Brain injury in children with diabetic ketoacidosis: Review of the literature and a proposed pathophysiologic pathway for the development of cerebral edema

Abstract

Cerebral edema (CE) is a potentially devastating complication of diabetic ketoacidosis (DKA) that almost exclusively occurs in children. Since its first description in 1936, numerous risk factors have been identified; however, there continues to be uncertainty concerning the mechanisms that lead to its development. Currently, the most widely accepted hypothesis posits that CE occurs as a result of ischemia–reperfusion injury, with inflammation and impaired cerebrovascular autoregulation contributing to its pathogenesis. The role of specific aspects of DKA treatment in the development of CE continues to be controversial. This review critically examines the literature on the pathophysiology of CE and attempts to categorize the findings by types of brain injury that contribute to its development: cytotoxic, vasogenic, and osmotic. Utilizing this scheme, we propose a multifactorial pathway for the development of CE in patients with DKA.

The management of diabetic ketoacidosis in adults—An updated guideline from the Joint British Diabetes Society for Inpatient Care

“…Reassuringly, these authors found no differences in neurological outcomes in children with ketoacidosis treated with rapid versus slower volume correction or with the use of 0.9% versus 0.45% sodium chloride. It is felt that the development of cerebral oedema is multifactorial, but often idiosyncratic 41 …”

Cerebral oedema and dural sinus thrombosis in an adolescent with diabetic ketoacidosis

“…4 The pathophysiology of cerebral oedema involves multiple pathways. 8 Hyperglycaemic and metabolic acidosis converge to produce hypoperfusion and subsequent hypoxic insult contributing to overall cytotoxic injury. [8][9][10][11][12][13] Systemic and neuroinflammatory processes, impaired cerebrovascular autoregulation…”

“…and reperfusion injury lead to the disruption of the bloodbrain barrier and contribute to vasogenic injury. [8][9][10][11][12][13] Clinically apparent cerebral oedema is more likely to occur with severe acidosis, severe hypocapnia and an elevated level of blood urea nitrogen. 4 13 14 Other cerebral complications of DKA are less common and can include haemorrhagic or ischaemic infarction of arterial/venous origin.…”

Diabetic ketoacidosis (DKA) induced cerebral edema complicating small chronic subdural hematoma/hygroma/ at Zewuditu memorial hospital: a case report

“…That is, the direct mass effect of the CSDH &/subdural hygroma/ & indirect mass effect from vasogenic edema tend to compress the adjacent sulci, ventricles & basal cisterns and causes cerebral edema if the thickness is significant and it appears to result a proportionate level of brain tightness for the amount of CSDH in majority of cases [ 2 ]; while cytotoxic & vasogenic brain edema mechanisms from direct metabolic effects of DKA, water re-distribution effect of DKA & treatment related changes seen in DKA (see Fig. 1 ) are responsible for cerebral edema from DKA [ 3 – 6 ].

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