Overview

Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes. It is most commonly seen in type 1 diabetes and is rare in people with type 2 diabetes. DKA is characterised by 3 key elements:

  • Hyperglycaemia – the degree of hyperglycaemia is not a reliable indicator of DKA
  • Ketosis – raised ketones or ketonuria
  • Acidosis – low bicarbonate

To help make sense of this chapter, it may be helpful to refer to Endocrine and Metabolic Physiology.

Epidemiology

  • DKA is most commonly seen in T1DM
  • DKA may be the first presentation of T1DM in children/young adults

Pathophysiology

Ketoacidosis

The lack of insulin in the body leads to the release of fatty acids from adipose tissue which are then metabolised into ketones, leading to ketosis. Ketones ordinarily act as a source of energy in states of energy deficiency (e.g. starvation), however, in DKA, they can lead to acidosis. The body initially resists the change in pH using the bicarbonate buffering system but becomes overwhelmed, leading to other compensatory mechanisms to combat the acidosis (e.g. hyperventilation to lower the blood CO2 levels, known as Kussmaul respiration if severe).

Potassium imbalance

Insulin normally causes cells to take up potassium. Without insulin, potassium remains in the blood, leading to high serum potassium, but low total body potassium as none is stored in the cells. This is important because treatment with insulin can lead to hypokalaemia which carries complications such as arrhythmia.

Dehydration

Hyperglycaemia can lead to glucose being filtered out in the urine, taking water along with it via osmotic diuresis. This leads to polyuria, polydipsia, and dehydration.

Risk Factors

Factors that may precipitate a DKA are often physical stresses. Some precipitants may be:

Presentation

The features of DKA usually develop over 24 hours. If you suspect a DKA, take capillary blood glucose and blood gases promptly and initiate treatment. Do not delay treatment time by taking a history.

Features may be:

  • Abdominal pain – may be the presenting complaint
  • Nausea and/or vomiting
  • Altered consciousness
  • Hyperventilation:
    • Usually a late sign
    • Kussmaul breathing may be seen – deep sighing breaths at a slow/normal rate
  • Polyuria
  • Polydipsia
  • Dehydration
  • Acetone-like breath smell:
    • Similar in smell to pear drops or nail varnish remover
  • Features of a precipitant (e.g. infection or discontinuation of insulin) 

It is important to note that the incidence of T1DM and DKA is increasing in children and young people. Always suspect them in a young child who is drinking more than usual, having more wet nappies, yet still losing weight. Glucose in the urine of a child should immediately warrant a referral to secondary care for management.

Differential Diagnoses

Hyperosmolar hyperglycaemic state (HHS)

  • Patients are generally older and have a history of type 2 diabetes
  • The onset of symptoms is usually over days to weeks
  • Focal neurological signs may be seen
  • Ketones are normal, urinary ketones are normal/slightly raised
  • On an arterial blood gas, the pH is usually >7.30

Alcoholic ketoacidosis

  • Consider alcoholic ketoacidosis in a patient with a similar presentation to a DKA but capillary blood glucose is normal or low
  • There may be a history of alcohol abuse
  • Examination may reveal signs associated with alcohol abuse (e.g. signs of liver disease, smelling like alcohol etc.)

Investigations

  • Capillary blood glucose:
    • Hyperglycaemia
  • Venous or arterial blood gas:
    • Shows metabolic acidosis with a raised anion gap
  • Blood ketones:
    • Ketones are raised
  • FBC:
    • May show leukocytosis which can suggest infection
  • U&Es:
  • Urinalysis:
    • Shows ketonuria
    • May show glycosuria
  • ECG:
    • To check for arrhythmias due to hypo-/hyper-kalaemia and to be used as monitoring during treatment

Diagnosis

Joint British Diabetes Societies

Diagnosis is made provided the following 3 criteria are all met:

  • Blood glucose is raised or known diabetes
  • Blood ketones are raised or there is ketonuria
  • Acidosis is present (reduced bicarbonate (<15.0 mmol/L) and/or reduced pH (<7.30))

Management

All patients

  • 1st-line: IV fluids + insulin + correct electrolyte disturbances
    • Isotonic saline is used initially, and a 500 ml bolus is generally given
    • Insulin is given at a rate of 0.1 units/kg/hour
    • Insulin drives potassium into cells, so treatment may lead to hypokalaemia. Potassium may need to be added.
  • If the patient is taking insulin treatment:
    • Long-acting insulin should be continued
    • Short-acting insulin should be stopped
  • If the ketonaemia and acidosis have not resolved within 24 hours, seek help from a senior endocrinologist.

Cautions for young adults and children

Children and young adults (generally <25 years of age) are susceptible to cerebral oedema. Dehydration and hyperglycaemia cause water to move from the brain cells into the extracellular space, causing them to shrink. Correcting the dehydration and hyperglycaemia too quickly leads to water moving from the extracellular space back into the brain cells leading to swelling and oedema, which can lead to death.

Features of cerebral oedema usually arise within 24 hours of treatment. Changes in consciousness or behaviour, headaches, or bradycardia are suggestive of cerebral oedema.

The risk of cerebral oedema can be mitigated through neuro-observations to assess for any neurological signs or changes in consciousness. If cerebral oedema is suspected:

  • Seek immediate senior care and critical care support
  • IV mannitol or hypertonic saline may be used to reduce the swelling
  • Consider ordering a CT head

Monitoring and Patient Advice

Monitoring

Patients are monitored continuously. They should be managed in a high-dependency unit type of setting. In general:

  • U&Es and venous blood gases are checked every 1-2 hours initially
  • Fluid balance and capillary blood glucose are measured hourly
  •  When plasma glucose is <12 mmol/L, then normal saline is replaced with 5% dextrose to avoid over-correcting the blood glucose concentration and causing hypoglycaemia.

Patient Advice

  • Patients should be safety-netted on the signs and symptoms of a DKA and should seek help should they arise.
  • Patients should be advised to measure their ketones if they are unwell as this can help with identifying ketosis.

Complications

  • Cerebral oedema
  • Pulmonary oedema
  • Iatrogenic hypokalaemia
  • Iatrogenic hypoglycaemia
  • Cardiac arrhythmia
  • Venous thromboembolism
  • Myocardial infarction
  • Acute respiratory distress syndrome
  • Pulmonary oedema

Prognosis

  • The prognosis worsens with age and the severity of the underlying precipitant (e.g. myocardial infarction).
  • Cerebral oedema is the most common cause of mortality, especially in children and young adults.
  • Mortality in adults is often due to hypokalaemia, acute respiratory distress syndrome, and comorbid precipitants (e.g. myocardial infarction, pneumonia etc.)

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