DKA – is early use of insulin therapy associated with development of cerebral oedema? (Updated Bet)
Date First Published:
September 10, 2015
Last Updated:
September 24, 2015
Report by:
Angela Lucas-Herald, Clinical Lecturer in Paediatrics and Child Health (University of Glasgow, Royal Hospital for Children, Glasgow)
Search checked by:
Amanda Wright, University of Glasgow, Royal Hospital for Children, Glasgow
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 admitted 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.
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, Embase and Cinahl searched.
Date range 1996-2015.
Exp Diabetic Ketoacidosis/ OR exp Ketosis/ OR exp Hyperglycemia/OR exp Diabetic Coma/AND Insulin/ OR sliding adj scale OR actrapid OR novorapid OR exp short acting insulin/ OR exp neutral insulin AND exp Brain Edema OR Cerebral ADJ ?edema.
Date range 1996-2015.
Exp Diabetic Ketoacidosis/ OR exp Ketosis/ OR exp Hyperglycemia/OR exp Diabetic Coma/AND Insulin/ OR sliding adj scale OR actrapid OR novorapid OR exp short acting insulin/ OR exp neutral insulin AND exp Brain Edema OR Cerebral ADJ ?edema.
Search Details:
Limited to human and English language.
Outcome:
48 references found - 8 relevant.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Treating diabetic ketoacidosis in children while preventing cerebral edema: one hospital's protocol. Berkley, K. 2004 USA | Children presenting with DKA | Clinical case and review of guideline in authors’ local Emergency Department | Development of cerebral oedema. | Too rapid correction of hyperglycaemia with fluid and insulin increases the risk of cerebral oedema. The authors’ ED defer starting insulin for 30 minutes. | Subjective report of 2 patients with DKA. No report as to how the authors’ ED developed their guideline. |
| The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children. Edge JA, Jakes RW, Roy Y et al. 2006 UK | Children <16 years with DKA, defined as ‘decompensated diabetes mellitus with evidence of ketoacidosis (pH<7.3 or plasma bicarbonate level <18mmol/l or heavy ketonuria) | Large multi centre case control study | Development of cerebral oedema, reported as sudden or unexpected deterioration in conscious level in a child with DKA or any death during assessment or management of DKA. | Insulin administration in the first hour increases risk of cerebral oedema (OR 12.7 [1.41-114.5, p=0.02) | Retrospective study, cases reported by different individuals in different centres, no guarantee of standardisation |
| Diabetic ketoacidosis. Wolfsdorf, J., Craig, M. E., Daneman, D., et al. 2007 International guidance | Children with DKA | International Society of Paediatric Diabetes Clinical Practice Consensus Guideline | Management of DKA | Start insulin infusion 1–2 h after starting fluid | No review date on guidance. No documentation regarding how guidance developed. |
| BSPED Recommended DKA Guidelines British Society of Paediatric Endocrinology and Diabetes 2009 UK | Children with DKA | National guidance from the British Society of Paediatric Endocrinology and Diabetes | Management of DKA | Once rehydration fluids and potassium are running, blood glucose levels will start to fall. Cerebral oedema is more likely if insulin is started early. Start insulin after IV fluids running for at least 1 hour. | No review date on guidance. No documentation regarding how guidance developed. |
| Cerebral crisis in severe diabetic ketoacidosis (DKA) despite adequate fluid and insulin therapy. Datz, N., Schuetz, W. V., Kordonouri, O., et al. 2009 Germany | Case presentation of child with DKA | Case presentation | Development of cerebral oedema | Cerebral oedema can develop despite following current clinical guidance regarding time of starting insulin therapy | Anecdotal. Does not refer to which guidelines are used for the treatment of DKA. Development of cerebral oedema may have been secondary to other factors. |
| Diabetic ketoacidosis Wolfsdorf, J., Craig, M. E., Daneman, D., et al 2009 International guidance | Children with DKA | ISPAD Clinical Practice Consensus Guideline | Management of DKA. | Start insulin infusion 1–2 hours after starting fluid | No review date on guidance. No documentation regarding how guidance developed. Update of 2007 guidance. |
| Diabetic ketoacidosis in children and adolescents with diabetes. Wolfsdorf, J., Craig, M. E., Daneman, D., et al. 2012 USA | Paediatric patients presenting with DKA. | Retrospective case record review. 113 emergency departments reviewed. | Differences in management of DKA in different hospitals. | Insulin started after 1 hour of fluids in 77% of new-onset cases and | Retrospective review. Dependent on documentation in case records. No detail regarding association between timing of insulin administration and rate of cerebral oedema. |
| NICE NICE Guideline Development Group 2015 UK | Children with type 1 diabetes presenting with DKA | National guidance based on systematic review of liteature | When to start insulin infusion | Start an intravenous insulin infusion 1–2 hours after beginning intravenous fluid therapy in children and young people with DKA | Search strategy and strength of recommendations not given in main guideline. |
Author Commentary:
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. Recent evidence suggests that the early administration of insulin may increase the risk of cerebral oedema. Current guidelines therefore suggest insulin therapy should be delayed by one hour after commencement of fluids. Further high quality research is however required.
Bottom Line:
Administration of insulin should be delayed until at least one hour after fluids have commenced. This is to reduce the risk of cerebral oedema in children presenting with DKA.
References:
- Berkley, K. . Treating diabetic ketoacidosis in children while preventing cerebral edema: one hospital's protocol.
- Edge JA, Jakes RW, Roy Y et al. . The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children.
- Wolfsdorf, J., Craig, M. E., Daneman, D., et al. . Diabetic ketoacidosis.
- British Society of Paediatric Endocrinology and Diabetes. BSPED Recommended DKA Guidelines
- Datz, N., Schuetz, W. V., Kordonouri, O., et al. . Cerebral crisis in severe diabetic ketoacidosis (DKA) despite adequate fluid and insulin therapy.
- Wolfsdorf, J., Craig, M. E., Daneman, D., et al. Diabetic ketoacidosis
- Wolfsdorf, J., Craig, M. E., Daneman, D., et al. . Diabetic ketoacidosis in children and adolescents with diabetes.
- NICE Guideline Development Group. NICE