidosis. Pediatric Research 61:3, 301-306
CrossRef76
Joseph Wolfsdorf, Maria E Craig, Denis Daneman, David Dunger, Julie Edge, WR Warren Lee, Arlan Rosenbloom, Mark A Sperling, Ragnar Hanas. (2007) Diabetic ketoacidosis. Pediatric Diabetes 8:1, 28-43
CrossRef77
Thomas Michael Kapellen, Esther M. Maier, Ania C. Muntau, Klemens Raile. 2007. Der Stoffwechselnotfall. , 337-351.
CrossRef78
J.A. Stockman. (2007) Population-Based Study of Incidence and Risk Factors for Cerebral Edema in Pediatric Diabetic Ketoacidosis. Yearbook of Pediatrics 2007, 434-436
CrossRef79
J. A. Edge, R. W. Jakes, Y. Roy, M. Hawkins, D. Winter, M. E. Ford-Adams, N. P. Murphy, A. Bergomi, B. Widmer, D. B. Dunger. (2006) The UK case–control study of cerebral oedema complicating diabetic ketoacidosis in children. Diabetologia 49:9, 2002-2009
CrossRef80
Michael SD Agus, Jamin L Alexander, Patricia A Mantell. (2006) Continuous non-invasive end-tidal CO2 monitoring in pediatric inpatients with diabetic ketoacidosis. Pediatric Diabetes 7:4, 196-200
CrossRef81
Alice Ackerman. (2006) Cerebral edema in pediatric diabetic ketoacidosis: Can six patients make a difference?*. Critical Care Medicine 34:8, 2258-2259
CrossRef82
Joan S. Roberts, Monica S. Vavilala, Kenneth A. Schenkman, Dennis Shaw, Lynn D. Martin, Arthur M. Lam. (2006) Cerebral hyperemia and impaired cerebral autoregulation associated with diabetic ketoacidosis in critically ill children*. Critical Care Medicine 34:8, 2217-2223
CrossRef83
Jeffrey A. Kraut, Ira Kurtz. (2006) Use of base in the treatment of acute severe organic acidosis by nephrologists and critical care physicians: results of an online survey. Clinical and Experimental Nephrology 10:2, 111-117
CrossRef84
MW Savage, A Kilvert, . (2006) ABCD guidelines for the management of hyperglycaemic emergencies in adults. Practical Diabetes International 23:5, 227-231
CrossRef85
Robert C. Tasker. (2006) Severe diabetic ketoacidosis: hyperventilation or relative hypoventilation. Pediatric Critical Care Medicine 7:3, 291-292
CrossRef86
A. N. Dixon, E. B. Jude, A. K. Banerjee, S. C. Bain. (2006) Simultaneous pulmonary and cerebral oedema, and multiple CNS infarctions as complications of diabetic ketoacidosis: a case report. Diabetic Medicine 23:5, 571-573
CrossRef87
Mohsen S. Eledrisi, Mohammed S. Alshanti, M Faiq Shah, Basem Brolosy, Nermeen Jaha. (2006) Overview of the Diagnosis and Management of Diabetic Ketoacidosis. The American Journal of the Medical Sciences 331:5, 243-251
CrossRef88
Josephine Ho, Jean K. Mah, Michael D. Hill, Daniele Pacaud. (2006) Pediatric stroke associated with new onset type 1 diabetes mellitus: case reports and review of the literature. Pediatric Diabetes 7:2, 116-121
CrossRef89
Mark A. Sperling. (2006) Cerebral edema in diabetic ketoacidosis: an underestimated complication?. Pediatric Diabetes 7:2, 73-74
CrossRef90
Nicole S Glaser, Sandra L Wootton-Gorges, Michael H Buonocore, James P Marcin, Arleta Rewers, John Strain, Joseph DiCarlo, E Kirk Neely, Patrick Barnes, Nathan Kuppermann. (2006) Frequency of sub-clinical cerebral edema in children with diabetic ketoacidosis. Pediatric Diabetes 7:2, 75-80
CrossRef91
Cabot, Richard C.Harris, Nancy Lee, Shepard, Jo-Anne O., Ebeling, Sally H.Peters, Christine C., Takayesu, J. Kimo, Bazari, Hasan, Linshaw, Michael, . (2006) Case 7-2006. New England Journal of Medicine 354:10, 1065-1072
Full Text92
Brendan J. Kilbane, Sanjeev Mehta, Philippe F. Backeljauw, Thomas P. Shanley, Nancy A. Crimmins. (2006) Approach to management of malignant hyperthermia-like syndrome in pediatric diabetes mellitus. Pediatric Critical Care Medicine 7:2, 169-173
CrossRef93
L. M. B. Laffel, K. Wentzell, C. Loughlin, A. Tovar, K. Moltz, S. Brink. (2006) Sick day management using blood 3-hydroxybutyrate (3-OHB) compared with urine ketone monitoring reduces hospital visits in young people with T1DM: a randomized clinical trial. Diabetic Medicine 23:3, 278-284
CrossRef94
Julie A Edge, Yvonne Roy, Andrea Bergomi, Nuala P Murphy, Martha E Ford-Adams, Ken K Ong, David B Dunger. (2006) Conscious level in children with diabetic ketoacidosis is related to severity of acidosis and not to blood glucose concentration. Pediatric Diabetes 7:1, 11-15
CrossRef95
Elisabeth A Northam, Debbie Rankins, Fergus J Cameron. (2006) Therapy Insight: the impact of type 1 diabetes on brain development and function. Nature Clinical Practice Neurology 2:2, 78-86
CrossRef96
2006. Insulin. , 1761-1783.
CrossRef97
Arlan L. Rosenbloom. (2005) Hyperglycemic Comas in Children: New Insights into Pathophysiology and Management. Reviews in Endocrine and Metabolic Disorders 6:4, 297-306
CrossRef98
Marc H. Gorelick, Elizabeth R. Alpern, Tasmeen Singh, Donald Snowdon, Richard Holubkov, J. Michael Dean, Nathan Kuppermann. (2005) Availability of Pediatric Emergency Visit Data from Existing Data Sources. Academic Emergency Medicine 12:12, 1195-1200
CrossRef99
K. Plikat, F. Rockmann. (2005) Coma diabeticum. Intensivmedizin und Notfallmedizin 42:7, 566-586
CrossRef100
Srikanth Bellary, Steve Bain. (2005) Bicarbonate treatment in patients with diabetic ketoacidosis. Practical Diabetes International 22:7, 260a-260a
CrossRef101
James P. Marcin, Nicole Glaser, Nathan Kuppermann. (2005) Ventilation in pediatric diabetic ketoacidosis???Not too much, but not too little*. Pediatric Critical Care Medicine 6:4, 489-490
CrossRef102
Rita S. Jerath, C. Lynne Burek, William H. Hoffman, Gregory G. Passmore. (2005) Complement activation in diabetic ketoacidosis and its treatment. Clinical Immunology 116:1, 11-17
CrossRef103
Robert C. Tasker, Daniel Lutman, Mark J. Peters. (2005) Hyperventilation in severe diabetic ketoacidosis*. Pediatric Critical Care Medicine 6:4, 405-411
CrossRef104
Mark A. Sperling. (2005) Diabetic ketoacidosis in children: the problems continue. Pediatric Diabetes 6:2, 67-68
CrossRef105
N. S. Glaser, M. H. Buonocore. (2005) Cerebral metabolic alterations in children with diabetic ketoacidosis. Diabetic Medicine 22:5, 515-516
CrossRef106
F. J. Cameron, M. J. Kean, R. M. Wellard, G. A. Werther, J. J. Neil, T. E. Inder. (2005) Insights into the acute cerebral metabolic changes associated with childhood diabetes. Diabetic Medicine 22:5, 648-653
CrossRef107
M. J. R. Kershaw, T. Newton, T. G. Barrett, K. Berry, J. Kirk. (2005) Childhood diabetes presenting with hyperosmolar dehydration but without ketoacidosis: a report of three cases. Diabetic Medicine 22:5, 645-647
CrossRef108
Gabriel J. Escobar. (2005) What have we learned from observational studies on neonatal sepsis?. Pediatric Critical Care Medicine 6:Supplement, S138-S145
CrossRef109
Monica S. Vavilala, Michael J. Souter, Arthur M. Lam. (2005) Hyperemia and impaired cerebral autoregulation in a surgical patient with diabetic ketoacidosis. Canadian Journal of Anesthesia/Journal canadien d'anesthésie 52:3, 323-326
CrossRef110
Viktor Rosival. (2005) Diabetic Ketoacidosis. Pediatric Emergency Care 21:1, 76
CrossRef111
Ramon E. Figueroa, William H. Hoffman, Zahir Momin, Ajay Pancholy, Gregory G. Passmore, Jerry Allison. (2005) Study of Subclinical Cerebral Edema in Diabetic Ketoacidosis by Magnetic Resonance Imaging T2 Relaxometry and Apparent Diffusion Coefficient Maps. Endocrine Research 31:4, 345-355
CrossRef112
M Jayashree, Sunit Singhi. (2004) Diabetic ketoacidosis Predictors of outcome in a pediatric intensive care unit of a developing country*. Pediatric Critical Care Medicine 5:5, 427-433
CrossRef113
Andrew C. Argent. (2004) What determines the outcome of children with diabetic ketoacidosis admitted to the pediatric intensive care unit of a developing country?*. Pediatric Critical Care Medicine 5:5, 492-493
CrossRef114
Nicole Glaser, Nathan Kuppermann. (2004) The Evaluation and Management of Children With Diabetic Ketoacidosis in the Emergency Department. Pediatric Emergency Care 20:7, 477-481
CrossRef115
Jason L Gaglia, Jennifer Wyckoff, Martin J Abrahamson. (2004) Acute hyperglycemic crisis in the elderly. Medical Clinics of North America 88:4, 1063-1084
CrossRef116
John G. Laffey, Donall O’Croinin, Paul McLoughlin, Brian P. Kavanagh. (2004) Permissive hypercapnia — role in protective lung ventilatory strategies. Intensive Care Medicine 30:3, 347-356
CrossRef117
Stuart A. Weinzimer, William V. Tamborlane. 2004. Diabetes Mellitus in Children and Adolescents. .
CrossRef118
Fredrik Ahlsson, Rolf Gedeborg, G??ran Hesselager, Torsten Tuvemo, Per Enblad. (2004) Treatment of extreme hyperglycemia monitored with intracerebral microdialysis. Pediatric Critical Care Medicine 5:1, 89-92
CrossRef119
O. Napolova. (2003) Assessing the degree of extracellular fluid volume contraction in a patient with a severe degree of hyperglycaemia. Nephrology Dialysis Transplantation 18:12, 2674-2677
CrossRef120
Abbas E. Kitabchi, Guillermo E. Umpierrez, Mary Beth Murphy. 2003. Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State. .
CrossRef121
SK Jha. (2003) Cerebral edema and its management. Medical Journal Armed Forces India 59:4, 326-331
CrossRef122
William H Hoffman, C.Lynne Burek, Jennifer L Waller, Lyle E Fisher, Mahmood Khichi, Larry B Mellick. (2003) Cytokine response to diabetic ketoacidosis and its treatment. Clinical Immunology 108:3, 175-181
CrossRef123
O. John Ma, Micheal D. Rush, Michelle M. Godfrey, Gary Gaddis. (2003) Arterial Blood Gas Results Rarely Influence Emergency Physician Management of Patients with Suspected Diabetic Ketoacidosis. Academic Emergency Medicine 10:8, 836-841
CrossRef124
(2003) The Pediatric Emergency Care Applied Research Network (PECARN): Rationale, development, and first steps. Pediatric Emergency Care 19:3, 185-193
CrossRef125
(2003) The Pediatric Emergency Care Applied Research Network (PECARN): Rationale, Development, and First Steps*. Academic Emergency Medicine 10:6, 661-668
CrossRef126
William H. Hoffman, Frank Kappler, Gregory G. Passmore, Renuka Mehta. (2003) Diabetic ketoacidosis and its treatment increase plasma 3-deoxyglucosone. Clinical Biochemistry 36:4, 269-273
CrossRef127
Mark W. J. Strachan, Graham R. Nimmo, Kathryn Noyes, David Simpson, Christopher J. H. Kelnar. (2003) Management of cerebral oedema in diabetes. Diabetes/Metabolism Research and Reviews 19:3, 241-247
CrossRef128
Pradip Kamat, Atul Vats, Matt Gross, Paul A. Checchia. (2003) Use of hypertonic saline for the treatment of altered mental status associated with diabetic ketoacidosis. Pediatric Critical Care Medicine 4:2, 239-242
CrossRef129
Guillermo E Umpierrez, Abbas E Kitabchi. (2003) Diabetic Ketoacidosis. Treatments in Endocrinology 2:2, 95-108
CrossRef130
Deirdre M. Fearon, Dale W. Steele. (2002) End-tidal Carbon Dioxide Predicts the Presence and Severity of Acidosis in Children with Diabetes. Academic Emergency Medicine 9:12, 1373-1378
CrossRef131
Laffey, John G., Kavanagh, Brian P., . (2002) Hypocapnia. New England Journal of Medicine 347:1, 43-53
Full Text132
Desmond Bohn, Denis Daneman. (2002) Diabetic ketoacidosis and cerebral edema. Current Opinion in Pediatrics 14:3, 287-291
CrossRef133
Irma Fiordalisi, Glenn D Harris, M.G.F Gilliland. (2002) Prehospital cardiac arrest in diabetic ketoacidemia. Journal of Diabetes and its Complications 16:3, 214-219
CrossRef134
Patel Neal Ramesh. (2002) Diabetic ketoacidosis in the pediatric patient. The Indian Journal of Pediatrics 69:1, 75-77
CrossRef135
E. A. McIntyre, P. Perros. (2001) Serum S-100beta protein as a biochemical marker for cerebral oedema complicating severe diabetic ketoacidosis. Diabetic Medicine 18:12, 1008-1008
CrossRef136
Jacqueline R Curtis, Desmond Bohn, Denis Daneman. (2001) Use of hypertonic saline in the treatment of cerebral edema in diabetic ketoacidosis (DKA). Pediatric Diabetes 2:4, 191-194
CrossRef137
Nobuo Matsuura, Yukifumi Yokota, Kouji Kazahari, Nozomu Sasaki, Shin Amemiya, Yoshiya Ito, Naoki Fukushima, Akemi Koike, Yutaka Igarashi, Takeki Hirano, Shigetaka Sugihara, Yuko Miki, Tatsuhiko Urakami, Yasuko Uchigata, Sachiko Kanematsu, Yukashi Ohki, Masaro Takesue, Yukihiro Hasegawa, Shigeki Miyamoto, Masatoshi Fujimoto, Satoshi Fujitsuka, Tetsuo Mori, Haruo Ogawa, Makoto Uchiyama, Kazumichi Onigata, Katsuhiko Tachibana, Nobuyuki Kikuchi, Tokuo Taketani, Hitoshi Kohno, Yoshihito Kasahara, Gen Isshiki, Masakuni Tokuda, Toshikazu Takahashi, Susumu Kanzaki, Ichiro Yokota, Kaichi Kida, Taisuke Okada, Soroku Nishiyama, Hidenari Masuda, Akihiko Kinugasa, Osamu Nukada. (2001) The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT): initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children. Pediatric Diabetes 2:4, 160-169
CrossRef138
Mary Dunne Roberts, Robert H Slover, H Peter Chase. (2001) Diabetic ketoacidosis with intracerebral complications. Pediatric Diabetes 2:3, 109-114
CrossRef139
Mark A Atkinson, George S Eisenbarth. (2001) Type 1 diabetes: new perspectives on disease pathogenesis and treatment. The Lancet 358:9277, 221-229
CrossRef140
(2001) Risk Factors for Cerebral Edema in Children with Diabetic Ketoacidosis. New England Journal of Medicine 344:20, 1556-1556
Full Text141
Nicole Glaser. (2001) Cerebral edema in children with diabetic ketoacidosis. Current Diabetes Reports 1:1, 41-46
CrossRef142
Dunger, David B., , Edge, Julie A., . (2001) Predicting Cerebral Edema during Diabetic Ketoacidosis. New England Journal of Medicine 344:4, 302-303
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