Diabetic Ketoacidosis

Life-threatening metabolic complication of insulin-dependent diabetes due to complete insulin deficiency resulting in:

Classically occurs in T1DM, but can also occur in ketosis-prone T2DM.

Epidemiology and Risk Factors

Pathophysiology

Alteration in normal carbohydrate metabolism due to insulin deficiency, which leads to:

  • ↑ Lipolysis
    Breakdown into glycerol and free fatty acids, in turn leading to:
    • ↑ Ketones
      • ↑ Serum levels occur via combination of:
        • ↑ Production via fatty acid oxidation
        • ↓ Ketone clearance
      • Causes HAGMA as ketones are a strong acid, dissociating completely at physiological pH
  • Hyperglycaemia
    • Due to:
      • ↑ Gluconeogenesis
      • ↓ Peripheral uptake of glucose
    • Leads to polyuria and hypovolaemia (and subsequently, polydipsia) due to the high filtered osmolar load
  • Electrolyte derangements
    • Potassium
      Serum level may be relatively normal in the setting of acidosis, although there is usually a total body deficit due to combination of:
      • Osmotic diuresis
      • Secondary hyperaldosteronism

Aetiology

In a known diabetic, DKA is usually precipitated by some antecedent pathology, which include:

  • Poor insulin compliance or access
  • Infection
  • ACS
  • Pancreatitis

Clinical Features

Develops over hours-days with:

  • Polyuria
  • Polydipsia
  • Weakness
  • Weight loss
  • Hypovolaemia

Neurological symptoms are more common in HHS than DKA, as they occurs secondary to a hyperosmolar state. Coma in a normoosmolar patient with DKA should prompt a search for another (particularly antecedent) cause.

Ketoacidosis results in:

  • Compensatory hyperventilation
    Rapid Jussmaul breathing.
  • Acetone breath
  • Profound acidosis

Other symptoms include:

  • Abdominal pain
    More common in children.

Assessment

History:

  • Known diabetes
  • Urine output
  • Volume intake

Exam:

Diagnostic Approach and DDx

Diagnosis is biochemical, and requires:

  • ↑ Ketones
    • >3mmol/L on blood
    • 2+ on urine dipstick
  • ↑ BSL
    • BSL >11mmol/L
    • Known DM
  • Metabolic acidosis
    • HCO3- <15mmol/L
    • pH <7.3

Investigations

Bedside:

  • ABG
    • ↑ BSL
    • ↑ Ketones
    • Metabolic acidosis
      Mixed NAGMA and HAGMA.
      • HAGMA due to ketoacidosis
      • NAGMA due to loss of strong cations which are co-excreted with ketones

Correcting sodium for glucose allows the presence of an underlying sodium disorder to be quantified. A variety of calculations exist, consider:

\(Na_{corr} = Na_{serum} - {Glucose \over 4}\)

Where:

  • \(Na_{corr}\) is the corrected sodium in mmol/L
  • \(Na_{serum}\) is the measured sodium in mmol/L
  • \(Glucose\) is the BSL in mmol/L

Note that the serum sodium is a true indication of the current electrolyte composition of the serum, and so the uncorrected value should be used for other calculations, such as the anion gap.

Laboratory:

  • Osmolality
    Raised, although not to the same degree as HHS.

Imaging:

Other:

Management

  • Fluid resuscitation
    Restore circulating volume and correct osmolarity.
  • Insulin administration
  • Correct electrolytes
  • Treat precipitant

Resuscitation:

  • C
    • Volume resuscitation
      • Balanced crystalloid preferred
        • 0.9% saline ↑ hyperchloraemic acidosis
        • Colloid may ↑ mortality
      • Addition of 20-30mmol/L of potassium to crystalloid may be performed to replete potassium stores
  • D
    • Insulin
      Fixed rate intravenous insulin infusion at 0.1 unit/kg/hr.
      • Bolus dose may precipitate hyperglycaemia and is not recommended
      • ↑ May be required if insulin resistant
      • ↓ To 0.02-0.05 unit/kg/hr when BSL is <12mmol/L
  • F
    • Electrolyte correction
      • Potassium
        • Begin correction of total body deficit once serum potassium is <5.5mmol/L
        • Consider only initiating insulin when potassium is >3.3mmol/L to avoid precipitating severe hypokalaemia

Supportive care:

  • F
    • Magnesium
      Often deplete, PRN replenishment is sufficient.

Disposition:

  • ICU admission for:
    • Neurological symptoms
      • GCS <12
    • Severe DKA
      • pH <7.0
      • HCO3- <5mmol/L
      • AG >16
    • Severe electrolyte derangements

Preventative:

  • Appropriate insulin administration
    • Baseline maintenance
    • ↑ Dosing in times of physiologic stress

Marginal and Ineffective Therapies

  • Bicarbonate
    Not recommended.

Anaesthetic Considerations

Complications

  • A
    • Aspiration
  • D
    • ↓ BSL
    • CVA
    • Cerebral oedema
      • More common in children and with high pre-treatment (>320mOsm/kg) osmolarity
      • Consider if headache and altered mental state occur during treatment
      • Treated with hypertonic fluid and slowing water resuscitation
  • F
    • ↓ K+
  • H
    • DVT

Hypoglycaemia and hypokalaemia are the most common serious complication. Both are due to excessive insulin replacement, hypokalaemia is precipitated by inadequate potassium supplementation.

Prognosis

Immediate mortality is low despite the profound metabolic derangements, however:

  • 1-month mortality: 8%
  • 1-year mortality: 18%
  • 5-year mortality: 35%

Key Studies

References