How to manage Hyperosmolar Hyperglycemic State (HHS) in an elderly patient with a urinary tract infection?

Management of Hyperosmolar Hyperglycemic State (HHS)

Aggressive fluid resuscitation with 0.9% sodium chloride is the cornerstone of HHS management and must be initiated immediately, with insulin withheld until blood glucose stops falling with fluids alone unless significant ketonaemia is present. 1, 2, 3

Initial Assessment and Diagnostic Criteria

HHS is diagnosed when all of the following are present 1, 2:

• Plasma glucose ≥600 mg/dL (≥30 mmol/L)
• Effective serum osmolality ≥320 mOsm/kg (calculated as: 2×[Na+] + glucose/18)
• Arterial pH >7.30
• Serum bicarbonate ≥15 mEq/L
• Small or absent ketones (serum ketones ≤3.0 mmol/L)
• Altered mental status (stupor/coma is typical)

Critical Initial Workup

Obtain immediately 1:

• Arterial blood gases
• Complete blood count with differential
• Comprehensive metabolic panel (electrolytes, BUN, creatinine, glucose)
• Serum osmolality (measured or calculated)
• Urinalysis with ketones
• Electrocardiogram
• Blood cultures, urine cultures, and chest X-ray if infection suspected

In elderly patients with UTI as the precipitant, obtain urine culture before starting antibiotics but do not delay empiric antibiotic therapy. 4 Start IV ceftriaxone as first-line therapy for complicated UTI in this population. 4

Phase 1: Initial Resuscitation (0-60 minutes)

Fluid Therapy - First Priority

Administer 0.9% sodium chloride at 15-20 mL/kg/hour (1-1.5 L in average adult) during the first hour. 1, 2 This equates to approximately 1000-1500 mL in the first hour for most patients. 1

Total body deficits in HHS are massive 1:

• Water: 9 liters (100 mL/kg)
• Sodium: 5-15 mEq/kg
• Potassium: 4-6 mEq/kg
• Phosphate: 3-7 mmol/kg

Critical Pitfall: Insulin Timing

Do NOT start insulin immediately—this is a key difference from DKA management. 2, 3 Fluid replacement alone will cause blood glucose to fall. 3 Early insulin use before adequate fluid resuscitation may be detrimental and can precipitate vascular collapse. 3

Withhold insulin until blood glucose stops falling with IV fluids alone, unless significant ketonaemia (>3.0 mmol/L) is present. 2, 3

Phase 2: Hours 1-6

Continued Fluid Resuscitation

After initial bolus, continue 0.9% sodium chloride at rates adjusted to clinical response 1, 2:

• Target: Replace 50% of estimated fluid deficit in first 12-24 hours
• Monitor vital signs, urine output (goal ≥0.5 mL/kg/hour), and mental status hourly 2
• An initial rise in sodium is expected and normal—do not switch to hypotonic fluids based on rising sodium alone 3

Osmolality Monitoring - Critical Safety Parameter

Measure or calculate serum osmolality every 1-2 hours initially. 2, 3

Target osmolality reduction: 3-8 mOsm/kg/hour. 2, 3 Faster correction risks osmotic demyelination syndrome (central pontine myelinolysis), which can be fatal. 3

Insulin Initiation (When Appropriate)

Once blood glucose plateaus or stops falling with fluids alone 2, 3:

• Give 10-15 units regular insulin IV bolus
• Start fixed-rate IV insulin infusion (FRIII) at 0.1 units/kg/hour 1, 5
• If significant ketonaemia present (>3.0 mmol/L), start insulin simultaneously with fluids 2

Potassium Replacement - Essential

Potassium deficits are substantial (4-6 mEq/kg) even if initial serum potassium appears normal. 1

Potassium replacement protocol 1:

• **If K+ <3.3 mEq/L:** Hold insulin, give 40 mEq/hour potassium until K+ >3.3 mEq/L
• If K+ 3.3-5.0 mEq/L: Add 20-30 mEq potassium to each liter of IV fluid
• If K+ >5.0 mEq/L: Do not give potassium; recheck every 2 hours

Phase 3: Hours 6-12

Glucose Management

When blood glucose falls to <14 mmol/L (<250 mg/dL), add 5% or 10% dextrose to IV fluids. 2

Target blood glucose: 10-15 mmol/L (180-270 mg/dL) in first 24 hours. 2 Do not aim for normoglycemia rapidly.

Reduce insulin infusion rate once glucose approaches target range. 1

Fluid Type Adjustment

Consider switching to 0.45% sodium chloride if 1:

• Corrected sodium is elevated (>150 mEq/L) AND
• Hemodynamic stability achieved AND
• Osmolality declining appropriately

Phase 4: Hours 12-24

Monitoring Frequency

Continue monitoring 2:

• Blood glucose: Every 1-2 hours
• Electrolytes: Every 2-4 hours
• Osmolality: Every 4-6 hours
• Vital signs and neurological status: Hourly

Treatment of Precipitating Cause

In elderly patients with UTI 4:

• Continue IV ceftriaxone or adjust based on culture results
• Consider changing urinary catheter if present before starting antibiotics
• Evaluate for urological obstruction or incomplete bladder emptying

Other common precipitants in elderly patients to address 6, 5:

• Myocardial infarction
• Stroke
• Pneumonia
• Gastrointestinal hemorrhage
• Medications (thiazides, steroids, phenytoin)

Phase 5: Hours 24-72

Resolution Criteria

HHS is resolved when ALL of the following are met 2:

• Osmolality <300 mOsm/kg
• Hypovolemia corrected (urine output ≥0.5 mL/kg/hour)
• Mental status returned to baseline
• Blood glucose <15 mmol/L (<270 mg/dL)

Transition to Subcutaneous Insulin

Once resolution criteria met and patient able to eat 1:

• Give subcutaneous basal insulin
• Continue IV insulin for 1-2 hours after first subcutaneous dose
• Many elderly patients with HHS will not require long-term insulin and can be managed with oral agents after recovery 5

Special Considerations for Elderly Patients

Age-Related Vulnerabilities

Elderly patients have significantly higher mortality from HHS (mortality 10-47% in this population). 6, 5 Age is the single best prognostic indicator. 6

Elderly-specific risk factors 1, 6:

• Reduced glomerular filtration rate limits glucose excretion
• Elevated renal threshold for glucose
• Impaired thirst mechanisms
• Inability to access fluids independently (nursing home residents)
• Polypharmacy (diuretics, steroids, beta-blockers)

Fluid Management Caution

Exercise extreme caution with aggressive fluid resuscitation in elderly patients with 6:

• Congestive heart failure: Risk of fluid overload
• Acute stroke: Risk of cerebral edema
• Renal impairment: Reduced ability to handle fluid loads

These comorbidities are frequent causes of death in elderly HHS patients. 6 Consider central venous pressure monitoring or reduced fluid rates (10 mL/kg/hour) in these high-risk patients. 6

Hypoglycemia Prevention

Elderly patients are at extremely high risk for severe hypoglycemia during and after HHS treatment. 7, 8

Fatal neuroglycopenic brain injury can occur within 2 hours of hypoglycemia onset. 7 Elderly patients often fail to perceive hypoglycemic symptoms, delaying recognition. 7, 8

Prevention strategies 7, 8:

• Maintain blood glucose 10-15 mmol/L (180-270 mg/dL) during acute phase
• Check blood glucose every 1-2 hours during insulin infusion
• Add dextrose to IV fluids once glucose <14 mmol/L
• Consider continuous glucose monitoring if available

Critical Pitfalls to Avoid

1. Starting insulin before adequate fluid resuscitation - can precipitate cardiovascular collapse 3
2. Correcting osmolality too rapidly (>8 mOsm/kg/hour) - risks central pontine myelinolysis 2, 3
3. Switching to hypotonic fluids based solely on rising sodium - initial sodium rise is expected 3
4. Aggressive fluid resuscitation in heart failure/stroke patients - increases mortality 6
5. Failing to identify and treat precipitating infection - UTI requires immediate empiric antibiotics 4
6. Allowing hypoglycemia - can cause permanent brain injury in elderly within 2 hours 7
7. Inadequate potassium replacement - total body deficits are massive despite normal initial levels 1

Disposition and Monitoring

All patients with HHS require ICU-level care. 9 The diabetes specialist team should be involved immediately. 3

Patients should be nursed in areas where staff are experienced in HHS management. 3