Non-ketotic hyperosmolar state (NKHS), also called Hyperosmolar Hyperglycaemic State (HHS), is a life-threatening acute complication of diabetes mellitus characterised by extreme hyperglycaemia, severe dehydration and high plasma osmolarity without significant ketosis.

It occurs most commonly in elderly patients with type 2 diabetes mellitus and has a higher mortality rate than diabetic ketoacidosis (DKA).

The main pathophysiology is:

Risk Factors

• Elderly age (>60 years)

• Undiagnosed diabetes

• Poor glycaemic control

• Dehydration or inability to drink water

• Dementia or physical disability

• Living alone

• Chronic kidney disease

• Cardiovascular disease

• Nursing home patients

Precipitating illnesses

• Sepsis

• Pneumonia

• Stroke

• Myocardial infarction

• Pancreatitis

• Trauma or surgery

Medications

• Thiazide diuretics

• Glucocorticoids

• Phenytoin

• Atypical antipsychotics

• Beta-blockers

• Immunosuppressants

Signs and Symptoms

Early

• Polyuria

• Polydipsia

• Weakness

• Weight loss

Progressive dehydration

• Dry mucous membranes

• Sunken eyes

• Poor skin turgor

• Tachycardia

• Hypotension

• Orthostatic hypotension

Neurological manifestations (hallmark)

• Lethargy

• Confusion

• Delirium

• Seizures

• Focal neurological deficits (mimics stroke)

• Coma

Unlike DKA

• No Kussmaul breathing

• No significant abdominal pain

• Minimal or no vomiting

• No fruity breath odor

Diagnostic Criteria

Typical findings:

• Severe hyperglycaemia (usually >33 mmol/L or >600 mg/dL)

• Profound dehydration

• Altered mental status

• Minimal or absent ketones

• High serum osmolarity

Clinical features

• Polyuria

• Hypotension

• Tachycardia

• Reduced fluid intake

• Neurological impairment

Investigations

Essential laboratory tests

• Blood glucose

• Serum electrolytes (Na⁺, K⁺, Cl⁻)

• Urea & creatinine

• Serum osmolarity

• Urine ketones (absent or mild)

• Blood gas (usually no severe acidosis)

Serum osmolarity calculation

Serum osmolarity=2(Na++K+)+Glucose+Urea(mmol/L)Serum\ osmolarity = 2(Na⁺ + K⁺) + Glucose + Urea \quad (mmol/L)Serum osmolarity=2(Na++K+)+Glucose+Urea(mmol/L)

• Normal: <310 mOsm/kg

• HHS: usually >330 mOsm/kg

Important notes

• Initial potassium may appear high due to extracellular shift

• Total body potassium is actually depleted

• If acidosis present → suspect sepsis or lactic acidosis (manage like DKA)

Search for precipitating cause

• FBC and cultures (sepsis)

• Chest X-ray (pneumonia)

• ECG & cardiac enzymes (MI)

• CT brain (stroke if focal signs)

Management

Medical emergency → Admit to High Dependency Unit / ICU

Treatment priorities (in order)

1. Restore circulation (fluids)

2. Correct electrolytes

3. Start insulin

4. Treat underlying cause

Non-Pharmacological

• Oxygen if hypoxic

• Strict fluid balance chart

• Urinary catheter monitoring

• Hourly neurological monitoring

• Treat infection source

• Temperature control

• Pressure sore prevention

Pharmacological

1. Fluid Replacement (MOST IMPORTANT STEP)

Severe dehydration: deficit usually 8–12 litres

Initial

• 0.9% Normal saline 1 L in first hour

Next

• If sodium normal → continue normal saline

• If hypernatremia → switch to 0.45% saline

After glucose <14 mmol/L

• Add 5% dextrose + saline to prevent hypoglycaemia

2. Insulin Therapy

Start only AFTER initial fluid resuscitation

• IV regular insulin infusion 0.05 units/kg/hour(lower than DKA dose)

Target fall in glucose:

• 3–4 mmol/L per hour

3. Potassium Replacement

Despite normal/high lab potassium → total body deficit exists

4. Treat Underlying Cause

• Antibiotics (sepsis)

• Anticoagulation (stroke risk)

• MI protocol if needed

5. Complication Prevention

• Thrombosis prophylaxis (LMWH recommended)

• Avoid rapid osmolar correction → prevent cerebral edema

Monitoring

Hourly:

• Glucose

• Neurological status

• Urine output

Every 2–4 hours:

• Electrolytes

• Osmolarity

Prevention

• Adequate hydration in elderly diabetics

• Sick-day diabetes education

• Early treatment of infections

• Medication review (avoid precipitating drugs)

• Regular glucose monitoring

• Caregiver education in frail patients