What are the typical presentation, laboratory findings, and acute management of hyperosmolar hyperglycemic state in an older adult with type 2 diabetes?

Hyperosmolar Hyperglycemic State (HHS) in Older Adults with Type 2 Diabetes

Older adults with type 2 diabetes presenting with HHS typically show severe hyperglycemia (>600 mg/dL), marked hyperosmolality (>320 mOsm/kg), profound dehydration, and altered mental status without significant ketoacidosis, and require immediate aggressive fluid resuscitation with isotonic saline at 15-20 mL/kg/h as the first priority before insulin therapy. 1, 2

Clinical Presentation

Cardinal Features

• Severe hyperglycemia: Blood glucose typically >600 mg/dL (often 800-1000 mg/dL) 3, 4
• Marked hyperosmolality: Effective serum osmolality ≥320 mOsm/kg, calculated as [2×Na+ + glucose/18] 4, 3
• Profound dehydration: Total body water deficit of 100-220 mL/kg (often 8-12 liters in adults) 4, 1
• Altered mental status: Ranging from confusion to lethargy to coma, correlating with degree of hyperosmolality 5, 3
• Absence of significant ketoacidosis: Ketones ≤3.0 mmol/L, pH >7.3, bicarbonate ≥15 mmol/L 4, 1

Unique Presentation in Elderly Patients

Older adults often present atypically, making diagnosis more challenging:

• Blunted thirst response: Elderly patients are less likely to experience polyuria and polydipsia due to impaired thirst mechanisms and increased renal threshold for glycosuria 6, 7
• Nonspecific symptoms: Weight loss, fatigue, confusion, and functional decline that may be incorrectly attributed to aging or dementia 6, 3
• Normothermia or hypothermia: Despite infection being present, patients may not mount a fever due to peripheral vasodilation; hypothermia is a poor prognostic sign 1
• High prevalence of cognitive impairment: Most HHS patients have pre-existing dementia, complicating recognition of altered mental status 3

Common Precipitating Factors

The most common precipitating factor is infection (present in 79% of elderly HHS cases), particularly:

• Urinary tract infections and pneumonia (most frequent) 3, 1
• Cardiovascular events: cerebral infarction, myocardial infarction 1, 7
• Medications: corticosteroids, thiazides, sympathomimetic agents (dobutamine, terbutaline) 1, 8
• Inadequate fluid intake: especially in nursing home residents, those living alone, or with ADL decline 3, 7
• Newly diagnosed diabetes: 4 out of 14 cases in one elderly cohort were new diagnoses 3

Critical pitfall: Half of elderly HHS patients have a history of cerebral infarction or hip fracture, limiting their ability to access fluids independently 3

Laboratory Findings

Initial Laboratory Evaluation

The following tests should be obtained immediately 1:

• Plasma glucose: Typically >600 mg/dL (mean 881 mg/dL in elderly) 3, 4
• Serum osmolality: ≥320 mOsm/kg (mean 353 mOsm/kg in elderly) 3, 4
• Electrolytes with calculated anion gap: Usually normal anion gap (<12 mEq/L) 1, 4
• BUN/Creatinine: Markedly elevated BUN/Cr ratio (often >30) indicating prerenal azotemia from volume depletion 2, 6
• Serum ketones: Minimal or absent (≤3.0 mmol/L) 4, 1
• Arterial blood gases: pH >7.3, bicarbonate ≥15 mmol/L 4, 1
• Complete blood count with differential: To assess for infection and leukocytosis 1
• HbA1c: Mean 10.3% in elderly HHS patients; useful to distinguish acute versus chronic poor control 3, 1
• Urinalysis and urine ketones: Minimal ketonuria 1
• Electrocardiogram: To assess for cardiac ischemia and electrolyte abnormalities 1

Infection Workup

Bacterial cultures (blood, urine, throat) must be obtained immediately and appropriate antibiotics started if infection is suspected, as infection is the most common precipitating cause 1

A chest X-ray should be obtained given the high prevalence of pneumonia 1, 3

Ongoing Monitoring

Monitor electrolytes, glucose, BUN, and creatinine every 2-4 hours initially to assess response to fluid resuscitation and guide potassium replacement 2, 9

Acute Management

Phase 1: Initial Resuscitation (0-60 minutes)

Step 1: Aggressive Fluid Resuscitation (FIRST PRIORITY)

• Begin with isotonic saline (0.9% NaCl) at 15-20 mL/kg/h (typically 1-1.5 liters in the first hour) 1, 2
• This is the single most important intervention and takes priority over insulin therapy 2, 4
• Goal: Restore intravascular volume and renal perfusion to correct prerenal azotemia 2, 8

Critical pitfall: Never give insulin before adequate fluid resuscitation, as this can worsen hypotension and renal perfusion 2

Special consideration in elderly: Exercise caution with aggressive fluid replacement in patients with:

• Congestive heart failure (necessitating avoidance of fluid excess) 7
• Cerebral stroke (which requires anti-edema therapy) 7
• These two precipitating factors are frequent causes of death in elderly HHS patients 7

Step 2: Potassium Assessment

• Check initial potassium level before starting insulin 1, 9
• Once renal function is assured, add 20-30 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO4) 1
• Insulin therapy will drive potassium intracellularly, risking life-threatening hypokalemia 9

Phase 2: Continued Fluid Therapy (1-6 hours)

Fluid selection after initial hour:

• If corrected serum sodium is normal or elevated: Switch to 0.45% NaCl at 4-14 mL/kg/h 1, 8
• If corrected serum sodium is low: Continue 0.9% NaCl at similar rate 1
• Goal: Gradual decline in osmolality at 3.0-8.0 mOsm/kg/h to minimize risk of neurological complications (osmotic demyelination) 4, 2

Expected clinical course: With appropriate fluid resuscitation, BUN and creatinine should normalize within 24-48 hours as prerenal azotemia resolves 2

Phase 3: Insulin Therapy

Timing: Insulin should be commenced only after osmolality stops falling with fluid replacement alone, unless there is significant ketonaemia present 4

Dosing regimen:

• Bolus: 10-15 units of regular insulin IV 8
• Continuous infusion: 0.1 units/kg/h (fixed rate intravenous insulin infusion) 8, 2
• Target glucose decline: 50-75 mg/dL per hour (avoid overly aggressive lowering in elderly) 2

Critical distinction from DKA: In critically ill and mentally obtunded patients, continuous IV insulin is standard of care 1. However, for uncomplicated cases, subcutaneous rapid-acting analogs combined with aggressive fluid management may be used 1

Phase 4: Glucose Management (6-12 hours)

• Once blood glucose approaches 250-300 mg/dL (13.9-16.7 mmol/L): Add 5% or 10% dextrose to IV fluids 8, 4
• Reduce insulin infusion rate to maintain glucose 10-15 mmol/L (180-270 mg/dL) in first 24 hours 4
• Target glucose range: 10-15 mmol/L in first 24 hours to prevent hypoglycemia 4

Phase 5: Resolution and Transition (12-72 hours)

HHS resolution criteria 4:

• Osmolality <300 mOsm/kg
• Hypovolemia corrected (urine output ≥0.5 mL/kg/h)
• Cognitive status returned to pre-morbid state
• Blood glucose <15 mmol/L (270 mg/dL)

Transition considerations:

• Many elderly patients presenting with HHS will not require long-term insulin therapy and can be managed with diet or oral agents, as insulin secretion capacity is often preserved 8, 3
• In one elderly cohort, 9 out of 14 patients were treatable with oral hypoglycemic agents alone after recovery 3

Critical Pitfalls to Avoid

1. Starting insulin before adequate fluid resuscitation: This worsens hypotension and renal perfusion 2
2. Overly aggressive osmolality correction: Target 3.0-8.0 mOsm/kg/h decline to prevent osmotic demyelination syndrome 4, 2
3. Ignoring potassium replacement: Insulin drives potassium intracellularly; monitor and replace aggressively 9, 1
4. Excessive fluid in heart failure patients: Balance fluid needs with cardiac status in elderly with comorbidities 7
5. Assuming abdominal pain is from HHS: May be precipitating cause (pancreatitis) rather than result; requires further evaluation if persistent 1
6. Missing underlying infection despite normothermia: Obtain cultures and start antibiotics empirically if suspected 1, 3
7. Using bicarbonate therapy: Not indicated in HHS (pH >7.3); only use if pH <6.9 in mixed DKA/HHS 9, 1

Prognosis and Outcomes

• Mortality: HHS carries high mortality, with age being the best known prognostic indicator 7, 5
• Functional outcomes: Even with high survival rates, functional prognosis is often impaired; in one series, 9 of 14 elderly patients were discharged to nursing homes or other hospitals 3
• Length of stay: Mean hospitalization 55 days in elderly patients 3
• ICU admission: These patients are critically ill and generally require intensive care unit admission 5

Prevention Strategies

The primary way to diminish mortality from HHS is prevention 7:

• Ensure appropriate fluid intake in elderly diabetics, especially those in nursing homes or living alone 7, 3
• Use caution with thiazides, steroids, and phenytoin in aged diabetics, particularly those with nephropathy 7, 1
• Recognize that more than half of elderly HHS patients were living alone or only with their spouse, with marked ADL deterioration 3
• Address social support deficits and cognitive impairment proactively 3