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Diabetic Ketoacidosis (DKA)

Definition

1. Hyperglycemia (or a history of diabetes) — glucose typically 250–1000+ mg/dL
2. Ketonuria/ketonemia — urine ketones ≥2+ or serum β-hydroxybutyrate ≥3.0 mmol/L
3. Metabolic acidosis — arterial or venous pH <7.3, serum bicarbonate <18 mmol/L

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Pathophysiology

1. Hyperglycemia

• Insulin deficiency → impaired peripheral glucose uptake + increased hepatic gluconeogenesis
• Counter-regulatory hormones deliver substrates to the liver: amino acids/lactate/pyruvate from muscle; free fatty acids (FFAs) and glycerol from adipose tissue
• Glucose released into circulation faster than it is utilized

2. Ketogenesis

• Insulin deficiency activates hormone-sensitive lipase → elevated circulating FFAs
• Long-chain FFAs undergo incomplete β-oxidation in the liver → acetoacetate, β-hydroxybutyrate, and acetone
• These ketone bodies accumulate → anion-gap metabolic acidosis

3. Osmotic diuresis and electrolyte depletion

• Hyperglycemia exceeds renal threshold → glucose enters the tubules, dragging water, Na⁺, K⁺, Mg²⁺, Ca²⁺, PO₄³⁻, and Cl⁻ into the urine
• Combined with vomiting and poor intake → profound dehydration and electrolyte deficits
• Hemoconcentration → worsens hyperglycemia and hyperosmolality in a vicious cycle

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Precipitating Factors

• Infections (pneumonia, UTI, sepsis)
• Inadequate insulin therapy / nonadherence
• New-onset type 1 diabetes
• Acute coronary syndrome

• Cerebrovascular accident, pulmonary embolism, acute pancreatitis
• Endocrinopathies: Cushing syndrome, thyrotoxicosis, acromegaly
• Drugs: corticosteroids, SGLT-2 inhibitors (euglycemic DKA), clozapine, olanzapine, cocaine, sympathomimetics, thiazide diuretics, lithium
• Severe burns, hyperthermia/hypothermia, alcohol intoxication

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Clinical Features

• Polyuria, polydipsia, polyphagia, weight loss
• Weakness, lethargy, nausea, vomiting
• Nonspecific upper abdominal pain (can mimic acute abdomen)
• Reduced GI motility / paralytic ileus

• Dry skin and mucous membranes
• Tachycardia, orthostatic or frank hypotension
• Kussmaul breathing — deep, rapid respirations (respiratory compensation for acidosis)
• Fruity breath (acetone)
• Altered mental status to frank coma (correlates with degree of hyperosmolality)
• Reduced jugular venous pressure (volume depletion)

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Diagnosis

Diagnostic Criteria

Key Lab Findings

• Elevated glucose: 250 mg/dL to >1000 mg/dL
• Anion-gap metabolic acidosis: anion gap generally proportional to the drop in bicarbonate
• Serum ketones: β-hydroxybutyrate is the predominant ketone (nitroprusside-based dipstick tests detect acetoacetate only — can underestimate severity)
• Serum Na⁺: typically low (pseudohyponatremia from osmotic shift); corrected Na⁺ = measured Na⁺ + 1.6 mEq/L per 100 mg/dL glucose above 100
• Serum K⁺: may appear normal or elevated on presentation despite total-body depletion (acidosis shifts K⁺ extracellularly; this reverses rapidly with treatment)
• Elevated WBC: can be elevated from acidosis alone — does not necessarily indicate infection
• Elevated amylase: usually of non-pancreatic origin; can lead to erroneous diagnosis of pancreatitis
• Elevated BUN/Cr: prerenal azotemia from dehydration
• Elevated Hct/Hgb: hemoconcentration

Note: In 95% of patients with DKA, total serum sodium is normal or low. — Rosen's Emergency Medicine, p. 2543

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Management

1. Fluids

• Initial bolus: 1–2 L (10–20 mL/kg in children) of isotonic saline (0.9% NaCl) over the first 1–2 hours to restore perfusion
• Ongoing replacement: Once hemodynamically stable, transition to 0.45% NaCl at 250–500 mL/hr; adjust based on corrected Na⁺
• When glucose falls to ~200 mg/dL: add dextrose 5% to IV fluids to allow continued insulin infusion without hypoglycemia

2. Insulin

• Do not start insulin until K⁺ ≥3.5 mEq/L (insulin drives K⁺ intracellularly → risk of fatal hypokalemia)
• Regular insulin infusion: 0.1 unit/kg/hr IV (preceded by an optional 0.1 unit/kg IV bolus)
• Target glucose decline: 50–75 mg/dL/hr
• Continue infusion until anion gap closes and pH >7.3, then transition to subcutaneous insulin (overlap IV/SC by 1–2 hours)

3. Potassium

• Despite apparent hyperkalemia on presentation, total-body K⁺ is depleted
• Replace aggressively:
  • K⁺ <3.5: hold insulin, replace K⁺ at 40 mEq/hr until ≥3.5, then start insulin
  • K⁺ 3.5–5.0: add 20–40 mEq K⁺ per liter of IV fluid
  • K⁺ >5.0: hold replacement, check every 2 hours
• Most patients require 20–40 mEq/hr for several hours

4. Bicarbonate

• Generally NOT recommended for pH >6.9 (no proven benefit; risks include paradoxical CNS acidosis, hypokalemia, delayed ketone clearance)
• May be considered if pH <6.9 or life-threatening hyperkalemia: 100 mEq NaHCO₃ in 400 mL sterile water + 20 mEq KCl over 2 hours

5. Phosphate

• Routine replacement not recommended (no clinical outcome benefit demonstrated)
• Consider if PO₄³⁻ <1 mg/dL, severe symptomatic hypophosphatemia, or cardiac dysfunction

6. Monitoring

• Blood glucose hourly
• Electrolytes (Na⁺, K⁺, HCO₃⁻, anion gap) every 2–4 hours
• Venous pH every 2–4 hours
• Urine output

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Resolution Criteria

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

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Complications

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DKA vs. HHS (Key Differences)