27th May 2025

Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is a potentially life threatening complication of T1DM, it can be the first presentation of T1DM in around 6% of cases and the mortality rate is estimated at 1%. Rarely, patients with type 2 diabetes mellitus (T2DM) can develop DKA under conditions of extreme stress. The presentation of DKA is the rapid onset of a triad of hyperglycaemia, ketonaemia and metabolic acidosis.

Aetiology 

DKA is caused by uncontrolled lipolysis which releases excess fatty acids that are converted into ketone bodies.

Precipitating factors and clinical presentation

Causes of DKA include the 7 I’s of DKA:

• Infection 
• Insulin missed 
• Ischaemia – acute coronary syndrome, critical limb ischaemia or ischaemic bowel  
• Initial presentation – new onset of diabetes especially in young children 
• Intoxication – cocaine, cannabis and acute intoxication with alcohol 
• Impregnation – pregnancy increases metabolic demands 
• Iatrogenic – drugs (corticosteroids, thiazides, sodium-glucose co-transporter 2 (SGLT2) inhibitors, symphathomimetics, second generation antipsychotics, immune checkpoint inhibitors)

Clinical Presentation

• Nausea and vomiting
• Abdominal pain
• Polydipsia, polyuria and dehydration 
• Kussmaul respiration (deep hyperventilation)
• Ketotic breath (acetone or ‘pear drops’ smell)
• Reduced consciousness
• Hypothermia

Investigations

All patients with suspected DKA should have the following investigations:

• Venous Blood Gas: pH <7.0 indicates severe DKA, hyperkalaemia is common
• Blood ketones or urinary ketones: ketonaemia is blood ketones >3.0 mmol/L
• Blood glucose: hyperglycaemia is >11mmol/L
• Bloods including:
  • Full Blood Count: leukocytosis is common, consider infection if markedly raised white cell count  
  • Urea and Electrolytes: hypernatraemia is common indicating dehydration, hyperkalaemia is common but hypokalaemia on arrival is an indicator of severe DKA as total body potassium is low

Other investigations to be considered include: 

• Urinalysis: ketonuria 2+ on standard urine sticks, may be positive for glucose, leukocytes and nitrites in the presence of urinary tract infection 
• ECG: looking for myocardial ischaemia 
• Amylase and Lipase 
• Cardiac enzymes: raised troponin I if myocardial infarction is suspected  
• Creatinine kinase: if rhabdomyolysis is suspected  
• Chest x-ray: look for consolidation in pneumonia and signs of pulmonary oedema if the patient is desaturating after fluid resuscitation
• Liver function tests: screen for an underlying hepatic cause of DKA 
• Blood, urine and sputum cultures: order if there are signs of infection 
• Pregnancy test: in women of child bearing age, pregnancy increases metabolic demands and can cause DKA in diabetic patients

Diagnostic criteria

The diagnosis of DKA should be made considering the clinical presentation, investigations and diagnostic criteria.

Three criteria must be met to diagnose DKA:

• Hyperglycaemia: blood glucose >11mmol/L OR known diabetes AND
• Ketonaemia: blood ketones >3mmol/L OR ketonuria (2+ or more on standard urine sticks) AND
• Acidosis: bicarbonate <15mmol/L AND/OR venous pH <7.3

Patients with DKA can become critically unwell, consider cardiac monitoring and escalate to a senior and consider critical care support if the patient has any of the following parameters:

• Persistent hypotension (systolic blood pressure <90mmHg) or oliguria (<0.5ml/kg/hr)  despite treatment with intravenous fluids 
• Tachycardia (heart rate >100bpm) or bradycardia (heart rate 60bpm)
• Oxygen saturations <92% on room air 
• Glasgow Coma Scale (GCS) <12 
• Potassium <3.5mmol/L on admission 
• Blood ketones >6mmol/L
• Venous pH <7 
• Venous bicarbonate <5mmol/L
• Anion gap >16
• The patient has kidney failure, is pregnant or other co-morbidities

Each trust has their own guidelines outlining when to escalate to critical care and these should be followed locally.

Management

The three main principles of management are fluid replacement, insulin infusion and correction of electrolyte disturbances.

Fluid replacement 

• Isotonic saline is used initially, even if the patient is severely acidotic. 
• Most patients with DKA are extremely dehydrated and depleted of fluid up to 5-8 litres.
• A slower infusion rate should be considered in young adults aged 18-25 due to the risk of cerebral oedema and patients aged 16-18 should be managed by a paediatric team.

Table 1: Example regime of typical fluid replacement in DKA (adapted from JBDS guidelines) for patients with a systolic BP on admission of 90mmHg and over.

Insulin infusion

• A fixed rate intravenous insulin infusion (FRIII) should be started at a rate of 0.1 unit/kg/hr.
• When the blood glucose reaches <14mmol/L, an infusion of 10% dextrose at 125ml/hr should be started alongside the 0.9% sodium chloride FRIII. The rate of FRIII can be reduced to 0.05units/kg/hr to reduce the risk of hypoglycaemia and hypokalaemia.

Correction of electrolyte disturbance 

• Serum potassium is high in DKA but total body potassium is low. 
• Serum potassium will fall quickly with treatment with insulin and causes hypokalaemia. 
• Potassium should be replaced with the intravenous fluid replacement. 
• Cardiac monitoring should be considered if the potassium correction is more than 20mmol/hour.

Table 2: Guidance for potassium management outlined by the JBDS (adapted from JBDS guidelines)

Other principles of management:

• Identify and treat the underlying cause e.g. infection, myocardial infarction, intoxication. 
• Long-acting insulin should always be continued and short acting insulin should be stopped. 
• Involve the specialist diabetes team.
• Thromboprophylaxis.

Monitoring 

• Monitor the airway and consider a nasogastric tube to prevent aspiration secondary to gastric paresis and low GCS.
• Measure pH, venous bicarbonate, potassium, blood glucose and ketones at 0, 1, 2, 4, 6 and 12 hours whilst measuring blood glucose and ketones hourly for the first 6 hours and then at 12 hours.
• Monitor for improvement with the following:
  • Reduction of ketones by at least 0.5mmol/L/hr OR 
  • Increase of venous bicarbonate by at least 3mmol/L/hr AND 
  • Reduction in blood glucose of 3mmol/L/hr
• Monitor for cerebral oedema by assessing GCS hourly.
• Monitor for pulmonary oedema by monitoring for desaturation, obtain a chest x-ray if suspected and consider an arterial blood gas.
• Monitor fluid input and output, insert a urinary catheter if anuric after one hour of starting DKA treatment.

Resolution 

Three criteria need to be met to confirm resolution of DKA:

• pH >7.3 AND 
• Blood ketones 0.6 mmol/L AND 
• Bicarbonate >15mmol/L

Both the acidosis and ketonaemia should have resolved within 24 hours, if this has not occurred then a review from a senior endocrinologist is required. When the above criteria are met and the patient has started eating and drinking then the patient should be switched to subcutaneous insulin; this should be started with a meal and the FRIII should be continued for 30-60 minutes after this is started to permit a successful switch. If DKA has resolved but the patient is not eating and drinking then the patient can be switched to a variable rate intravenous insulin infusion (VRIII) and intravenous fluids should be continued. The patient should be reviewed by a diabetes specialist nurse before they are discharged.

Complications

Complications can occur from DKA itself or from the treatment. These include:

• Gastric stasis which can increase the risk of aspiration
• Thromboembolism 
• Arrhythmias secondary to hyperkalaemia or iatrogenic hypokalaemia 
• Acute respiratory distress syndrome 
• Acute kidney injury 
• Iatrogenic complications due to incorrect fluid therapy: hypokalaemia, hypoglycaemia and cerebral oedema (children and young adults are most commonly at risk of this following fluid resuscitation, patients should be monitored for signs of cerebral oedema using neuro-observations and monitor for headache, irritability, visual disturbance, focal neurology)