Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics

N Engl J Med. 2001 Jan 25;344(4):264-9. doi: 10.1056/NEJM200101253440404.


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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Bicarbonates / adverse effects
  • Bicarbonates / blood
  • Bicarbonates / therapeutic use
  • Blood Urea Nitrogen*
  • Brain Edema / etiology*
  • Carbon Dioxide / blood
  • Case-Control Studies
  • Child
  • Diabetes Mellitus, Type 1 / complications
  • Diabetic Ketoacidosis / complications*
  • Diabetic Ketoacidosis / drug therapy
  • Diabetic Ketoacidosis / physiopathology
  • Female
  • Hospitalization
  • Humans
  • Hypocapnia / complications*
  • Incidence
  • Logistic Models
  • Male
  • Multivariate Analysis
  • Random Allocation
  • Risk Factors


  • Bicarbonates
  • Carbon Dioxide