Diabetic Ketoacidosis
Last updated 25th Feb 2020 - Tom Heaton
Diabetic ketoacidosis is a potentially life-threatening complication of diabetes mellitus.
It is most commonly associated with type 1 DM, but has some occurrence in type 2, which may also be drug related.
This video from the Osmosis team provides an introduction: https://www.youtube.com/watch?v=-B-RVybvffU
It is most commonly associated with type 1 DM, but has some occurrence in type 2, which may also be drug related.
This video from the Osmosis team provides an introduction: https://www.youtube.com/watch?v=-B-RVybvffU
Pathophysiology
There is usually an absolute insulin deficiency (hence being primarily a feature of type 1).
This leads to inadequate intracellular utilisation of glucose.
This leads to a number of physiological responses:
The hyperglycaemia results in a significant osmotic diuresis, with dehydration and electrolyte disturbances, including due to osmotic loss in the urine.
The high level of ketone production leads to an acidosis as the buffering capacity is outstripped, also contributing to the electrolyte disturbance.
This may be additionally contributed to by the vomiting and reduced oral intake that may arise from the condition
This all results in the triad of DKA
This leads to inadequate intracellular utilisation of glucose.
This leads to a number of physiological responses:
- Increased glucagon
- Increased growth hormone
- Increased cortisol
- Increased catecholamines
- Glycogenolysis
- Increased gluconeogenesis - amino acid utilisation
- Increased lipid utilisation - increased lipase activity, increased free fatty acids
- Hyperglycaemia
- Ketosis - outstripping the buffering capacity
The hyperglycaemia results in a significant osmotic diuresis, with dehydration and electrolyte disturbances, including due to osmotic loss in the urine.
The high level of ketone production leads to an acidosis as the buffering capacity is outstripped, also contributing to the electrolyte disturbance.
This may be additionally contributed to by the vomiting and reduced oral intake that may arise from the condition
This all results in the triad of DKA
- Hyperglycaemia
- Ketonaemia
- Acidaemia
Presentation
DKA may be the first presentation of DM in a child or young adult, or may be triggered by an event.
Some key triggers include:
The presentation can be related to the presenting illness as well as the effects of the pathophysiology i.e. of notable dehydration and acidosis.
Some key triggers include:
- Intercurrent illness
- Infection
- Ischaemia
- Trauma
- Infection
- Non compliance with medications
- New medications e.g. steroids
- Pregnancy
- Trauma, inc. surgery
The presentation can be related to the presenting illness as well as the effects of the pathophysiology i.e. of notable dehydration and acidosis.
- Polyuria
- Polydipsia
- Abdominal upset - vomiting, pain
- Weight loss
- Altered conscious level
Clinical Features
Resp
- Tachypnoea
- Kussmaul breathing
- Acetone breath (like pear drops)
- Features of respiratory tract infection
- Tachycardia
- Hypotension
- Shock
- Dry mucous membranes
- Altered mental state e.g. confusion
- Decreased conscious level
- Temperature - low or high
Investigations
These are to assess for the complications of the DKA, as well as investigate for potential triggers.
Bloods
Microbiology
Venous blood gases are recommended for assessment as there are minimal differences in the values, with venous usually being more easily obtained. .
This can also provide electrolyte values, with intermittent laboratory testing.
Plasma osmolality can be calculated:
[2Na]+[k]+[Urea]+[Glucose]
Bloods
- FBC - raised WBC
- U&E - electrolyte disturbances, AKI
- Osmolality
- Blood gas - profound metabolic acidosis with incomplete resp compensation
- Ketones - near patient testing of blood ketones should be available
- Pregnancy test - potential trigger
- CXR - assessing for consolidation
- CT head may be needed in cases of altered consciousness
Microbiology
- Urine dip
- Blood cultures
Venous blood gases are recommended for assessment as there are minimal differences in the values, with venous usually being more easily obtained. .
This can also provide electrolyte values, with intermittent laboratory testing.
Plasma osmolality can be calculated:
[2Na]+[k]+[Urea]+[Glucose]
Diagnosis
The diagnostic criteria are based on the components of the triad.
Markers of severe DKA include:
- Hyperglycaemia - blood glucose >11mol/l or known diabetic
- Ketosis - ketonaemia >3mmol/l or significant ketonuria (>2+ on dip)
- Acidaemia - pH <7.3 or bicarbonate <15mmol/L
Markers of severe DKA include:
- Blood ketones > 6 mmol/l
- pH < 7.0
- Bicarb < 5 mmol/l
- GCS <12
- CVS disturbance (SBP<90mmHg, HR>100)
- Hypokalaemia at presentation
- High anion gap (>16)
- SpO2 <92%
Management
The management principles centre on:
This is in parallel to assessing the severity of this illness and minimising the risk of complications.
Some patients can be severely unwell at presentation, and may warrant an A to E approach.
Compromise of major systems in this approach (e.g. airway compromise due to altered conscious level) need urgent intervention.
The specifics of the management can be challenging and is very well structured, so reference to a clear guideline is important.
There are usually local guidelines, and national guidance is available here:
Adults - https://www.diabetes.org.uk/resources-s3/2017-09/Management-of-DKA-241013.pdf
Paediatric - https://www.bsped.org.uk/media/1712/new-dka-guideline-v6-final.pdf
Patients should be monitored and cared for in an appropriate care environment, which is likely to be a critical care area in cases of more severe disease.
- Fluid resuscitation
- Correcting electrolyte disturbances
- Switching off ketogenesis
- Identifying trigger
This is in parallel to assessing the severity of this illness and minimising the risk of complications.
Some patients can be severely unwell at presentation, and may warrant an A to E approach.
Compromise of major systems in this approach (e.g. airway compromise due to altered conscious level) need urgent intervention.
The specifics of the management can be challenging and is very well structured, so reference to a clear guideline is important.
There are usually local guidelines, and national guidance is available here:
Adults - https://www.diabetes.org.uk/resources-s3/2017-09/Management-of-DKA-241013.pdf
Paediatric - https://www.bsped.org.uk/media/1712/new-dka-guideline-v6-final.pdf
Patients should be monitored and cared for in an appropriate care environment, which is likely to be a critical care area in cases of more severe disease.
Fluid Resuscitation
Correction of the fluid deficit is a priority of treatment.
These patients are usually profoundly dehydrated - on average 10% of total.
Crystalloid resuscitation is therefore the first step in their management, after securing large bore IV access.
0.9% NaCl is commonly used, but other balanced crystalloids are acceptable.
0.9% is generally more available with supplementary potassium, as is needed.
In the shocked patient, this may need to be done aggressively to support the circulation.
In CVS stable patients, this is still rapid, but with slight more caution because of the risk of cerebral oedema.
Guidelines exist which are quite prescriptive on the amount and rates, especially in children.
Monitoring fluid balance is important here.
Catheterisation may be indicated in severe cases.
These patients are usually profoundly dehydrated - on average 10% of total.
Crystalloid resuscitation is therefore the first step in their management, after securing large bore IV access.
0.9% NaCl is commonly used, but other balanced crystalloids are acceptable.
0.9% is generally more available with supplementary potassium, as is needed.
In the shocked patient, this may need to be done aggressively to support the circulation.
In CVS stable patients, this is still rapid, but with slight more caution because of the risk of cerebral oedema.
Guidelines exist which are quite prescriptive on the amount and rates, especially in children.
Monitoring fluid balance is important here.
Catheterisation may be indicated in severe cases.
Correcting Electrolyte Disturbance
The patient may have normal potassium measurements but is likely to have significant total body deficit due to the osmotic diuresis.
With the subsequent initiation of insulin, this will drop further as the K+ is driven intracellularly.
As such, potassium replacement in fluids is essential, being commenced when the value is below 5.5 mmol/L.
There are also usually notable deficits of sodium and chloride, hence the common use of 0.9% NaCl as the crystalloid.
The metabolic acidosis is often profound, with partial respiratory compensation.
This will respond to correction of the other metabolic components (rehydration, switching off ketogenesis) and specific correction is not recommended.
It is important to be mindful of how important the respiratory compensation is, which may be compromised during transition to mechanical ventilation, and hard to maintain with a ventilator.
Bicarbonate administration is not recommended except in cases of profound hypokalemia or acidosis leading to CVS dysfunction.
There can be significant phosphate depletion in these patients, although replacement is not advocated unless there are significant symptoms e.g. muscle weakness.
With the subsequent initiation of insulin, this will drop further as the K+ is driven intracellularly.
As such, potassium replacement in fluids is essential, being commenced when the value is below 5.5 mmol/L.
There are also usually notable deficits of sodium and chloride, hence the common use of 0.9% NaCl as the crystalloid.
The metabolic acidosis is often profound, with partial respiratory compensation.
This will respond to correction of the other metabolic components (rehydration, switching off ketogenesis) and specific correction is not recommended.
It is important to be mindful of how important the respiratory compensation is, which may be compromised during transition to mechanical ventilation, and hard to maintain with a ventilator.
Bicarbonate administration is not recommended except in cases of profound hypokalemia or acidosis leading to CVS dysfunction.
There can be significant phosphate depletion in these patients, although replacement is not advocated unless there are significant symptoms e.g. muscle weakness.
Switching Off Ketogenesis
This goal involves both reducing ketosis and hyperglycaemia by providing the insulin needed for the body to effectively utilise glucose again.
Goals
Treatment is with a fixed rate insulin infusion (FRII).
This has been shown to have better correction of ketosis than a variable one.
A rate of 0.1 unit/kg/hr is used in adults, with a lower starting rate also possible in children.
An initial bolus is not recommended.
There is some evidence that excessively early administration (within the first hour) is a risk factor for cerebral oedema, so paediatric guidance recommends waiting until 1 hour after presentation to allow fluid repletion to commence.
It is recommended that any long acting insulin that the patient is normally on is continued.
Hypoglycemia should be avoided, and may occur with insulin treatment despite ongoing ketosis.
As such, glucose administration is recommended once the glucose drops below 14 mmol/L.
This 10% glucose, in addition to crystalloid fluid resuscitation.
Resolution of DKA is identified as:
Goals
- Reduce ketones by 0.5 mmol/l/hr
- Raise venous bicarb by 3 mmol/l/hr
- Reduce glucose by 3mmol/l/hr
- Avoid hypoglycemia - commence glucose
Treatment is with a fixed rate insulin infusion (FRII).
This has been shown to have better correction of ketosis than a variable one.
A rate of 0.1 unit/kg/hr is used in adults, with a lower starting rate also possible in children.
An initial bolus is not recommended.
There is some evidence that excessively early administration (within the first hour) is a risk factor for cerebral oedema, so paediatric guidance recommends waiting until 1 hour after presentation to allow fluid repletion to commence.
It is recommended that any long acting insulin that the patient is normally on is continued.
Hypoglycemia should be avoided, and may occur with insulin treatment despite ongoing ketosis.
As such, glucose administration is recommended once the glucose drops below 14 mmol/L.
This 10% glucose, in addition to crystalloid fluid resuscitation.
Resolution of DKA is identified as:
- pH > 7.3
- Bicarb > 15 mmol/L
- Ketones < 0.6 mmol/L
Complications
These include:
Cerebral oedema remains the main cause of mortality, especially in children.
This is less of a risk in adults.
The pathophysiology is unclear, but may involved:
- Hypoglycaemia
- Cerebral oedema
- Venous thrombosis
- Hyperchloremic acidosis
- Aspiration
- Pulmonary oedema
Cerebral oedema remains the main cause of mortality, especially in children.
This is less of a risk in adults.
The pathophysiology is unclear, but may involved:
- Changes in osmolality
- Relative hyperperfusion of brain after pretreatment hypoperfusion
- Children
- More severe acidosis
- Insulin in first hour
- Greater fluid administration in first 4 hours
- Bicarbonate administration
Links & References
- Joint British Diabetes Societies Inpatient Care Group. The management of diabetic ketoacidosis in adults (2nd ed). 2013. https://www.diabetes.org.uk/resources-s3/2017-09/Management-of-DKA-241013.pdf
- BSPED. BSPED Interim Guideline for the Management of Children and Young People under the age of 18 years with Diabetic Ketoacidosis. 2020. https://www.bsped.org.uk/media/1712/new-dka-guideline-v6-final.pdf
- Kerr, D. Wenham, T. Endocrine problems in the critically ill 1: diabetes and glycaemic control. BJA Education. 2017. 17(11):370-376. https://academic.oup.com/bjaed/article/17/11/370/3870459
- Nickson, C. Diabetic ketoacidosis. LITFL. 2019. https://litfl.com/diabetic-ketoacidosis/
- Rosenbloom, A. The management of diabetic ketoacidosis in children. Diabetes Ther. 2010. 1(2):103-120. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138479/
- Tidy, C. Diabetic ketoacidosis. 2016. Patient.info. https://patient.info/doctor/diabetic-ketoacidosis
- Nickson, C. Sodium bicarbonate and diabetic ketoacidosis. 2019. LITFL. https://litfl.com/sodium-bicarbonate-and-diabetic-ketoacidosis/
- Osmosis. Diabetes mellitus (type 1 & 2) & diabetic ketoacidosis. Youtube. 2019. https://www.youtube.com/watch?v=-B-RVybvffU
