Management of Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS)

Comparison at a Glance

Common Precipitants (Both DKA and HHS)

• Infections (most frequent)
• Inadequate insulin/non-adherence
• New-onset diabetes
• Acute coronary syndrome
• Unknown cause

Pathophysiology

DKA

1. Hepatic glucose production (glycogenolysis + gluconeogenesis) and impaired peripheral uptake -> hyperglycemia
2. Lipolysis -> elevated free fatty acids -> hepatic ketogenesis -> β-hydroxybutyrate + acetoacetate -> anion-gap metabolic acidosis
3. Osmotic diuresis -> dehydration, electrolyte loss (Na, K, Mg, PO4)
4. Cells starved of glucose despite hyperglycemia -> proteolysis, amino acid release

HHS

• Enough insulin to suppress ketogenesis - no significant ketonaemia
• Higher portal vein insulin concentrations than in DKA
• Sustained hyperglycemic osmotic diuresis over days/weeks
• Patient cannot compensate fluid loss (elderly, dementia, debilitation, prior stroke)
• Hemoconcentration -> decreased GFR -> further glucose retention
• Result: extreme hyperglycemia, profound dehydration, hyperosmolality without significant acidosis

Diagnostic Criteria

DKA (all three required - the "D-K-A" triad)

HHS

• Blood glucose >600 mg/dL
• Serum osmolality >320 mOsm/L (calculated: 2[Na] + glucose/18 + BUN/2.8)
• pH >7.3 and/or bicarbonate >18 mmol/L
• Absent or mild ketonuria (starvation ketosis only)
• Prerenal azotemia prominent
• Corrected sodium: add 1.6 mEq for each 100 mg/dL rise in glucose above normal

Management

1. Initial Assessment & Monitoring

• IV access x2, continuous cardiac monitoring
• Bloods: glucose (hourly), electrolytes, VBG/ABG (1-2 hourly initially), ketones, renal function, FBC, culture, lipase, troponin if ACS suspected
• Urine output monitoring (catheter if needed)
• ECG (hypo/hyperkalaemia changes; rule out MI as precipitant)
• Admit to HDU/ICU for moderate-severe DKA, all HHS

2. Fluid Resuscitation

• 0.9% NaCl: 2-4 L in first 2-4 hours
• After haemodynamic stabilisation, switch to 0.45% NaCl if Na >150 mmol/L or osmolality not correcting
• Once blood glucose drops to 250 mg/dL (13.9 mmol/L), add dextrose 5% or 10% to IV fluids to prevent hypoglycaemia while continuing insulin to clear ketones
• Total deficit typically 5-8 L - replace over 24-48 hours

• More profound dehydration (8-12+ L deficit) accumulated over days-weeks
• Start with 0.9% NaCl: 1-3 L over first 2-3 hours for haemodynamic stabilisation
• Do NOT correct hyperosmolality too rapidly - risk of cerebral oedema. Target osmolality reduction of ~3-8 mOsm/kg/hour
• If Na >150 mmol/L, switch to 0.45% NaCl after volume restored
• Serum Na may paradoxically rise as glucose falls (expected) - focus on total osmolality trending down, not Na alone
• Add dextrose to fluids when glucose drops below 300 mg/dL
• Monitor for volume overload in elderly (CHF, renal disease common)

3. Potassium Replacement

• Total body potassium is always depleted in both DKA and HHS, even if serum K appears normal or high (acidosis and insulin deficiency shift K+ extracellularly)
• Insulin will rapidly shift K+ into cells - without replacement, life-threatening hypokalaemia can develop
• In HHS, because acidosis is minimal, initial K+ readings more accurately reflect body stores than in DKA
• Target serum K+ 4.0-5.0 mEq/L throughout treatment

4. Insulin Therapy

• Start only after K+ >3.5 mEq/L is confirmed (or being repleted)
• Fixed-rate IV insulin infusion: 0.05-0.1 units/kg/hour (0.1 units/kg/hr standard starting dose)
• Some protocols use an optional 0.1 units/kg IV bolus first
• Goal: glucose fall of 50-75 mg/dL/hour
• When glucose reaches 250 mg/dL, reduce insulin to 0.05 units/kg/hour and add dextrose to IV fluids - do NOT stop insulin; must continue until ketones clear
• Continue until: ketones <1.0 mmol/L (or anion gap normalized), pH >7.3, bicarbonate >18 mEq/L
• Transition to SC insulin: overlap by 30-60 minutes before stopping infusion; restart home insulin or initiate new regimen at meal time

• IV fluids alone will lower glucose initially (increased glycosuria) - insulin is not the first-line treatment
• Start insulin (0.05 units/kg/hr IV) only when glucose stops falling on fluids alone
• Lower doses needed than in DKA (relative, not absolute insulin deficiency)
• If patient was on background long-acting SC insulin, continue it throughout
• No strict ketone clearance target (minimal ketonaemia) - titrate to glucose
• Transition to SC insulin when patient is eating, clinically stable, and glucose controlled

5. Other Electrolytes

• Routine replacement is NOT recommended in mild-moderate DKA (no proven benefit, risks hypocalcaemia)
• Replace if: severe hypophosphataemia (<1.0 mg/dL), haemolytic anaemia, respiratory depression, or cardiac dysfunction

• Replace if severely depleted, especially with refractory hypokalaemia

• Measured Na is artifactually low due to hyperglycaemia (osmotic dilution)
• Corrected Na = measured Na + 1.6 mEq per 100 mg/dL glucose rise above 100 mg/dL
• Use corrected Na to guide fluid choice

6. Bicarbonate

• NOT routinely recommended in DKA, even with severe acidosis
• May be considered if pH <6.9, or if severe hyperkalaemia is causing cardiac arrhythmias
• Risk: paradoxical CSF acidosis, worsening hypokalaemia, altered oxyhemoglobin dissociation
• No role in HHS (acidosis is not a major feature)

7. Treat the Precipitant

• Antibiotics if infection is identified (most common precipitant)
• ACS protocol if MI is precipitant
• DVT/PE prophylaxis: Low-molecular-weight heparin indicated, particularly in HHS where arterial and venous thromboses are common and frequently complicate the picture
• SGLT-2 inhibitors should be stopped in acute illness

8. Resolution Criteria

1. pH >7.3
2. Serum bicarbonate >18 mEq/L
3. Serum ketones <1.0 mmol/L (or anion gap closed)
4. Blood glucose <200-250 mg/dL (not a hard criterion alone)

1. Serum osmolality <315 mOsm/L (trending toward normal)
2. Normal mental status
3. Blood glucose consistently <300 mg/dL
4. Patient able to eat and drink

9. Special Situations

• Glucose may be <200 mg/dL despite significant ketoacidosis
• High index of suspicion needed; check ketones in any sick patient on SGLT-2i
• Management same as standard DKA but require dextrose infusion from the outset

• Can occur at lower glucose levels (<200 mg/dL in some cases)
• More rapid progression, fetal compromise possible at maternal pH <7.2
• Aggressive fluid replacement and insulin; fetal monitoring essential

• Risk factors: rapid fluid shifts, excessive free water, young age, initial low pCO2, high BUN
• Warning signs: headache, slowing heart rate, BP rise, decreased consciousness during treatment
• Treatment: mannitol 0.5-1 g/kg IV or hypertonic saline; reduce fluid rate

Summary: Key Management Priorities

• Fluids (0.9% NaCl, brisk)
• Insulin (0.1 units/kg/hr, only after K+ corrected)
• Search for and treat the precipitant
• Hypokalaemia prevention (K+ before insulin)
• Ketone clearance as the end-point (not just glucose)

• Fluids first and foremost (large volumes, gradual)
• Look for and treat the precipitating illness
• Osmolality guided correction (avoid rapid reversal)
• Watch for thrombosis, monitor comorbidities

• Goldman-Cecil Medicine, 26th Ed., Chapter 210 (Diabetes Mellitus)
• Rosen's Emergency Medicine, 9th Ed., Chapter 115 (DKA & HHS)
• Harrison's Principles of Internal Medicine, 22nd Ed. (2025), Chapter 416
• ADA consensus on hyperglycaemic crises (foundational guidelines)