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Diabetic Ketoacidosis (DKA)

Definition

1. Hyperglycemia (glucose >250 mg/dL, though may vary) - or a known history of diabetes
2. Ketonemia/Ketonuria - urinary ketones ≥2+ or serum ketones ≥3.0 mmol/L
3. Acidosis - arterial or venous pH <7.3 (serum bicarbonate <18 mEq/L)

• Goldman-Cecil Medicine, p. 2484

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Severity Classification

• Goldman-Cecil Medicine, p. 2484-2485

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Pathophysiology

Central Mechanism

• Decreased peripheral glucose uptake
• Increased glycogenolysis and gluconeogenesis in the liver
• Substrates (amino acids, lactate, pyruvate) delivered from muscle; glycerol and free fatty acids (FFAs) from adipose tissue
• Glucose released into circulation faster than it can be utilized

• Hormone-sensitive lipase is activated by insulin deficiency → massive FFA release
• Long-chain FFAs delivered to the liver → partially oxidized → converted to acetoacetate and β-hydroxybutyrate (and acetone)
• Peripheral ketone utilization is also impaired (similar to starvation response)

• Hyperglycemia surpasses the renal threshold → glucose excreted in urine
• Osmotic diuresis pulls water, Na⁺, K⁺, Mg²⁺, Ca²⁺, PO₄³⁻ into the urine
• Combined with poor intake and vomiting → profound dehydration and electrolyte imbalance
• Hemoconcentration → worsens hyperglycemia (vicious cycle)

• Ketoacids consume bicarbonate buffer → elevated anion gap metabolic acidosis
• Kussmaul breathing (deep, rapid respirations) = respiratory compensation

Note: β-hydroxybutyrate does NOT react with the nitroprusside test (only acetoacetate does), so qualitative ketone tests may underestimate the true degree of ketosis. After treatment begins, β-hydroxybutyrate converts to acetoacetate, which can falsely appear as worsening ketosis.

• Rosen's Emergency Medicine, p. 2542; Goldman-Cecil Medicine, p. 2484

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Average Fluid and Electrolyte Deficits in Severe DKA

• Rosen's Emergency Medicine, Table 115.3

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Precipitating Factors

• Infections (pneumonia, UTI, sepsis) - most frequent trigger
• Inadequate insulin / non-adherence - omitting doses, pump failure
• New-onset type 1 diabetes (~25% of DKA episodes occur in undiagnosed diabetes)
• Acute coronary syndrome

• Cerebrovascular accident, pulmonary embolism, acute pancreatitis
• Endocrinopathies: Cushing syndrome, thyrotoxicosis, acromegaly
• Alcohol intoxication
• Drugs: corticosteroids, SGLT-2 inhibitors, clozapine, olanzapine, cocaine, thiazides, sympathomimetics
• Severe burns, hyperthermia/hypothermia
• Goldman-Cecil Medicine, Table 210-11

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Clinical Features

Symptoms

• Progressive polyuria, polydipsia, polyphagia
• Weakness, lethargy, nausea, vomiting
• Abdominal pain (~50% of patients, especially children - usually idiopathic; in adults, may signify true intra-abdominal pathology)
• Visual blurring, weight loss
• Deterioration over hours to days

Signs

• Kussmaul breathing - deep, rapid respirations (respiratory compensation for acidosis)
• Fruity/acetone odor on breath
• Tachycardia, hypotension (orthostatic or frank)
• Dry skin and mucous membranes, reduced jugular venous pressure (dehydration)
• Depressed mental status - ranges from lethargy to frank coma
• Fever is not caused by DKA itself - suggests underlying infection
• Rosen's Emergency Medicine, p. 2543; Goldman-Cecil Medicine, p. 2483

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Diagnosis

Key Labs

DKA vs HHS - Comparison

• Rosen's Emergency Medicine, Table 115.4

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Treatment

1. Fluid Resuscitation - First Priority

• Initial: 0.9% normal saline (NS), even if serum osmolality is high (NS is still relatively hypotonic compared to the patient)
• Rate: 2-4 liters in the first 2-4 hours in adults; in shock: boluses of 20 mL/kg until systolic >80 mmHg
• When glucose falls to ≤250-300 mg/dL: switch to D5W/0.45% NS to prevent hypoglycemia while continuing insulin to clear ketones
• Recent evidence: Balanced electrolyte solutions (e.g., lactated Ringer's, Plasma-Lyte) may achieve faster DKA resolution than 0.9% NS and reduce hyperchloremic acidosis (PMID: 38925619)

2. Insulin

• Do NOT start insulin until K⁺ ≥3.5 mEq/L (risk of fatal hypokalemia)
• Standard regimen: 0.1 unit/kg/hour regular insulin IV infusion
• No bolus required (or optional 0.1 unit/kg bolus followed by 0.1 unit/kg/hr)
• Target: glucose fall of 50-75 mg/dL/hour
• Continue insulin until anion gap closes and ketosis resolves (not just until glucose normalizes)
• Subcutaneous insulin in mild-moderate DKA: Recent meta-analysis (PMID: 39090718) shows subcutaneous insulin is an effective alternative to continuous IV infusion in adult DKA management

3. Potassium Replacement

4. Phosphate Replacement

• Replace if K⁺ <1.0 mEq/L or cardiac/skeletal muscle dysfunction develops
• Use potassium phosphate 20-30 mEq in fluids

5. Magnesium

• Replace if symptomatic or <1.0 mg/dL: 1-2g MgSO₄ IV

6. Bicarbonate

• Generally not recommended (worsens hypokalemia, paradoxical CNS acidosis, delays ketone clearance)
• Consider only if: pH <6.9, hemodynamic instability despite fluid resuscitation, or severe hyperkalemia with cardiac arrhythmia
• Cerebral edema risk may be increased with aggressive bicarbonate use

7. Treat the Precipitant

• Blood and urine cultures if infection suspected
• ECG (rule out MI as trigger)
• Broad-spectrum antibiotics if infection confirmed

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Complications of DKA and Its Treatment

• Bradley and Daroff's Neurology, p. 2144-2147; Goldman-Cecil Medicine, p. 2485

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Monitoring During Treatment

• Vital signs, urine output: every 1 hour
• Serum glucose: every 1 hour
• Serum K⁺, HCO₃⁻, anion gap: every 2-4 hours
• Venous pH: every 2-4 hours
• Ketones: every 2-4 hours (bedside capillary ketone monitors preferred)
• Continuous cardiac monitoring

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Resolution Criteria ("DKA Cleared")

• Glucose <250 mg/dL
• Serum bicarbonate ≥18 mEq/L
• Venous pH >7.3
• Anion gap ≤12 (most reliable endpoint for ketone clearance)

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Disposition

• Mild DKA: May be treated in observation/ED; discharge possible if pH ≥7.35, HCO₃⁻ ≥20, tolerating oral fluids, reliable follow-up
• Moderate-severe DKA: Admit to hospital or ICU
• Pregnant patients: Always admit; requires endocrinology + obstetrics consultation
• ICU criteria: pH <7.0, altered mental status, hemodynamic instability, requiring intensive monitoring

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Prevention

• Diabetes education and "sick-day rules":
  • Never omit insulin during illness (often need MORE insulin)
  • Frequent blood glucose monitoring
  • Check ketones when glucose >250 or when unwell
  • Small, frequent carbohydrate-containing fluids
  • Early contact with healthcare provider
• Hospital admission is an opportunity for education and addressing adherence barriers

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Prognosis

• Overall mortality: ~4% for DKA (up to 20% for HHS)
• Mortality is higher at extremes of age, with severe comorbidities, and with severe precipitating illness
• Cerebral edema (rare, mostly children): mortality 20-90%
• Goldman-Cecil Medicine, p. 2485

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Recent Evidence Updates (2024-2025)

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