Long Answer Question: Management of Diabetic Ketoacidosis (DKA)

Definition

1. Hyperglycemia (blood glucose >250 mg/dL)
2. Ketosis (urine/serum ketones 2+ or more; serum beta-hydroxybutyrate ≥3 mmol/L)
3. Metabolic acidosis (arterial pH <7.3, serum bicarbonate <18 mEq/L, anion gap >12)

Precipitating Factors ("6 I's")

Pathophysiology (Brief)

• Hyperglycemia - from increased gluconeogenesis, glycogenolysis, decreased peripheral glucose uptake
• Ketogenesis - unrestrained lipolysis releases free fatty acids which are oxidized to acetoacetate, beta-hydroxybutyrate, and acetone in the liver
• Metabolic acidosis - accumulation of ketone bodies (anion gap acidosis)
• Osmotic diuresis - causes dehydration, and loss of Na+, K+, phosphate, Mg2+

Clinical Features

• Polyuria, polydipsia, weakness, nausea, vomiting
• Abdominal pain (can mimic acute abdomen)
• Change in mental status, coma in severe cases

• Dehydration - dry skin, dry mucous membranes, sunken eyes
• Tachycardia, hypotension (orthostatic to frank shock)
• Kussmaul breathing - deep, sighing respirations (compensatory respiratory alkalosis)
• Fruity/acetone breath (acetone)
• Reduced consciousness / Glasgow Coma Score

Diagnostic Criteria (Severity)

Investigations

• Blood glucose (hourly monitoring)
• Serum electrolytes: Na+, K+, Cl-, HCO3-
• ABG (pH, pCO2, HCO3-)
• Blood/urine ketones
• Serum BUN and creatinine
• CBC (WBC elevated - not necessarily infection; reflects acidosis)
• Urinalysis, urine culture
• ECG (for hyperkalemia or hypokalemia), chest X-ray
• Blood cultures if sepsis suspected
• Serum phosphate, magnesium
• Serum osmolality = 2(Na) + glucose/18 + BUN/2.8

MANAGEMENT

"FIFE" - Fluids, Insulin, electrolyte (Electrolyte) replacement, treat underlying Factor (cause)

1. FLUID REPLACEMENT (Most Urgent Step)

• 0.9% Normal Saline (NS) is the initial fluid of choice
• Start with 1 litre over the first hour IV
• Then 500 mL/hour for 2-4 hours
• Then reduce to 250 mL/hour based on clinical status (BP, urine output, CVP)

• 0.45% NS if corrected serum Na+ is high (hypernatremia) or normal
• 5% Dextrose in 0.45% NS when blood glucose falls to 200-250 mg/dL (to prevent hypoglycemia while continuing insulin to clear ketones)

2. INSULIN THERAPY (Central Treatment)

• Never use NPH or long-acting analogues in acute DKA
• Subcutaneous insulin absorption is unreliable in dehydration

• Loading dose (optional in adults): 0.1 U/kg IV bolus
• Infusion: 0.1 U/kg/hour IV continuous infusion
  • Example: 70 kg patient → 7 U/hour
• Expected fall in blood glucose: ~50-75 mg/dL/hour (or ~10% per hour)
• If glucose does not fall by at least 10% in the first hour, double the infusion rate

• Blood glucose target: 150-200 mg/dL (not <150)
• Once blood glucose reaches 200 mg/dL: switch to 5% dextrose + 0.45% NS and reduce insulin infusion to 0.05-0.1 U/kg/hour
• Continue insulin infusion until pH >7.3, HCO3- >18 mEq/L, and anion gap normalises (resolution of ketoacidosis takes longer than normalisation of glucose)

• Do not stop IV insulin abruptly - overlap subcutaneous insulin by 1-2 hours before stopping IV infusion
• Administer a dose of long-acting insulin (e.g., glargine) before discontinuing the infusion
• Switch to basal-bolus subcutaneous regimen once patient is eating

3. POTASSIUM (K+) REPLACEMENT - CRITICAL

• Monitor serum K+ every 2-4 hours throughout treatment
• Adequate urine output must be confirmed before giving K+ (to prevent hyperkalemia)

4. BICARBONATE THERAPY - CONTROVERSIAL / RESTRICTED

• Paradoxical CNS acidosis
• Hypokalemia (bicarb shifts K+ into cells)
• Worsening of intracellular acidosis
• Delayed ketone clearance

• Only if pH < 7.0 (severely acidotic)
• Give 50-100 mEq NaHCO3 in 200 mL of sterile water over 2 hours (not rapid push)
• Repeat until pH >7.0
• Must add 20 mEq KCl to bicarbonate infusion to prevent hypokalemia

5. PHOSPHATE REPLACEMENT

• Routine phosphate replacement is not recommended (no proven clinical benefit)
• Considered if phosphate <1 mg/dL, or if there is cardiac dysfunction, haemolytic anaemia, or respiratory muscle weakness
• Give potassium phosphate 20-30 mEq IV if needed

6. TREATMENT OF PRECIPITATING CAUSE

• Infection: Broad-spectrum antibiotics if infection suspected (do not wait for cultures)
• Acute MI: Standard protocol (ECG, troponin, cardiology consult)
• Medication review: Withhold SGLT2 inhibitors, corticosteroids, thiazides if causative

MONITORING DURING TREATMENT

CRITERIA FOR RESOLUTION OF DKA

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

COMPLICATIONS OF DKA / ITS TREATMENT

SPECIAL SITUATIONS

• Seen with SGLT2 inhibitor use, pregnancy, fasting, alcohol
• Diagnosis often delayed - must check ketones and pH even with near-normal glucose
• Management same as standard DKA

• More dangerous; can precipitate fetal distress
• Occurs at lower glucose levels
• Aggressive fluid and insulin therapy required; obstetric consultation mandatory

• Disconnect the pump; start IV insulin infusion per standard protocol

KEY PHARMACOLOGICAL POINTS (KDT Emphasis)

SUMMARY FLOW CHART

DKA Suspected
     ↓
Confirm: Glucose >250 + Ketones + pH <7.3
     ↓
IV Access + Labs (BMP, ABG, ketones, ECG)
     ↓
Start 0.9% NS - 1L over 1st hour
     ↓
Check K+:
  K+ <3.3 → Give KCl first, then insulin
  K+ ≥3.3 → Start Regular insulin 0.1 U/kg/hr IV
     ↓
Add K+ 20-30 mEq/L to fluids
     ↓
Monitor BG hourly → target fall 50-75 mg/dL/hr
     ↓
BG reaches 200 mg/dL → Add 5% Dextrose, reduce insulin
     ↓
Treat precipitating cause
     ↓
Resolution criteria met → Transition to SC insulin

References:

• Katzung BG. Basic and Clinical Pharmacology, 16th ed. - Diabetic Ketoacidosis, Chapter 41
• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed. - Insulin Treatment of Ketoacidosis (p. 1053)
• Goldman-Cecil Medicine, International Edition - Diabetic Ketoacidosis (Chapter 210)
• KD Tripathi, Essentials of Medical Pharmacology, 8th ed. - Insulin and Oral Hypoglycaemics