Paediatric Diabetic Ketoacidosis

Context

Young people with type 1 diabetes mellitus (T1DM) can present with life threatening complications to the emergency department (ED).

Diabetic ketoacidosis (DKA) occurs following an absolute or relative deficit in insulin and has a risk of 1-10% per patient per year. [1-6] Mortality is estimated at 0.15-0.3% [7,8] with 60-90% of deaths related to cerebral oedema. [9,10]

DKA can also occur as the initial presentation of diabetes in 15-70% of cases. [11-18]

During this session we will explore the management of this condition with reference to published evidence and national guidelines.

All unwell children should have their blood sugar checked as part of the initial assessment.

Definition

Diagnosis of DKA is based upon the presence of biochemical criteria [19-22]:

• Hyperglycaemia (blood glucose >11 mmol/L)
• Acidosis (pH < 7.3 OR bicarbonate <15 mmol/L)
• Ketosis (blood ketones >3mmol/L or, if blood ketone monitoring is not available, moderate to large ketonuria)

The severity of DKA [19,22] can be classified as:

• Mild DKA: pH 7.2- 7.29 &/or bicarb < 15
• Moderate DKA: pH 7.1-7.19 &/or bicarb < 10
• Severe DKA: pH< 7.1 &/or bicarb < 5

Pathophysiology of DKA

Fig 1: Pathophysiology of DKA [22]

 

Insulin

Consequence of a deliberate or inadvertent failure to take exogenous insulin (known patient) or as part of the initial presentation of T1DM.

Counter-regulatory hormones

Low levels of insulin stimulate the release of glucagon, ACTH, growth hormone, prolactin and catecholamines.

Gluconeogenesis

Amino acids, lactate and glycerol are converted to glucose within the liver and released into the circulation.

Glycogenolysis

Breakdown of glycogen stores within the striated muscle and liver release glucose into the circulation.

Reduced glucose uptake

Despite the presence of high blood glucose, low levels of insulin inhibit uptake by the peripheral tissues, further exacerbating hyperglycaemia.

Lipolysis

Triglycerides within adipose tissue are broken down due to release of free fatty acids. These are subsequently oxidised to form ketone bodies (acetoacetate and -hydroxybutyrate).

Osmotic diuresis

Plasma glucose concentration increases until it exceeds the reabsorptive capacity of the nephron. At this point, glucose is excreted into the urine along with water and solutes (osmotic diuresis). This leads to significant dehydration and electrolyte imbalance.

Ketoacidosis

As ketone bodies accumulate, the bicarbonate buffering system is overcome resulting in a progressive metabolic acidosis.

 

Clinical Manifestations

The clinical manifestations of DKA include [22]:

• Dehydration
• Kussmaul respiration (deep, rapid, laboured, can appear like hyperventilation)
• Nausea and vomiting
• Abdominal pain (can mimic an acute abdomen)
• Progressive reduction in consciousness, drowsiness and coma
• Ketotic breath
• Increased heart rate

Fever is not a feature of DKA. Think about sepsis in a child or young person with DKA who has any of the following:

• fever or hypothermia
• hypotension
• refractory acidosis
• lactic acidosis

 

Risk Factors

The risk factors for DKA include [3,4]:

• New diagnosis in children of young age
• Delayed diagnosis
• Poor diabetic control/previous DKA
• Peri-pubertal or adolescent girls
• Patients with psychiatric morbidity (including eating disorders)
• Patients with unstable family circumstances
• Patients who omit insulin (deliberate or unintentional)
• Patients with limited access to medical services
• Patients who use an insulin pump[1,23]:
  • Such devices only utilise rapid acting insulin (i.e. Novorapid )
  • Hence, any interruption in supply can lead to rapid ketosis

Initial Emergency Assessment

Fig 2: Patients with DKA can be critically ill at presentation and should be managed systematically

Airway, breathing and circulation form part of the initial emergency management of paediatric DKA [19,22]:

Airway

• Ensure patent
• Consider adjuncts or definitive airway if indicated
• Seek anaesthetic support if there are concerns
• Due to the high risk of aspiration pneumonia an NG tube should be seriously considered in the following situations:
  • a child with reduced level of consciousness
  • and/or recurrent vomiting
  • and or recent consumption of a large volume of fruit juice or high sugar drinks [24, 25]

Breathing

• Give 100% oxygen by non re-breathe mask

Circulation

• Obtain IV access
  • Ideally 2 points of access
  • Avoid central access due to increased risk of thrombus
• Attach patient to a cardiac monitor [26] a 12 lead ECG, and evaluate for T wave changes
  • Assess for signs of shock
• All patients should be given fluid replacement and this should occur before insulin. The rate of fluid is dependent on if they are shocked or not.
• Shock is defined as tachycardia, prolonged central capillary refill, poor peripheral pulses and hypotension. Hypotension is a late sign of shock. Shock is not just poor peripheral perfusion as this can be due to acidosis and hyocapnia, both of which can cause peripheral vasoconstriction.
• Shocked patients should receive 10ml/kg bolus of 0.9% Saline over 15 minutes.
• Following the initial 10 ml/kg bolus shocked patients should be reassessed and further boluses of 10 ml/kg up to a total of 40 ml/kg may be given if required, at which stage inotropes should be considered.
• Non shocked patients, with mild, moderate or severe DKA should receive a 10 ml/kg 0.9% sodium chloride bolus over 30 minutes.

Initial investigations

• Blood glucose
• Blood gases (venous or capillary)
• Ketones- point of care blood tests (are superior to urinary ketones as they provide a rapid result and a quantitative rather than qualitative result)
• FBC
• Urea and electrolytes (electrolytes on blood gas sample may give a guide until accurate results available)
• CRP
• If able to obtain sufficient blood and this is a new diagnosis, send new diagnosis investigations (HbA1c,TFT, Coeliac screen)

Other investigations should be done only if indicated e.g. CXR, blood or urine culture etc.

 

Full clinical assessment

1) Assessment of conscious level

• Assessed using the Glasgow Coma Score [27]
• If the child is comatose or has a reduced conscious level:
  • Consider transfer to PICU/HDU if available
  • Consider treatment for raised intracranial pressure (if clinical suspicion)
  • Seek anaesthetic and senior paediatric support

2) Full physical examination

• The presence of the following should be excluded:
  • Cerebral oedema
  • Infection
  • Ileus

3) Weigh the child

• If not possible due to the childs clinical condition:
  • Most recent clinic weight
  • Estimated weight from centile charts

Observations and monitoring

DKA may be precipitated by sepsis or intercurrent infection. Fever is not part of DKA. Suspect sepsis if there is fever or hypothermia, hypotension, refractory acidosis or lactic acidosis.

• Hourly
  • Neurological & basic observations
    • NB: Half-hourly neurological observations should be employed in children under 2 years and/or those with severe DKA (increased risk of cerebral oedema)
  • Strict fluid balance
  • Capillary blood glucose and ketones
    • Urine ketones can be used if blood testing not available
• Medical review, venous blood gases, U&Es and glucose
  • Check 2 hours after management commenced
  • Then at least 4 hourly
• Medical staff should be informed immediately if:
  • Headache, change in CGS or behaviour
  • Slowing of pulse, changes in the ECG trace (especially T wave changes)

Introduction

Fig 3: The trinity of managing paediatric DKA: intravenous fluids, potassium and insulin

The management of DKA is largely dependant upon three factors:

1. Intravenous fluid therapy:

• Volume of fluid required
• Type of fluid required

2. Potassium

3. Insulin:

• Intravenous
• Subcutaneous

Volume of fluid required

The volume of fluid needed depends upon the following factors [19,22]:

Resuscitation fluid

• Shocked patients should receive 10ml/kg fluid bolus over 15 minutes. If required, further 10ml/kg boluses up to a maximum of 40ml/kg can be given, at which point inotropes should be considered.
• Non shocked patients should receive 10ml/kg fluid bolus over 30 minutes.

Example

What is the fluid requirement for a 20kg boy who has a pH of 7.15 who is not clinically shocked?

Answer

Fluid bolus= 10ml x 20kg = 200ml

Deficit percentage= 5%
Deficit volume= 5% x 20kg x 10 = 1000ml
Deficit volume minus bolus volume = 1000ml 200ml = 800ml

Deficit replacement rate = 800ml 48 hours = 16.7ml/hour

Daily maintenance volume = 1500ml
Maintenance rate = 1500ml 24 = 62.5ml/hour

Fluid rate = deficit replacement rate + maintenance rate = 79.2ml/hour

The BSPED has an online DKA calculator [28] that enables you to create a personalised DKA protocol for your patient which includes fluid calculations.

Intravenous fluid volumes should be calculated carefully and documented in the patients notes.

Type of fluid required

Resuscitation Fluid

• 0.9% salin

Intravenous Fluid Therapy

All fluids, except any initial blouses should contain Potassium Chloride (unless there is evidence of renal failure).

Every 500ml of 0.9% Saline should have 20mmol potassium chloride (40mmol in 1L).

The average child in DKA is depleted in total body potassium irrespective of plasma level [29] and average losses are 3-6mmol/kg. [28-33] In addition, once insulin is started potassium will be driven into the intracellular compartment and plasma levels with decline rapidly. [31]

If at presentation, the Potassium is elevated, Potassium should only be added to the fluids after the patient has passed urine or gives a history of having recently passed urine to ensure they are not anuric; or after the Potassium has fallen to the normal range, which generally occurs after the first fluid bolus.

If the Potassium is <3, then the patient should be discussed with critical care as central access will be required for higher concentration Potassium replacement.

When glucose levels drop

With the continued intravenous fluid therapy, patients will receive concurrent insulin therapy (see next section). This will drop their glucose level and the type of fluid given is therefore changed.

• When blood sugar <14 mmol/l give: 0.9% saline & 5% glucose with 20mmol KCl in 500ml
• When blood sugar <6 mmol/l give: 0.9% saline & 10% glucose with 20mmol KCl in 500ml

Do not stop the insulin infusion

If blood glucose levels fall below <4 mmol/l:

• Give: bolus of 2ml/kg 10% dextrose
• Give: 0.9% saline & 10% glucose with 20mmol KCl in 500ml

Reduce: insulin rate to 0.05 units/kg/hour. If already running at this rate, consider temporarily reducing this further.

Insulin

Insulin is required to normalise blood glucose and suppress ketogenesis. There is evidence that insulin given within the first hour of treatment increases the risk of cerebral oedema. [34-36] Therefore, do NOT start insulin until intravenous fluids have been running for at least an hour. [34]

A continuous low dose IV infusion should be used:

50 units of Actrapid in 50ml of 0.9% saline (1unit/ml solution).

An infusion rate of 0.05units/kg/hour of insulin is likely to be sufficient in most cases. Some local policies may advise commencing insulin at a rate of 0.1units/kg/hour, but there is currently no evidence that one infusion rate is superior to another. The BSPED suggest a starting dose of 0.05Units/kg/hr unless severe DKA or in adolescents.

The infusion rate of the insulin therapy may need to be altered according to glucose levels (see previous section).

Patients who are already on insulin:

• Those who use an insulin pump, the device should be turned off when starting DKA treatment.

• Those who are already on Long Acting Insulin (e.g. Lantus), the long acting insulin may be given subcutaneously at the normal dose & time during DKA treatment.

Your local policy may give advice on when/ if to start long acting insulin concurrently in newly diagnosed diabetics in DKA.

 

Other Considerations

• Continue IV therapy until:
  • pH normal or blood ketones <1.0mmol/L
  • Clinically well
  • Eating & drinking
• First give SC insulin (usual regimen of basal and bolus)
  • At least 30 minutes before stopping the infusion
  • 60 minutes if on an insulin pumps
• Then stop insulin infusion
  • The aim is to avoid rebound hyperglycaemia

On-going home management and follow-up should be discussed with the young persons Consultant or Diabetic Specialist Nurse.

Pitfalls

Non-resolution of acidosis and ketosis

Table 3: Causes of persistent acidosis and ketosis in young people with DKA

Acidosis not improving	Ketosis not improving
Underlying sepsis?	Underlying sepsis?
Insufficient insulin or drug error?	Insufficient insulin prescribed?
Inadequate resuscitation?	Incorrect preparation of insulin infusion?
Hyperchloraemic acidosis? (related to excessive use of chloride containing fluids)	Inadequate fluid input?
Recreational or prescription drugs?	Check infusion lines

Cerebral oedema

Cerebral oedema has high mortality and morbidity. [9,10,48]

Late signs are associated with extremely poor prognosis.

Senior staff must be informed immediately if suspected.

Discuss with PICU consultant and arrange urgent transfer.

Table 4

Warning signs [19,22]	Risk factors [22]
Headache	Younger age
Change in neurological status (reduction in GCS, change in restlessness, irritability or incontinence)	Initial presentation of T1DM [7]
Focal neurological signs (i.e. cranial nerve palsies)	Longer duration of symptoms
Relative bradycardia & hypertension (Cushings reflex)	Greater volumes of fluid within the first 4 hours of treatment [50]
Reduced oxygen saturations	Insulin infusion started within the first hour of treatment [50]
Abnormal posturing	Use of bicarbonate during treatment [9]
Oculomotor palsies, pupillary inequality or dilatation	Greater hypocapnia at presentation [9,51]
Late signs: convulsions, coma, papilloedema, respiratory arrest	Increased serum nitrogen at presentation[9,51]
	More severe acidosis at presentation [50]

Immediate management of cerebral oedema involves the following [19]:

• Exclude hypoglycaemia
• Give hypertonic (2.7%) saline or mannitol urgently
• Adjust IV fluids
  Reduce to 1/2 maintenance
• Do not intubate and ventilate until an experienced doctor is available
• Once stable a CT scan should be conducted to exclude other intra-cerebral events (thrombosis, haemorrhage or infarction) that have a similar presentation.

Key Learning Points

• Diagnosis of DKA is:
  • Blood glucose >11 mmol/l
  • pH < 7.3 or bicarbonate <15 mmol/L
  • Blood ketones >3mmol/L
• All children with DKA should receive a fluid bolus, the rate of which should be based on whether they are clinically shocked or not.
• The severity of DKA is based upon the degree of acidosis and can be categorised as mild, moderate and severe.
• Each category is associated with an assumed dehydration fluid deficit and this must be replaced along with the required maintenance fluids, over 48 hours.
• Replacement fluid is : 0.9% Saline with 20mmol KCL in 500ml.
• Insulin at a rate of 0.05units/kg/hour ( or 1 unit/kg/hour if severe DKA or adolescent) should be started at least 1 hour after starting fluid replacement therapy.
• As glucose levels drop, glucose will need to be added the fluid.
• Risk factors for cerebral oedema include young age, new onset T1DM, longer duration of symptoms, severe acidosis & bicarbonate correction.
• Suspected cerebral oedema should be treated with hypertonic saline.
• Patients will need regular observations and repeat blood tests whilst they are on they are being treated for DKA.

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Further reading:

• Dunger DB, Sperling MA, et al. ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents. Arch Dis Child. 2004 Feb;89(2):188-94.
• Wolfsdorf JI, Glaser N, Agus M, et al., ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatric Diabetes. 2018;19:155-177.
• Durward A, et al. The temporal relationship between glucose-corrected serum sodium and neurological status in severe diabetic ketoacidosis. Arch Dis Child. 2011 Jan;96(1):50-7.
• Fiordalisi I, Novotny WE, et al. An 18-yr prospective study of pediatric diabetic ketoacidosis: an approach to minimizing the risk of brain herniation during treatment. Pediatr Diabetes. 2007 Jun;8(3):142-9.