Diabetic ketoacidosis

Disclaimer These guidelines have been produced to guide clinical decision making for the medical, nursing and allied health staff of Perth Children’s Hospital. They are not strict protocols, and they do not replace the judgement of a senior clinician. Clinical common-sense should be applied at all times. These clinical guidelines should never be relied on as a substitute for proper assessment with respect to the particular circumstances of each case and the needs of each patient. Clinicians should also consider the local skill level available and their local area policies before following any guideline.  Read the full PCH Emergency Department disclaimer.

Aim

This protocol outlines the assessment and management of Diabetic Ketoacidosis (DKA) in children and adolescents (0-18 years) and is to be used for Emergency Department (ED) and inpatient management of DKA.

Background 

DKA is characterised by the triad of hyperglycaemia, metabolic acidosis and increased total body ketone concentration. DKA results from absolute or relative deficiency of circulating insulin and the effects of increased levels of counter-regulatory hormones.

The biochemical criteria for the diagnosis of DKA:

1. Hyperglycaemia: blood glucose level (BGL) > 11mmol/L
2. Ketonaemia (blood beta hydroxybutyrate > 3mmol/L or moderate or large ketonuria
3. Acidosis: venous pH <7.3 or bicarbonate < 15mmol/L

Rarely DKA may present with near normal glucose levels “euglycaemic ketoacidosis”.

If a child is hyperosmolar with a very high BGL (>30mmol/L), with little or no acidosis or ketones, this is a Hyperosmolar Hyperglycaemic State (HHS) and requires different treatment.  Discuss this with the senior doctor – these children can be very difficult to manage.

Where to manage patients with DKA

• Patients with a pH ≤7.2 and /or bicarbonate level ≤10mmol/L at initial presentation require admission to Paediatric Critical Care (PCC) at PCH.
• Patients with pH >7.2 who are 2 years of age and under, or have complications of DKA may also require admission to PCC. Other patients with a pH >7.2 can generally be managed on the ward with subcutaneous insulin.

DKA is life threatening and requires immediate treatment.

Causes and precipitants of DKA

• Insufficient insulin, newly diagnosed type 1 diabetes mellitus (T1DM)
• Missed insulin dose(s)
• Infection/illness.

Assessment

1. Is the patient shocked / haemodynamically unstable?  

• Reduced peripheral pulse volume
• Tachycardia +/- hypotension
• Altered Glasgow Coma Score (GCS) or coma

2. Assess ABCs and fluid resuscitate (consult Serious illness guideline) 
3. Contact ED Consultant, PCC and Endocrinology 
4. Confirm diagnosis and determine causes. 

Symptoms and signs of diabetic ketoacidosis

Symptoms	Signs	Biochemistry prior to arrival
Polyuria Polydipsia Weight loss Abdominal pain Weakness Nausea & vomiting Confusion	Dehydration Deep sighing respiration (Kussmaul) Smell of ketones	Elevated BGL (>11mmol/L) Acidaema (pH <7.3) Moderate or large ketones in urine and/or blood ketonameia >3mmo/L

  

Management

The goals of therapy are to:  

• Correct dehydration
• Correct acidosis and reverse ketosis
• Restore normal BGL 
• Avoid complications of therapy
• Priorities of management are fluid resuscitation, then insulin.

Consult on-call Paediatric Endocrinologist and PCC if considering PCC admission.

Children who are alert, not clinically dehydrated, and not nauseated or vomiting do not always require IV fluids, even if their ketone levels are high (when pH is > 7.3). They usually tolerate oral rehydration and subcutaneous insulin but do require monitoring regularly to ensure that they are improving and their ketone levels are falling.

If a child is hyperosmolar with a very high BGL (>30mmol/L), with little or no acidosis or ketones, this is a Hyperosmolar Hyperglycaemic State (HHS) and requires different treatment. Discuss this with the senior doctor– these children can be very difficult to manage. 

Shocked or haemodynamically unstable patients

1. General Resuscitation

Airway  

• Ensure that the airway is patent. If the child is comatose with an obstructed airway,provide airway support e.g. airway manoeuvres, Guedel airway or endotracheal tube.
• If consciousness is reduced or child has recurrent vomiting, consider inserting N/G tube; aspirate and leave on open drainage.
• Consult Paediatric Critical Care specialist if the patient has a reduced level of consciousness and is unable to protect their airway.

Breathing 

• Give oxygen by face-mask.

Circulation

• Measure blood pressure and heart rate and capillary refill time
• Cardiac monitor for T waves (peaked in hyperkalaemia).  

Insert two IV cannulas for resuscitation and blood sampling (see below).

Initial fluid bolus

Shock is defined by the APLS definition of tachycardia, prolonged central capillary refill, poor peripheral pulses and hypotension (though this is a late sign of shock). It is not just poor peripheral perfusion.

• All children and young people with mild, moderate or severe DKA who are not shocked and are felt to require IV fluids should receive a 10mL/kg sodium chloride 0.9% bolus over 60 minutes.
• Patients with shock require appropriate restoration of their circulation and circulatory volume with an initial 20mL/kg bolus of sodium chloride 0.9% over 15 minutes. 
• Following the initial 20mL/kg bolus shocked patients should be reassessed and further boluses of 10mL/kg may be given if required to restore adequate circulation up to a total of 40mL/kg at which stage inotropes should be considered.
• Whilst excessive fluid should be avoided because of the risk of cerebral oedema it is important to ensure that the circulation is adequate and fluid should be given to support this.

Cerebral perfusion is dependent on both blood pressure and intracranial pressure (cerebral perfusion pressure). Hypotension will increase the risk of brain injury.

2. Initial Investigations

• Blood glucose
• Blood gases (venous or capillary)
• FBC
• Urea and electrolytes (electrolytes on blood gas machine are acceptable and the same measuring system should be used throughout management of DKA
• Ketones (beta-hydroxybutyrate)
• New diagnosis bloods including HbA1c when possible during first admission.

Other investigations should be done only if indicated e.g. CXR, CSF, throat swab, blood cultures, urinalysis, culture and sensitivity etc. (a raised white blood cell count is common in DKA and does not necessarily indicate infection). 

3. Full clinical assessment

Assess and record the follow parameters in the notes so that comparisons can be made by others later:

Conscious Level: Institute hourly neurological observations including Glasgow Coma Score and whether or not drowsy on admission. If reduced conscious level on admission, or there is any subsequent deterioration: 

• seek urgent anaesthetic review if the airway cannot be protected 
• discuss with the responsible senior paediatrician 
• discuss with a paediatric critical care specialist to decide the appropriate care setting
• conscious level is directly related to degree of acidosis, but signs of raised intracranial pressure suggest cerebral oedema 
• if cerebral oedema is suspected, see section on  cerebral oedema under Potential complications for details on urgent management. 

Comprehensive Examination: looking particularly for evidence of:

• cerebral oedema i.e. headache, irritability, slowing pulse, rising blood pressure, reducing conscious level (N.B. papilloedema is a late and unreliable sign)
• infection 
• ileus (which is common in DKA)

Weigh patient: If this is not possible because of the clinical condition, use the most recent clinic weight.

• To avoid excessive amounts of fluid in overweight and obese children it is recommended that consideration be given to using a maximum weight of 80kg or 97th centile weight for age (whichever is lower).

4. Ongoing fluid requirements

Intravenous or oral fluids that have been given at another hospital should be factored into the assessment and calculation of fluid deficit and replacement needs.

• All fluids given must be documented
• Calculate fluid requirement:
  • Requirement = maintenance + deficit
  • Deficit tends to be overestimated. Do not use greater than 5% dehydration in calculations
  • Deficit (mL) = % dehydration x body weight (kg) x 10 

Maintenance fluid requirements

Body weight	Fluid requirement
3-10 kg	100mL / kg / day
10 - 20 kg	1000mL + (50mL / kg per day for each kg > 10kg
> 20 kg	1500mL + (20mL / kg per day for each kg > 20 kg)

Add calculated maintenance for 48 hours and estimated deficit then subtract amount already given as resuscitation fluid to give total evenly over 48 hours.

Hourly rate = 48 hour maintenance + deficit - resuscitation fluid already given)
48

A calculator tool using these formulae is available here: kidshealthwa | DKA Calculator.

Example

A 20 kg boy who is >5% dehydrated and has already had 20mL/kg sodium chloride 0.9% as a resuscitation fluid will require:  Deficit (mL) = % dehydration x body weight (kg) x 10 Deficit (mL) = 5 x 20 x 10 = 1000mL deficit   PLUS Maintenance = 1500mL each 24 hours = 3000mL each 48 hours MINUS Resuscitation fluid = 20kg x 20mL = 400mL resuscitation fluid 3000mL (48 hour maintenance) + 1000mL (deficit) - 400mL (resusitation fluid given) 48 Fluid requirement is 3600mL over 48 hours = 75mL/hr

 

• Do not include urinary losses in calculations.
• Continue sodium chloride 0.9% until the plasma glucose is less than 15mmol/L.
• When the plasma glucose falls below 15mmol/L, change fluids to glucose 5% with sodium chloride 0.9% to prevent rapid decrease in plasma glucose and hypoglycaemia
• Glucose concentration may be increased to 7.5% if the plasma glucose falls below 5mmol/L in the presence of persisting ketosis (> 3mmol/L).  Increase the glucose concentration rather than the fluid rate. 
• The use of large amounts of sodium chloride 0.9% is associated with the development of hyperchloraemic metabolic acidosis. 
  • The acidifying effect of chloride can mask recognition of resolution of ketoacidosis when total base deficit is used to monitor biochemical improvement.  A persisting base deficit or low bicarbonate can be erroneously interpreted as being due to ongoing ketosis. To avoid this misinterpretation, measurement of bedside ketone levels can demonstrate that the ketosis has resolved.  Hyperchloraemic acidosis resolves spontaneously. This needs to be factored in to the assessment of acid-base status, particularly in assessing the timing of conversion to subcutaneous insulin (see below).
• Oral fluids only offered after substantial clinical improvement and no vomiting.
• Include oral intake in fluid calculations.
• Rapid changes in fluid, electrolytes and serum osmolality can contribute to development of cerebral oedema. Monitor changes in mental state (using Glasgow Coma Score (GCS), Neurological Observations). Fluid management may need to be altered accordingly. If in doubt, discuss with senior clinician.

5. Potassium

Once a child has been resuscitated, potassium should be commenced immediately with rehydration fluid unless anuria present. Potassium replacement therapy is required for treatment of DKA because there will be a total body deficit of potassium and correction of the acidosis in the absence of potassium therapy will usually rapidly result in hypokalaemia. Although patients may have hyperkalaemia, hypokalaemia or normokalaemia at presentation there is always massive depletion of total body potassium. Levels in the blood will fall once insulin is commenced.

• Initially use intravenous infusions with potassium chloride 40mmol per litre once patient has passed urine and serum potassium is <5mmol/L.
• Use standard manufacturer’s infusions whenever possible.
• It may be necessary to give molar potassium chloride through a sideline in PCC. Sideline potassium chloride – start at 2mmol/kg/day and increase if hypokalaemia persists. 
• Continuous electrocardiogram (ECG) monitoring is required for all patients receiving potassium at a rate exceeding 0.2mmol/kg/hour (or >10mmol/hour).
• Give no more than 0.2mmol/kg/hour without prior discussion with a PCC Consultant.
• In general no more than 6mmol/kg/day is required. 
• If serum potassium is >5mmol/L, cease the potassium infusion.
• When metabolic acidosis is corrected, potassium supplementation may be reduced.
• Refer to the Potassium Chloride Monograph for further information on administration and monitoring.

6. Insulin administration (begins after the initial fluid resuscitation)

• Insulin is essential to switch off ketogenesis and reverse the ketoacidosis.
• Continuous low dose insulin is the preferred method.
  • Venous pH ≤ 7.2 = intravenous insulin recommended with admission to PCC.
  • Venous pH > 7.2 = subcutaneous insulin and ward management.
• Refer to the Insulin Monograph (WA Health only) for further information on administration and monitoring.

Intravenous infusion

• Patients having IV insulin infusion must be managed in PCC.
• Dilute 50units (0.5mL) of Actrapid® up to 50mL with sodium chloride 0.9%.
• Flush the line using 20mL of the prepared insulin infusion solution to prevent loss of insulin through binding to the tubing. 
• Give insulin infusion at a rate of ⁴:
  • < 5 years: 0.05units/kg/hour  
  • ≥ 5 years: 0.1units/kg/hour (max 5 units/hour) 
• Do not give insulin boluses while ketosis persists; reduce the insulin rate.⁴
• When the ketoacidosis is corrected the insulin infusion may be reduced if the blood glucose level is less than 5mmol/L and glucose is being infused. 
• If the blood glucose level does not decrease after the first 4 hours of the infusion, consider increasing the infusion rate e.g. in a child >5 years increase to 0.15units/kg/hour; seek advice from intensivist or endocrinologist for a younger child.
• Once the child is rehydrated, the keto acidosis corrected (i.e. pH >7.30 and bicarbonate >15mmol/L) and the blood glucose level is stable, give subcutaneous insulin (Actrapid®) 0.1units/kg and 2 hours later cease the insulin infusion. Continue subcutaneous insulin (Actrapid®) every 4 hours or as directed by the treating endocrine team.

Subcutaneous administration

• For patients with mild DKA, managed on the inpatient wards
• Initially 0.1units/kg of Actrapid®, then 0.1units/kg every 2 hours or as directed by the treating endocrine team.
• When the acidosis is corrected change to Actrapid® 0.1units/kg every 4-6 hours.

7. Bicarbonate

Bicarbonate administration is not routinely recommended as it may cause paradoxical CNS acidosis. Continuing acidosis indicates either insufficient fluid or, more likely, inadequate insulin replacement. In rare circumstances some extremely sick children may benefit from cautious administration of bicarbonate. This should only be done in discussion with PCC Consultant.

8. Phosphate

• Depletion of intracellular phosphate occurs in DKA and phosphate is also lost from osmotic diuresis. Plasma phosphate levels fall after starting treatment and this is exacerbated by insulin, promoting phosphate entry into cells. 
• This usually occurs within the first 24 hours of treatment with ongoing IV therapy and no food consumption.
• Severe hypophosphatemia (plasma phosphate < 0.32 mmol/L) can occur and result in metabolic encephalopathy, impaired myocardial contractility, respiratory failure, rhabdomyolysis, haematological complications, proximal myopathy and ileus.
• Consider phosphate replacement if level <0.6mmol/L. 
• Repeat phosphate level after replacement.
• Refer to PCH Phosphate Monograph (WA Health only) for dose, administration and monitoring information.

Monitoring and management

• Patient initially should be “Nil by mouth” except for ice to suck.
• Strict fluid balance hourly, use a urinary catheter in the comatose child.
• Hourly observations (more frequent if clinically indicated):
  • Pulse, blood pressure, respiratory rate 
  • Neurological status (pupillary responses, assess for change e.g. restlessness, irritability, headache)
• Monitor blood glucose and ketone levels hourly while on insulin infusion.
• Blood gases every 2 hours until stable, then 4 hourly until acidosis is corrected.
• 2 peripheral IV cannulas should be sited – one for infusions and one for blood gas samples. Capillary blood samples can be used if a second IV cannot be obtained.

Patients in PCC may have an arterial line which can be used for blood sampling.

Potential complications

1. Hypernatraemia / Hyponatraemia

Measured serum sodium is decreased by the dilutional effect of the hyperglycaemia. To ‘correct’ sodium concentration, use the following formula:

Corrected sodium = measured sodium + 0.3 x (glucose - 5.6) mmol/L

• Effective osmolality = 2 x sodium + glucose.
• If sodium is >160mmol/L discuss with senior doctor.
• If sodium does not rise as the glucose falls during treatment or if hyponatraemia develops, overzealous volume correction or insufficient electrolyte replacement should be considered. This may place the patient at risk of cerebral oedema.

2. Hypoglycaemia

• If blood glucose falls below 4mmol/L and the patient is still ketoacidotic, give IV glucose 10% 2mL/kg (max 100mL) over 5-10 minutes and increase IV infusion glucose concentration to 10% for ongoing IV fluids (with sodium chloride 0.9% and potassium supplementation). Do not discontinue the insulin infusion.
• If hypoglycaemia occurs despite use of glucose 10% in the preceding 2 or more hours, the rate of the insulin infusion should be decreased.
• Continue with a glucose 10% concentration in IV fluids until blood glucose stable.
• If blood glucose falls below 4mmol/L and most recent pH is >7.3, oral treatment for hypoglycaemia  (jelly beans + 1 serve of complex carbohydrate) can be used instead of an IV bolus of glucose 10% (if clinically well enough to tolerate oral treatment for hypoglycaemia).

3. Cerebral Oedema

• Cerebral oedema may suddenly develop clinically, usually between 6-12 hours after starting therapy (range 2-24 hours). Mortality or severe morbidity rate is very high without early treatment.

Prevention

• Slow correction of fluid and biochemical abnormalities. The optimal rate of fall of blood glucose and serum osmolality should not exceed 5mmol/hour but in children there is often a quicker initial fall in glucose.
• Patients should be nursed head up (i.e. elevate the head of the bed).

Risk factors

• First presentation
• Long history of poor control
• Age <5 years
• Low pH and elevated serum urea at presentation.

Warning signs

• Headache, irritability, lethargy, depressed consciousness, incontinence, thermal instability.
• Very late signs – bradycardia, increased blood pressure and respiratory impairment
• No sodium rise as glucose falls, hyponatraemia during therapy, initial adjusted hypernatraemia.
• Always exclude hypoglycaemia.

Treatment

• Inform senior staff immediately and manage in PCC
• Sodium chloride 3% - 5mL/kg of over 5 mins and repeat if no initial response
  OR if not available,
  Mannitol 20% - 0.5g/kg (2.5mL/kg) IV over 10-15 min and repeat if there is no initial response in 30 min to 2 hours
• Give above immediately when clinical diagnosis is suspected – do not delay for confirmatory brain CT scan.
• Reduce fluid input by 30% 
• Nurse head up
• Sedation, intubation and ventilation may be necessary (must hyperventilate to the same level or lower than that achieved by the patient with spontaneous breathing).

References

1. BSPED Interim Guideline for the Management of Children and Young People under the age of 18 years with Diabetic Ketoacidosis 2020
2. Royal Children’s Hospital Melbourne. Dehydration Clinical Guideline. 2015
3. Royal Children’s Hospital Melbourne. Diabetic Ketoacidosis Clinical Guideline. 2018
4. Wolsfdorf JI, Glaser N, Agus M et al; ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatric Diabetes. 19; (suppl.27):155-177. 2018
5. Craig ME, Twigg SM, Donaghue KC, Cheung NW, Cameron FJ, Conn J, Jenkins AJ, Silink M, for the Australian Type 1 Diabetes Guidelines Expert Advisory Group. National evidence‐based clinical care guidelines for type 1 diabetes in children, adolescents and adults. Australian Government Department of Health and Ageing. Canberra. 2011.

Endorsed by:	Drug and Therapeutics Committee	Date:	Jul 2020
		Review date:	Aug 2023

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