Diabetic Ketoacidosis (DKA) is a medical emergency caused by uncontrolled Type 1 Diabetes Mellitus (T1DM).

It is quite common for children with undiagnosed T1DM to present as DKA, and for these patients to present acutely unwell. Therefore, it’s important to be able to recognise the presentation and start appropriate management.

Epidemiology

• The frequency of DKA at clinical onset of diabetes varies by location, but is approximately 15-75%.
• DKA at diagnosis is more common in children < 5 years of age, and in children who do not have ready access to medical care.
• There is increased risk of presenting with DKA in:
  • Children with previous episodes of DKA or poor hyperglycaemic control,
  • Children newly diagnosed with T1DM,
  • Children with psychiatric and eating disorders,
  • Children who miss their insulin doses (This can happen for a variety of reasons including: they are trying to lose weight, or because of poor compliance in general due to embarassment or mental health problems, or poor understanding of their condition)
  • Children with limited access to medical care.

Etiology

DKA develops when insulin levels are insufficient to meet the body’s metabolic requirements. In patients with T1DM, the pancreas is not able to synthesise insulin and the body relies on exogenous insulin doses.

The insulin deficiency that precipitates DKA can be absolute (e.g., new presentation of diabetes not yet started on insulin therapy, or omitting insulin dosages) or relative (the usual insulin dose is not enough to meet needs during physiologic stress). Common stressors in children and adolescents include:

• Infections: urinary tract infections, gastroenteritis, pneumonias,
• Poor compliance to insulin therapy,
• Dehydration,
• Fasting state,
• Heatstroke
• Trauma.

Pathophysiology

Without insulin, glucose cannot enter the cells and remains in the blood causing hyperglycaemia. This hyperglycaemia is further exacerbated by the increase of contra-insulin hormones (glucagon, growth hormone, cortisol, epinephrine). The plasma glucose levels exceed the re-absorptive capacity of the renal tubules, leading to increased glucose in the urine- glucosuria. Glucose is an osmotically active substance, meaning that it will lead to osmotic diuresis and loss of electrolytes. This will manifest with signs and symptoms of hypovolaemia. 

Insulin deficiency also increases lipolysis and hepatic oxidation of free fatty acids to produce ketone bodies (ketogenesis). The ketone bodies act as an energy source as the cells cannot utilise the glucose. There are three types of ketone bodies; acetoacetate, β- hydroxybutyrate and acetone. Acetoacetate and β- hydroxybutyrate lead to metabolic acidosis with a raised anion gap. The raised anion gap is due to bicarbonate consumption to compensate for the acidosis. This lipolysis can lead to rapid weight loss. Hence, often parents of children with undiagnosed T1DM will often present complaining their child is very thirsty all of the time, weeing a lot and losing weight.

Another consequence of insulin deficiency is hyperglycaemic hyperosmolality. This means that the blood is more concentrated with glucose and electrolytes than normal, particularly potassium. Potassium shifts with water from the inside of cells to the extracellular fluid and is lost in diuresis. This is further exacerbated by the fact that there is no insulin to promote potassium uptake back into the cells hence a total body potassium deficit develops (hypokalaemia), however serum potassium may be normal on labs or paradoxically elevated.

Clinical features

Symptoms

• Polyuria and/or polydipsia
• Weight loss
• Abdominal pain (may mimic an acute abdomen)
• Nausea and vomiting
• Altered mental status- confusion, drowsiness, or coma

Signs

• Signs of dehydration:
  • Hypotension, tachycardia, poor skin turgor, and weakness, dry and cracked lips, sunken eyes, prolonged capillary refill time (CRT).
• Kussmaul breathing: rapid and deep breathing to expel carbon dioxide, to compensate for the metabolic acidosis
• Fruity- smelling breath: due to raised levels of acetone
• Raised temperature (in case of infection that has precipitated DKA)

Classifying Dehydration

Biochemical criteria for DKA and investigations

DKA is characterised by the triad of:

1. Hyperglycaemia: > 11.1mmol/L
2. Metabolic acidosis: pH < 7.3 and serum bicarbonate < 15mEq/L
3. Hyperketonaemia: > 3mmol/L, or ketonuria

The severity of DKA depends on the pH and bicarbonate levels at the time of presentation:

• pH < 7.3 or HCO3 10-15 mmol/L: mild DKA (5% dehydration)
• pH < 7.2 or HCO3 5-10 mmol/L: moderate DKA (5% dehydration)
• pH < 7.1 or HCO3 < 5 mmol/L: severe DKA (10% dehydration)

Other early investigations include:

• Checking levels of urea, electrolytes, and creatinine (identify dehydration).
• Searching for a precipitating cause e.g., in case of infection, it is recommended to perform blood and urine cultures.
• Compare the weight with the most recent previous reading. (This will give you an idea of percentage dehydration).
• Assessment and monitoring of consciousness.
• HbA1C to assess glucose control (or review the most recent HbA1C from the clinic).
• ECG: to monitor T wave changes due to hypokalaemia.

ECG features of Hypokalaemia:

• Increased P wave amplitude (peaked P waves)
• Prolonged PR interval
• Widespread ST depression
• T wave flattening or inversion
• Prominent U waves (most noticeable in the precordial leads)

Treatment

In acute settings, the immediate management of DKA should be done using the ABCDE approach, and all complications should be dealt with as they are discovered.

Airway

The most efficient way to check for airway patency would be seeing if the patient can speak in complete sentences. Signs of airway compromise include use of accessory muscles, diminished breath sounds and adventitious sounds, and cyanosis. The presence of these signs or an increasingly drowsy patient warrants immediate support from anaesthetists. Whilst awaiting help, airway manoeuvres like the head-tilt-chin-lift may restore airway patency.

If the child is unconscious or has vomiting, nasogastric suction should be done to prevent pulmonary aspiration.

Airway adjuncts that can be used are oropharyngeal and nasopharyngeal airways. If a child is tolerating an oropharyngeal airway, it means that their GCS is 8 or less and anaesthetics should be called if they have not been already.

Breathing

The respiratory rate should be reviewed. Patients with DKA can develop Kussmaul breathing and thus tachypnoea, hence it is vital to monitor for hypoxaemia with Sp02

If a child in DKA is acutely unwell with tachypnoea and has signs of cyanosis or decompensation, they should be given 15L oxygen via a non rebreathe face mask (as in all resus situations with any acutely unwell patient).

Circulation

We should assess the pulse and blood pressure; in DKA it is common to see tachycardia and hypotension secondary to hypovolaemia. Bradycardia is an ominous sign and could foreshadow a cardiac arrest, therefore continuous ECG monitoring should be performed.  

It is also vital to do a fluid balance assessment. Majority of DKA patients are in a fluid deficit and present acutely with shock. Therefore, they require fluid resuscitation to restore blood pressure, correct the ketonemia and electrolyte abnormalities, and oliguria.

Signs of shock to be mindful for are tachycardia, hypotension, prolonged CRT, pallor, and a weak thready pulse.

Fluid boluses are given according to local guidelines, but generally shocked patients should receive a 10ml/kg 0.9% NaCl fluid bolus over 15 minutes. Patients should be reassessed after this initial bolus, and if there is still inadequate circulation, further boluses of 10ml/kg can be given up to 40ml/kg. After this stage, inotropes need to be considered to restore circulation.

At least two peripheral IV lines should be established, one for giving IV fluids and insulin, and the other for drawing bloods from. Blood tests to collect after gaining access include: Blood gas, FBC, U&Es, CRP, and serum glucose levels.

Disability

In DKA there may be a reduced level of consciousness. Consciousness can be assessed using the AVPU scale or the Glasgow Coma Scale (GCS).

Neurological observations should be done hourly. It is also important to assess the pupils for size and symmetry as this will give a clue of changes in intracranial pressure seen in cerebral oedema. If there are signs of progressive deterioration of consciousness (e.g., patient is becoming drowsy), seek anaesthetic assistance straight away for airway management.

The patient’s blood capillary glucose and ketones must be measured to confirm the diagnosis and DKA and guide management.

Exposure

The different factors that can lead to DKA should be considered here. On inspection, assess insulin injection sites, and try to gauge compliance to insulin therapy.

Also, note the amount and appearance of urine; urine may appear cloudy in cases of UTI.

Throughout therapy it is important to monitor fluid input and urine output so that fluid resuscitation measures can be adjusted. Monitoring is usually done by weighing the urine output in bed pans, however if the child is severely ill in the ICU with impaired consciousness, then urine output would be closely monitored via catheterisation.

Similarly, body temperature should be assessed as this can reveal exposure to infections which may have precipitated DKA, or some patients may be hypothermic if they have been unconscious for some time. If fever is present, co-existing infection should be kept as a differential and IV antibiotics should be started as soon as possible. In cases of hypothermia, re-warming can be done passively (with blankets), or active techniques can be implemented in severe cases.

Febrile patients may also be treated with antipyretics, and analgesics or antiemetics may be considered for abdominal pain and vomiting.

After each intervention, the patient should be re-assessed using the A-E approach.

Fluids

When treating DKA, fluid resuscitation is priority to correct the dehydration, electrolyte imbalance and acidosis. This is followed by a fixed rate insulin infusion so the cells can utilise glucose.

For shocked patients fluid resuscitation should begin as quickly as possible. This is done with an initial bolus of 10ml/kg 0.9% NaCl. Any fluids given for resuscitation in shocked patients should not be subtracted from the calculated fluid deficit, but the 10ml/kg bolus given to non-shocked patients should be taken away from the fluid deficit. The fluid deficit is added onto maintenance fluid requirements, and should be replaced slowly over 48 hours; this is to avoid the risk of cerebral oedema. Maintenance fluids are given according to the Holliday-Segar formula:

• 100ml/kg/day for the first 10kg of weight
• 50ml/kg/day for the next 10kg of weight
• 20ml/kg/day for weight over 20kg

Potassium

Potassium replacement therapy is needed regardless of the serum potassium concentration as DKA leads to a total body potassium deficit. If laboratory results show the patient is hypokalaemic, then potassium replacement should commence at the time of initial rehydration therapy, before starting insulin therapy, with a dose of 20mmol/L. However, if the patient is ‘hyperkalaemic’ then potassium replacement therapy should be withheld until urine output is determined.

Insulin

Insulin therapy should begin 1-2 hours after rehydration therapy, starting insulin therapy earlier than this increases the risk of cerebral oedema. The dosage of insulin as per BSPED guidelines is 0.05 units/kg/hour IV insulin in 50ml normal saline for most cases of DKA. For severe DKA, an infusion rate of 0.1units/kg/hour may be used instead.

After rehydration therapy the plasma glucose will begin to fall, and more so after insulin therapy. To prevent a sharp fall in glucose and hypoglycaemia, glucose levels should be monitored and when they become < 14 mmol/L, then 5% glucose should be added to the IV fluid.

Overview of DKA management as per BSPED

Worked example:

A 20kg 4-year-old boy with a history of T1DM presents to A&E with polyuria, vomiting and lethargy. On assessment he is normotensive and tachycardic, has dry mucous membranes and a prolonged capillary refill time of 3 seconds. A VBG is performed which shows: pH: 7.18, bicarbonate 11 mmol/L, ketones 6mmol/L, and blood glucose of 40mmol/L.

Complications

Cerebral oedema

The main complication of DKA is cerebral oedema, which usually manifests within the first 12-24 hours. Dehydration and hyperglycaemia cause water to move from the intracellular compartment to the extracellular compartment. Rapid correction of this with fluid resuscitation and insulin causes a shift in water back into the intracellular space causing swelling and oedema. Due to this risk, the fluid deficit correction is recommended to be performed slowly, over 48 hours and neurological observations should be monitored regularly and closely.

Warning signs of cerebral oedema include:

• Headache
• Bradycardia
• Change in neurological status: drowsiness, irritable, incontinence, reduced GCS
• Hypertension
• Decreased oxygen saturation

As soon as you suspect cerebral oedema, treatment must begin straight away. Immediately ask for help and call anaesthetics, elevate the head of the bed, reduce IV fluids by at least a third, and administer either:

• Hypertonic saline, 3% 5ml/kg over 10-15 minutes, or
• Mannitol, 20% 0.5-1g/kg IV over 20 minutes. Repeat if no improvement within 30-60 minutes.

Hypokalaemia and Hypernatremia

Patients with DKA have a total body potassium deficit, but serum potassium levels may be normal, high, or low. When we treat the patients with insulin it will shift potassium back to the intracellular space, rapidly resulting in hypokalaemia if potassium is not replaced. To avoid this, it is recommended that every 500ml bag of fluid contains 20mmol potassium chloride. If the patient develops hypokalaemia, consideration should be given to temporarily stopping the insulin infusion and further action should be discussed with a critical care specialist.

Hypernatremia can be a late complication of DKA. It is picked up later due to the hyperosmolar state of the blood. All DKA patients should have 4 hourly U&Es, and 1-2 hourly blood gasses to monitor sodium and potassium levels. The corrected sodium should be calculated based on the serum glucose at that time using the following equation:

Corrected sodium= measured sodium + 0.016 * (serum glucose in mg/dL – 100)

You can also input your patients serum sodium and glucose into MDcalc and it will give you the corrected sodium.

If the corrected value is > 150 mmol/L or the rise is > 5mmol/L in 4-8 hours, it could be a sign of severe hypernatraemic dehydration and this requires an increased fluid rate. A fall in corrected sodium > 5mmol/L in 4-8 hours is suggestive of too much fluid gain or rapid replacement, hence a reduced fluid rate would be required.

Stepping down management of DKA

Once blood ketones are < 1.0mmol/l and the patient is able to tolerate oral food and fluids, IV insulin may be transitioned to subcutaneous insulin. The subcutaneous insulin should be started at least 30 minutes before stopping IV insulin, this is to avoid fluctuations in blood glucose. If the patient uses insulin pump therapy to manage their diabetes, then the pump should be restarted at least 60 minutes before stopping IV insulin.

Prevention of DKA

Patient education and compliance to current therapy is vital to prevent a future DKA episode. Newly diagnosed diabetics should be informed of the triggers of DKA, such as missed insulin doses, illness, infection and of early signs of a preceding DKA episode (excessive thirst, polyuria, hyperglycaemia, nausea), to aid quicker diagnosis.

Especially important is educating children and their carers on sick day rules- proper sick day management at home could reduce the risk of progression to DKA. Sick day rules include:

• Frequent self-monitoring of blood glucose
• Self-monitoring of blood ketones
• Timely administration of supplemental insulin
• Timely administration of fluids
• Never stop insulin

Investigations for New Diabetics

For newly diagnosed diabetics who have presented in DKA it is worthwhile conducting further investigations to assess the underlying cause and guide management. Such investigations include:

• Thyroid function tests: T1DM is associated with autoimmune thyroid diseases such as Graves disease and Hashimoto’s thyroiditis. Patients should be screened annually.
• Coeliac disease testing: 4-9% of patients with T1DM also have coeliac disease. For most patients, T1DM is diagnosed before coeliac disease. Initial screening should take place shortly after the diagnosis of T1DM by testing for specific antibodies (anti-tissue transglutaminase, anti-endomysial antibodies), and subsequent screenings every 1-2 years.
• T1DM specific autoantibodies: antibodies against islet cells, glutamic acid decarboxylase (GADA) and insulin help differentiate T1DM from other forms of diabetes. In newly diagnosed diabetic patient presenting with DKA, presence of these antibodies would support the diagnosis of T1DM.

MDT Involvement

Managing poorly controlled diabetes often involves a multidisciplinary team (MDT) to address different aspects of the patient’s health. Team members who may be involved in the counselling include:

• A paediatric endocrinologist
• General practitioner
• Dieticians
• Pharmacists
• Clinical psychologists
• Diabetes educators
• Nurses

In every paediatric unit across the UK there is always a diabetes consultant on call. If there is an encounter with a child who has poorly controlled diabetes, it is important to inform the consultant and seek guidance on management.

References

(2021). BSPED Guideline for the Management of Children and Young people under the age of 18 with DKA.

Diabetic Ketoacidosis. (2018, November ). Retrieved from The Royal Children’s Hospital Melbourne : https://www.rch.org.au/clinicalguide/guideline_index/Diabetic_Ketoacidosis/

ISPAD. (n.d.). ISPAD Guideline for Diabetes in Childhood and Adolescence . International Diabetes Federation .

Karen J. Marcdante, R. M. (2022). Nelson Essentials of Paediatrics, 9th ed. Elsevier.

Robert C. Tasker, R. J. (2013). Oxofrd Handbook of Paediatrics, 2nd ed. Oxford University Press.

SM Ng, A. S. (2021). Management of T1DM during illness in children and young people under 18 years (Sick Day Rules). BSPED.

Tom Lissauer, W. C. (2022). Illustrated Textbook of Paediatrics, 6th ed. Elsevier .

Written by Nikhita Rathod, Final year medical student, Medical University of Varna. Edited by Dr Bex Evans, Paediatric Registrar