EMA Cited · Endocrine & metabolic

Hyperosmolar hyperglycemic state

Updated Oct 28, 2026Adults · ED management8 sources · 6 in PubMed2 figures2024 international consensus · JBDS 2023

Bottom line

HHS is a fluid problem first. Diagnose it on glucose ≥ 600 mg/dL, effective osmolality > 300 mOsm/kg, β-hydroxybutyrate < 3.0 mmol/L, pH ≥ 7.3 and bicarbonate ≥ 15.¹ Typical water losses are 100–220 mL/kg.²
Fluids before insulin. Fluid alone lowers glucose. The UK guideline starts insulin only once glucose stops falling, unless ketones are high, and then at a fixed 0.05 units/kg/h.^1,2
Lower osmolality slowly: 3–8 mOsm/kg per hour, glucose no faster than 90–120 mg/dL per hour, and sodium no more than 10 mEq/L in 24 hours.^1,2
An early rise in sodium is expected as glucose falls. It is not a reason for hypotonic fluid unless osmolality has stopped falling.^1,2
Mixed DKA/HHS is the most dangerous form. It was 27% of crises in one cohort and carried higher in-hospital mortality (adjusted OR 2.7). Treat significant ketosis with DKA-rate insulin, 0.1 units/kg/h.^3,1

Diagnosis

	2024 consensus (ADA, EASD, JBDS, AACE, DTS)	UK JBDS 2023
Glucose	≥ 600 mg/dL (33.3 mmol/L)	Usually ≥ 540 mg/dL (30 mmol/L)
Osmolality	Effective > 300 mOsm/kg, or total > 320	Usually ≥ 320 mOsm/kg (2 × Na + glucose + urea)
Ketones	β-hydroxybutyrate < 3.0 mmol/L, or urine ketones < 2+	≤ 3.0 mmol/L
Acid–base	pH ≥ 7.3 and bicarbonate ≥ 15 mEq/L	pH > 7.3 and bicarbonate ≥ 15
Volume	—	Marked hypovolemia

The consensus needs all four criteria.¹ The UK guideline warns against diagnosing HHS from the numbers alone, without the clinical picture.² The consensus formulas use mmol/L: effective osmolality is 2 × Na + glucose, and total osmolality adds urea.¹ In US units, divide glucose (mg/dL) by 18 and BUN (mg/dL) by 2.8 first.

Presentation

Who: mostly middle-aged and older adults with type 2 diabetes (88% in one US dataset).¹ It can be the first sign of type 2 diabetes, including in younger adults.²
Tempo: develops over days to weeks, unlike the hours to days of DKA.¹
Brain: confusion through to coma. Focal deficits and seizures can occur.⁴ Cognitive changes are more common once osmolality is above 330 mOsm/kg.²
Gut: nausea, vomiting and abdominal pain are common in DKA but uncommon in HHS.¹
Looks less dry than they are. Hypertonicity holds water in the vessels, so the circulation can look preserved despite large losses.^1,2

Precipitants

Infection in 30–60%, most often urinary tract infection and pneumonia.¹
Stroke, myocardial infarction, surgery and pancreatitis.¹
Drugs: corticosteroids, sympathomimetics, antipsychotics¹ and thiazides.² Missed diabetes medicines.²
Poor access to water: impaired thirst with age and limited access to fluids drive the volume depletion.¹

Mixed DKA/HHS

In 1,211 admissions at two US hospitals, 38% were DKA, 35% HHS and 27% mixed. Mixed cases had higher in-hospital mortality after adjustment (OR 2.7).³ The consensus gives inpatient mortality of 8% for mixed crises, 5% for HHS and 3% for DKA in that cohort.¹ Mild ketonemia can occur in HHS.¹ Treat β-hydroxybutyrate ≥ 3.0 mmol/L, urine ketones ≥ 2+, pH < 7.30 or bicarbonate < 18 as mixed DKA/HHS.¹

First hours

Send labs and look for the cause. Glucose, electrolytes, venous gas, CBC, ketones and an ECG. Examine for infection and ischemia.¹ Check lactate as well.²
Calculate osmolality and decide: HHS, or mixed DKA/HHS?¹
Start fluids: 0.9% saline or a balanced crystalloid at 500–1000 mL/h for the first 2–4 hours. For older adults, heart failure or dialysis, give 250 mL boluses and reassess often.¹
Hold insulin in pure HHS until glucose stops falling on fluids alone, then start 0.05 units/kg/h. In mixed DKA/HHS, start insulin with the fluids.^2,1
Replace potassium to the table below.²
Monitor: osmolality hourly at first,² glucose every 1–2 hours, and electrolytes, creatinine and osmolality every 4 hours.¹

FIG 1 · Decision flowCited

Suspect HHS in a dehydrated, confused patient with diabetes. Send glucose, electrolytes, venous gas, ketones and CBC, get an ECG, and look for infection or ischemia.¹
β-hydroxybutyrate ≥ 3.0, pH < 7.30 or bicarbonate < 18?
Yes
Mixed DKA/HHS. Start fixed-rate insulin at 0.1 units/kg/h together with fluids, and follow the DKA pathway.^1,2
No: HHS
Fluids first: saline or balanced crystalloid at 500–1000 mL/h for 2–4 h. Use 250 mL boluses if older, in heart failure or on dialysis.¹
Measure osmolality hourly at first. Aim for a fall of 3–8 mOsm/kg/h and glucose no faster than 90–120 mg/dL/h.^1,2
Glucose stopped falling on fluids alone?
Yes
Start insulin at a fixed 0.05 units/kg/h. If an infusion is already running, increase it by 1 unit/h.²
Sources differ on how long to wait. See Insulin.^1,2
Either way
Potassium: add 40 mEq/L to fluids for K 3.5–5.5. None for 5.5–5.9. Get senior help for K under 3.5 or ≥ 6.0.²
Sodium rising as glucose falls?
Yes
Expected. Switch to 0.45% saline only if osmolality has stopped falling despite a positive fluid balance.^1,2
Either way
Add 5–10% dextrose once glucose is under about 250 mg/dL (14 mmol/L). Aim for 180–270 mg/dL in the first 24 h.²
Prophylactic-dose LMWH for the whole admission unless contraindicated. Treat the precipitant and protect the heels.^2,1
Admit to ICU or high dependency. Resolved when osmolality is < 300, urine output ≥ 0.5 mL/kg/h, cognition is back to baseline and glucose is controlled.^1,2

FIG 1The first day of HHS. Drawn for this page from the 2024 international consensus and the UK JBDS guideline. Each box carries its own citations.^1,2

Fluids, osmolality and sodium

Deficits are large: water 100–220 mL/kg, which is 6–13 L in a 60 kg adult. Potassium losses are 4–6 mEq/kg.²
Pace: replace about half the estimated loss in the first 12 hours and the rest over the next 12.² The consensus aims to correct deficits within 24–48 hours.¹
Fluid alone lowers glucose, by about 50–70 mg/dL per hour even without insulin in DKA, and possibly more in HHS.¹
Speed limits: osmolality should fall 3–8 mOsm/kg per hour and sodium no more than 10 mEq/L in 24 hours.^1,2 Hyperglycemia usually takes 8–10 hours to resolve.¹
Hypotonic fluid: use 0.45% saline only if osmolality is not falling despite a positive balance and adequate glucose lowering. There are no data for anything more dilute.^1,2
Complete correction can take up to 72 hours.²

Sources disagree

Fluid choice: the UK guideline uses 0.9% saline as the main fluid.² The consensus accepts saline or a balanced crystalloid, noting faster DKA resolution with balanced fluids.¹ Sodium rise: the consensus expects about 1.6 mEq/L for every 100 mg/dL fall in glucose.¹ The UK guideline uses 2.4 mEq/L per 5.5 mmol/L (about 100 mg/dL), and reads a much larger rise as too little fluid.²

FIG 2The fluid clock. Drawn for this page from the consensus fluid rate and resolution time and the UK replacement pace.^1,2 Times are targets for an adult without heart or kidney compromise. Full correction can take up to 72 hours.²

Insulin, potassium and dextrose

Agent	Adult dose	When	Notes
Insulin
Regular insulin IV, HHS	0.05 units/kg/h, fixed rate	Once glucose stops falling on fluids (UK)	Increase by 1 unit/h if already running. Keep usual basal insulin going.^2,1
Regular insulin IV, mixed DKA/HHS	0.1 units/kg/h, fixed rate	With the fluids	For β-hydroxybutyrate ≥ 3.0, pH < 7.30 or bicarbonate < 18.^1,2
Subcutaneous rapid-acting insulin	Not recommended	—	Not for HHS or severe DKA.¹
Potassium in each liter of fluid (UK, first 24 h)
K ≥ 6.0 mEq/L	Senior review	—	ICU or outreach.²
K 5.5–5.9	None	—	²
K 3.5–5.5	40 mEq/L	With fluids	Hyperkalemia is possible with acute kidney injury.²
K < 3.5	Senior review; more needed	—	Give via central line in a high-dependency unit.²
Dextrose
Dextrose 5% or 10%	Alongside insulin and fluids	Glucose < 14 mmol/L (about 250 mg/dL)	Target 180–270 mg/dL in the first 24 h.²

Unreviewed doses. Verify against the current label and your institution's protocol before giving anything.

Sources disagree

When to start insulin. The UK guideline gives fluids first and starts insulin only when glucose stops falling, to avoid large osmotic shifts and circulatory collapse.² The consensus sets the 0.05 units/kg/h dose and notes that some advise withholding insulin this way, without making it a firm rule.¹ Older US and Canadian guidelines used 0.1 units/kg/h for HHS.⁵

Potassium falls with treatment. Hypokalemia (< 3.5 mEq/L) occurred in 51% of HHS patients and severe hypokalemia (< 2.5) in 9%.¹ Across hyperglycemic crises, potassium ≤ 2.5 was linked to higher in-hospital mortality (adjusted OR 4.9), as was glucose < 40 mg/dL during treatment (adjusted OR 4.8).³ The consensus starts replacement once potassium falls below 5.0 mEq/L, aiming for 4–5.¹

Complications

Cerebral edema is rare in adults (under 0.1% of episodes) but carries about 30% mortality. Watch mental status and image early. Correct osmolality slowly.¹
Osmotic demyelination can follow rapid sodium shifts in HHS. Keep the osmolality fall within 3–8 mOsm/kg per hour.^1,2
Acute kidney injury affects about half of adults admitted with DKA or HHS, and usually resolves with fluids.¹
Foot ulcers: check the feet on admission and daily, and use heel protection if the patient is immobile or confused.²
Low phosphate and magnesium are common in HHS. No studies have tested replacing them in HHS.²

Thrombosis

The UK guideline gives prophylactic-dose LMWH to everyone with HHS for the whole admission unless contraindicated. Full anticoagulation is only for suspected thrombosis or acute coronary syndrome.² The consensus also advises prophylactic LMWH.¹

Sources disagree

In California discharge data (2,859 patients), hyperosmolarity tripled the risk of VTE compared with uncomplicated diabetes (HR 3.0). Ketoacidosis did not raise it (HR 1.2).⁶ A Taiwanese national cohort (46,000 HHS admissions) found no higher 90-day VTE risk than in other diabetic admissions (adjusted OR 1.06).⁷ Both guidelines still recommend prophylaxis.^1,2

Disposition and resolution

The consensus treats HHS in the ICU.¹ The UK guideline lists findings that should prompt a high-dependency bed and senior review:²

Osmolality > 350 mOsm/kg, sodium > 160 mEq/L, or pH < 7.1.²
Potassium < 3.5 or ≥ 6.0 mEq/L on arrival.²
GCS < 12, SpO₂ < 92% on air, systolic BP < 90 mm Hg, or pulse > 100 or < 60.²
Urine output < 0.5 mL/kg/h, creatinine > 200 µmol/L (about 2.3 mg/dL) or acute kidney injury, or hypothermia.²
A heart attack, stroke or other serious illness.²

Resolved when	2024 consensus	UK JBDS 2023
Osmolality	< 300 mOsm/kg	< 300 mOsm/kg
Urine output	> 0.5 mL/kg/h	≥ 0.5 mL/kg/h
Cognition	Improved	Back to pre-illness state
Glucose	< 250 mg/dL (13.9 mmol/L)	< 15 mmol/L (270 mg/dL)

Resolution criteria from the consensus¹ and the UK guideline.² Every patient with HHS should see the diabetes team before discharge.²

Pitfalls

Running a DKA protocol in pure HHS. Early, high-dose insulin lowers osmolality too fast.²
Treating the expected early rise in sodium with hypotonic fluid.^1,2
Driving glucose down faster than 90–120 mg/dL per hour.¹
Giving full-rate fluid to frail patients or those with heart failure or on dialysis. Use 250 mL boluses and reassess.¹
Stopping at the glucose. Look for the precipitant: infection, stroke, myocardial infarction, drugs.¹
Being reassured that the patient doesn't look dry.^1,2
Forgetting VTE prophylaxis and heel protection.²

How strong is the evidence?

Weak. A 2026 systematic review found no randomized trials in HHS. Guidelines are built on consensus, and they differ on the glucose threshold, how fast to lower osmolality, and the insulin dose.⁵ The UK guideline says the same of its own advice.² Outcome data come from retrospective cohorts and administrative databases.^3,6,7

On-shift teaching

Questions to ask a learner at the bedside. Tap a question to see the answer. Every answer uses facts cited above.

Q1Why not start insulin straight away in HHS, as in DKA?

Fluid alone lowers glucose.¹ Insulin before enough fluid shifts water out of the vessels, risking circulatory collapse and fast osmotic shifts. The UK guideline waits until glucose stops falling, then gives 0.05 units/kg/h.²

Q2The sodium has risen from 138 to 145 mEq/L as glucose fell. Do you switch to half-normal saline?

Not yet. A rise is expected as glucose falls: about 1.6 mEq/L per 100 mg/dL by the consensus, 2.4 by the UK guideline. Use 0.45% saline only if osmolality has stopped falling despite a positive balance. A much larger rise suggests too little fluid.^1,2

Q3How common is mixed DKA/HHS, and why does it matter?

It was 27% of 1,211 admissions in one US cohort, with higher in-hospital mortality (adjusted OR 2.7).³ It gets DKA-rate insulin, 0.1 units/kg/h, started with the fluids.^1,2

Q4Which treatment complications were linked to death in hyperglycemic crises?

Glucose < 40 mg/dL during treatment (adjusted OR 4.8) and potassium ≤ 2.5 mEq/L (adjusted OR 4.9).³

Q5Does HHS really raise the risk of VTE?

In California data, hyperosmolarity tripled VTE risk compared with uncomplicated diabetes (HR 3.0), and DKA did not raise it.⁶ A Taiwanese cohort found no difference (adjusted OR 1.06).⁷ The UK guideline still gives prophylactic LMWH to everyone.²

Q6When is HHS resolved?

Osmolality < 300 mOsm/kg, urine output ≥ 0.5 mL/kg/h, cognition back to baseline, and glucose < 250 mg/dL (consensus) or < 270 mg/dL (UK).^1,2

References

Evidence base

What this page is built on

8 sources, cited 128 times. Dots are sources, filled by how far each was read; stronger color means a larger share of the citations. Tap a tier to see its sources.

Read in full · 3Abstract read · 4Record only · 0Link checked · 1

Checked by the writer, not a physician. The dots show how each source was read, not that anyone has confirmed the claims.

Not for clinical use

AI-generated draft. Not reviewed by a physician. This page is for education only and may contain errors, including in doses. Do not use it to diagnose, treat or make decisions about any patient. Rely on your own clinical judgment, your institution's protocols and current drug labeling. Reading this page does not create a physician-patient relationship. Full terms