Overview
Hyperosmolar Hyperglycaemic State (HHS)
1. Clinical Overview
Summary
Hyperosmolar Hyperglycaemic State (HHS) is a medical emergency predominantly occurring in Type 2 Diabetes. It is characterised by severe hyperglycaemia (often >30-50 mmol/L), profound dehydration (average 8-10L deficit), hyperosmolality (>320 mOsm/kg), and the absence of significant ketoacidosis. Mortality is significantly higher than DKA (15-20% vs 1-5%) due to the older, comorbid patient population and the high risk of thrombosis and complications from too-rapid correction. Management focuses on slow, careful rehydration (over 48-72 hours), VTE prophylaxis, and low-dose insulin (often delayed). [1,2]
Clinical Pearls
HHS is MORE Dangerous than DKA: The mortality is 10-20x higher. These are older, frailer patients with massive fluid deficits and hyperviscous blood (clot risk).
Insulin is NOT First Line: Giving insulin before adequate fluids causes glucose to plummet. Water follows glucose into cells, dropping plasma volume further and causing cardiovascular collapse. Rehydrate first.
SLOW Correction: The brain equilibrates to hyperosmolality. If you drop the osmolality too fast (>10 mOsm/kg/h or >3-8 mmol/L/h glucose drop), water shifts into brain cells causing cerebral oedema or osmotic demyelination.
Prophylactic Anticoagulation is MANDATORY: HHS causes profound blood viscosity. DVT, PE, Stroke, and Mesenteric Ischaemia are common. All patients need LMWH unless contraindicated.
2. Epidemiology
Demographics
- Incidence: Less common than DKA. 1-2 per 1000 diabetic patient-years.
- Age: Typically elderly (>60 years). Rare in young people.
- Diabetes Type: Almost exclusively T2DM (they have enough residual insulin to suppress lipolysis/ketogenesis but not gluconeogenesis).
- Mortality: 15-20% (Much higher than DKA's ~1-5%).
Precipitants
- Infection: Pneumonia, UTI (Most common trigger).
- Poor Compliance / New Diagnosis: Often undiagnosed T2DM.
- Stroke / MI: Stress hyperglycaemia.
- Drugs: Steroids, Diuretics (Thiazides), Atypical Antipsychotics.
- Inability to Access Fluids: Dementia, Institutionalised, Stroke.
3. Pathophysiology
Mechanism
- Residual Insulin: In T2DM, some insulin is still produced. This is enough to suppress lipolysis (so no significant ketones), but NOT enough to suppress hepatic gluconeogenesis.
- Profound Hyperglycaemia: Glucose rises progressively (can exceed 50-100 mmol/L).
- Osmotic Diuresis: High blood glucose spills into urine, drawing massive amounts of water with it.
- Dehydration: Over days to weeks, patients lose 8-10 litres of fluid. They become profoundly dehydrated.
- Hyperosmolality: The combination of hyperglycaemia and water loss raises serum osmolality to >320 mOsm/kg.
- Hyperviscosity: Dehydrated, concentrated blood becomes thick and prone to clotting.
- Neurological Impairment: Hyperosmolality causes altered mental state, progressing to coma.
Key Difference from DKA
- DKA: Primarily T1DM. Absolute insulin deficiency. Lipolysis is unchecked, generating Ketones and Acidosis. Glucose usually 15-30 mmol/L.
- HHS: Primarily T2DM. Relative insulin deficiency (enough to suppress ketones). Profound hyperglycaemia (>30-50). No significant acidosis (unless mixed picture).
4. Differential Diagnosis (Hyperglycaemic Emergency)
| Condition | Glucose | Ketones | Acidosis (pH) | Osmolality |
|---|---|---|---|---|
| DKA | Usually 15-30 | High (>3) | less than 7.3 (Acidotic) | Variable (can be high) |
| HHS | Usually >30, often >50 | less than 3 | >7.3 (Normal) | >320 |
| Mixed DKA/HHS | High | High | less than 7.3 | >320 |
| Hypoglycaemia | less than 4 | Normal | Normal | Normal |
5. Clinical Presentation
History
Signs
Insidious Onset
Develops over days to weeks.
Polyuria, Polydipsia
Eventually patient becomes too obtunded to drink, worsening dehydration.
Weakness, Confusion
Progressing to Drowsiness, Coma.
Precipitant
Often an underlying infection.
6. Investigations
Diagnostic Criteria (JBDS Guidelines)
- Hypovolaemia: Clinical assessment. Often >8L deficit.
- Glucose >30 mmol/L (Often >50).
- Osmolality >320 mOsm/kg.
- Calculated: 2(Na+) + Glucose + Urea.
- No significant Ketosis: Blood ketones less than 3 mmol/L.
- pH usually >7.3 (No significant acidosis).
Other Investigations
- U&Es: Often raised Urea (Pre-renal failure), Hypokalaemia or Hyperkalaemia (shifts).
- FBC: Raised WCC (Infection? Or stress response).
- Blood Cultures / Urine Cultures / CXR: Find the precipitant.
- VBG / ABG: Check pH, Lactate.
- ECG: Check for MI (Silent in elderly diabetics), K+ effects.
7. Management
Management Algorithm
HHS DIAGNOSED
(Glucose >30, Osm >320, Kless than 3, pH>7.3)
↓
HDU / ITU ADMISSION
(Close Monitoring)
↓
SECURE IV ACCESS x 2
↓
INITIAL BLOODS (VBG, U&E, FBC, Cultures)
↓
┌──────────────────────────────────────────┐
│ STEP 1: FLUID RESUSCITATION (SLOW) │
│ ---------------------------------------- │
│ Goal: Replace 50% of deficit over 24h │
│ Then remaining 50% over next 24h │
│ Use: 0.9% Saline │
│ Rate: ~1L/hr for 1-2h, then slower │
│ (Fluid balance hourly) │
└──────────────────────────────────────────┘
↓
┌──────────────────────────────────────────┐
│ STEP 2: POTASSIUM REPLACEMENT │
│ ---------------------------------------- │
│ K+ will drop as insulin starts. │
│ Keep K+ 4-5 mmol/L. │
│ Add 40mmol KCl per litre as needed. │
└──────────────────────────────────────────┘
↓
┌──────────────────────────────────────────┐
│ STEP 3: INSULIN (DELAYED / LOW DOSE) │
│ ---------------------------------------- │
│ Do NOT start immediately. │
│ Fluid alone will drop glucose. │
│ START only if: │
│ - Ketones >1 mmol/L (mixed picture), OR│
│ - Glucose stops falling with fluids. │
│ Rate: 0.05 units/kg/hr (HALF DKA rate). │
└──────────────────────────────────────────┘
↓
┌──────────────────────────────────────────┐
│ STEP 4: VTE PROPHYLAXIS (ESSENTIAL) │
│ ---------------------------------------- │
│ All patients: LMWH (e.g., Enoxaparin) │
│ High clot risk (viscosity). │
│ Consider treatment dose if thrombosis. │
└──────────────────────────────────────────┘
↓
MONITOR HOURLY:
- Glucose, Osmolality, K+
- Fluid Balance
- Neuro Obs (GCS)
↓
TARGET CORRECTION RATES:
- Glucose fall: 3-8 mmol/L/h
- Osmolality fall: 3-8 mOsm/kg/h
- Na should RISE as glucose falls (Corrected)
Key Correction Targets
- Osmolality: Aim for decrease of 3-8 mOsm/kg per hour.
- Glucose: Aim for decrease of 3-8 mmol/L per hour.
- Sodium: Sodium usually RISES as glucose falls (Corrected Sodium formula). This is expected and desired. The actual osmolality is what matters.
Sodium Correction in HHS
- As glucose drops, water leaves the intravascular space, concentrating sodium. Measured Na will rise. This is NOT new hypernatraemia; it was masked.
- Corrected Sodium: Na + 2.4 x ((Glucose - 5.5)/5.5). Use this to track true sodium status.
8. Complications
Immediate
- Thrombosis: DVT, PE, Arterial Stroke, Mesenteric Ischaemia. Due to hyperviscosity.
- Cerebral Oedema: From too-rapid osmolar correction.
- Osmotic Demyelination Syndrome (CPM): From too-rapid sodium/osmolality correction.
- Acute Kidney Injury: Pre-renal from severe dehydration.
- Arrhythmias: From electrolyte shifts (K+).
Late
- Increased Mortality: 15-20%.
- Foot Complications: May have underlying foot sepsis.
- Recurrence: If underlying precipitants not addressed.
9. Prognosis and Outcomes
- Mortality: 15-20% (Much higher than DKA).
- Poor Prognostic Factors: Older age, Severe hyperosmolality (>350), Coma, Underlying sepsis, Delays in treatment, Thrombotic complications.
- Survivors: Usually recover neurologically if managed correctly.
10. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| HHS | JBDS (UK) 2022 | Slow rehydration (48-72h). Low-dose insulin (0.05 units/kg/hr). Prophylactic LMWH for all. |
| Hyperglycaemic Emergencies | ADA | Classification of DKA vs HHS. |
Landmark Evidence
JBDS Guideline (2012, Updated 2022)
- Established the principle of slow correction in HHS.
- Defined the target rates for glucose and osmolality drop.
- Emphasised the high thrombosis risk and need for LMWH.
11. Patient and Layperson Explanation
What is HHS?
It is a serious emergency in people with Type 2 Diabetes where the blood sugar rises to very high levels (often over 30-50 mmol/L). This causes severe dehydration ("drying out").
How is it different from DKA?
In DKA (Diabetic Ketoacidosis), the body makes lots of acids (ketones). In HHS, ketones are minimal but the blood becomes extremely thick and concentrated. This makes HHS dangerous in a different way, especially for blood clots.
What is the treatment?
- Fluids: We give you lots of salt water through a drip, very slowly over 1-2 days, to rehydrate you safely.
- Insulin: We may give a small amount of insulin if needed, but fluids are the most important thing.
- Blood thinners: We give an injection to prevent blood clots, as your blood is very thick.
How can I prevent it?
- Keep your blood sugars well controlled.
- Stay hydrated, especially if you are unwell or have a fever.
- Seek medical help early if you feel very thirsty, are urinating a lot, or feel confused.
12. References
Primary Sources
- Joint British Diabetes Societies (JBDS). The Management of the Hyperosmolar Hyperglycaemic State (HHS) in Adults with Diabetes. 2022.
- Kitabchi AE, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009.
13. Examination Focus
Common Exam Questions
- Diagnosis: "Key difference from DKA?"
- Answer: No significant ketones (less than 3 mmol/L), No significant acidosis (pH >7.3), Glucose usually much higher (>30-50).
- Management: "Insulin rate?"
- Answer: Lower than DKA: 0.05 units/kg/hr. Often delayed until glucose stops falling with fluids alone.
- Complication: "Why VTE prophylaxis mandatory?"
- Answer: Hyperviscosity from dehydration causes very high thrombosis risk (DVT, PE, Stroke).
- Fluid: "Why slow rehydration?"
- Answer: Rapid correction of osmolality causes fluid shifts, leading to Cerebral Oedema or Osmotic Demyelination Syndrome.
Viva Points
- Corrected Sodium: Explain the formula and why sodium appears to rise as glucose falls.
- Mechanism of No Ketosis: T2DM has enough residual insulin to suppress lipolysis in adipose tissue, preventing FFA release and ketogenesis.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.