A 17-year-old with nausea and vomiting

Diabetic Ketoacidosis (DKA)

• Abdominal pain
• Polyuria
• Polydipsia

• Appendicitis
• Ectopic pregnancy
• Diabetic Ketoacidosis

Acute pancreatitis is also a differential!

• Addisonian crisis

Abdominal pain in both DKA and Addisonian crisis may be associated with Mesenteric ischemia.

• Non-compliance
• Infections – Commonly UTI and Pneumonia
• Infarction – myocardial infarction and stroke
• Treatment failure +/- inability to afford treatment
• Surgery
• Trauma
• Burns
• Drugs e.g. Glucocorticoids, Cocaine

Anything that leads to an increased requirement of insulin can lead to DKA in patients with Type I Diabetes

• Etiology
  • DKA is commonly seen in T1DM, an autoimmune disease where the patients have complete/near total insulin deficiency. 70-80% of beta cells are destroyed in patients with T1DM and insulin is required for survival. Skipping a single day of insulin can have devastating consequences.
  • Insulin deficiency and increased counter-regulatory hormones cause inhibition of glycolysis and increased gluconeogenesis and glycolysis → Hyperglycemia
  • Insulin deficiency increases lipolysis through disinhibition of Hormone-sensitive lipase (HSL) → Lipolysis and generation of Free Fatty Acids → Ketogenesis
• Osmotic diuresis and hypovolemia
  • Hyperglycemia causes hyperosmolality and osmotic diuresis which leads to volume depletion and hypovolemia
• Metabolic acidosis with increased anion gap
  • Non-esterified fatty acids (NEFAs) generated from lipolysis are converted into ketones in the liver (acetoacetate, Beta-hydroxybutyrate)
  • These ketones are acidic and bicarbonate is consumed as it buffers them.
  • This causes metabolic acidosis with an elevated anion gap
• Intracellular potassium deficit
  • Hyperglycemic hyperosmolality shifts potassium along with water from the intracellular to extracellular space
  • Shifted potassium in the extracellular space is lost through urine
  • Insulin is absent in DKA and can therefore not promote intracellular potassium uptake
  • Total body potassium deficit develops although serum potassium may be normal or paradoxically elevated

• Ill-looking
• Signs of dehydration: dry skin, dry mucous membranes, decreased skin turgor
• Hypotension
• Tachycardia
• Tachypnoea (Kussmaul breatheing)
• Confusion

• Hyperglycemia
• Acidemia
• Hypovolemia
• Depleted total body sodium, potassium and magnesium
• Acute Kidney Injury from volume depletion

• Acidemia: Venous Blood pH <7.3 or HCO3- <15.0mmol
• Hyperglycemia: Blood Glucose >11mmol/L, Know Diabetic
• Ketonemia or significant ketonuria: ≥3.0mmol/L or 2+ on urinalysis respectively

• Hyperglycemia of 40 mmol/L. The degree of hyperglycemia does not correlate with severity. DKA can be seen with blood glucose ranging from “low” as 11 mmol/L to as high as 40 mmol/L as in this case.
• Pseudohyponatremia of 126 mEq/L. Corrected sodium (can be done using an online calculator) in this patient is 141 mEq/L which is within normal limit.
• Potassium of 4.3 mEq/L which is within the lower end. Concern for hypokalemia once treatment with insulin is started.
• Hypomagnesemia of 1.2 mEq/L which is common in DKA. Can be replaced with IV Magnesium.
• Low Bicarbonate of 10 mmol/L reflects metabolic acidosis (as bicarbonate is used as a buffer)
• Hypochloremia of 88 mEq/L from volume depletion resulting from vomiting and osmotic diuresis
• The anion gap is elevated and this is typical of DKA

• Carbon Monoxide, Cyanide
• Alcohol (Ethanol, Methanol)
• Toluene
• Uraemia
• DKA
• Propylene glycol, Paraldehyde, Paracetamol
• Iron tablets, Isoniazid
• Lactic acidosis
• Ethylene glycol
• Renal failure
• Salicylates, sepsis, starvation

• Diabetic Ketoacidosis
• Alcoholic Ketoacidosis
• Starvation Ketoacidosis

• DKA
• Sepsis
• Acute pancreatitis

• Potassium
• Intravenous Fluid
• Insulin

• Check blood glucose, ketone bodies, and potassium
• Administer IVF to replace fluid loss (usually NS at 2L in the first hour and 1L in subsequent hours) and Insulin
• Re-check blood glucose and ketone bodies
• If glucose is normal and ketones are high continue insulin and now give dextrose with potassium
• When glucose is normal and ketones are normal stop infusion and give potassium as needed

Potassium (K) is given before insulin, as insulin shifts K into cells and the large volume of IVF increases urine output and K wasting

IVF is given in large volume (LR = NS); if glucose lowers, but the anion gap doesn’t close, switch to a D5-containing solution

Insulin is given IV until the anion gap closes; once the anion gap is closed, switch to SQ insulin and start food (remember, in DKA the body thinks it is starving and activates starvation ketosis, which creates an anion gap)

• 1-3 L of NS in the first hour
• 1 L in the second hour
• 1L next four hours

IV Insulin at 0.1 u/kg/h

• To drive glucose into cells
• To inhibit HSL and stop ketone body production

• 4.4-5.5 mmol/L per hour

Hence, start the insulin drip at 0.1 U/kg/hr.

When glucose levels reach 13.9-16.6 mmol/L or it drops > 5.5 mmol/L/hr, add D5 to the fluids.

Once pH > 7.3, HCO3 > 16 mmol/L, anion gap is normal and the patient is eating, start SQ insulin and discontinue insulin drip after 1 hr.

• Once ketones return to normal and not when glucose levels are normal

Ketone bodies will still be produced even when glucose levels are normal. Insulin is needed for its inhibitor effects on HSL.

• Serum bicarbonate (anion gap) and not blood glucose

If serum bicarb is very low (very high anion gap) the patient is at risk of death.

• Bicarbonate is converted into CO2 which causes widespread cerebral vasodilation and cerebral oedema.
• Bicarbonate increases the work of breathing and can exacerbate acidosis

• Cerebral oedema

Especially in children when fluids are given too rapidly. Insulin bolus can also cause a sharp decrease in serum glucose and serum osmolarity.

Typically 10-20ml/kg NS boluses are given over 1 hour followed by repletion of the remaining fluid over 24-48 hours + maintenance fluid.