Diabetic Ketoacidosis (DKA) - Management

Definition and Diagnostic Criteria

• Mild: pH 7.25-7.30, HCO3 15-18 mEq/L
• Moderate: pH 7.00-7.24, HCO3 10-14 mEq/L
• Severe: pH <7.00, HCO3 <10 mEq/L

Pathophysiology

1. Hyperglycemia: Reduced glucose uptake + increased gluconeogenesis and glycogenolysis → glucose spills into urine → osmotic diuresis
2. Ketogenesis: Hormone-sensitive lipase activates → free fatty acids flood the liver → β-hydroxybutyrate and acetoacetate produced → anion gap metabolic acidosis
3. Dehydration and electrolyte loss: Osmotic diuresis drags water, Na⁺, K⁺, Mg²⁺, PO₄³⁻ into the urine

• Water: 70-120 mL/kg
• Sodium: 8-10 mEq/L
• Potassium: 5-7 mEq/L
• Phosphorus: ~3 mEq/L

Note: Serum K⁺ is often normal or HIGH on presentation due to acidosis (H⁺/K⁺ exchange). Total body potassium is always depleted. K⁺ drops rapidly once insulin is started.

Common Precipitants

• Infection (most frequent trigger)
• Inadequate insulin / non-adherence
• New-onset type 1 diabetes
• Acute coronary syndrome

• Stroke, PE, pancreatitis, mesenteric ischemia
• Alcohol intoxication
• Drugs: corticosteroids, SGLT-2 inhibitors, clozapine, olanzapine, cocaine, sympathomimetics
• Endocrinopathies: Cushing's, thyrotoxicosis, acromegaly
• Severe burns, hyperthermia/hypothermia

Clinical Features

• Polyuria, polydipsia, nausea, vomiting, abdominal pain (can mimic acute abdomen)
• Weakness, lethargy, altered consciousness (coma in severe cases)
• Kussmaul breathing - deep, rapid respirations (respiratory compensation for acidosis)
• Fruity/acetone breath
• Signs of dehydration: dry mucous membranes, reduced JVP, tachycardia, orthostatic hypotension
• Mental status correlates with degree of hyperosmolality

Management Overview: The Four Pillars

1. FLUIDS

• Adult fluid deficit is typically 3-5 L (up to 10 L in severe cases)
• Hypovolemic shock: Isotonic crystalloid (0.9% NaCl) as fast as possible; boluses of 20 mL/kg in children until systolic BP >80 mmHg
• Marked dehydration without shock: 1 L in first hour; 2-4 L over first 2-4 hours total with 0.9% NaCl
• After initial resuscitation: switch to 0.45% NaCl (hypotonic) if corrected Na is normal or elevated
• When BG drops to ~200-250 mg/dL: add dextrose 5% to IV fluids to allow continued insulin without causing hypoglycemia
• Balanced crystalloids (e.g., Plasmalyte) may restore physiologic parameters more rapidly and avoid hyperchloremic acidosis from large NS volumes
• Target urine output: 1-2 mL/kg/h

Avoid intubation if possible - patients often have extreme respiratory drive (Kussmaul breathing) that is difficult to replicate mechanically.

2. INSULIN

• Do NOT start insulin until potassium is ≥3.5 mEq/L - insulin drives K⁺ into cells and can precipitate fatal hypokalemia
• Regular insulin IV infusion: 0.1 units/kg/h (standard rate)
  • Low-dose protocol: 0.05-0.1 units/kg/h works equally well in mild-moderate DKA
  • Optional bolus: 0.1 units/kg IV bolus before starting infusion (debated)
• Target glucose reduction: 50-75 mg/dL per hour; if falling >100 mg/dL/h, reduce insulin rate
• Subcutaneous insulin is an acceptable alternative to IV infusion in mild-moderate DKA (meta-analysis PMID 39090718 confirms non-inferior outcomes with SQ insulin vs. continuous IV infusion)
• Continue insulin drip until DKA resolves, then transition to subcutaneous insulin with at least 1-2 hour overlap before stopping the drip

3. POTASSIUM REPLACEMENT

• Expect serum K⁺ to fall by 0.5-1.0 mEq/L for every 0.1 unit rise in pH
• Continuous cardiac monitoring is mandatory (hypokalemia causes fatal arrhythmias)

4. OTHER ELECTROLYTES

• Routine replacement is NOT recommended
• Considered if serum PO₄ <1.0 mg/dL, cardiac dysfunction, hemolytic anemia, or respiratory depression
• Excessive phosphate replacement risks hypocalcemia

• Controversial - generally NOT recommended for pH >6.9
• If pH <6.9: consider 100 mEq NaHCO₃ over 2 hours with potassium supplementation
• Risks: paradoxical CSF acidosis, delayed ketone clearance, hypokalemia, cerebral edema
• The 2024 ADA Consensus Report updated criteria caution against routine bicarbonate use

Monitoring During Treatment

• Blood glucose (hourly)
• Serum electrolytes (Na⁺, K⁺, Cl⁻, HCO₃⁻)
• Venous blood gas / pH
• Urine output

• BUN, creatinine
• Phosphate, magnesium

Ketone monitoring caveat: Standard nitroprusside-based urine/serum ketone tests measure acetoacetate only - NOT β-hydroxybutyrate (the dominant ketone in DKA). Tests may appear falsely worsening as insulin converts β-OHB back to acetoacetate. Point-of-care capillary β-hydroxybutyrate meters are the preferred monitoring tool where available.

Resolution Criteria (DKA)

1. Blood glucose <200-250 mg/dL
2. Serum bicarbonate ≥15 mEq/L
3. Venous pH ≥7.3
4. Anion gap closed (≤12 mEq/L)

Transition to Subcutaneous Insulin

• Once DKA resolves and patient tolerates oral intake:
• Give the first dose of SQ long-acting insulin (e.g., glargine)
• Overlap the IV insulin for 1-2 hours after starting SQ to prevent rebound ketoacidosis
• Patients with known diabetes: resume their usual insulin regimen + address the precipitant
• New-onset T1DM: calculate total daily dose and divide into basal-bolus regimen

Complications to Monitor For

Special Considerations

• BG may be only mildly elevated (180-250 mg/dL) - can be missed
• Mechanism: SGLT-2 inhibitors increase glucagon and reduce insulin secretion, promoting ketogenesis independent of glucose level
• Hold SGLT-2 inhibitors; management otherwise the same

• DKA can occur at lower glucose levels (even ~200 mg/dL)
• Higher risk of fetal loss; aggressive management required
• Maternal/fetal monitoring in ICU setting

• Cerebral edema is the main feared complication - avoid rapid drops in osmolality
• Slower fluid repletion recommended (do not give >10-20 mL/kg boluses routinely)
• Outpatient management possible in very mild cases (pH ≥7.35, HCO₃ ≥20) with reliable caregiver

Recent Evidence (2024-2025)

• A 2024 meta-analysis (PMID 39090718) confirmed subcutaneous insulin is non-inferior to IV insulin infusion for mild-moderate DKA, with similar time to resolution and comparable safety - supporting subcutaneous protocols in appropriate patients
• The 2024 ADA Consensus Report (reviewed in Cleveland Clinic J Med 2025) introduced revised diagnostic and resolution criteria and updated management recommendations for both DKA and HHS