Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is a serious complication which usually affects people with type 1 diabetes.

Pathophysiology

A quick recap; when serum glucose rises e.g. following a meal, insulin is produced and released by beta cells in the pancreas. This results in the uptake of glucose by various tissues such as skeletal muscle, and also results in the inhibition of gluconeogenesis (new glucose production) and glycogenolysis (glycogen breakdown into glucose).

Hyperglycaemia and Dehydration

• Type 1 diabetics, however, usually have an absolute deficiency of insulin due to autoimmune destruction of these beta cells in the pancreas. In certain situations, e.g. infections, there is a rise in hormones that counteract insulin, such as cortisol and glucagon.
• These hormones increase gluconeogenesis and glycogenolysis, which contribute to the pre-existing hyperglycaemia alongside the insulin deficiency. This results in further osmotic diuresis, resulting in dehydration.

Ketosis and Metabolic Acidosis

• These counter-regulatory hormones also work to break down fat (lipolysis), to use as energy since the body is unable to actually use glucose. This produces free fatty acids, which are then metabolised into ketones by the body.
• Ketones are acidic in nature, and thus result in a metabolic acidosis. They also cause nausea and vomiting resulting in further fluid loss, exacerbating the dehydration seen in DKA.

Hypokalaemia

The excess acidic ketones in the blood stream also impacts potassium homeostasis.
 

• H/K exchanger: Exchanges one proton into the cell for one potassium ion out of the cell. As there are lots of acidic ketones in the blood i.e. protons, it drives this exchanger to push out potassium ions into the extracellular fluid.
• Na/K pump: Pumps 3 sodium ions out of the cell and 2 potassium ions into the cell. Due to the H/K exchanger, there are more potassium ions outside in the extracellular fluid which slows down this pump, further increasing the amount of potassium in the extracellular fluid.

This all results in high levels of potassium in the extra-cellular fluid. Eventually, this potassium is excreted which is why patients may be hyperkalaemic at presentation with a DKA, but then eventually develop hypokalaemia – particularly once treatment begins with insulin as insulin drives potassium into cells.

Causes

• First presentation of type 1 diabetes: If someone does not know they have type 1 diabetes, a DKA may be their first presentation
• Infection
• Acute illness e.g. Myocardial infarction or pancreatitis
• Inadequate insulin therapy for type 1 diabetics
• Discontinuation of insulin by patient
• Physiological stress e.g. pregnancy

Clinical Features

If you understand the pathophysiology of DKA, the signs and symptoms are easy to remember. You can categorise them based on if they’re due to the hyperglycaemia or due to the ketones.

Diagnostic Criteria

Investigations

Bedside

• Urinalysis: Ketones in urine/glucose in urine
• ECG: Signs of hyper or hypokalaemia and also rule out a silent myocardial infarction
• Cardiac monitoring: Watch out for arrhythmias secondary to hyper or hypokalaemia
• Capillary blood glucose and capillary ketones: >11 and >3 respectively

Bloods

• Venous blood gas: This will give us the bicarbonate, lactate (along with other useful information such as electrolytes)
• FBC, U&E, LFT: Baseline
• Amylase: Rule out pancreatitis
• Blood cultures: If suspecting an infection as the underlying cause

Management

There are three main things we need to fix in DKA.

The Joint British Diabetes Societies Inpatient Care Group has produced a set of guidelines for managing DKA. In practice, consulting local guidelines is always advisable but in these notes we’ll discuss management based on these guidelines.

Fluids
 

1. SBP <90mmHg: Fluid resuscitation with 500ml sodium chloride 0.9% should be given over 10-15 minutes. If the pressure is still <90mmHg, a senior should be consulted, and it may be necessary to repeat the fluid bolus.
    
2. SBP >90mmHg: Sodium chloride 0.9% fluid infusion is started in the following way. These quantities and rates can vary, so again, check local guidance.

Extra caution should be given in those between 18-25, elderly patients, renal/cardiac failure patients, pregnant patients and those with multiple co-morbidities i.e. it may be necessary to go slower with the infusion.

Potassium

As discussed, patients with DKA are at risk of hypokalaemia, particularly was insulin treatment is started as insulin physiologically drives potassium into cells. Thus, guidelines state potassium should be replaced alongside the IV fluids.
 

• K is high (>5.5mmol/L), you can hold potassium replacement.
• K is normal (3.5-5.5mmol/L), 40mmol/L of KCl should be given.
• K is low (<3.5mmol/L), a senior should be consulted as additional potassium will need to be given.

Insulin

• A fixed rate intravenous insulin infusion (FRIII) is used to replace insulin in a DKA.
• The dosage of this is weight dependent – we give 0.1 units/kg/hour of human soluble insulin i.e. Actrapid or Humulin S. 50 units of this insulin are diluted with 50ml of 0.9% saline to give a concentration of 1 unit/ml (50 units in 50ml).
• Thus, someone who weighs 60kg would require 0.1 x 60 = 6 units of insulin/hour i.e. 6ml of the infusion.

If patients are already on long-acting insulin such as insulin glargine, this should be continued – do not stop regular basal insulins.

Due to the FRIII, it is possible for patients to be overtreated and subsequently become hypoglycaemic – which we do not want. Guidelines state that if glucose falls <14mmol/L, 10% dextrose at a rate of 125ml/hour should be administered alongside the 0.9% sodium chloride infusion.

Treatment Aims

When treating DKA, we aim for:

• Ketones: Fall 0.5mmol/L per hour
• Glucose: Fall 3mmol/L per hour
• Venous bicarbonate: Rise 3mmol/L per hour

If we are not meeting these targets, it may be necessary to increase the FRIII.

Resolving DKA

With this treatment, the patient should have the following:

Ketones < 0.6mmol/L

Bicarbonate >18mmol/L

Venous pH >7.3

If the patient is eating and drinking, fast-acting insulins can be restarted. You shouldn’t be stopping insulin infusions until an hour after subcutaneous insulins have been administered.

Complications

• Venous thromboembolism: Increased risk, so VTE prophylaxis may be necessary
• Hypokalaemia
• Hyperkalaemia
• Cerebral oedema: Younger patients are at higher risk of this, which is why we are more cautious with fluids in younger patients. Signs include weakness, seizures, diplopia, headache, nausea, vomiting, confusion etc. CT scan can show the oedema.
• Aspiration: Patients may be at risk of aspiration due to vomiting + altered consciousness. It may be necessary to insert an NG tube in patients where there is potential airway compromise.

References

https://emedicine.medscape.com/article/118361-overview#a3

https://www.ncbi.nlm.nih.gov/books/NBK560723/

https://www.health.harvard.edu/a_to_z/diabetic-ketoacidosis-a-to-z

https://bnf.nice.org.uk/treatment-summary/diabetic-ketoacidosis.html

https://www.diabetes.org.uk/resources-s3/2017-09/Management-of-DKA-241013.pdf