Childhood Ketoacidosis

The primary cause of diabetic ketoacidosis (DKA) is absolute or relative insulin deficiency:

• Absolute - e.g. previously undiagnosed type 1 diabetes mellitus (T1DM) or patient with known T1DM who does not take their insulin
• Relative - stress causes a rise in counter-regulatory hormones with relative insulin deficiency

Children with type 2 diabetes mellitus (T2DM) may also present with DKA but is much less common compared to adult cases. Also T2DM is still less common than T1DM in children, although numbers are showing an upward trend.

• Deficiency of insulin
• Rise in counterregulatory hormones including - glucagon, cortisol, growth hormone, and catecholamines
• Thus inappropriate gluconeogenesis and liver glycogenolysis occurs compounding the hyperglycaemia, which causes hyperosmolarity and ensuing polyuria, dehydration and loss of electrolytes.
• Accelerated catabolism from lipolysis of adipose tissue leads to increased free fatty acid circulation, which on hepatic oxidation produces the ketone bodies (acetoacetic acid and β-hydroxybutyric acid) that cause the metabolic acidosis.

A vicious circle is usually set up as vomiting usually occurs compounding the stress and dehydration - the cycle can only be broken by providing insulin and fluids otherwise severe acidosis occurs and can be fatal.

The incidence of DKA at diagnosis in children with T1DM in Europe is approximately 23 per 100,000 children where as that of T2DM is estimated at 1.52 per 100,000.³ T2DM probably only accounts for 5% of all diabetic children, although this number is on the rise.⁴ DKA is more commonly found at diagnosis of T1DM in children aged <4 years old, children from families with low socioeconomic standing and children with no first degree relative with T1DM. In children with established T1DM the risk of an episode of DKA is in the region of 1-10% per child per year and many of these will occur as a result of poor adherence to a therapeutic regime.⁵

Young children (under 4 years) are more likely to have T1DM and present with atypical symptoms. They are more likely to have DKA and thus a high index of suspicion is required. Other children with DKA may present with any or all of the following common features of the condition:

• Dehydration
• Lethargy
• Confusion
• Polyuria ± polydypsia
• Weight loss
• Abdominal pain ± vomiting (may mimic a surgical abdomen)
• Rapid respiratory rate (Kussmaul's respirations)
• Ketotic breath - fruity, pear drops smell
• Fever
• Shock
• Coma

Other causes of metabolic acidosis:

• Overdose e.g. salicylates, iron, ethylene glycol, ethanol
• Lactic acidosis
• Inborn errors of metabolism such as ethylmalonic acidaemia
• Renal failure
• Gram negative septicaemia

Investigations should include:

• BM stix can be performed but glucose level should be confirmed on plasma samples
• Urine dipstick - looking for ketones and infection
• FBC - leukocytes increased with left shift (not necessarily caused by infection)
• Renal function - may reveal pattern consistent with dehydration; potassium may also be abnormal
• Liver function tests
• Venous pH and bicarbonate
• Amylase - may be non-specifically raised
• If any suspicion of infection send blood cultures and other appropriate samples

Always look for precipitating causes e.g. urinary tract infection, chest infection etc.

Correct dehydration⁶

Ideally weigh the patient to calculate exact fluid replacement. However, this may not be possible and either a recent weight can be used or an estimated weight. Weight can be estimated by calculating for the child's age or surface area. Serial weights may also help chart the child's progress.

Assessing Dehydration

Assess severity of dehydration using a combination of the following:

• Capillary refill time
• Skin turgor
• Abnormal respiratory pattern
• Dry mucous membranes
• Sunken eyes
• Weak pulse
• Cool peripheries
• Hypotension and oliguria are late signs in children and indicate severe dehydration

Fluid replacement

• If severely dehydrated or shocked (quite rare): 10ml/kg 0.9% Normal Saline over 15-30min (may be repeated).
• There is a balance here between restoring an adequate circulating volume and fears of precipitating cerebral oedema so the usual multiple 20ml/kg boluses are not recommended. In most protocols this fluid is included in subsequent fluid calculations.
• Calculate the deficit (by weight or, less accurately, by clinical assessment) and replace over 48hrs along with usual maintenance requirements using 0.9% saline initially, which can later be changed to 0.45% saline with 5% glucose when the BG has fallen to 12-15mmol/L.
• Because the severity of dehydration may be overestimated, it is important to know that the rate required will rarely exceed 1.5-2.0 times the usual daily requirement based on age, weight, or body surface area.

Treatment using fluid replacement and insulin will correct even severe acidosis. Bicarbonate is not recommended during initial treatment of DKA.⁶

Replace insulin

Treatment with insulin is essential to return the blood sugar level to normal limits, and to prevent further lipolysis and ketogenesis. The current recommendations for insulin therapy are as follows:^6,2

• Insulin should be given IV at a dose of 0.1U/kg/hour (some favour 0.05U/kg/hour especially in younger children). An initial bolus is not usually recommended.⁷
• After an initial, often sizable, drop in BG from rehydration the aim is to reduce the BG by <= 4mmol/L/hr.
• When the BG falls to 12-15mmol/L change fluids to 0.45% saline with 5% glucose. If the BG drops below 8mmol/L add a sideline of 10% glucose and titrate the BG to 8-12mmol/L. Do not decrease the insulin infusion.
• If the BG rises reduce the amount of glucose infused and if necessary increase the insulin infusion.
• If the pH and anion gap ( [Na+] ) - ( [Cl-]+[HCO3-] )
  fail to improve, review the insulin therapy and consider other causes e.g. infection, errors in insulin preparation, adhesion of insulin to tubing in dilute solutions.
• In the rare event that IV administration cannot be used, insulin may be given intramuscularly or subcutaneously, although absorption may be variable due to poor perfusion.
• Once the patient is eating, convert to sc insulin 30mins before a meal and stop infusion 60-90mins later.

Replace potassium²

• There is always depletion in total body potassium, however the initial serum K values may not be low, instead they can be normal to high reflecting the transcellular shift caused by the ketoacidosis.
• This masks the deficit which is uncovered once insulin has commenced.
• Potassium replacement therapy should be started immediately if the patient is hypokalaemic, but should otherwise be started when insulin therapy is begun.
• If the patient is hyperkalaemic, do not give potassium therapy until urine output has been documented.
• The potassium concentration of the IV fluids given should be 40 mmol/L, and potassium replacement therapy should continue until IV fluids are no longer necessary.

Phosphate replacement²

• Although serum phosphate levels fall as a result of the osmotic diuresis, and this fall is further aggravated by insulin therapy which encourages phosphate to enter cells, there is no evidence that replacement has clinical benefit.⁸
• If severe and associated with neurology, hypophosphatemia may be treated using potassium phosphate salts as an alternative to, or combined with potassium chloride/acetate.
• Replacement of phosphate may induce hypocalcaemia.

• Children who have long duration of symptoms, any element of confusion or a compromised circulation should be admitted to a children's unit or high dependency unit where staff have considerable experience in treating children with DKA.
• Children aged less than 5 and new onset T1DM are at high risk of developing cerebral oedema and should be referred for consideration for treatment in an intensive care unit.⁶

• Cerebral oedema is associated with nearly 25% mortality and usually manifests within the first 12 hours.
• Risk factors include:
  • Younger age
  • New onset DM
  • Longer duration of symptoms
• Patients develop:
  • Headache
  • Vomiting,
  • Confusion or irritability
  • Rising BP and bradycardia
  • Decreased oxygen saturation
  • Focal neurology e.g. cranial nerve palsies
• Treatment:
  • Mannitol 0.5-1g/kg IV should be given immediately over 20mins
  • Reduce rate of fluid administration
  • Elevate head of bed
  • Transfer to ICU - may need intubation
  • 5-10ml/kg of 3% saline is an alternative

One core issue in cerebral oedema is early identification. Major and minor criteria have been put forth with improved detection rates.⁹

The mortality rate of children with DKA in the United Kingdom is approximately 0.31%, the majority of these deaths occurring as a result of cerebral oedema.¹⁰