Endocrine · Topic 2 of 13

Hyperosmolar Hyperglycemic State (HHS)

Endocrine · hyperglycemic crisis

Hyperosmolar Hyperglycemic State (HHS)

Glucose ≥ 600 and osmolality > 300 without ketoacidosis: fluids first, then low-dose insulin, and bring osmolality down slowly.

Key numbers

Glucose ≥ 600, osmolality > 300glucose ≥ 600 mg/dL

Fluids first: isotonic crystalloid 500–1000 mL/h500–1000 mL/h × 2–4 h

Low-dose insulin 0.05 U/kg/h, after fluids0.05 U/kg/h

Lower osmolality 3–8 mOsm/kg per hourosm ↓ 3–8 mOsm/kg/h

Potassium above 3.5 before insulinK⁺ > 3.5 mmol/L

01 · Defined byGlucose ≥ 600, osmolality > 300

HHS needs all four: glucose ≥ 600 mg/dL; effective osmolality > 300 mOsm/kg (or total > 320); β-hydroxybutyrate < 3.0 mmol/L (urine ketones < 2+); pH ≥ 7.3 and bicarbonate ≥ 15 mmol/L.

02 · DoFluids first: isotonic crystalloid 500–1000 mL/h

Fluid is the first treatment: 0.9% saline or balanced crystalloid at 500–1000 mL/h for 2–4 hours (deficits often exceed 10 L), then adjust to hemodynamics; fluid alone lowers glucose substantially.

03 · The ruleLower osmolality 3–8 mOsm/kg per hour

Correct slowly: glucose fall ≤ 90–120 mg/dL per hour, osmolality fall 3–8 mOsm/kg per hour, and sodium fall ≤ 10 mmol/L in 24 hours, to avoid cerebral edema and osmotic demyelination.

Causes & risk factors

Why it happens

Triggers: infection, steroids, diuretics, poor intakeCommon precipitants are infection and other acute illness, glucocorticoids, diuretics, nonadherence and inadequate water intake (impaired thirst or access, e.g., nursing-home residents).

Presentation

What you'll see

Older type 2 patient, confused, profoundly dryHHS typically affects older adults with type 2 diabetes over days to weeks: polyuria, severe dehydration and altered mental status from confusion to coma; focal seizures or transient hemiplegia can mimic stroke.

Diagnosis & monitoring

Work-up

Resolved: osmolality < 300, mental status improvingConsider HHS resolved when osmolality is < 300 mOsm/kg, glucose < 250 mg/dL, urine output > 0.5 mL/kg/h and cognition has improved.

Effective osmolality = 2 × Na + glucose/18Effective serum osmolality = 2 × Na⁺ (mmol/L) + glucose (mg/dL)/18; urea is left out because it crosses cell membranes. Mental status changes track rising osmolality.

Do right now

In this order

First moves

Fluids first: isotonic crystalloid 500–1000 mL/h500–1000 mL/h × 2–4 h

→

Potassium above 3.5 before insulinK⁺ > 3.5 mmol/L

→

Low-dose insulin 0.05 U/kg/h, after fluids0.05 U/kg/h

→

Add dextrose as glucose reaches 250–300

Why each step

Fluids first: isotonic crystalloid 500–1000 mL/hFluid is the first treatment: 0.9% saline or balanced crystalloid at 500–1000 mL/h for 2–4 hours (deficits often exceed 10 L), then adjust to hemodynamics; fluid alone lowers glucose substantially.

Potassium above 3.5 before insulinPotassium rules match DKA: hold insulin and replace potassium if K⁺ < 3.5 mmol/L; add 20–30 mmol per liter once K⁺ < 5.0, targeting 4–5 mmol/L.

Low-dose insulin 0.05 U/kg/h, after fluidsStart a fixed-rate IV insulin infusion at 0.05 U/kg/h once fluids are running and potassium is adequate; use 0.1 U/kg/h only for mixed DKA/HHS (ketones ≥ 3.0, pH < 7.3 or HCO₃⁻ < 18).

Add dextrose as glucose reaches 250–300Add dextrose to the IV fluids once glucose falls to about 250–300 mg/dL and reduce the insulin rate, holding glucose there until the patient is rehydrated, alert and eating.

Management

Orders

Admit every HHS patient to the ICUManage HHS in the ICU with glucose checks every 1–2 hours and electrolytes, creatinine and osmolality every 4 hours.

Give VTE prophylaxis — HHS is prothromboticHHS (more than DKA) is a prothrombotic state; give prophylactic-dose low-molecular-weight heparin unless contraindicated.

Red flags & don'ts

Avoid harm

Fast correction risks cerebral edema and ODS complicationToo-rapid falls in osmolality or sodium risk cerebral edema and osmotic demyelination; a falling level of consciousness during treatment needs urgent brain imaging.

HHS or DKA?

Commonly confused

Glucose	≥ 600 mg/dL
Ketones	β-hydroxybutyrate < 3.0 mmol/L
Acid–base	pH ≥ 7.3 and HCO₃⁻ ≥ 15
Onset	Days to weeks
Insulin start	0.05 U/kg/h after fluids

Commonly confused

Tell apart

Rising sodium alone: no hypotonic fluidAs glucose falls, sodium rises (1.6 mmol/L per 100 mg/dL glucose drop); that alone is not an indication for 0.45% saline — switch only if osmolality stops falling despite positive fluid balance and insulin.

More detail

Reference

Show 5 reference facts

HHS mortality is higher than DKA (Merck cites up to about 2% vs < 1%), driven by age, comorbidity and circulatory collapse.

Older adults and patients with heart failure or dialysis-dependent kidney disease should get smaller boluses (about 250 mL) with frequent reassessment.

About half of adults with DKA or HHS have acute kidney injury, more often with older age and higher osmolality; it usually resolves with rehydration — check renal function daily.

Some experts withhold insulin until glucose stops falling with fluids alone, to avoid a too-rapid fall in osmolality; insulin needs may be lower than expected.

After recovery, switch to subcutaneous insulin (basal given before stopping the infusion) and review the discharge regimen rather than deferring changes to clinic.

Pearl

HHS is a water problem first and an insulin problem second — fill the tank, then lower the sugar slowly.

Sources · ADA. 16. Diabetes Care in the Hospital: Standards of Care in Diabetes—2026. Diabetes Care 2026;49(Suppl 1) · Umpierrez GE et al. Hyperglycemic Crises in Adults With Diabetes: A Consensus Report (ADA/EASD/JBDS/AACE/DTS). Diabetes Care 2024;47:1257–1275, doi:10.2337/dci24-0032 (open copy read: Diabetologia 2024;67:1455–1479, PMC11343900) · Merck Manual Professional — Acute Complications of Diabetes Mellitus (DKA, HHS, alcoholic ketoacidosis) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).