creation date: 2025-11-28 09:18
tags: Pathologies

Diabetic Ketoacidosis

Background

Definitions

Diabetic ketoacidosis (DKA) is one of two conditions representing hyperglycemic crises, the other being hyperosmolar hyperglycemic state. DKA is a life-threatening emergency characterized by the complete deficiency of insulin.

Etiology

The predisposing factor of DKA is diabetes mellitus, especially type 1 diabetes. However, it can occur in type 2 diabetes under conditions of extreme stress.

SGLT2 inhibitors have been associated with an increase risk of DKA as well.

Generally, causes can be distinguished between a lack/insufficient insulin or an increase in insulin demand, which can be categorized by the following:

Infection (eg. pna, UTI, pyelonephritis, cellulitis)
Inflammation (eg. pancreatitis)
Infarction (eg. MI, CVA)
Intoxication (eg. alcohol, cocaine)
Iatrogenic (eg. corticosteroids, surgical)

Pathogenesis

Diabetic ketoacidosis occurs when there is a near-absolute deficiency in insulin.

Hypovolemia
The lack of insulin driving cellular glucose uptake results in hyperglycemia. Osmotic diuresis causes volume depletion and associated loss of electrolytes. In the most extreme cases, acute kidney injury and hypovolemic shock can occur.

Metabolic acidosis with increased anion gap
Insulin deficiency induces lipolysis as counteracting hormone (lipase) is more active. Free fatty acids from lipolysis become ketones, which includes acetoacetic acid and beta-hydroxybutyric acid (ketosis).

Serum bicarbonate is consume and metabolic acidosis occurs. An elevated anion gap is present due to ketoacids.

Intracellular potassium deficit
Potassium shifts extracellularly to compensate for acidosis.

Hyperosmolality results in the movement of water extracellularly, which further potassium shifts along with. With the absence of insulin, cellular update of potassium ceases too. This results in a total body deficit of potassium despite a normal or even paradoxically elevated serum potassium.

Clinical Presentation

Signs & Symptoms

Findings are consistent with hyperglycemia:

Polyuria
Polydipsia
Recent weight loss
Nausea and vomiting
Signs of dehydration
Neurological abnormalities (AMS, lethargy, coma, blurred vision, weakness)

DKA also presents with:

Rapid onset (<24 hours)
Abdominal pain
Fruity odour on breath
Hyperventilation / Kussmaul breathing (deep, rapid, laboured breathing)

History & Physical Exam

History and physical should be rapidly completed including an ABCDE approach with volume status assessment.

A few components to note include:

Mental status
Possible precipitating events (eg. source of infection, MI)
Volume status

Risk factors

Diagnosis

Criteria

DKA is diagnosed with the triad of:

Hyperglycemia (blood glucose ≥14 mmol/L) and/or history of diabetes
Ketosis (serum beta-hydroxybutyrate ≥3.0 mmol/L and/or ≥2+ on urine strip)
Metabolic acidosis (pH <7.3 and/or bicarbonate <18 mEq/L)

Severity

	Arterial pH	Serum bicarbonate	Serum β-hydroxybutyrate	Mental status
Mild	7.26–7.29	15–18 mEq/L	3.0–6.0 mmol/L	Alert
Moderate	7.0–7.25	10–14 mEq/L	3.0–6.0 mmol/L	Alert or drowsy
Severe	< 7.0	< 10 mEq/L	> 6.0 mmol/L	Stuporous or comatose

Work-up

Initial evaluation consist of laboratory studies:

Serum glucose
Serum electrolytes (calculate anion gap), blood urea nitrogen, plasma creatinine
CBC with differential
Urinalysis and urine ketones by dipstick
Plasma osmolality
Serum beta-hydroxybutyrate

ABG or VBG should be obtained if serum bicarbonate is substantially reduced, with an ABG preferred if hypoxia is suspected. Additionally, an ECG should be obtained.

Differential

Other causes of ketosis include:

Alcoholic ketoacidosis
Stavation ketosis
Low-carb diets

Other causes of anion gap elevated metabolic acidosis is described by the mnemonic CAT-MUDPILES:

Cyanide, carbon monoxide
Alcoholic ketoacidosis
Toluene
Methanol
Uremia
Diabetic ketoacidosis
Phenformin, pyroglutamic acid, paraldehyde, propylene glycol
Iron, isoniazid
Lactic acidosis (eg. due to metformin
Ethanol, ethylene glycol
Salicylates

Red Flags / Complications

Complications include:

Cerebral edema (possible during fluid resuscitation)
Cardiac arrhythmias
Heart failure
Kidney failure
Hypophosphatemia
Mucormycosis (rare, life-threatening fungal infection) - presents like sinusitis

Management

Management of DKA occurs in the emergency room followed by the ICU due to the intensity of monitoring needed.

Fluid replacement

IV normal saline or lactated Ringer should be used. In patients with an initial serum glucose <13.9 mmol/L, dextrose is added to the IV fluids as insulin therapy used may precipitate hypoglycemia otherwise.

In patients with hypovolemic shock, isotonic fluid should be infused as quickly as possible. DKA patients generally present with approximately 6L of deficit.

In patients without shock, heart failure, or kidney failure, isotonic fluid is infused at a rate of 15-20 mL/kg of lean body weight per hour (on average, 1000 mL/hr).

After 2-3 hours of infusion, hypotonic fluid may be used in place of isotonic saline if sodium concentration is ≥135 mEq/L. It should be noted that sodium concentration must be corrected for degree of hyperglycemia (add 2 mEq/L for each 5.5 mmol/L elevation of glucose over 5.5 mmol/L).

For patients with kidney or cardiac function impairment, care must be given to avoid iatrogenic fluid overload. Small-volume boluses may be preferred over continuous infusion.

If major potassium replacement is needed, KCl may be added to the fluid.

Electrolytes correction

The primary electrolyte of concern is potassium. Potassium replacement almost always necessary due to the osmotic diuresis occurring during DKA.

The method of replacement depends on the the initial serum potassium levels.

Initial serum potassium <3.5 mEq/L (low)
Potassium must be corrected to >3.5 mEq/L prior to insulin initiation.

IV potassium chloride at 10-20 mEq/hr (if severe can use up to 30 mEq/hr but requires cardiac monitoring)

Initial serum potassium 3.5-5.0 mEq/L (normal)
Potassium and insulin are started simultaneously.

IV potassium chloride at 10-20 mEq/hr
IV insulin
Maintain potassium concentration at 4-5 mEq/L

Initial serum potassium >5.0 mEq/L (high)
Potassium replacement is not started. Start insulin to shift potassium intracellularly. Potassium can be started once serum levels ≤5.0 mEq/L

Add potassium chloride (10-20 mEq) to each litre of IV fluid

Monitoring
Monitor serum potassium levels q1-2h and adjust plan accordingly to maintain adequate potassium concentration.

Other electrolytes
Bicarbonates and phosphate only administered in severe cases.

Insulin treatment

Moderate to severe DKA
Regular insulin should be given with a fixed-rate continuous infusion of 0.1 units/kg per hour. Rapid-acting insulin analogs are equally effective and choice comes down to institutional and clinician preference.

If infusion is delayed, an IV or IM bolus of regular insulin of 0.1 units/kg should be administered.

When serum glucose is <13.9 mmol/L:

Add 5-10% dextrose to IV fluid
Decrease insulin infusion to 0.05 units/kg per hour

If patient presented with normoglycemic DKA, dextrose can be added immediately with concurrent insulin therapy. Note that if the normoglycemic DKA occurred with SGLT2i use, the SGLT2i should be discontinued.

Glucose should be maintained between 8.3-11.1 mmol/L.

Mild to moderate DKA
Rapid-acting insulin analogs can be given subcutaneously.

Initial bolus of 0.1 units/kg
0.1 units/kg q1h OR 0.2 units/kg q2h