Background Information
Definition
DKA is an acute, life-threatening complication of diabetes mellitus, characterised by a triad of:
- Hyperglycaemia
- Ketosis
- Metabolic acidosis
See below for its diagnostic criteria.
Pathophysiology
The trigger of DKA development is insulin deficiency + ↑ counter-regulatory hormones (glucagon, cortisol, growth hormone, catecholamines) [Ref]
Subsequent consequences: [Ref]
- ↓ Peripheral glucose uptake + ↑ hepatic gluconeogenesis → hyperglycaemia
- ↑ Lipolysis → ketogenesis (acetoacetic acid and beta-hydroxybutyric acid) → metabolic acidosis
Role of insulin:
- Promote glucose uptake + inhibit hepatic gluconeogenesis (net effect = reduced blood glucose)
- Inhibits lipolysis and ketogenesis
Role of counterary hormones:
- Increase hepatic gluconeogenesis (increase blood glucose)
- Stimulate lipolysis and ketogenesis
In DKA, there is less insulin and more counter-regulatory hormones.
Aetiology
Primarily affects those with T1DM as it is associated with insulin deficiency. [Ref]
Precipitators of DKA: [Ref]
- Insulin deficiency
- New-onset T1DM (1/3 of children and adolescents present initially as DKA)
- Insulin omission / non-adherence
- ↑ Insulin demand (→ relative deficiency)
- Infection (esp. UTI and pneumonia)
- Trauma
- Surgery
- Systemic steroids
Complications
Electrolyte abnormalities: [Ref]
- Phosphate / potassium disturbances
- On presentation (due to insulin deficiency/acidosisTrigger extracellular shift of phosphate / potassium ) → hyperphosphataemia/hyperkalaemia
- Note: despite a normal/high potassium on presentation, total body potassium is depleted
- Therefore, potassium supplementation is required even if initial levels are within range (see Management below)
- After insulin therapy (with correction of acidosis) → hypophosphataemia/hypokalaemia
- Routine phosphate supplementation is not recommended, but replacement should be considered in patients with severe hypophosphatemia or symptomssevere hypophosphatemia may lead to complications such as muscle weakness, respiratory failure, hemolytic anemia, and, rarely, seizures or cardiac arrest
- On presentation (due to insulin deficiency/acidosisTrigger extracellular shift of phosphate / potassium ) → hyperphosphataemia/hyperkalaemia
- Hyponatraemia / hypomagnesaemia (from hyperglycaemia-induced osmotic diuresis)
- Dehydration and hypovolaemia (can progress into AKI and shock)
Iatrogenic complications: [Ref]
- Cerebral oedema (common in younger patients) – most common cause of mortality
- Cerebral oedema happens from rapid hyperglycaemia correction
- The rapid drop in plasma osmolality shifts water into brain cells
- Strict adherence to DKA protocols regarding fluid therapy is essential to prevent cerebral oedema
- Hypoglycaemia (from insulin therapy)
- To prevent this, the insulin rate should be reduced and IV glucose should be added once plasma glucose drops below 14 mmol/L (see management below)
- Pulmonary oedema and ARDS (from fluid overload)
Diagnosis
Clinical Features
DKA typically occurs in the context of T1DM.
Non-specific findings (in both DKA and HHS): [Ref]
- Dehydration (e.g. dry mucous membrane, reduced skin turgor, tachycardia)
- Polyuria, polydipsia (from hyperglycaemia)
- Nausea and vomiting
- Altered mental status
- Fatigue / generalised weakness
Specific findings in DKA (absence in HHS): [Ref]
- Rapid onset (<24 hours)
- Abdominal pain (this occurs due to ketoacidosis irritating the peritoneum, thus it is absent in HHS)
- “Pearl-drop” / fruity breath odour (from exhaled ketones)
- Kussmaul respiration (compensatory hyperventilation in response to metabolic acidosis)
DKA Diagnostic Criteria
All 3 of the following must be present:
| Component | Cut-off |
|---|---|
| Diabetic- |
|
| -Keto- |
|
| -Acidosis |
|
Euglycaemic DKA is increasingly common due to its association with SGLT-2 inhibitor use. Diagnostic criteria are as above, minus the hyperglycaemia.
Prevention
Patient Education
Emphasise sick-day rules:
- NEVER stop insulin, and adjust insulin doses as instructed
- Monitor blood glucose more frequently (every 2-4 hours)
- Monitor ketones regularly (blood / urine)
- Stay hydrated and eat easily digestible carbohydrates
Acute DKA Management
Step 1 – Fluid Resuscitation
Fluid replacement to rehydrate the patient is the FIRST PRIORITY in DKA management to restore circulatory volume and stabilise the patient. Although not the definitive management, it alone will not resolve DKA. Insulin is the definitive treatment, but fluids should always be given first. This is important in both exams and clinical practice.
If systolic BP <90 mmHg (i.e. patient is shocked) → fluid bolus (500 mL of 0.9% NaCl over 10-15 min)
Once systolic BP >90 mmHg (or >90 mmHg from the start):
- Give 1L of 0.9% NaCl over 1 hour with NO potassium
- Potassium only to be considered in 2nd bag onwards – see step 3 below
Step 2 – Insulin Therapy
Insulin is the definitive treatment that resolves DKA. However, note that insulin is NOT the first priority in managing DKA. The first priority is always fluid resuscitation.
Insulin’s main effects in treating DKA are:
- Suppression of ketogenesis
- Reduction of blood glucose
- Correction of electrolyte disturbance
Commence fixed rate intravenous insulin infusion (FRIII)
- Rate: 0.1 unit/kg/hour
- Choice of insulin: short-acting insulin (JBDS recommends human soluble insulin – Actrapid® or Humulin S®)
- Preparation: 50 units of insulin made up to 50 mL with 0.9% NaCl
Changes to Existing Insulin Therapy
- Stop any short-acting insulin
- Continue long-acting insulin (e.g. glargine, detemir, degludec) at usual dose and time
When Glucose Falls <14 mmol/L
- Consider reducing the insulin rate to 0.05 units/kg/hour
- Add 10% dextrose at 125 mL/hr
Step 3 – Ongoing Management
Continue FRIIIFixed rate intravenous insulin infusion and fluid replacement:
- 2nd bag of fluid: 1L of 0.9% NaCl over 2 hours + potassium replacement if ≤5.5 mmol/L
- 3rd bag of fluid: 1L of 0.9% NaCl over 2 hours + potassium replacement if ≤5.5 mmol/L
- 4th bag of fluid: 1L of 0.9% NaCl over 4 hours + potassium replacement if ≤5.5 mmol/L
- 5th bag of fluid: 1L of 0.9% NaCl over 4 hours + potassium replacement if ≤5.5 mmol/L
- 6th bag of fluid: 1L of 0.9% NaCl over 6 hours + potassium replacement if ≤5.5 mmol/L
Adherence to DKA fluid protocol is important to prevent cerebral oedema (from correcting hyperglycaemia too rapidly) and fluid overload complications (e.g. pulmonary oedema).
Potassium Replacement
Potassium replacement depends on potassium levels:
- >5.5 mmol/L → no potassium replacement needed
- 3.5-5.5 mmol/L → 40 mmol/L of potassium infusion solution
- <3.5 → senior review (as additional potassium required)
If the potassium delivery rate exceeds 20 mmol/hour, continuous cardiac monitoring is required.
Such that if 40 mmol/L of potassium replacement is indicated in the 2nd or 3rd bag of fluids, that corresponds to 20 mmol/hour as these fluids are 1L given over 2 hours. These patients would require cardiac monitoring.
Aims of Treatment
- Ketone ↓ at least 0.5 mmol/L/hr / bicarbonate ↑ at least 3 mmol/L/hr
- Blood glucose ↓ at least 3 mmol/L/hr
- Maintain serum potassium in normal ranges
It is more important to be aware of what parameters to monitor, and their expected trend (i.e. what should go up and go down, to indicate treatment is working).
In clinical practice, these exact rates would be easily accessible, and in exams, the questions tend to assess one’s understanding of principles, rather than recalling exact cut-offs.
Euglycaemic DKA
Diagnostic Criteria/Definition
- Euglycaemic DKA has the same diagnostic criteria as DKA, however, with a glucose level that does NOT meet the cut-off for DKA (i.e., glucose is <11 mmol/L)
Management
- Fluid therapy /Insulin therapy/ Ongoing management (step 1-3) is the same as acute DKA (see above)
- The only difference is when to start glucose/dextrose infusion
- Initiate dextrose/glucose infusion 10% straight away at 125 ml/hr alongside the FRIII (to prevent hypoglycaemia) – since glucose is already <14 mmol/L by definition
- If glucose keeps falling despite 10% glucose, JBDS guidelines recommend reducing FRIII to 0.05 units/kg/hr to avoid hypoglycaemia
- Initiate dextrose/glucose infusion 10% straight away at 125 ml/hr alongside the FRIII (to prevent hypoglycaemia) – since glucose is already <14 mmol/L by definition
Post-DKA Resolution
Resolution Criteria
DKA should resolve by 24 hours (if not → seek senior review)
Resolution criteria:
- Ketones <0.6 mmol/L, and
- Venous pH >7.3
Management Post-Resolution
- Convert to subcutaneous insulin
- Only discontinue the IV insulin infusion until 30 min after subcutaneous insulin has been given
- Patient should be eating and drinking
Paediatric DKA
The BSPEDBritish Society for Paediatric Endocrinology and Diabetes has a specific guideline for the management of DKA in children and young people who are <18 y/o
The following section compares the similarities and main differences to adult DKA management
Similarities
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Management Aspect
|
Details
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|---|---|
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Diagnosis
|
Same diagnostic criteria
|
|
Initial Priority
|
Restoration of circulating volume (fluid replacement) is the most important initial therapeutic intervention
|
|
Insulin Type/Method
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Both use a Fixed Rate Intravenous Insulin Infusion (FRIII), typically made up of soluble human insulin (e.g., Actrapid or Humulin S) diluted in 0.9% sodium chloride solution
|
|
Potassium
|
If potassium is in the normal range:
Both guidelines recommend a standard concentration of 40 mmol/L potassium chloride be added to the intravenous fluid bags (EXCEPT during initial fluid resuscitation / first bag) during the majority of the treatment phase
|
|
Glucose/Dextrose Addition
|
Both require adding glucose (dextrose) infusions once blood glucose levels fall below 14.0 mmol/L to prevent hypoglycemia while continuing the insulin infusion to suppress ketogenesis
|
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Metabolic Targets
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Same resolution rate criteria:
|
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Resolution Criteria
|
Same DKA resolution definition:
|
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Transition to SC Insulin
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Transition from intravenous to subcutaneous insulin should occur:
IV infusion should not be discontinued until 30 min after the subcutaneous dose has been given |
Differences
Timing of Insulin Initiation (The Most Significant Difference)
|
Management Aspect
|
Adults
|
Children
|
|---|---|---|
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Timing
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Commence FRIII immediately (within the first 60 minutes) after fluid therapy has begun
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Start intravenous insulin infusion 1–2 hours after beginning intravenous fluid therapy
|
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Rationale
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Effective suppression of ketogenesis is prioritised
|
Delay is implemented because there is some evidence that cerebral oedema is more likely if insulin is started early
|
Fluid Therapy
|
Management Aspect
|
Adults
|
Children
|
|---|---|---|
|
Initial Bolus (Non-Shocked)
|
1L 0.9% NaCl over the first 60 minutes
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10 ml/kg bolus of 0.9% NaCl over 30 minutes
|
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Bolus (Shocked Patients)
|
500 ml bolus of 0.9% NaCl over 10-15 minutes, repeated as needed
|
10 ml/kg bolus of 0.9% NaCl over 15 minutes, repeated as required up to 40 ml/kg
|
|
Potassium (response to low K+)
|
Insulin administration must be deferred if potassium is <3.0 mmol/L until potassium level is >3.0 mmol/l
|
Insulin is commenced promptly alongside fluid resuscitation
If potassium is <3.5 mmol/L, immediate senior review is required for additional potassium replacement
|
Definitions of ‘shock’ for initial DKA fluid resuscitation:
Adults: based on systolic blood pressure
- SBP <90 → Shock
- SBP ≥90 → Non-Shocked
Children: based on clinical signs (as outlined by APLSAdvanced Pediatric Life Support) rather than a single blood pressure threshold, including:
- Tachycardia
- Prolonged CRTCapillary refill time
- Poor peripheral pulses
- Hypotension (late sign of shock)
Non-shocked children do NOT exhibit the above signs of shock, but may still be dehydrated.
Insulin Dosage
|
Management Aspect
|
Adults
|
Children
|
|---|---|---|
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Starting Rate
|
Standard fixed rate is 0.1 units/kg/hour
|
Dosage can be 0.05 units/kg/hour OR 0.1 units/kg/hour
Guideline states that 0.05 units/kg/hour would be sufficient in most cases, especially in children younger than 5 years, to reduce hypoglycemia incidence
|