Diabetic ketoacidosis (DKA) is a form of high anion gap metabolic acidosis (HAGMA). It is a complication of T1DM and is commonly the first presentation of T1DM in children. T2DM patients can also develop DKA, but it is less common and less severe.
The anion gap is a useful tool that can be used to:
- Confirm that an acidosis is metabolic.
- Narrow down the cause of metabolic acidosis.
- Monitor the progress of treatment.
Our blood contains both cations (Na+ and K+) and anions (Cl- and HCO3-). The anion gap is measured by subtracting the anions (chloride and bicarbonate) from the cations (sodium and potassium, however, potassium is negligible so it is often left out).
The formula can be deduced to:
The number of cations is more than anions usually, thus it is normally positive, between 3-16.
A true high anion gap metabolic acidosis is usually >30.
The main unmeasured anions are albumin and phosphate. Therefore, hypoalbuminaemia may present with a normal anion gap metabolic acidosis (NAGMA).
Other causes of NAGMA
A simple list of the causes of HAGMA can be remembered with the mnemonic KARMEL:
- Ketones
- Aspirin (and paracetamol)
- Renal failure
- Methanol
- Ethanol and ethylene glycol (used to make antifreeze and brake fluid, ink, paint, plastics and cosmetics)
- Lactate
Some causes of NAGMA are ABCD:
- Addisons and acetazolamide
- Bicarbonate loss
- Chloride excess
- Drugs, diuretics and diarrhoea
NAGMA is most commonly due to bicarbonate loss. Bicarbonate is subsequently replaced in plasma by chloride ion (thus keeping the anion concentration stable) → hyperchloraemic acidosis.
Pathophysiology
Let’s first discuss ketogenesis:
Ketogenesis occurs when there is an insufficient supply of glucose and exhausted glycogen stores. Our body still will need energy and it resorts to breaking down fats (lipolysis). The liver will convert the fatty acids → acetyl CoA (through ß-oxidation) → ketogenesis to form ketones within the liver. Ketones are ultimately water soluble fatty acids which are able to be used as an energy source. This is a normal process and may happen with prolonged fasting or low carb diets.
In T1DM, the body is not producing insulin and if the patient is not injecting enough insulin, the muscle and liver cells as well as adipose tissue will not take up the glucose and this leads to hyperglycaemia which can lead to 3 issues:
- Ketoacidosis - ketogenesis occurs as insulin is not present and our body needs fuel. The kidney produces bicarbonate ions to buffer these ketone acids and maintain the pH of the blood. However, as the ketones build up, the bicarbonate ion gets used up and the blood becomes more acidic.
- Dehydration - as there is hyperglycaemia, the glucose in the urine draws water out through osmotic diuresis → polyuria → severe dehydration → polydipsia.
- Potassium imbalance - insulin causes potassium to enter cells where it may be stored. Serum potassium may be elevated or it may remain normal (due to renal compensation) in DKA. However, the total body potassium may be low as no potassium is stored in the cells. Therefore, once the patient is started on insulin they can develop a severe hypokalaemia which can lead to fatal arrhythmias.
As the blood pH drops and we get metabolic acidosis, the lungs try to compensate with hyperventilation as they try to breathe out more CO2. The kidneys also try to compensate with excretion of H+ in exchange for K+ → hyperkalaemia.
In T2DM, the body is not insulin deficient, but insulin resistant. So, some insulin is still present and remains a potent inhibitor of lipolysis and ketogenesis.
⚠️ Risk factors
- Infections - infections increase adrenaline and cortisol → suppresses insulin and increases lipolysis.
- Missed insulin doses or inadequate insulin
- Myocardial infarction
- Drugs - corticosteroids, thiazides, sympathomimetics, SGLT2 inhibitors.
- Physiological stress - such as pregnancy, trauma and surgery.
It is important to note that SGLT2 inhibitors such as dapagliflozin may result in DKA without hyperglycaemia. Therefore it is important to not rule out DKA if they are acutely unwell with normal glucose levels.
😷 Presentation
- Nausea
- Vomiting
- Abdominal pain - must be excluded prior to any emergency surgery.
- Hyperventilation (Kussmaul’s respiration) - late sign of DKA.
- Dehydration
- Reduced consciousness - can range from alert → coma.
- Acetone-smelling breath - a distinctly “pear drops” or “nail varnish remover” smell. However, a significant proportion of people are unable to smell this even if it is present.
- Palpitations
🔍 Investigations
- Venous blood gas (VBG) - preferred over ABG in patients with suspected DKA.
- pH >7.0 - mild - moderate DKA
- pH <7.0 - severe DKA
- Anion gap > 16
- Hyperkalaemia is common
- Osmolality is high (>320mmol/kg) and can be an indicator of dehydration
- Blood ketones
- Ketonaemia >3.0 mmol/L
- Urinary ketones shout be done if blood ketone testing is unavailable. Above 2+ is considered DKA usually.
- Blood glucose
- Hyperglycaemia (>11.0mmol/L)
- U&Es
- Hyponatraemia is common but hypernatraemia may indicate severe dehydration.
- Hyperkalaemia is common but hypokalaemia may indicate severe DKA as described in the pathophysiology.
- FBC
- Leukocytosis - infection may precipitate DKA.
- Glucose >11mmol
AND
- Blood ketones >3mmol/L
AND
- pH <7.3
AND/OR
- Bicarbonate <15mmol/L
🧰 Management
- Correct dehydration - fluid replacement is necessary as DKA patients are depleted 5-8 litres. Dehydration needs to be corrected evenly over 48 hours increasing it faster may risk cerebral oedema.
- Initially isotonic saline is given, even if the patient is severely acidotic. This will dilute the hyperglycaemia and ketonaemia.
- Insulin - to rectify the hyperglycaemia and ketonaemia definitively.
- IV infusion of insulin should be given at 0.1unit/kg/hour. Once the blood glucose is <14mmol/L then an infusion of 10% dextrose should be started as well until the patient is eating and drinking normally. The IV insulin infusion should also be slowed to 0.05units/kg/hour. This is to prevent risk development of hypoglycaemia and hypokalaemia.
- Long-acting insulin should be continued, while stopping the short-acting insulin.
- Electrolytes
- Potassium - serum potassium is high on admission but it is important to remember that total body potassium is actually low. Insulin treatment will correct the hyperkalaemia → hypokalaemia. Therefore we need to add potassium to the replacement fluids.
- If potassium infusion >20mmol/hour then cardiac monitoring is needed.
IV antibiotics may be started ASAP if infection is suspected.
JBDS example of fluid regimen
Fluid | Volume |
0.9% NaCl 1L | 1000ml over 1st hour |
0.9% NaCl 1L + potassium chloride | 1000ml over next 2 hours (500ml per hour) |
0.9% NaCl 1L + potassium chloride | 1000ml over next 2 hours (500ml per hour) |
0.9% NaCl 1L + potassium chloride | 1000ml over next 4 hours (250ml per hour) |
0.9% NaCl 1L + potassium chloride | 1000ml over next 4 hours (250ml per hour) |
0.9% NaCl 1L + potassium chloride | 1000ml over next 6 hours (167ml per hour) |
JBDS potassium guidelines
Potassium level in first 24 hours | Potassium replacement in mmol/L of infusion replacement |
>5.5 | 0 |
3.5-5.5 | 40mmol/L |
<3.5 | Senior review needed as additional potassium to be given. |
Usually local protocols outline the management of the disease. An example of a protocol that may be used is FIG-PICK:
- F - Fluids: IV fluid resuscitation with NaCl and potassium (as above)
- I - Insulin: Insulin infusion (e.g. actrapid at 0.1units/kg/hr)
- G - Glucose: Monitor blood glucose and add dextrose if it drops below an indicated level.
- P - Potassium: monitor serum potassium closely and correct it as needed (remember that it cannot be given more than 10mmol per hour generally).
- I - Infection: not only infection but any other trigger should be treated accordingly.
- C - Chart: fluid balance.
- K - Ketones: monitor blood ketones or bicarbonate levels.
3 things define DKA resolution:
- pH >7.3
- Blood ketones - <0.6mmol/L
- Bicarbonate >15.0mmol/L
🚨 Complications
Complications from the management of DKA are:
- Gastric stasis
- Thromboembolism
- Arrhythmias - due to hyperkalaemia/iatrogenic hypokalaemia.
- Cerebral oedema - especially in children and young adults. These patients often need 1:1 nursing for neuro-observations. It is vital to slowly correct fluid deficits over 48 hours as a result.
- ARDS
- AKI