Cerebral oedema during treatment of diabetic ketoacidosis: are we any nearer finding a cause?

Edge, Julie

doi:10.1002/1520-7560(2000)9999:9999<::aid-dmrr143>3.0.co;2-r

Cited by 88 publications

(78 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Clinical studies have linked newly diagnosed diabetes, young age, low blood CO 2 , high blood urea nitrogen, and administration of bicarbonate to the development of DKA-CE (5,8,9). While these epidemiologic studies may identify children at risk for developing of DKA-CE, animal translational studies will provide insight into the cellular mechanisms contributing to DKA-CE.…”

supporting

confidence: 77%

See 1 more Smart Citation

Combined Insulin and Bicarbonate Therapy Elicits Cerebral Edema in a Juvenile Mouse Model of Diabetic Ketoacidosis

Rose

Wang

et al. 2007

Pediatr Res

View full text Add to dashboard Cite

Cerebral edema in diabetic ketoacidosis (DKA-CE) occurs primarily in children and can develop during DKA therapy. The treatment factors contributing to DKA-CE remain elusive. Our objectives were to characterize an age-appropriate DKA mouse model and to determine which DKA therapies contribute to DKA-CE. Juvenile mice were briefly fed a high-fat diet and injected with two pancreatic ␤-cell toxins: streptozocin and alloxan. Severe insulin and leptin deficiencies associated with hyperosmolar ketoacidosis rapidly developed, indicating DKA. DKA mice were treated with re-hydration Ϯ insulin and brain water content (BWC) measured as an indicator of DKA-CE. As expected, glucose and ␤-OH-butyrate corrected in DKA mice that received rehydration and insulin. BWC significantly increased above control levels only in DKA mice that received combined insulin and bicarbonate therapy, indicating the development of DKA-CE. Microscopically, DKA-CE brains had perineuronal and perivascular edema, with microvacuolation in the white matter tracts. These results indicate that insulin-deficient juvenile mice develop biochemical changes that are similar to those of DKA in children. Increased BWC was observed only in DKA mice that received combined insulin and bicarbonate therapy, suggesting that rapid systemic alkalinization in the presence of insulin may contribute to DKA-CE. (Pediatr Res 61: 301-306, 2007)

show abstract

supporting

confidence: 77%

“…Free water was not actively administered to the DKA mice in our study, which could explain the significantly lower BWC than control mice. Our model therefore examined only DKA-CE associated with DKA treatment (5,6,8). Of note, the DKA treatments in this study were administered as a single i.p.…”

Section: Discussionmentioning

confidence: 99%

Combined Insulin and Bicarbonate Therapy Elicits Cerebral Edema in a Juvenile Mouse Model of Diabetic Ketoacidosis

Rose

Wang

et al. 2007

Pediatr Res

View full text Add to dashboard Cite

show abstract

“…Because symptoms of increased intracranial pressure often become apparent during DKA treatment, many investigators hypothesized that rapid changes in serum osmolality and/or rapid fluid infusion during DKA treatment are responsible (28,32,33). This hypothesis has been questioned, however, because studies (5,6,10) have documented the occurrence of both subclinical CE and overt, symptomatic CE before DKA treatment.…”

Section: Discussionmentioning

confidence: 99%

Cerebral Blood Flow and Cerebral Edema in Rats With Diabetic Ketoacidosis

et al. 2008

View full text Add to dashboard Cite

OBJECTIVE-Cerebral edema (CE) is a potentially life-threatening complication of diabetic ketoacidosis (DKA) in children. Osmotic fluctuations during DKA treatment have been considered responsible, but recent data instead suggest that cerebral hypoperfusion may be involved and that activation of cerebral ion transporters may occur. Diminished cerebral blood flow (CBF) during DKA, however, has not been previously demonstrated. We investigated CBF and edema formation in a rat model of DKA and determined the effects of bumetanide, an inhibitor of Na-K-Cl cotransport.RESEARCH DESIGN AND METHODS-Juvenile rats with streptozotocin-induced DKA were treated with intravenous saline and insulin, similar to human treatment protocols. CBF was determined by magnetic resonance (MR) perfusion-weighted imaging before and during treatment, and CE was assessed by determining apparent diffusion coefficients (ADCs) using MR diffusion-weighted imaging.RESULTS-CBF was significantly reduced in DKA and was responsive to alterations in pCO 2 . ADC values were reduced, consistent with cell swelling. The reduction in ADCs correlated with dehydration, as reflected in blood urea nitrogen concentrations. Bumetanide caused a rapid rise in ADCs of DKA rats without significantly changing CBF, while saline/insulin caused a rapid rise in CBF and a gradual rise in ADCs. DKA rats treated with bumetanide plus saline/insulin showed a trend toward more rapid rise in cortical ADCs and a larger rise in striatal CBF than those observed with saline/insulin alone.CONCLUSIONS-These data demonstrate that CE in DKA is accompanied by cerebral hypoperfusion before treatment and suggest that blocking Na-K-Cl cotransport may reduce cerebral cell swelling. Diabetes 57:2588-2594, 2008 D iabetic ketoacidosis (DKA) occurs frequently in children with type 1 diabetes. A total of 25-40 percent of children with new-onset type 1 diabetes present with DKA, and DKA can occur in children with known diabetes during episodes of illness, poor compliance, or malfunction of diabetes care equipment such as insulin pumps (1,2). Cerebral edema (CE) is the most feared complication of DKA in children (3-5). CE has a high mortality rate (21-24%), and survivors often have permanent neurological deficits (15-35%) (5,6). CE is the major diabetes-related cause of mortality in children with type 1 diabetes and is responsible for 50 -85% of diabetes-related deaths (7-9).Asymptomatic CE is thought to occur with much greater frequency than clinically apparent CE and may be present in the majority of DKA episodes in children (10 -12). Studies utilizing sequential computed tomography or magnetic resonance (MR) scanning in children with DKA without significant neurological abnormalities have shown evidence of CE at presentation (10), demonstrated by decreased size of the cerebral ventricles, and that this edema likely worsens during therapy (10 -12). Thus, the development of symptomatic CE in 1% of children with DKA may represent the most severe presentation of a more common pathophysiological phen...

show abstract

“…The aetiology is still unclear though recent hypotheses suggest that, as extracellular fluid hyperosmolarity and dehydration increase, the brain accumulates intracellular, osmotically active molecules (including glucose and unidentified molecules collectively http://pmj.bmj.com/ termed ''idiogenic osmoles'') that maintain cellular volume. [65][66][67] In addition intracellular acidosis (possibly exacerbated by the passage of ketone bodies into cells as well as hypoxia) leads to intracellular sodium accumulation as hydrogen is extruded from the cells by the sodium/hydrogen membrane pump. If extracellular osmolarity falls at a rate exceeding that at which the brain can excrete its accumulated idiogenic osmoles, then oedema occurs.…”

Section: Complicationsmentioning

confidence: 99%

“…If extracellular osmolarity falls at a rate exceeding that at which the brain can excrete its accumulated idiogenic osmoles, then oedema occurs. [65][66][67] The idea that the treatment of DKA itself might be the cause of cerebral oedema has gained support over the years, but no single aspect of therapy has been implicated in studies to date and cerebral oedema has been shown to be present before treatment even begins. 51 68 Low partial pressures of arterial carbon dioxide, high serum urea, and bicarbonate therapy are the risk factors most predictive of cerebral oedema, 51 though these may merely reflect the severity and duration of DKA in those who subsequently develop this complication.…”

Section: Complicationsmentioning

confidence: 99%

Hyperglycaemic crises and lactic acidosis in diabetes mellitus

English

Williams

2004

Postgraduate Medical Journal

View full text Add to dashboard Cite

Diabetic ketoacidosis, hyperglycaemic hyperosmolar state, and lactic acidosis represent three of the most serious acute complications of diabetes. There have been some advances in our understanding of the pathogenesis of these conditions over the last three decades, together with more uniform agreement on their treatment and innovations in technology. Accordingly their incidence, morbidity, and mortality are decreasing, but at rates that fall short of our aspirations. Hyperglycaemic crises in particular remain an important cause of morbidity and mortality in diabetic populations around the world. In this article, understanding of these conditions and advances in their management, and the available guidelines for their treatment, are reviewed. As far as is possible, the recommendations are based on clear published evidence; failing that, what is considered to be a common sense synthesis of consensus guidelines and recommendations is provided.

show abstract

Cerebral oedema during treatment of diabetic ketoacidosis: are we any nearer finding a cause?

Cited by 88 publications

References 85 publications

Combined Insulin and Bicarbonate Therapy Elicits Cerebral Edema in a Juvenile Mouse Model of Diabetic Ketoacidosis

Combined Insulin and Bicarbonate Therapy Elicits Cerebral Edema in a Juvenile Mouse Model of Diabetic Ketoacidosis

Cerebral Blood Flow and Cerebral Edema in Rats With Diabetic Ketoacidosis

Hyperglycaemic crises and lactic acidosis in diabetes mellitus

Contact Info

Product

Resources

About