This document provides clinical guidance for all staff involved in the care and management of a child or adolescent with diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) presenting to an Emergency Department (ED) in Queensland.
This guideline has been developed by senior ED clinicians and Paediatricians across Queensland, with input from Endocrinology, Critical Care and Pharmacy, Queensland Children’s Hospital, Brisbane. It has been endorsed for statewide use by the Queensland Emergency Care of Children Working Group in partnership with the Queensland Emergency Department Strategic Advisory Panel and the Healthcare Improvement Unit, Clinical Excellence Queensland.
Diabetes ketoacidosis (DKA)
DKA is a metabolic disorder and the leading cause of morbidity and mortality in children and adolescents with type 1 diabetes. It is caused by a decrease in effective circulating insulin, insulin resistance and increased production of counter-regulatory hormones.1,2 The resulting increased hepatic and renal glucose production, and impaired peripheral glucose utilisation, causes hyperglycaemia and hyperosmolality. In addition, increased lipolysis with the overproduction of ketones leads to ketonaemia and metabolic acidosis. Hyperglycaemia and acidosis causes osmotic diuresis, dehydration and obligate loss of electrolytes.
Children may present with DKA at any age, with or without a previous diagnosis of type 1 diabetes. DKA can also occur in newly diagnosed type 2 diabetes. Rarely, patients diagnosed with diabetes may have symptomatic ketoacidosis without a raised blood glucose level.
Management of an episode of DKA is not complete until an attempt has been made to identify and treat the cause. DKA without a preceding febrile illness or gastroenteritis in a patient with known diabetes is almost always the result of psychosocial problems and failure to appropriately administer insulin.
Cerebral oedema is a rare but devastating complication of diabetes, occurring in approximately 1% of children with DKA. It is typically described as a sudden onset of rapidly progressing neurological deterioration including altered/fluctuating level of consciousness, headache, vomiting, bradycardia, hypertension, cranial nerve palsy and abnormal posturing.
Clinical cerebral oedema can occur at any time but most commonly occurs 4-12 hours after commencement of treatment.
Risk factors for cerebral oedema
- New onset Type 1 diabetes
- Elevated serum urea
- Severe dehydration
- Severe DKA (pH less than or equal to 7.1)
- Lower bicarbonate levels
- Age less than five years
- Reduced level of consciousness
Hyperglycaemic Hyperosmolar State (HHS)
HHS is a state of extreme hyperglycaemia (and hence hyperosmolality) without ketosis which is usually, but not exclusively, seen in type 2 diabetes. It can also occur in neonatal diabetes and in type 1 diabetes in children and adolescents with an intellectual impairment who are unable to indicate thirst. In young persons, it is much rarer than DKA, but it is rising as the incidence of type 2 diabetes increases.
Polyuria and polydipsia may not be recognised and especially in hot temperatures, there can be extreme dehydration, fluid loss and electrolyte disturbance. Dehydration can be difficult to assess clinically and the hyperosmolality preserves intravascular volume initially. Initial treatment can cause movement of fluid out of the intravascular compartment and shock. More aggressive fluid replacement than in DKA is required to expand the intra and extravascular volume, restore normal renal perfusion and promote a gradual decline in corrected serum sodium concentration and osmolality.
Complications of HHS
- Venous thromboembolism associated with central venous catheters
- Rhabdomyolysis secondary to hypophosphataemia (leading to kidney injury)
- Malignant hyperthermia (rare)
Requires ALL of the following:
- Hyperglycaemia (BGL greater than 11mmol/L)
- Venous pH less than 7.3 and/or HCO3 less than 15 mmol/L
- Moderate/large ketonaemia/ketonuria
|pH between 7.2 – 7.3
or HCO3 less than 15 mmol/L
|pH between 7.1 – 7.2
or HCO3 less than 10 mmol/L
|pH less than 7.1
or HCO3 less than 5 mmol/L
||Method of testing
||Bedside meter Abott
||Less than 0.6 mmol/L
||0.6 to less than 1.5 mmol/L
||Greater than or equal to 1.5 mmol/L
||0.5 to less than 1.5 mmol/L
||Greater than or equal to 1.5 mmol/L
||Less than 1.0 mmol/L
||Greater than or equal to 1.0 mmol/L
Requires ALL of the following:
- Hyperglycaemia (BGL greater than 33.3 mmol/L)
- Venous pH greater than 7.25 and/or HCO3 greater than 15 mmol/L (lactic acid can cause a mild acidosis)
- Small ketonuria
- Absent to mild ketonemia less than 1.1 mmol/L
- Effective serum osmolality greater than 320 mOsm/kg
Altered level of consciousness is usual but cerebral oedema is rare.
Risk factors include:
- Signs of insulin resistance (acanthosis nigricans)
- Family history of type 2 diabetes
History should include specific information on:
- Polydipsia and polyuria (may be absent in the young child)
- Enuresis and/or wetting ‘accidents’ in a toilet trained child
- Weight loss and/or increased appetite
- Abdominal pain
- Non-specific symptoms and signs of general malaise
Physical examination should include an assessment of:
- Respiration (hyperventilation is a feature of acidotic respiration)
- Potential cerebral oedema (signs and symptoms include headache, irritability, slowing pulse, rising BP and reducing level of consciousness. Papilloedema is a late sign)
- Potential infection including appendicitis, ileus and pancreatitis
Includes assessment of BP, pulse rate and volume, perfusion (capillary refill time, skin colour, mentation), mucous membranes and tissue turgor. Volume deficit is difficult to assess accurately in DKA, particularly in the young child.
|Mild ~ 3%
||Moderate ~ 5%
||Severe ~ 8%
||Life -threatening – shock
|Only just clinically detectable
||Dry mucous membranes, reduced skin turgor
||Dry mucous membranes, reduced skin turgor, sunken eyes, poor capillary return
||Severely ill with poor perfusion, thready rapid pulse (reduced BP is a very late sign)
Specific considerations in DKA
- Tachypnoea secondary to acidosis can exacerbate dryness of oral mucosa2
- Vasoconstriction from acidosis may contribute to the appearance of cool extremities2
- Catabolism due to insulin deficiency can result in weight loss
|BGL (may be inaccurate via finger prick in circulatory compromise and acidosis)
|Finger-prick blood ketones (superior to urinary ketones)
|Urine ketones only if blood ketones not available
|Urea and electrolytes (serum urea greater than 9.0 mmol/L may indicate severe dehydration)
|Venous pH and acid-base status
|HbA1C (for later analysis)
Additional tests required in a child with newly diagnosed diabetes include:
- TFT (thyroid screen)
- Total IgA and TTG (coeliac screen)
Other investigations including FBC, urine M/C/S, CXR, CSF M/C/S, throat swab, and blood culture may be required on senior emergency/paediatric advice for a child who is hypothermic, hypotensive or has a refractory acidosis or lactic acidosis.
Note that an elevated WCC is common in DKA and does not necessarily indicate sepsis.
Refer to emergency management flowchart for a summary of the emergency management of a child with DKA.
Emergency care should always involve a rapid primary survey with evaluation of (and immediate management of concerns with) airway, breathing, circulation and disability (ABCD).
Aims of treatment
DKA is characterised by a loss of water and electrolytes. Administration of IV fluid, prior to giving insulin results in substantial falls in blood glucose because the resultant increase in glomerular filtration rate (GFR) leads to increased urinary glucose excretion.3,4
The aims of fluid and electrolyte replacement therapy in DKA are:
- restoration of circulating volume
- replacement of sodium and water deficit over 48 hours
- management of the predictable fall in the serum potassium concentration after insulin therapy commences and the ketoacidosis starts to reverse
- restoration of GFR with enhanced clearance of glucose and ketones from the blood
- administration of insulin therapy to normalise the BGL and to suppress lipolysis and ketogenesis
- avoidance of cerebral oedema, which may be caused by rapid fluid shifts from the extracellular fluid to the intracellular fluid compartment
Management of moderate to severe DKA
Shock at presentation
Child is severely ill with poor perfusion and thready rapid pulse.
||Sodium Chloride 0.9% administered in 10 mL/kg bolus.
Repeat as necessary to a maximum of 20 mL/kg.
There is no evidence to support the use of colloids/volume expanders over crystalloids.
Altered level of consciousness at presentation
Altered level of consciousness is directly related to degree of acidosis. However, consider instituting cerebral oedema management (outlined below) if signs of raised ICP.
IV rehydration fluids and insulin therapy
IV fluids and insulin are the recommended initial management.
If necessary, use Ondansetron. Other antiemetics are not recommended due to sedation/neurological side effects which may make assessments for onset of cerebral oedema difficult.
All patients with moderate to severe DKA should initially remain ‘nil by mouth’ except for ice to suck.
Consider a nasogastric tube if gastric paresis is present (vomiting caused by non-mechanical delayed gastric emptying associated with the DKA illness).
Oral fluids should only be offered after substantial clinical improvement (i.e. blood sugar less than 15mmol/l and level of consciousness has improved if initially reduced) and no vomiting. If this occurs prior to the completion of the 48-hour rehydration period, proceed with oral intake and reduce IV infusions.
Calculate fluid replacement based on dehydration assessment. View DKA fluid calculator (desktop only).
Requirement = Maintenance + ([Deficit – fluid bolus already given] over 48hrs)
Urinary losses should not be added to the initial calculation of replacement fluids.
Use 1 litre 0.9% NaCl + 40mmol KCl (pre-mixed bag) as the initial default fluid unless anuria (after catheterisation) or hyperkalaemia (greater than 5.5mmol/L) is present. If either of these are present, use 0.9% NaCl as per specialist advice.
Rehydration alone will decrease the BGL to some extent, however insulin therapy is required to normalise the BGL and to suppress lipolysis and ketogenesis. In moderate and severe DKA, insulin IV is required.
Only short-acting insulins (examples include but are not limited to Actrapid or Humulin R) should be used for insulin IV administration. The insulin infusion set should be changed every 24 hours due to the potential for the insulin to denature.
If a patient on an insulin pump presents in DKA, the pump should be stopped, and an assumption made that there is a pump problem. The pump should only be restarted on advice from a Paediatric Endocrinologist or local equivalent with a new site and a new set recommended.
|Short-acting insulin dose
||Ideal continuous insulin IV infusion dose is 0.1 units/kg/hr.
Seek specialist advice for dosing in obese patients. It may be prudent to base insulin infusion on ideal body weight.
There is no evidence to support an initial infusion dose of 0.05 units/kg/hr5 however it may be considered in infants and very severe DKA.
If using a syringe pump:
Add 50 units (0.5 mL) to 49.5 mL of Sodium Chloride 0.9% in a syringe. [Insulin concentration = 1 U/mL]. Infusion to be delivered by syringe pump into the side arm of the IV line.
If no syringe pump available:
Add 50 units (0.5 mL) to a 500 mL bag of Sodium Chloride 0.9%. [Insulin concentration = 0.1U/ml]
The infusion should be delivered using a volumetric pump into the side arm of the IV line. If this is not available a separate IV site may be required for low infusion rates.
||All children on insulin IV must have hourly BGLs.
Refer to ongoing management flowchart for a summary of the ongoing management of a child with moderate to severe DKA.
If acidosis fails to improve or BGL rises, consider insulin error, inadequate resuscitation or alternative diagnosis including sepsis, drug overdose (such as salicylate, other prescription drugs or recreational drugs) or hyperchloraemic acidosis.
- BGL will often fall quickly because of rehydration.
- No evidence supports the practice of adding glucose to protect against cerebral oedema.6
- Only add glucose if BGL is less than or equal to 15 mmol/L (see below).
- DO NOT reduce rate.
- The insulin dose needs to be ideally maintained at 0.1 units/kg/hr to switch off ketogenesis.
- Increase glucose concentration to Sodium Chloride 0.9% + Glucose 10% + Potassium Chloride 40 mmol (See Appendix 2 of CHQ Intravenous Fluid Guidelines: Paediatric and Neonatal* QH only)
- Seek specialist advice when mixing solution as some mixtures are significantly hyponatraemic and may contribute to cerebral oedema.
- Monitor site for local reactions as solution is hypertonic.
- Only reduce the rate if BGL remains below the target range despite this glucose supplementation.
- Note problems with hypoglycaemia can occur if there has been a miscalculation of the insulin dose. Consider preparing the insulin infusion again and recommencing.
- Administer a bolus of 2 mL/kg of Glucose 10% over three minutes.
- Ensure fluid running has Glucose 5% and consider Glucose 10%.
- Temporarily reduce by 50% and seek urgent paediatric endocrine/critical care advice.
- DO NOT stop the infusion.
- It takes ~20 minutes for insulin infusion cessation to take clinical effect so will not assist in acute hypoglycaemia.
- Ongoing insulin administration is necessary while glucose is being infused,5 as insulin is required to switch off ketone production.
Electrolyte considerations in IV fluid management
Sodium replacement and osmolality
Correction of dehydration and electrolyte abnormalities should occur over 72 hours.
Hypotonic solutions may be associated with raised intracranial pressure (ICP).
Plan for the predictable fall in the serum potassium concentration after insulin therapy commences and the ketoacidosis starts to reverse. Serum potassium levels in DKA at presentation are not a reliable indicator of total body potassium stores. Serum potassium may be reduced, normal or elevated at the time of presentation. The administration of insulin and the correction of acidosis will drive potassium back into the cells, decreasing serum potassium levels. The maximum potassium concentration should be 40mmol/L.
Do not exceed a maximal potassium infusion rate of 0.3 mmol/kg/hr without consultation.
Potassium replacement should continue throughout IV fluid therapy.
Check potassium measurements every two hours (iStat, blood gas or formal U&Es). All patients with DKA must be on a cardiac monitor while in ED to alert clinicians to arrhythmias and ECG/T wave changes.
- Hypokalaemia causes T wave flattening. If hypokalemia occurs, temporarily reduce insulin infusion rate by 50% and discuss with Paediatric Critical Care regarding central access and increased potassium replacement.
- T wave peaking may be a sign of hyperkalaemia in a patient with pre-renal failure. Check the venous potassium and, if necessary, reduce the potassium replacement until a good urine output (greater than or equal to 1 ml/kg/hour) occurs and the potassium level falls to the top of the normal range. Reducing the potassium replacement is done by changing the fluid to 0.9% NaCl with 20mmol/L KCl which is available as a premix bag.
Severe acidosis is usually reversible by fluid and insulin administration. Bicarbonates only purpose is to improve cardiac contractility in severe shock.
Resolution of acidosis
The dose of insulin should remain at 0.1 units/kg/hr at least until the resolution of acidosis (pH greater than 7.3, HCO3 greater than 15mmol/L) and/or closure of anion gap. As the resolution of ketosis takes much longer, ketosis alone will not delay the transition to SC insulin.
Seek specialist advice on transitioning to SC insulin providing all of following have occurred:
- resolution of acidosis
- clinical improvement and no vomiting
- tolerating oral fluids
Insulin IV infusion must continue for one hour after administration of SC insulin.
Clinical and laboratory monitoring
Refer to the Queensland DKA Subcutaneous Insulin Order and Blood Glucose Level Record Form (QH only).
The monitoring outlined below should continue until the child is well.
|Vital Signs (HR, RR, BP)
||2-4th hourly or hourly if febrile
- Blood ketones aid in determining resolution of DKA.
- The bedside meter (Abbott brand) ketone readings greater than 4mmol/L are less accurate.
- DO NOT use either blood or urinary ketones alone as the indicator for changes to fluid or insulin regimes. Assess the whole child.
- Venous glucose
- Blood gases
Consider hourly electrolyte monitoring in severe DKA.
- Capillary glucose methods may be inaccurate if poor peripheral circulation or acidosis.
- Consider an IV cannula for repetitive blood sampling. An IA line may be necessary in some critically ill patients managed in PICU/ICU
|Strict fluid balance
- Watch carefully for polyuria
- Consider a urinary catheter if impaired level of consciousness.
- In non-toilet trained children, nappies should be weighed to ensure accurate fluid balance
||Hourly or more if high risk
||See below for groups at high risk of cerebral oedema.
||Assess T waves for hyperkalaemia or hypokalaemia
|Urinalysis for ketones
||Only required if blood ketones not available
||On admission and daily
Management of cerebral oedema
When to suspect cerebral oedema
Warning signs and symptoms:
- inappropriate slowing of heart rate
- recurrence of vomiting
- change in neurological status (restlessness, irritability, increased drowsiness, incontinence)
- specific neurological signs (such as cranial nerve palsies, pupillary response)
- rising BP
- decreased oxygen saturation
Biochemical red flags:
- rapid fall in the calculated osmolarity with treatment (usually serum sodium rises as the glucose falls resulting in a relatively stable calculated osmolarity)
- development of hyponatraemia during therapy or rapidly falling sodium
- initial sodium in the hypernatraemic range
Immediate management of cerebral oedema
- raise the head of the bed to 200
- administer high-flow oxygen via a non-rebreathing mask with a reservoir bag
- reduce the rate of fluid administration as per specialist advice
- administer Mannitol or Hypertonic Saline 3% IV in patients with signs of cerebral oedema before impending respiratory failure6
- consider intubation and ventilation. Aim for CO2 35-40mmHg. Aggressive hyperventilation has been associated with poor outcome in retrospective studies of DKA related cerebral oedema7
|Sodium Chloride 3%
(Hypertonic Saline 3%) (IV)
|3 mL/kg/dose (1–5 mL/kg/dose) over 10-15 minutes
3 mL/kg is expected to increase plasma sodium by approximately 2-3 mmol/L
Central pontine myelinosis
||0.25-0.5 g/kg over 10-15 minutes
Higher doses i.e. 1 g/kg may be administered on senior advice.
Rebound elevations in ICP
Management of mild DKA
The following management is recommended in a child who meets ALL of the following criteria:
- clinically well (stable vital signs, normal GCS)
- tolerating oral fluids and normal perfusion
- less than 5% dehydrated
- pH between 7.2 and 7.3
(Actrapid or Humulin R)
Ultra-short acting insulin analog
(Humalog [lispro] or NovoRapid [aspart]))
|0.1– 0.2 units/kg every four to six hours depending on the response.
For children less than 5 years of age, a smaller dose of 0.05 units/kg may be used. If the BGL remains elevated, a further dose of 0.05 units/kg can be given after 2 – 3 hours.
Refer to the Queensland DKA Subcutaneous Insulin Order and Blood Glucose Level Record Form.
Clinical reassessment of the child at frequent intervals is mandatory.
|Vital Signs (HR, RR)
|Temperature and BP
||4th hourly (or hourly temperature if febrile)
|Capillary (fingerprick) BGL
||Standard BGL (before meals and 2am)
|Strict fluid balance
||Hourly – unless advised otherwise by endocrinologist/treating paediatrician.
Emergency assessment and management should always involve a rapid primary survey with evaluation and management of airway, breathing, circulation and disability (ABCD).
Shock at presentation
Patient is severely ill with poor perfusion and thready rapid pulse. Occurs more commonly than in DKA.
||Sodium Chloride 0.9% administered in 20 mL/kg bolus.
Repeat boluses as needed to reverse shock.
IV rehydration fluids
Assume 12-15% fluid deficit as starting point for patients presenting with HHS.
Fluid Requirement = Maintenance + (Deficit – to be given over 48hrs) + Urinary Losses
Use 0.9% NaCl + 40mmol KCl (pre-mixed bag) as the initial default fluid unless:
- potassium is greater than 5.5mmol/L
- renal function is compromised
- the patient is anuric
If any of these three are present, use 0.9% NaCl with no added KCl as initial fluid, and seek urgent advice.
Replace urinary losses with 0.45% NaCl.
Fluid replacement alone will reduce the glucose by 4-5mmol/hr (measure hourly). If level falls faster the intensivist will consider adding glucose to the bag, however this should only be done on critical care advice.
Start insulin 0.025-0.05u/kg/hr ONLY WHEN the BGL is not falling with rehydration alone. Titrate to achieve reduction of blood glucose by no more than 3-4mmol/hr.
Accurate fluid balance is critical to guide initial and ongoing management. Urinary catheter insertion or strict fluid balance with weighing of nappies or measuring all output is recommended.
Complications of HHS
||Consider prophylaxis in patient with central venous catheter
|Rhabdomyolysis secondary to hypophosphataemia
||Measure phosphate, calcium, magnesium and creatinine kinase levels every two hours.
- In hypophosphataemic states, replace phosphate as IV potassium phosphate/potassium chloride mixture 0.2-0.5mmol/kg in 24 hours if less than 0.5mmol/L
- In hypomagnesaemia, replace magnesium as magnesium chloride 25-50mg/kg/dose for 4 doses (administered 6–hourly)
||Occurs rarely. Discuss with Critical Care. Dantrolene may be required.
Mild and moderate cases of DKA may be managed in a general paediatric ward depending on local practice. A Paediatrician with training and expertise in the management of DKA should direct inpatient management.
The child with mild to moderate DKA should receive care in a facility with all of the following:
- Experienced nursing staff trained in the monitoring and management of DKA
- Written guidelines for DKA management in children
- Access to laboratories that can provide frequent and timely measurements of biochemical variables
- Access to appropriate education and psychosocial assessment services
Transfer to a Paediatric Critical Care service may be considered for the following:
- Lack of appropriate staff/facilities to care of a child with mild/moderate DKA
- Long duration of symptoms
- Cardiovascular compromise or shock not responding to treatment
- Requirement for respiratory support (intubation/ventilation)
- Depressed level of consciousness/neurological deterioration/cerebral oedema
- Increased risk for cerebral oedema (including less than five years of age and new onset)
All patients with severe DKA and HHS will require admission to a Paediatric Critical Care service.