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DKA - is early use of insulin therapy associated with development of cerebral oedema?

Three Part Question

[In children with DKA] is [the early use of insulin] associated with [development of cerebral oedema]?

Clinical Scenario

A 15 year old boy with type 1 DM is admittd to the ED unwell, with a BM of 29.
O/E he is pale, sweaty and lethargic with a BP of 90/40 and pulse 120. Otherwise exam is unremarkable.
You site an iv cannula and take a VBG which shows pH 7.1 and HCO3- 10.
You give a 900ml 0.9% NaCl fluid bolus (20ml/kg) and are about to start a sliding scale when the paediatric SpR tells you that local policy is to hold off insulin for the first 2-3 hours as it may increase the risk of development of cerebral oedema.
You wonder what the evidence shows.

Search Strategy

Medline 1966-March 2007 - OVID interface
diabetic OR OR OR OR diabetic OR exp diabetic ketoacidosis/ OR (diabetic adj5 ketoacidosis).af. OR AND insulin sliding OR sliding OR exp insulin/ OR OR OR short acting AND cerebral OR (cerebral adj5 oedema).af. OR (cerebral adj5 edema).af. OR cerebral OR brain OR brain OR (brain adj edema).af. OR (brain adj5 oedema).af. limit to human and english language.

Search Outcome

71 references found - 3 relevant

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
TB Brown
PUBMED search using "cerebral edema" and "diabetic ketoacidosis". 133 refs found, 25 selected for inclusion. 21 used as evidence (only trials, case control studies, case series, and cohort studies.)Literature reviewGlaser et al, (2000) Retrospective case control6977 DKA cases, 61 CO cases. no relation between treatment and COnot just RCTs used low incidence of cerebral oedema few prospective trials
Mel, Werther, (1995) Retrospective comparison of two different treatment cohorts6 CO of 3134 DKA cases, 6CO of 3373 DKA cases. no relation between CO and treatment
Of all 21 studies cited, none showed relation between early insulin use and CO
8 studies concluded that CO may depend on declining sodium levels secndary to fluid adminsmall studies, no controls,
However, 2 small studies based on CT scans concluded that cerebral oedema is present before therapysmall studies, no CO cases
Dunger et al
Paediatric patients with DKAConsensus document from the ESPE and LWPES based on literature review, and evidence based recommendations (based on criteria used by the American Diabetes Association)Onset of cerebral oedematypically occurs 4-12 hrs post start of treatment, but can present before treatment has begunNo data given - the statement is purely prose
Need for insulinAlthough rehydration alone causes some decrease in blood glu conc, insulin therapy is essential to normalize the blood glu concentration and suppress lipolysis and ketogenesis.IV insulin should be given at a dose of 0.1u/kg/hr. A bolus need not be given, but may be used if insulin treatment has been delayed.
Risk factors for development of cerebral oedemahypocapnia, elevated serum urea at presentation, ?severity of acidosis. There is little evidence to show assocaition with vol/Na content of IV fluid or rate of change of blood glu.
NICE guidelines
July 2004
National guidelines for treatment of DKA in childrenbased on ESPE guidelinesInsulin is essential to switch off ketogenesis and reverse the acidosis0.1ml/kg/hr of insulin via continuous IV infusion is reqd


Cerebral oedema occurs in 0.3 - 1% episodes of DKA, with estimates of mortality ranging from 20-50%. Its low incidence has limited the number of prospective trials carried out, and understanding of the cause remains poor. From the literature search, there is no evidence that early use of insulin has a causative role in development of cerebral oedema.

Editor Comment

Update at BET 2781

Clinical Bottom Line

In children presenting with DKA, continuous iv insulin therapy at a rate of 0.1u/kg/hr as per NICE guidlines can be commenced immediately.


  1. TB Brown Cerebral oedema in childhood diabetic ketoacidosis: Is treatment a factor? EMJ 2004;21;141-144
  2. Dunger et al European Society for Paediatric Endocrinology/Lawson Wilkins Pediatric Society Consensus Statement on Diabetic Ketoacidosis in Children and Adolescents Pediatrics Feb 2004, Vol 113 No 2
  3. NICE guidelines TYPE 1 DM - treatment of DKA