Endocrinology & Metabolic

Hyperosmolar Hyperglycaemic State (HHS)

In hyperosmolar hyperglycaemic state (HHS), residual insulin suppresses ketone production but not hyperglycaemia, so days of osmotic diuresis produce extreme dehydration and hyperosmolality rather than acidosis.

In a nutshell

Hyperosmolar hyperglycaemic state (HHS) is hypovolaemia with osmolality 320 mOsm/kg or above and glucose 30 mmol/L or above, without significant ketones or acidosis. Give 0.9% sodium chloride 1 litre IV over 1 hour and, unlike DKA, do not start insulin initially unless significant ketonaemia is present.

Classic presentation

An older person with type 2 diabetes, several days of thirst, polyuria and worsening confusion, profoundly dehydrated after a chest infection, with glucose above 30 mmol/L and no ketones.

Key points

A fixed rate intravenous insulin infusion (FRIII) runs at a set weight-based rate and ignores the glucose reading; a variable rate infusion (VRIII) is titrated to glucose.
Potassium losses reach 4 to 6 mmol/kg and water losses 100 to 220 mL/kg, which is 10 to 22 litres in a 100 kg adult.
Potassium goes in ready-mixed bags. Never faster than 20 mmol/hour intravenously, and not above 40 mmol/L in a peripheral line.
JBDS 06, the Joint British Diabetes Societies for Inpatient Care guideline, is a consensus document: there are almost no data on fluid regimens in HHS, and NICE has none.
HHS occurs up to seven times less often than DKA, typically over 45 years old, and its usual precipitant is a chest or urinary tract infection.
No recent UK mortality data exists for HHS. JBDS 06 quotes reported series at 15 to 20%, well above the mortality of DKA.
Confusion is commoner once osmolality passes 330 mOsm/kg, but hypertonicity preserves intravascular volume, so people can look far less dehydrated than they are.
Assess cognition formally at presentation and daily against the pre-morbid state, because return of cognition is one of the four resolution criteria.
JBDS 06 states the glucose ceiling twice: the executive summary says no more than 5.0 mmol/L/hour, the evidence section says a safe fall is 4.0 to 6.0 mmol/hour.

First-line investigation

Capillary glucose, blood ketones, venous gas and U&E, then calculated osmolality = (2 x sodium) + glucose + urea. Expect at least 320 mOsm/kg, glucose at least 30 mmol/L, ketones 3.0 mmol/L or below.

Management

0 to 60 minutes: fluid, not insulin

Diagnostic triad: hypovolaemia, osmolality 320 mOsm/kg or above, glucose 30 mmol/L or above, with ketones 3.0 mmol/L or below. Not biochemistry alone.^1,2
Give 0.9% sodium chloride 1 litre IV over 1 hour; consider faster replacement below 90 mmHg. Use a slower individual plan below 50 kg or with heart or renal disease.^1,2
Initially avoid insulin unless ketones exceed 1.0 mmol/L. If glucose later plateaus despite fluid, start 0.05 units/kg/hour; premature insulin can cause cardiovascular collapse.¹
Assess cognition formally, foot risk and contraindications to heparin. Send glucose, ketones, U&E, venous gas, cultures, ECG and chest radiograph.¹

60 minutes to 6 hours: hit the balance targets

Continue 0.9% sodium chloride at 0.5 to 1 litre/hour, targeting positive balance of 2 to 3 litres by 6 hours. Reduce and individualise the rate below 50 kg or with heart or renal disease.^1,2
Target an osmolality fall of 3.0 to 8.0 mOsm/kg/hour, and no more than 3 mOsm/kg/hour if at high risk of cerebral oedema.¹
Potassium above 5.5 mmol/L: none. 3.5 to 5.5 mmol/L: 40 mmol/L of infusate. Below 3.5 mmol/L: senior review. Identical to DKA.^1,3
Glucose must not fall faster than 5.0 mmol/L/hour. Hold it at 10 to 15 mmol/L for the first 24 hours.^1,2

Insulin, when it is needed at all

Start soluble insulin 0.05 units/kg/hour IV once glucose plateaus on fluid alone: 50 units made up to 50 mL with 0.9% sodium chloride, so 3.5 units/hour at 70 kg.¹
If it is already running and glucose is not falling, increase by 1.0 unit/hour. If glucose falls faster than 5.0 mmol/L/hour, halve the rate.¹
Mixed DKA/HHS is marked hypovolaemia, marked hyperosmolality, pH below 7.3 and ketones above 3.0 mmol/L. Use the DKA pathway at 0.1 units/kg/hour.^1,2
Below 14 mmol/L add 5% or 10% glucose at 125 mL/hour and continue the 0.9% sodium chloride. Unlike DKA, that is not a trigger to reduce insulin.^1,2,3

Thromboprophylaxis, feet and the precipitant

Give prophylactic LMWH unless contraindicated. If enoxaparin is selected: creatinine clearance at least 30 mL/min, 40 mg subcutaneously daily; 15 to 30 mL/min, 20 mg daily; avoid below 15 mL/min outside haemodialysis.^1,5,6
Consider extended treatment if judged very high risk. Full anticoagulation only for suspected thrombosis or acute coronary syndrome. Thrombotic risk exceeds that in DKA.¹
Assume everyone is at high risk of foot ulceration. Off-load heels, provide a suitable mattress and check feet daily.¹
Treat the precipitant. Chest or urinary tract infection is commonest; also myocardial infarction, stroke, corticosteroids and interrupted diabetes treatment.^1,2

Markers of severity: level 2 care

Any one of these prompts high dependency or level 2 care: osmolality above 350 mOsm/kg, sodium above 160 mmol/L, venous pH below 7.1.^1,2
Potassium below 3.5 or above 6.0 mmol/L on admission, GCS below 12 or an abnormal AVPU (alert, voice, pain, unresponsive) score, saturation below 92% on air.¹
Systolic BP below 90 mmHg, pulse above 100 or below 60, urine output below 0.5 mL/kg/hour, creatinine above 200 micromol/L or acute kidney injury.¹
Hypothermia, other serious comorbidity, or a macrovascular event such as stroke or myocardial infarction. JBDS 06 gives no separate severe-HHS definition.¹

Resolution and recovery

Resolution needs all four: osmolality below 300 mOsm/kg, urine output at or above 0.5 mL/kg/hour, pre-morbid cognition, and glucose below 15 mmol/L.¹
Full normalisation of electrolytes and osmolality can take 72 hours. Do not expect normal biochemistry at 24 hours.¹
Continue IV fluids until eating and drinking, using a variable rate infusion meanwhile, then convert to subcutaneous insulin when biochemically stable.¹
Arrange diabetes education, sick-day rules, home ketone testing advice and diabetes team review before discharge, with a written care plan copied to the GP.¹

Exam traps

HHS is not DKA. Titrate fluid to positive-balance and osmolality targets rather than automatically copying the DKA bag sequence; use the local HHS chart.
The glucose rule is inverted: DKA chases a fall of at least 3.0 mmol/L/hour, HHS must not exceed about 5.0 mmol/L/hour.
Insulin is halved and usually delayed: 0.05 units/kg/hour, and only for ketonaemia or a plateaued glucose. Too early, it causes cardiovascular collapse.
Prophylactic low molecular weight heparin runs until the day of discharge in HHS. Do not carry over a fixed number of days from DKA.
A sodium rise of about 2.4 mmol/L per 5.5 mmol/L fall in glucose is expected. A much larger rise means too little fluid.
JBDS 06 has no severe-HHS criteria list to match severe DKA. It has markers indicating the need for level 2 care.
The potassium bands are the one figure that transfers from DKA unchanged. Everything else in the fluid, insulin and glucose regimen differs.
Normal glucose is not resolution. Osmolality, urine output and cognition must also be back before HHS is over.
JBDS 06 gives two insulin escalation rules: increase by 1 unit/hour or to 0.1 units/kg/hour. They diverge above 70 kg; use the local HHS chart.

Key sources

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.