Diabetic Ketoacidosis (DKA)

Definition

1. Hyperglycemia - glucose >250 mg/dL (or known diabetes)
2. Ketonemia/ketonuria - urine ketones 2+ or serum ketones ≥3.0 mmol/L
3. Acidosis - arterial or venous pH <7.3 and/or serum bicarbonate <15 mmol/L

• Goldman-Cecil Medicine, p. 2483

Pathophysiology

1. Glycogenolysis + Gluconeogenesis
   • Muscle releases amino acids, lactate, and pyruvate to the liver
   • Liver converts them to glucose → hyperglycemia
2. Lipolysis and Ketogenesis
   • Insulin deficiency activates hormone-sensitive lipase in adipose tissue
   • Free fatty acids (FFAs) flood the circulation
   • Liver partially oxidizes long-chain FFAs → acetoacetate, β-hydroxybutyrate, and acetone (ketone bodies)
   • Peripheral tissues also reduce ketone utilization (as in starvation)
3. Osmotic Diuresis
   • Hyperglycemia exceeds the renal threshold → glycosuria
   • Glucose in renal tubules draws water, Na⁺, K⁺, Mg²⁺, Ca²⁺, phosphorus into urine
   • Profound dehydration, electrolyte depletion, hemoconcentration → further worsens hyperglycemia and hyperosmolality

• Rosen's Emergency Medicine, p. 2542

Precipitants

• Infections (most frequent single precipitant)
• Inadequate insulin or non-adherence
• New-onset type 1 diabetes (~25% of DKA episodes are the first presentation)
• Acute coronary syndrome

Note: SGLT-2 inhibitors can cause euglycemic DKA - glucose may be normal or only mildly elevated.

• Goldman-Cecil Medicine, p. 2484

Clinical Features

• Polyuria, polydipsia, polyphagia
• Nausea, vomiting, anorexia
• Weakness, lethargy
• Abdominal pain - present in ~50% of patients; in children usually idiopathic (gastric distension or liver capsule stretch, resolves with treatment); in adults more often signals a true abdominal precipitant

• Kussmaul breathing - deep, rapid respirations (respiratory compensation for metabolic acidosis)
• Fruity/acetone odor on breath (from acetone)
• Dry skin and mucous membranes
• Tachycardia, orthostatic hypotension or frank hypotension
• Depressed mental status to frank coma (correlates with degree of hyperosmolality and acidosis)
• Temperature is usually normal or low - fever suggests underlying infection

Diagnosis

Severity Classification (ADA Criteria for Adults)

• Goldman-Cecil Medicine, p. 2484

Key Lab Findings

• Water: 70-120 mL/kg
• Sodium: 8-10 mEq/L/kg
• Potassium: 5-7 mEq/L/kg
• Rosen's Emergency Medicine, Table 115.3

Differential Diagnosis

• Alcoholic ketoacidosis (often euglycemic or hypoglycemic; alkalemia more common; β-hydroxybutyrate is the dominant ketone)
• Starvation ketosis (mild, rarely acidotic)
• Lactic acidosis (sepsis, hypoperfusion)
• Toxic ingestions (methanol, ethylene glycol, salicylates)
• Hyperosmolar hyperglycemic state (HHS) - glucose usually >700 mg/dL, bicarbonate >15, no significant ketosis, more common in elderly type 2 diabetics

Treatment

1. IV Fluids (Most Important Initial Step)

• Hypovolemic shock: Give isotonic crystalloid (0.9% NaCl) as rapidly as possible in adults; in children, 20 mL/kg boluses until systolic BP ≥80 mmHg
• Stable/moderate dehydration: 0.9% NaCl at 1 L/hour initially; switch to 0.45% NaCl once hemodynamically stable
• When glucose drops to ≤300 mg/dL: Switch to D5W/0.45% NaCl (add dextrose) to allow continued insulin infusion without causing hypoglycemia
• Once glucose <250 mg/dL: Add 10% dextrose to the fluid regimen

2. Insulin

• Start at 0.1 units/kg/hour regular insulin IV infusion as soon as DKA is confirmed
• Do NOT start insulin until potassium is ≥3.5 mEq/L (risk of fatal hypokalemia)
• Once glucose <250 mg/dL AND ketones <1.0 mmol/L, reduce to 0.05 units/kg/hour
• If the patient was already on long-acting subcutaneous insulin, continue that dose alongside IV insulin
• Transition to subcutaneous insulin when the patient can eat; allow a 1-2 hour overlap between subcutaneous dose and IV insulin discontinuation to prevent rebound ketosis

3. Potassium Replacement

• K⁺ 3.5-5.5 mEq/L: Add 20-40 mEq KCl to each liter of IV fluid
• K⁺ <3.5 mEq/L: Hold insulin until K⁺ repleted; give KCl aggressively first
• K⁺ >5.5 mEq/L: Hold potassium replacement but monitor closely

4. Bicarbonate

• Not routinely recommended - risks paradoxical CNS acidosis and may worsen outcome
• Consider only if pH <7.0 AND patient not responding to IV fluids and insulin

5. Phosphate and Magnesium

• Measure and monitor both
• IV phosphate replacement only if phosphate <1.0 mg/dL with profound muscle weakness or respiratory failure
• Magnesium: correct with 1-2 g MgSO₄ if deficient

6. Identify and Treat the Precipitant

7. Airway / ICU

• Avoid intubation if possible - patients have a strong respiratory drive and matching ventilator to Kussmaul breathing is challenging
• Intubate comatose patients, especially if vomiting
• Admit to ICU for severe DKA (pH <7.0, altered sensorium, hemodynamic instability)

Monitoring During Treatment

• Blood glucose, K⁺, HCO₃⁻, pH, anion gap
• Fluid intake and urine output
• Vital signs and mental status
• Amount of insulin administered

• Blood glucose <200 mg/dL
• Serum bicarbonate ≥15 mmol/L
• Venous pH >7.3
• Anion gap ≤12

Complications of DKA Itself and Its Treatment

• Cerebral edema - most common fatal complication, especially in children; caused by too-rapid osmotic shifts during fluid/glucose correction
• Hypokalemia - from insulin therapy and fluid resuscitation
• Hypoglycemia - from inadequate glucose supplementation as insulin continues
• Hyperchloremic metabolic acidosis - from large volumes of normal saline
• Aspiration - from ileus/vomiting + depressed consciousness

Recent Evidence Update

• A 2024 systematic review (PMID 39090718) comparing subcutaneous vs IV insulin in DKA management found subcutaneous protocols to be a viable alternative in mild-moderate DKA, which may expand outpatient-adjacent management options.
• A 2026 meta-analysis (PMID 41208563) on early subcutaneous basal insulin co-administered with IV insulin infusion found it reduced DKA recurrence/rebound ketosis after IV insulin discontinuation.

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