The Journal of Pediatrics
Volume 150, Issue 5 , Pages 455-456, May 2007

Choosing the Right Fluid and Electrolytes Prescription in Diabetic Ketoacidosis

  • Aaron L. Friedman, MD

      Affiliations

    • Corresponding Author InformationReprint requests: Aaron L. Friedman, MD, Department of Pediatrics, Hasbro Children’s Hospital, 593 Eddy Street, Providence, RI 02903.

Sylvia Kay Hassenfeld Professor of Pediatrics, Chairman, Department of Pediatrics, Brown Medical School, Pediatrician-in-Chief, Rhode Island Hospital, Medical Director, Hasbro Children’s Hospital, Providence, RI

Article Outline

Abbreviations: DKA, Diabetic ketoacidosis

 

The acute management of children with diabetic ketoacidosis (DKA) is a complex blend of urgent therapy and underlying disease management. A serious, potentially life-threatening complication of DKA and its treatment is cerebral edema.1

See related article, p 467

Cerebral edema in DKA usually is noted within 12 hours after therapy begins.2 Some have suggested that cerebral edema may be present before the start of therapy.3 The etiology of cerebral edema in DKA is complex, with ischemia and reperfusion, inflammation, increased blood flow, intracellular osomolyte generation and osmotic “imbalance,” and cytotoxins all implicated. Risk factors associated with the development of cerebral edema include: new onset type 1 diabetes mellitus, younger age, longer duration of symptoms, severity of acidosis, greater hypocapnia, and elevated blood urea nitrogen.3, 4 Physicians caring for a child with DKA reasonably are concerned with assuring that treatment does not worsen the outcome. The hallmarks of treatment—provision of fluids, electrolytes, and insulin—are at the same time life-saving and potentially life-threatening. The article by Hoorn and colleagues5 points to observations regarding fluid therapy and cerebral edema in children with DKA. These observations fall into two categories: (1) those that corroborate previously published information; and (2) those that advance or may advance our understanding of cerebral edema in DKA.

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Corroborative Information 

The study compares patients with DKA and clinical and/or imaging evidence of cerebral edema with control patients with DKA and hypernatremia but no cerebral edema, and with control patients with DKA, no hypernatremia, and no cerebral edema. The demographic and biochemical/hemodynamic data in the article show that the patients with cerebral edema and the control without cerebral edema but with hypernatremia, were younger (smaller), had a higher serum glucose at presentation, had somewhat lower blood pressures, and had higher blood urea levels than the control nonhypernatremia, no cerebral edema patients. Serum pH was not different among the three groups. Interestingly, the hematocrits of patients with DKA, no cerebral edema, and no hypernatremia at admission were higher than the cerebral edema group or hypernatremic, noncerebral controls. This presumably is because of the lower serum glucose and blood urea levels found in the no cerebral edema, no hypernatremia group, and therefore a smaller shift of water from the intracellular space to the extracellular and plasma spaces.

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Observations that May Advance Our Understanding 

The article by Hoorn et al5 found that children who developed cerebral edema were more likely to receive an insulin bolus of ≥0.1 units/kg and were more likely to receive more fluid and more solute in the first 6 hours of therapy than patients who did not develop cerebral edema. Further, the fluid-given patients who developed cerebral edema were of a lower tonicity than the controls. The consensus statement of the European Society of Paediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society published in 20046 states: “There is little evidence, however, to show associations between the volume or sodium content of intravenous fluid” and the development of cerebral edema. The observation by Hoorn and colleagues does provide evidence to suggest that the fluid volume and sodium content of IV fluids may impact the risk of cerebral edema. Indeed, as the Hoorn et al article states, “A more moderate regime (fluids and electrolytes) may therefore be advisable if there is no compelling evidence to be aggressive.” The consensus statement6 also says “there is evidence that an attenuated rise in measured serum sodium concentrations during therapy for DKA may be associated with increased risk of cerebral edema.” Here, too, the article by Hoorn et al5 adds to our knowledge. A gradual decline in effective plasma osmolality as reflected by a decrease on serum glucose and a concomitant increase in serum sodium appears to decrease the likelihood of cerebral edema. This finding may not teach us precisely why cerebral edema occurs or progresses in children with DKA. Many of the proposed pathogenic mechanisms or risk factors may be in place when the patient presents to the physician. Our responsibility is to assure that the therapy we provide does not exacerbate the risk of cerebral edema. Here attention to insulin therapy and the fluid and electrolyte prescription (both therapies over which we have control) become important in reducing the risk of cerebral edema associated with DKA.

The study by Hoorn et al is descriptive. The observations are from two sites over a period of 11 years. It was not possible to match controls so as to single out the effect of a slow fall in effective plasma osmolality alone. The authors admit they could not control for oral intake of fluids among the groups. Oral intake could have been different enough to influence outcomes. Nonetheless, the study affirms that fluid and electrolyte therapy during DKA should restore extracellular volume–but not too aggressively or quickly. Second, it confirms that fluid therapy should aim to decrease gradually the effective plasma osmolality. This gradual decrease is manifest by an increase in the serum sodium concentration. Hypernatremia per se may not protect against cerebral edema, but it may indicate that the effective plasma osmolality is falling at a rate that reduces the risk of developing cerebral edema. Such an approach is prudent and could further reduce the risk of cerebral edema in DKA.

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References 

  1. Edge JA, Hawkins MM, Winter DL, Dimger DB. The risk and outcome of cerebral edema developing during diabetic ketoacidosis. Arch Dis Child. 2001;85:16–22
  2. Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, Louie J, et al. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics Risk factor for cerebral edema in children with diabetic ketoacidosis. N Engl J Med. 2001;344:264–269
  3. Glaser N, Wooten-Gorges SL, Marcin JP, Buonocore MH, Dicarlo J, Neely EK, et al. Mechanisms of cerebral edema in children with diabetic ketoacidosis. J Pediatr. 2004;145:164–171
  4. Mahoney CP, Vleek BW, DelAguila M. Risk factors for developing brain herniation during diabetic ketoacidosis. Pediatr Neurol. 1999;21:721–727
  5. Hoorn EJ, Carlotti A, Costa L, MacMahon B, Bohn G, Zietse R, et al. Preventing a fall in the effective plasma osmolality to minimize the likelihood of cerebral edema during therapy of children with diabetic ketoacidosis. J Pediatr. 2007;150:467–473
  6. Dunger DB, Sperling MA, Acerini CL, Bohn DJ, Daneman D, Danne TP, et al. European Society of Paediatric Endocrinology/Lawson Wilkins Pediatric Endocrine Society consensus statement on diabetic ketoacidosis in children and adolescents. Pediatrics. 2004;113:e133–e140

PII: S0022-3476(07)00096-0

doi:10.1016/j.jpeds.2007.01.028

Refers to article:

  • Preventing a Drop in Effective Plasma Osmolality to Minimize the Likelihood of Cerebral Edema During Treatment of Children with Diabetic Ketoacidosis

    Ewout J. Hoorn, Ana P.C.P. Carlotti, Leila A.A. Costa, Beth MacMahon, Gareth Bohn, Robert Zietse, Mitchell L. Halperin, Desmond Bohn
    The Journal of Pediatrics May 2007 (Vol. 150, Issue 5, Pages 467-473)

The Journal of Pediatrics
Volume 150, Issue 5 , Pages 455-456, May 2007