Hyperosmolar hyperglycaemic state

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

serum potassium <3.5 mmol/L (<3.5 mEq/L)

1st line – intravenous fluids and potassium replacement

Back

1st line –

intravenous fluids and potassium replacement

Start intravenous fluids as soon as you suspect hyperosmolar hyperglycaemic state (HHS). Request immediate critical care support if you cannot get intravenous access.[6]

Give 1 L of 0.9% sodium chloride (normal saline) over 1 hour (or according to local protocols). Consider giving more rapid fluid replacement if the systolic blood pressure is <90 mmHg.[6]
In practice, seek urgent advice from the diabetes specialist team if the serum sodium on admission is very high (>150 mmol/L [>150 mEq/L]) to determine management.

Add potassium to intravenous fluids using pre-mixed 0.9% sodium chloride with potassium chloride. Involve senior or critical care support as a high dose of additional potassium needs to be given.[6]

Practical tip

Determine the initial rate of intravenous fluid by assessing the degree of initial dehydration and any coexisting comorbidities. Maintain caution, particularly with older patients, because giving intravenous fluids too quickly may precipitate heart failure, but giving them too slowly may fail to reverse acute kidney injury.[6]

Typical fluid losses in HHS may be 100 to 220 mL/kg (10-22 litres in a person weighing 100 kg).[6]

Adjust the rate and type of ongoing intravenous fluid replacement according to the degree of dehydration, fluid balance, risk of heart failure, and monitoring of glucose, urea, electrolytes, and serum osmolality (monitor these hourly for the first 6 hours). [ Osmolality Estimator (serum) Opens in new window ] The rate of intravenous fluids should usually be 0.5 to 1 L/hour. The Joint British Diabetes Societies (JBDS) guideline recommends the following:[6]

Consider continuing 0.9% sodium chloride at the same rate if:[6]
- Sodium is increasing
  AND
- Serum osmolality is decreasing by 3 to 8 mOsm/kg/hour (3-8 mmol/kg/hour)
Consider increasing the rate of 0.9% sodium chloride if:[6]
- Sodium is increasing
  AND
- Serum osmolality is increasing (or declining at less than 3 mOsm/kg/hour [<3 mmol/kg/hour])
  AND
- Positive fluid balance is inadequate
OR
- Blood glucose is decreasing by <5 mmol/L/hour (<90 mg/dL/hour)
  AND
- Positive fluid balance is inadequate
Consider switching to 0.45% sodium chloride and continuing this at the same rate if:[6]
- Serum osmolality is increasing
  AND
- Positive fluid balance is adequate
Aim to keep blood glucose 10-15 mmol/L (180-270 mg/dL) in the first 24 hours.[6]
- If blood glucose falls below 14 mmol/L (<252 mg/dL), start 5% or 10% glucose at 125 mL/hour (or according to local protocols) and continue 0.9% sodium chloride solution.[6]

Practical tip

In practice, local recommendations for monitoring may vary and measurement of serum osmolality to monitor the patient's response to treatment may not be commonly used; check your local protocol and seek senior advice if you are unsure about the patient’s fluid requirements.

Practical tip

Be aware that hypotonic (0.45% sodium chloride) solutions may be appropriate for people with HHS and significant hypernatraemia. However, you should only give hypotonic solutions to prevent a rise in sodium levels if serum osmolality is not declining concurrently.[6]

A rise in sodium level is inevitable because fluid replacement (without insulin) will lower blood glucose which will reduce osmolality causing a shift of water into the intracellular space.[6]

In practice, seek urgent advice from the diabetes specialist team if the serum sodium on admission is very high (>150 mmol/L [>150 mEq/L]) to determine management.

Continue intravenous fluids until the patient is eating and drinking normally. Start and maintain a fluid balance chart until intravenous fluids are no longer required.

Plus – supportive care and referral to critical care

Back

Plus –

supportive care and referral to critical care

Treatment recommended for ALL patients in selected patient group

Involve senior or critical care support if:[6]

Serum osmolality is >350 mOsm/kg (>350 mmol/kg) [ Osmolality Estimator (serum) Opens in new window ]
Serum sodium is >160 mmol/L (>160 mEq/L)
Venous/arterial pH is <7.1
Serum potassium is <3.5 mmol/L (<3.5 mEq/L) or >6 mmol/L (>6 mEq/L) on admission
Glasgow Coma Scale (GCS) score is <12 or AVPU (Alert, Voice, Pain, Unresponsive) scale score is abnormal [ Glasgow Coma Scale Opens in new window ]
Oxygen saturation is <92% on air (assuming normal baseline respiratory function)
Systolic blood pressure is <90 mmHg
Pulse is >100 or <60 bpm
Urine output is <0.5 mL/kg/hour
Serum creatinine is >200 micromol/L (>2.3 mg/dL)
The patient is hypothermic
The patient has a concurrent macrovascular event such as myocardial infarction or stroke, or other significant comorbidity.
- In practice, heart failure and significant renal impairment (chronic kidney disease and/or acute kidney injury, particularly if eGFR <30 mL/minute/1.73 m²) should also warrant senior or critical care support.

Start a fluid balance chart.[6]

Insert a urinary catheter to monitor urine output (aim for 0.5 mL/kg/hour).[6]
Stop the fluid balance chart once intravenous fluids are no longer required.[6]

Involve the diabetes specialist team early and ensure all patients are reviewed by a senior colleague within 1 hour of presentation.[6]

Check that the patient’s heels and other pressure areas are protected and that daily foot checks are in place.[6]

Plus – insulin

Back

Plus –

insulin

Treatment recommended for ALL patients in selected patient group

Timing of a fixed-rate intravenous insulin infusion (FRIII) (which should be started either at initial presentation to hospital or later during admission) depends on the presence of ketones, and monitoring of fluid balance and glucose.[6]

Practical tip

Always start intravenous fluids before giving insulin.

Insulin treatment prior to adequate fluid replacement may cause cardiovascular collapse.[6]

Start an FRIII if there is significant ketonaemia (beta-hydroxybutyrate >1 mmol/L) or ketonuria.[6]

Use a rate of 0.05 units/kg/hour if blood ketones (beta-hydroxybutyrate) are ≤3.0 mmol/L and the patient is not acidotic (venous pH ≥7.3 and bicarbonate ≥15.0 mmol/L), or according to local protocols.[6]
Use a rate of 0.1 units/kg/hour if the patient is acidotic (pH <7.3 and bicarbonate <15 mmol/L) and blood ketones (beta-hydroxybutyrate) are >3.0 mmol/L or ketonuria (2+ or more), or according to local protocols (i.e. if the patient has mixed DKA and HHS).[6]

During the first 6 hours, monitor the patient carefully; if blood glucose is decreasing by <5 mmol/L/hour (90 mg/dL/hour) and positive fluid balance is adequate:[6]

Increase the rate of FRIII to 0.1 units/kg/hour (or according to local protocols) if this has been started already.
Start a FRIII at a rate of 0.05 units/kg/hour (or according to local protocols) if this has not been started.

After 6 hours, increase or decrease the rate of FRIII by 1 unit/hour (or according to local protocols) to maintain blood glucose in the range 10 to 15 mmol/L (180-270 mg/dL).[6]

After 24 hours, make sure the patient has been reviewed by the diabetes specialist team; they will convert the patient to a subcutaneous insulin regimen when biochemically stable.[6]

Give a variable rate intravenous insulin infusion if the patient is not eating and drinking.
Most patients should go home on subcutaneous insulin.[6]
If the patient has previously undiagnosed diabetes, or known diabetes that was previously well controlled with oral medication, they may be switched to oral medication if they remain stable for a period of time (usually weeks to months).[6]

Primary options

insulin neutral: consult local protocols for dosing guidelines

Plus – identify and treat any precipitating acute illness

Plus – monitor biochemical markers

Back

Plus –

monitor biochemical markers

Treatment recommended for ALL patients in selected patient group

Establish a monitoring regimen for your patient according to your local protocol. The Joint British Diabetes Societies (JBDS) guideline recommends.[6]

Continued hourly blood glucose monitoring for 24 hours
Hourly sodium, potassium, urea, and calculated serum osmolality for the first 6 hours, which can be reduced to every 2 hours after 6 hours if serum osmolality is decreasing by 3 to 8 mOsm/kg/hour (3-8 mmol/kg/hour) [ Osmolality Estimator (serum) Opens in new window ]
- Monitoring of sodium, potassium, urea, and serum osmolality may be reduced to every 4 hours after 12 hours if the patient is continuing to improve[6]
Continuous pulse oximetry[6]
Continuous cardiac monitoring if necessary[6]
Vital signs including early warning score (EWS).

Practical tip

Reduce monitoring of blood glucose to every 2 hours after 6 hours if the blood glucose is stable (around 12-15 mmol/L [216-270 mg/dL])
Reduce monitoring of sodium, potassium, and urea to every 2 hours after 6 hours if these are improving.

Plus – monitor and treat complications

Plus – thromboprophylaxis

serum potassium 3.5 to 5.5 mmol/L (3.5 to 5.5 mEq/L)

1st line – intravenous fluids and potassium replacement

Back

1st line –

intravenous fluids and potassium replacement

Start intravenous fluids as soon as you suspect hyperosmolar hyperglycaemic state (HHS). Request immediate critical care support if you cannot get intravenous access.[6]

Give 1 L of 0.9% sodium chloride (normal saline) over 1 hour (or according to local protocols). Consider giving more rapid fluid replacement if the systolic blood pressure is <90 mmHg.[6]
In practice, seek urgent advice from the diabetes specialist team if the serum sodium on admission is very high (>150 mmol/L [>150 mEq/L]) to determine management.

Add 40 mmol/L potassium (or according to local protocols) to intravenous fluids using pre-mixed 0.9% sodium chloride with potassium chloride.[6]

Practical tip

Typical fluid losses in HHS may be 100 to 220 mL/kg (10-22 litres in a person weighing 100 kg).[6]

Consider continuing 0.9% sodium chloride at the same rate if:[6]
- Sodium is increasing
  AND
- Serum osmolality is decreasing by 3 to 8 mOsm/kg/hour (3-8 mmol/kg/hour)
Consider increasing the rate of 0.9% sodium chloride if:[6]
- Sodium is increasing
  AND
- Serum osmolality is increasing (or declining at less than 3 mOsm/kg/hour [3 mmol/kg/hour])
  AND
- Positive fluid balance is inadequate
OR
- Blood glucose is decreasing by <5 mmol/L/hour (<90 mg/dL/hour)
  AND
- Positive fluid balance is inadequate
Consider switching to 0.45% sodium chloride and continuing this at the same rate if:[6]
- Serum osmolality is increasing
  AND
- Positive fluid balance is adequate
Aim to keep blood glucose 10-15 mmol/L (180-270 mg/dL) in the first 24 hours.[6]
- If blood glucose falls below 14 mmol/L (<252 mg/dL), start 5% or 10% glucose at 125 mL/hour (or according to local protocols) and continue 0.9% sodium chloride solution.[6]

Practical tip

A rise in sodium level is inevitable because fluid replacement (without insulin) will lower blood glucose which will reduce osmolality causing a shift of water into the intracellular space.[6]

In practice, seek urgent advice from the diabetes specialist team if the serum sodium on admission is very high (>150 mmol/L [>150 mEq/L]) to determine management.

Continue intravenous fluids until the patient is eating and drinking normally. Start and maintain a fluid balance chart until intravenous fluids are no longer required.

Plus – supportive care and referral to critical care

Back

Plus –

supportive care and referral to critical care

Treatment recommended for ALL patients in selected patient group

Involve senior or critical care support if:[6]

Serum osmolality is >350 mOsm/kg (>350 mmol/kg) [ Osmolality Estimator (serum) Opens in new window ]
Serum sodium is >160 mmol/L (>160 mEq/L)
Venous/arterial pH is <7.1
Serum potassium is <3.5 mmol/L (<3.5 mEq/L) or >6 mmol/L (>6 mEq/L) on admission
Glasgow Coma Scale (GCS) score is <12 or AVPU (Alert, Voice, Pain, Unresponsive) scale score is abnormal [ Glasgow Coma Scale Opens in new window ]
Oxygen saturation is <92% on air (assuming normal baseline respiratory function)
Systolic blood pressure is <90 mmHg
Pulse is >100 or <60 bpm
Urine output is <0.5 mL/kg/hour
Serum creatinine is >200 micromol/L (>2.3 mg/dL)
The patient is hypothermic
The patient has a concurrent macrovascular event such as myocardial infarction or stroke, or other significant comorbidity.
- In practice, heart failure and significant renal impairment (chronic kidney disease and/or acute kidney injury, particularly if eGFR <30 mL/minute/1.73 m²) should also warrant senior or critical care support.

Start a fluid balance chart.[6]

Insert a urinary catheter to monitor urine output (aim for 0.5 mL/kg/hour).[6]
Stop the fluid balance chart once intravenous fluids are no longer required.[6]

Involve the diabetes specialist team early and ensure all patients are reviewed by a senior colleague within 1 hour of presentation.[6]

Check that the patient’s heels and other pressure areas are protected and that daily foot checks are in place.[6]

Plus – insulin

Back

Plus –

insulin

Treatment recommended for ALL patients in selected patient group

Practical tip

Always start intravenous fluids before giving insulin.

Insulin treatment prior to adequate fluid replacement may cause cardiovascular collapse.[6]

Start an FRIII if there is significant ketonaemia (beta-hydroxybutyrate >1 mmol/L).[6]

Use a rate of 0.05 units/kg/hour if blood ketones (beta-hydroxybutyrate) are ≤3.0 mmol/L and the patient is not acidotic (venous pH ≥7.3 and bicarbonate ≥15.0 mmol/L), or according to local protocols.[6]
Use a rate of 0.1 units/kg/hour if the patient is acidotic (pH <7.3 and bicarbonate <15 mmol/L) and blood ketones (beta-hydroxybutyrate) are >3.0 mmol/L or ketonuria (2+ or more), or according to local protocols (i.e. if the patient has mixed DKA and HHS).[6]

During the first 6 hours, monitor the patient carefully; if blood glucose is decreasing by <5 mmol/L/hour (<90 mg/dL/hour) and positive fluid balance is adequate:[6]

Increase the rate of FRIII to 0.1 units/kg/hour (or according to local protocols) if this has been started already.
Start a FRIII at a rate of 0.05 units/kg/hour (or according to local protocols) if this has not been started.

After 6 hours, increase or decrease the rate of FRIII by 1 unit/hour (or according to local protocols) to maintain blood glucose in the range 10 to 15 mmol/L (180-270 mg/dL).[6]

After 24 hours, make sure the patient has been reviewed by the diabetes specialist team; they will convert the patient to a subcutaneous insulin regimen when biochemically stable.[6]

Give a variable rate intravenous insulin infusion if the patient is not eating and drinking.
Most patients should go home on subcutaneous insulin.[6]
If the patient has previously undiagnosed diabetes, or known diabetes that was previously well controlled with oral medication, they may be switched to oral medication if they remain stable for a period of time (usually weeks to months).[13]

Primary options

insulin neutral: consult local protocols for dosing guidelines

Plus – identify and treat any precipitating acute illness

Plus – monitor biochemical markers

Back

Plus –

monitor biochemical markers

Treatment recommended for ALL patients in selected patient group

Establish a monitoring regimen for your patient according to your local protocol. The Joint British Diabetes Societies (JBDS) guideline recommends:[6]

Continued hourly blood glucose monitoring for 24 hours
Hourly sodium, potassium, urea, and calculated serum osmolality for the first 6 hours, which can be reduced to every 2 hours after 6 hours if serum osmolality is decreasing by 3 to 8 mOsm/kg/hour (3-8 mmol/kg/hour) [ Osmolality Estimator (serum) Opens in new window ]
- Monitoring of sodium, potassium, urea, and serum osmolality may be reduced to every 4 hours after 12 hours if the patient is continuing to improve[6]
Continuous pulse oximetry[6]
Continuous cardiac monitoring if necessary[6]
Vital signs including early warning score (EWS).

Practical tip

Reduce monitoring of blood glucose to every 2 hours after 6 hours if the blood glucose is stable (around 12-15 mmol/L [216-270 mg/dL])
Reduce monitoring of sodium, potassium, and urea to every 2 hours after 6 hours if these are improving.

Plus – monitor and treat complications

Plus – thromboprophylaxis

serum potassium >5.5 mmol/L (>5.5 mEq/L)

1st line – intravenous fluids

Back

1st line –

intravenous fluids

Start intravenous fluids as soon as you suspect hyperosmolar hyperglycaemic state (HHS). Request immediate critical care support if you cannot get intravenous access.[6]

Give 1 L of 0.9% sodium chloride (normal saline) over 1 hour (or according to local protocols). Consider giving more rapid fluid replacement if the systolic blood pressure is <90 mmHg.[6]
In practice, seek urgent advice from the diabetes specialist team if the serum sodium on admission is very high (>150 mmol/L [>150 mEq/L]) to determine management.

Practical tip

Typical fluid losses in HHS may be 100 to 220 mL/kg (10-22 litres in a person weighing 100 kg).[6]

Consider continuing 0.9% sodium chloride at the same rate if:[6]
- Sodium is increasing
  AND
- Serum osmolality is decreasing by 3 to 8 mOsm/kg/hour (3-8 mmol/kg/hour)
Consider increasing the rate of 0.9% sodium chloride if:[6]
- Sodium is increasing
  AND
- Serum osmolality is increasing (or declining at less than 3 mOsm/kg/hour [<3 mmol/kg/hour])
  AND
- Positive fluid balance is inadequate
OR
- Blood glucose is decreasing by <5 mmol/L/hour (<90 mg/dL/hour)
  AND
- Positive fluid balance is inadequate
Consider switching to 0.45% sodium chloride and continuing this at the same rate if:[6]
- Serum osmolality is increasing
  AND
- Positive fluid balance is adequate
Aim to keep blood glucose 10-15 mmol/L (180-270 mg/dL) in the first 24 hours.[6]
- If blood glucose falls below 14 mmol/L (<252 mg/dL), start 5% or 10% glucose at 125 mL/hour (or according to local protocols) and continue 0.9% sodium chloride solution.[6]

Practical tip

Be aware that hypotonic (0.45% sodium chloride) solutions may be appropriate for people with HHS and significant hypernatraemia. However, you should only hypotonic solutions to prevent a rise in sodium level unless serum osmolality is not declining concurrently.[6]

A rise in sodium level is inevitable because fluid replacement (without insulin) will lower blood glucose which will reduce osmolality causing a shift of water into the intracellular space.[6]

In practice, seek urgent advice from the diabetes specialist team if the serum sodium on admission is very high (>150 mmol/L [>150 mEq/L]) to determine management.

Continue intravenous fluids until the patient is eating and drinking normally. Start and maintain a fluid balance chart until intravenous fluids are no longer required.

Plus – supportive care and referral to critical care

Back

Plus –

supportive care and referral to critical care

Treatment recommended for ALL patients in selected patient group

Involve senior or critical care support if:[6]

Serum osmolality is >350 mOsm/kg (>350 mmol/kg) [ Osmolality Estimator (serum) Opens in new window ]
Serum sodium is >160 mmol/L (>160 mEq/L)
Venous/arterial pH is <7.1
Serum potassium is <3.5 mmol/L (<3.5 mEq/L) or >6 mmol/L (>6 mEq/L) on admission
Glasgow Coma Scale (GCS) score is <12 or AVPU (Alert, Voice, Pain, Unresponsive) scale score is abnormal [ Glasgow Coma Scale Opens in new window ]
Oxygen saturation is <92% on air (assuming normal baseline respiratory function)
Systolic blood pressure is <90 mmHg
Pulse is >100 or <60 bpm
Urine output is <0.5 mL/kg/hour
Serum creatinine is >200 micromol/L (>2.3 mg/dL)
The patient is hypothermic
The patient has a concurrent macrovascular event such as myocardial infarction or stroke, or other significant comorbidity.
- In practice, heart failure and significant renal impairment (chronic kidney disease and/or acute kidney injury, particularly if eGFR <30 mL/minute/1.73 m²) should also warrant senior or critical care support.

Start a fluid balance chart.[6]

Insert a urinary catheter to monitor urine output (aim for 0.5 mL/kg/hour).[6]
Stop the fluid balance chart once intravenous fluids are no longer required.[6]

Involve the diabetes specialist team early and ensure all patients are reviewed by a senior colleague within 1 hour of presentation.[6]

Check that the patient’s heels and other pressure areas are protected and that daily foot checks are in place.[6]

Plus – insulin

Back

Plus –

insulin

Treatment recommended for ALL patients in selected patient group

Practical tip

Always start intravenous fluids before giving insulin.

Insulin treatment prior to adequate fluid replacement may cause cardiovascular collapse.[6]

Start an FRIII if there is significant ketonaemia (beta-hydroxybutyrate >1 mmol/L).[6]

Use a rate of 0.05 units/kg/hour if blood ketones (beta-hydroxybutyrate) are ≤3.0 mmol/L and the patient is not acidotic (venous pH ≥7.3 and bicarbonate ≥15.0 mmol/L), or according to local protocols.[6]
Use a rate of 0.1 units/kg/hour if the patient is acidotic (pH <7.3 and bicarbonate <15 mmol/L) and blood ketones (beta-hydroxybutyrate) are >3.0 mmol/L or ketonuria (2+ or more), or according to local protocols (i.e. if the patient has mixed DKA and HHS).[6]

During the first 6 hours, monitor the patient carefully; if blood glucose is decreasing by <5 mmol/L/hour (<90 mg/dL/hour) and positive fluid balance is adequate:[6]

Increase the rate of FRIII to 0.1 units/kg/hour (or according to local protocols) if this has been started already.
Start an FRIII at a rate of 0.05 units/kg/hour (or according to local protocols) if this has not been started.

After 6 hours, increase or decrease the rate of FRIII by 1 unit/hour (or according to local protocols) to maintain blood glucose in the range 10 to 15 mmol/L (180-270 mg/dL).[6]

After 24 hours, make sure the patient has been reviewed by the diabetes specialist team; they will convert the patient to a subcutaneous insulin regimen when biochemically stable.[13]

Give a variable rate intravenous insulin infusion if the patient is not eating and drinking.
Most patients should go home on subcutaneous insulin.
If the patient has previously undiagnosed diabetes, or known diabetes that was previously well controlled with oral medication, they may be switched to oral medication if they remain stable for a period of time (usually weeks to months).

Primary options

insulin neutral: consult local protocols for dosing guidelines

Plus – identify and treat any precipitating acute illness

Plus – monitor biochemical markers

Plus – potassium replacement (once serum potassium is ≤5.5 mmol/L)

Plus – monitor and treat complications

Plus – thromboprophylaxis

Use of this content is subject to our disclaimer

Hyperosmolar hyperglycaemic state

Treatment algorithm

serum potassium <3.5 mmol/L (<3.5 mEq/L)

intravenous fluids and potassium replacement

Practical tip

Practical tip

Practical tip

supportive care and referral to critical care

insulin

Practical tip

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

identify and treat any precipitating acute illness

monitor biochemical markers

Practical tip

monitor and treat complications

thromboprophylaxis

serum potassium 3.5 to 5.5 mmol/L (3.5 to 5.5 mEq/L)

intravenous fluids and potassium replacement

Practical tip

Practical tip

Practical tip

supportive care and referral to critical care

insulin

Practical tip

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

identify and treat any precipitating acute illness

monitor biochemical markers

Practical tip

monitor and treat complications

thromboprophylaxis

serum potassium >5.5 mmol/L (>5.5 mEq/L)

intravenous fluids

Practical tip

Practical tip

Practical tip

supportive care and referral to critical care

insulin

Practical tip

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

identify and treat any precipitating acute illness

monitor biochemical markers

Practical tip

potassium replacement (once serum potassium is ≤5.5 mmol/L)

monitor and treat complications

thromboprophylaxis