Hypopituitarism following cerebral oedema with diabetic ketoacidosis

Clinical evidence of cerebral oedema occurs in approximately 1% of diabetic ketoacidosis episodes. Mortality from this serious complication is falling, but little is known of long term outcome. We describe hypopituitarism and executive dysfunction developing two years after cerebral oedema complicating diabetic ketoacidosis in a 12 year old with type 1 diabetes.     

The risk and outcome of cerebral oedema developing during diabetic ketoacidosis.

BACKGROUND: Cerebral oedema is a major cause of morbidity and mortality in children with insulin dependent diabetes. AIMS: To determine the risk and outcome of cerebral oedema complicating diabetic ketoacidosis (DKA). METHODS: All cases of cerebral oedema in England, Scotland, and Wales were reported through the British Paediatric Surveillance Unit between October 1995 and September 1998. All episodes of DKA were reported by 225 paediatricians identified as involved in the care of children with diabetes through a separate reporting system between March 1996 and February 1998. Further information about presentation, management, and outcome was requested about the cases of cerebral oedema. The risk of cerebral oedema was investigated in relation to age, sex, seasonality, and whether diabetes was newly or previously diagnosed. RESULTS: A total of 34 cases of cerebral oedema and 2940 episodes of DKA were identified. The calculated risk of developing cerebral oedema was 6.8 per 1000 episodes of DKA. This was higher in new (11.9 per 1000 episodes) as opposed to established (3.8 per 1000) diabetes. There was no sex or age difference. Cerebral oedema was associated with a significant mortality (24%) and morbidity (35% of survivors). CONCLUSIONS: This first large population based study of cerebral oedema complicating DKA has produced risk estimates which are more reliable and less susceptible to bias than those from previous studies. Our study indicates that cerebral oedema remains an important complication of DKA during childhood and is associated with significant morbidity and mortality. Little is known of the aetiology of cerebral oedema in this condition and we are currently undertaking a case control study to address this issue.     

Cerebral oedema complicating diabetic ketoacidosis

Signs of raised intracranial pressure (ICP) developed during treatment of diabetic ketoacidosis in a young child. A CT scan revealed cerebral oedema and direct measurement confirmed elevated ICP. Aggressive treatment was successful in maintaining cerebral perfusion pressure. The child survived with mild handicap in contrast to the poor outcome of previous reports.     

The risk and outcome of cerebral oedema developing during diabetic ketoacidosis

BACKGROUND—Cerebral oedema is a major cause of morbidity and mortality in children with insulin dependent diabetes.AIMS—To determine the risk and outcome of cerebral oedema complicating diabetic ketoacidosis (DKA).METHODS—All cases of cerebral oedema in England, Scotland, and Wales were reported through the British Paediatric Surveillance Unit between October 1995 and September 1998. All episodes of DKA were reported by 225 paediatricians identified as involved in the care of children with diabetes through a separate reporting system between March 1996 and February 1998. Further information about presentation, management, and outcome was requested about the cases of cerebral oedema. The risk of cerebral oedema was investigated in relation to age, sex, seasonality, and whether diabetes was newly or previously diagnosed.RESULTS—A total of 34 cases of cerebral oedema and 2940 episodes of DKA were identified. The calculated risk of developing cerebral oedema was 6.8 per 1000 episodes of DKA. This was higher in new (11.9 per 1000 episodes) as opposed to established (3.8 per 1000) diabetes. There was no sex or age difference. Cerebral oedema was associated with a significant mortality (24%) and morbidity (35% of survivors).CONCLUSIONS—This first large population based study of cerebral oedema complicating DKA has produced risk estimates which are more reliable and less susceptible to bias than those from previous studies. Our study indicates that cerebral oedema remains an important complication of DKA during childhood and is associated with significant morbidity and mortality. Little is known of the aetiology of cerebral oedema in this condition and we are currently undertaking a case control study to address this issue.     

Sub-clinical cerebral oedema does not occur regularly during treatment for diabetic ketoacidosis

Fulminant cerebral oedema is an uncommon, fatal complication of diabetic ketoacidosis (DKA) in children. This study aimed to find out whether the sub-clinical compression of the brain ventricles found by an earlier study, is a general phenomenon during intravenous treatment for DKA. Four boys and four girls were examined. Blood glucose values ranged from 40 to 24. 6mmol/l, base excess -34. 6 to - 13. 6 and capillary blood pH 6. 89–7. 22. The patients received fluids containing both glucose and electrolytes, and insulin intravenously. After about lOh, blood glucose was 8. 7–21. 8mmol/l and base excess had decreased substantially (-9. 5 to -2. 9) in seven of the eight cases. Computerized tomography of the brain was then performed, and again after full recovery. Only two of the patients had an initial decrease in intercaudate distance, which exceeded the variability found in a reference group. Compression of the cerebral ventricles does not occur regularly during treatment for DKA.     

Importance of timing of risk factors for cerebral oedema during therapy for diabetic ketoacidosis.

Cerebral oedema is the most common cause of mortality and morbidity during the first day of conventional treatment for diabetic ketoacidosis in paediatric patients. It is possible that therapy contributes to its development. Risk factors that predispose to cerebral oedema should lead to an expansion of the intracellular and/or the extracellular fluid compartment(s) of the brain because water normally accounts for close to 80% of brain weight. With respect to the intracellular fluid compartment, the driving force to cause cell swelling is a gain of effective osmoles in brain cells and/or a significant decline in the effective osmolality of the extracellular fluid compartment. Factors leading to an expansion of the intracerebral extracellular fluid volume can be predicted from Starling forces acting at the blood-brain barrier. Some of these risk factors have an early impact, while others have their major effects later during therapy for diabetic ketoacidosis. Based on a theoretical analysis, suggestions to modify current therapy for diabetic ketoacidosis in children are provided.     

Importance of timing of risk factors for cerebral oedema during therapy for diabetic ketoacidosis

Cerebral oedema is the most common cause of mortality and morbidity during the first day of conventional treatment for diabetic ketoacidosis in paediatric patients. It is possible that therapy contributes to its development. Risk factors that predispose to cerebral oedema should lead to an expansion of the intracellular and/or the extracellular fluid compartment(s) of the brain because water normally accounts for close to 80% of brain weight. With respect to the intracellular fluid compartment, the driving force to cause cell swelling is a gain of effective osmoles in brain cells and/or a significant decline in the effective osmolality of the extracellular fluid compartment. Factors leading to an expansion of the intracerebral extracellular fluid volume can be predicted from Starling forces acting at the blood-brain barrier. Some of these risk factors have an early impact, while others have their major effects later during therapy for diabetic ketoacidosis. Based on a theoretical analysis, suggestions to modify current therapy for diabetic ketoacidosis in children are provided.     

Mechanism of cerebral edema in children with diabetic ketoacidosis

OBJECTIVES: Cerebral edema during diabetic ketoacidosis (DKA) has been attributed to osmotic cellular swelling during treatment. We evaluated cerebral water distribution and cerebral perfusion during DKA treatment in children. STUDY DESIGN: We imaged 14 children during DKA treatment and after recovery, using both diffusion and perfusion weighted magnetic resonance imaging (MRI). We assessed the apparent diffusion coefficients (ADCs) and measures reflecting cerebral perfusion. RESULTS: The ADC was significantly elevated during DKA treatment (indicating increased water diffusion) in all regions except the occipital gray matter. Mean reductions in the ADC from initial to postrecovery MRI were: basal ganglia 4.7 +/- 2.5 x 10(-5) mm(2)/s (P=.002), thalamus 3.7 +/- 2.8 x 10(-5) mm(2)/s, (P=.002), periaqueductal gray matter 4.3 +/- 5.1 x 10(-5) mm(2)/s (P=.03), and frontal white matter 2.0 +/- 3.1 x 10(-5) mm(2)/s (P=.03). In contrast, the ADC in the occipital gray matter increased significantly from the initial to postrecovery MRI (mean increase 3.9 +/- 3.9 x 10(-5) mm(2)/s, P=.004). Perfusion MRI during DKA treatment revealed significantly shorter mean transit times (MTTs) and higher peak tracer concentrations, possibly indicating increased cerebral blood flow (CBF). CONCLUSIONS: Elevated ADC values during DKA treatment suggests a vasogenic process as the predominant mechanism of edema formation rather than osmotic cellular swelling.     

Frequency of sub-clinical cerebral edema in children with diabetic ketoacidosis

Symptomatic cerebral edema occurs in approximately 1% of children with diabetic ketoacidosis (DKA). However, asymptomatic or subclinical cerebral edema is thought to occur more frequently. Some small studies have found narrowing of the cerebral ventricles indicating cerebral edema in most or all children with DKA, but other studies have not detected narrowing in ventricle size. In this study, we measured the intercaudate width of the frontal horns of the lateral ventricles using magnetic resonance imaging (MRI) in children with DKA during treatment and after recovery from the DKA episode. We determined the frequency of ventricular narrowing and compared clinical and biochemical data for children with and without ventricular narrowing. Forty-one children completed the study protocol. The lateral ventricles were significantly smaller during DKA treatment (mean width, 9.3 +/- 0.3 vs. 10.2 +/- 0.3 mm after recovery from DKA, p < 0.001). Children with ventricular narrowing during DKA treatment (22 children, 54%) were more likely to have mental status abnormalities than those without narrowing [12/22 vs. 4/19 with Glasgow Coma Scale (GCS) scores below 15 during therapy, p = 0.03]. Multiple logistic regression analysis revealed that a lower initial PCO2 level was significantly associated with ventricular narrowing [odds ratio (OR) = 0.88, 95% confidence interval (95% CI) = 0.78-0.99, p = 0.047). No other variables analyzed were associated with ventricular narrowing in the multivariate analysis. We conclude that narrowing of the lateral ventricles is evident in just over half of children being treated for DKA. Although children with ventricular narrowing did not exhibit neurological abnormalities sufficient for a diagnosis of 'symptomatic cerebral edema', mild mental status abnormalities occurred frequently, suggesting that clinical evidence of cerebral edema in children with DKA may be more common than previously reported.     

儿童糖尿病酮症酸中毒并发脑水肿临床分析

目的探讨儿童糖尿病酮症酸中毒并发脑水肿的临床特点及危险因素。方法对糖尿病酮症酸中毒并发脑水肿患儿的临床特点及病因进行分析,并与无脑水肿的患儿资料进行对比。结果在47例糖尿病酮症酸中毒患儿中,并发脑水肿4例（8.51%）,均为重度酮症酸中毒。与未并发脑水肿同等程度的酮症酸中毒患儿相比,并发脑水肿者在治疗期间血钠上升缓慢、甚至降低,尿素氮水平较高。4例患儿中有3例应用了碳酸氢盐,用量大于未并发组。结论糖尿病患儿并发重度酮症酸中毒时易并发脑水肿。血钠上升缓慢甚或降低、血尿素氮升高及碳酸氢盐的不适当应用,可增加脑水肿发生的危险。     

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目的探讨儿童糖尿病酮症酸中毒并发脑水肿的临床特征及危险因素。方法对重庆医科大学附属儿童医院1993—2005年住院治疗的糖尿病酮症酸中毒并发脑水肿患儿的临床特征及病因进行分析,并与未并发者进行对照比较。结果在71例酮症酸中毒患儿中,有6例临床表现符合脑水肿的诊断标准,临床确定为并发脑水肿,并发率为8·4%。6例均为重型酮症酸中毒。与未发生脑水肿同等程度的重型酮症酸中毒患儿相比较,并发脑水肿患儿酸中毒更为严重,在治疗期间血钠上升缓慢及持续低钠血症,尿素氮水平升高。6例患儿中有5例应用碳酸氢盐治疗,用量大于未并发者。结论糖尿病儿童并发重型酮症酸中毒易发生脑水肿。严重酸中毒、血钠上升缓慢或持续低钠血症、血尿素氮升高及碳酸氢盐的使用有可能增加脑水肿发生的危险性。     

Hyperventilation in severe diabetic ketoacidosis.

OBJECTIVE: To explore whether the carbon dioxide-bicarbonate (P(CO(2))-HCO(3)) buffering system in blood and cerebrospinal fluid (CSF) in diabetic ketoacidosis should influence the approach to ventilation in patients at risk of cerebral edema. DATA SOURCE: Medline search, manual search of references in articles found in Medline search, and use of historical literature from 1933 to 1967. DESIGN: A clinical vignette is used--a child with severe diabetic ketoacidosis who presented with profound hypocapnia and then deteriorated--as a basis for discussion of integrative metabolic and vascular physiology. STUDY SELECTION: Studies included reports in diabetic ketoacidosis where arterial and CSF acid-base data have been presented. Studies where simultaneous acid-base, ventilation, respiratory quotient, and cerebral blood flow data are available. DATA EXTRACTION AND SYNTHESIS: We revisit a hypothesis and, by reassessing data, put forward an argument based on the significance of low [HCO(3)](CSF) and rising Pa(CO(2))- hyperventilation in diabetic ketoacidosis and the limit in biology of survival; repair of severe diabetic ketoacidosis and Pa(CO(2))-and mechanical ventilation. CONCLUSION: The review highlights a potential problem with mechanical ventilation in severe diabetic ketoacidosis and suggests that the P(CO(2))--HCO(3) hypothesis is consistent with data on cerebral edema in diabetic ketoacidosis. It also indicates that the recommendation to avoid induced hyperventilation early in the course of intensive care may be counter to the logic of adaptive physiology.     

Cerebral edema in diabetic ketoacidosis.

OBJECTIVE: To review the causes of cerebral edema in diabetic ketoacidosis (CEDKA), including pathophysiology, risk factors, and proposed mechanisms, to review the diagnosis, treatment, and prognosis of CEDKA and the treatment of diabetic ketoacidosis as it pertains to prevention of cerebral edema. DATA SOURCE: A MEDLINE search using OVID was done through 2006 using the search terms cerebral edema and diabetic ketoacidosis. RESULTS OF SEARCH: There were 191 citations identified, of which 150 were used. An additional 42 references listed in publications thus identified were also reviewed, and two book chapters were used. STUDY SELECTION: The citations were reviewed by the author. All citations identified were used except 25 in foreign languages and 16 that were duplicates or had inappropriate titles and/or subject matter. Of the 194 references, there were 21 preclinical and 40 clinical studies, 35 reviews, 15 editorials, 43 case reports, 29 letters, three abstracts, six commentaries, and two book chapters. DATA SYNTHESIS: The data are summarized in discussion. CONCLUSIONS: The causes and mechanisms of CEDKA are unknown. CEDKA may be due as much to individual biological variance as to severity of underlying metabolic derangement of the child's state and/or treatment risk factors. Treatment recommendations for CEDKA and diabetic ketoacidosis are made taking into consideration possible mechanisms and risk factors but are intended as general guidelines only in view of the absence of conclusive evidence.     

A teenage girl with cystic fibrosis-related diabetes, diabetic ketoacidosis, and cerebral edema

Abstract:  Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes, most commonly associated with type 1 diabetes. Here, we report the case of a 17-yr-old girl with cystic fibrosis and a prior diagnosis of cystic fibrosis -related diabetes (CFRD) who presented with DKA in the setting of insulin omission and glucocorticoid use. During the course of treatment for DKA, her neurologic status declined and head computerized tomography confirmed cerebral edema. Recognition of DKA and cerebral edema allowed for timely treatment, and the patient recovered without sequelae. This is the first report of DKA complicated by cerebral edema that is attributable to CFRD.