The management of the hyperosmolar hyperglycaemic state (HHS) in adults with diabetes

• Rationale for Guidelines
• Aims
• Scope
• Exception
• Definition/Diagnosis
• Assessment of Severity
• Investigations
• Treatment Goals
• Management
• Monitoring
• Resolution of HHS
• Appendices
  1. See HHS Treatment Summary Algorithm Quick Reference Guide
  2. See HHS Troubleshoot Flowchart
  3. See HHS Prescription Chart

Rationale for guidelines

HHS (Hyperosmolar Hyperglycaemic State) is a well-known hyperglycaemic emergency with HHS being different and less common than diabetic ketoacidosis (DKA). Management of HHS needs a specialised and different approach to DKA. HHS is common in elderly and with multiple comorbidities and has a higher mortality than DKA. It can be accompanied by vascular complications such as myocardial infarction, stroke or peripheral arterial thrombosis.

HHS develops over many days and subsequently, the dehydration and metabolic complications are usually severe. Rapid correction of hyperglycaemia and hyperosmolality can lead to cerebral oedema because of an osmotic gradient between brain and plasma. The guideline proposed is largely based on Joint British Diabetes Societies (JBDS) inpatient care group for management of diabetes.

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Aims

The guideline aims to provide guidance on the management of hyperosmolar hyperglycaemia state in adult patients in Leeds Teaching Hospital NHS Trust

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Scope

This guideline is aimed at clinicians and staff nurses working in Leeds Teaching Hospital NHS Trust. It is also aimed at health professionals across the city in order to assist in making diagnosis of HHS and appropriate referral to the hospital.

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Exception

Patients with overlap criteria of DKA and HHS at diagnosis should be managed as per DKA protocol.
Please follow the clinical guideline on HHS by BSPED (British Society for Paediatric Endocrinology and Diabetes) for patients less than 18 years of age.
Management of HHS in end stage renal disease (ESRD) needs to be discussed with both renal physician and a diabetes specialist given lack of evidence/guideline in this area.

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Definition/Diagnosis

The following characteristics are required to make a diagnosis of HHS^iv:

• High osmolality (≥ 320 mosmol/kg)
• Hyperglycaemia (≥ 30 mmol/L) without significant ketosis (<3mmol/L) or acidosis (pH >7.3, bicarbonate >15mmol/L)
• Hypovolaemia

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Assessment of severity

The presence of one or more of the following may indicate the need for admission to a high-dependency unit / level 2 environment, where the insertion of a central venous catheter to aid assessment of fluid status and immediate senior review by a clinician skilled in the management of HHS should be considered ⁱⁱ:

• Osmolality greater than 350 mosmol/kg
• Sodium above 160 mmol/L
• Venous/arterial pH below 7.1
• Hypokalaemia (less than 3.5 mmol/L) or hyperkalaemia (more than 6 mmol/L) on admission
• Glasgow Coma Scale (GCS) less than 12 or abnormal
• Oxygen saturation below 92% on air (assuming normal baseline respiratory function)
• Systolic blood pressure below 90 mmHg
• Pulse over 100 or below 60 bpm
• Urine output less than 0.5 ml/kg/hr
• Serum creatinine > 200 μmol/L
• Hypothermia
• Macrovascular event such as myocardial infarction or stroke
• Other serious co-morbidity

We suggest further discussion is made with intensive care specialist or outreach team in order to evaluate need for intensive monitoring in high dependency care if appropriate.

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Investigations

Always at presentation

• Renal function, bicarbonate and lab venous glucose
• Measured or calculated serum osmolality (calculated as 2Na++ glucose + urea)
• Capillary blood glucose (CBG)
• Full blood count, liver function test and clotting screen
• Urine analysis and send for microscopy and culture
• Capillary blood ketones

Often indicated (depending on clinical suspicion)

• 12 lead ECG
• CXR
• Blood cultures
• CRP

Sometimes indicated

• Arterial blood gas (if oxygen saturation <95% on air or atypical venous blood gas result)

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Treatment Goals

The goals of treatment of HHS are to treat the underlying cause and to gradually and safely:

• Normalise the osmolality and restoration of volume deficit
• Replace fluid and electrolyte losses
• Normalise blood glucose

Other goals include prevention of:

• Arterial or venous thrombosis
• Other potential complications e.g. cerebral oedema/ central pontine myelinolysis
• Foot ulceration

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Management

A) Fluid therapy

Hyperglycaemia results in an osmotic diuresis and also renal losses of water in excess of sodium and potassium.  The estimated fluid losses in HHS are between 100-220 ml/kg.

Typical deficitsⁱⁱ

Fluid to use
0.9% sodium chloride is the initial fluid of choice^v (with or without potassium as required). The aim is to replace 50% of estimated fluid within the first 12 hours and the balance within the next 12 hours. However, this needs to be tailored according to patient’s initial severity, degree of renal impairment and other comorbidities such as heart failure.

Potassium therapy
Replacement of potassium in HHS is important similar to DKA management, although potassium shifts are less pronounced due to minimal acidaemia and lower rate of insulin infusion. These patients have frequent co-existent renal impairment.

Phosphate and magnesium

• Hypophosphatemia: There is no evidence to replace phosphate in the acute phase of HHS.
• Hypomagnesaemia: magnesium replacement should only be considered if the patient is symptomatic or has symptomatic hypocalcaemia. Please refer to following link for the symptoms/management of hypomagnesaemia: http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?ID=2105

Glucose infusion
In order to avoid hypoglycaemia, once the CBG has fallen <14mmol/l then 5% or 10% glucose should be commenced at 125ml/hr in addition to 0.9% sodium chloride.

B) Insulin therapy

• Adequate fluid replacement with 0.9% sodium chloride alone will lower blood glucose and therefore if significant ketonaemia is not present (blood ketone is ≤ 1 mmol/litre or urinary ketone less than 1), DO NOT start intravenous insulin initially.
• Once the blood glucose ceases to fall at the required rate (5mmol/l/hour) following the initial fluid replacement, insulin may be started after re-assessment of fluid balance and renal function.
• A fixed rate intravenous short acting insulin (e.g. actrapid) infusion at a rate of 0.05units/kg per hour should be used.
• Aim for an initial target blood glucose of 10-15mmol/l.
• If significant ketosis is present (blood ketones ≥3mmol/l or urinary ketones >2+) on admission, consider following trust DKA protocol.

As above, once CBG has fallen <14mmol/litre, commence 5% or 10% glucose should be commenced at 125/ml/hr in addition to 0.9% sodium chloride.

In patient with established intermediate/long acting insulin, this can be continued at the usual dose. Stop rapid acting insulin and other oral agents.

C) Thromboprophylaxis

Due to the increased risk of arterial and venous thromboembolism:

• All patients should receive prophylactic low-molecular weight heparin (LMWH) as per LTHT guidelines for the duration of admission unless contra-indicated.
• There is currently insufficient evidence to give treatment dose LMWH in patients admitted with HHS.

D) Anti-microbial prescription

Antibiotics should be prescribed when there are clinical or radiological signs of infection.
Pyrexia does not always accompany sepsis in acutely unwell patients. Infection (pneumonia and urinary tract infection) is the commonest precipitating cause of HHS^vi and occurs in 40% to 60% of patients. It is important to strongly consider intravenous antibiotics in patients admitted with HHS.

E) Foot protection

• Heel protectors should be applied to patients with neuropathy, peripheral arterial disease or lower limb deformity.
• Feet should be examined daily for signs of ulceration

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Monitoring

Aim to measure blood glucose, sodium, potassium, urea and calculated osmolality (2Na+ + glucose + urea) on admission and at 1 hour, 2 hours, 4 hours and 6 hours. If the response is adequate (see below) then repeat tests at 12 hours, 24 hours, followed by daily.

There are three elements that need to be measured to monitor treatment response in HHS:

• Serum osmolality
• Plasma sodium
• Glucose

Serum osmolality
A fall in the calculated plasma osmolality of 3-8mosmol/kg per hour indicates a satisfactory response to treatment. Aim to lower osmolality by no more than 5 mosmol/kg per hour

• If plasma Na+ increasing but osmolality declining at appropriate rate, continue 0.9% sodium chloride infusion.
• If osmolality declining at a rate less than 3mosmol/kg/hr (or is increasing) AND sodium levels rising, then check fluid balance:
  • If inadequate positive fluid balance (2-3L in first 6 hours, 3-6L in first 12 hours) increase rate of 0.9% sodium chloride infusion
  • If adequate fluid balance, consider switching to 0.45% sodium chloride at same rate of infusion
• If osmolality falling at >8mosmol/kg per hour, then reduce infusion rate if IV fluids and or insulin (if already commenced).

Plasma Sodium
Sodium levels may rise following initial fluid resuscitation and is expected. So, as long as the osmolality is declining at an appropriate rate, this is NOT an indication to give hypotonic solutions.

• After 24 hours, sodium levels should start to fall, which should not exceed 10mmol/l in 24 hours.

Glucose
Blood glucose levels should fall at a rate of approximately 5mmol/l per hour. If the rate of decline is less than this then check fluid balance:

• If positive fluid balance is inadequate, then increase the rate of infusion of 0.9% sodium chloride solution.
• If positive fluid balance is adequate, then commence low dose fixed rate intravenous insulin infusion at 0.05 units/kg/hour or increase to 0.1units/kg/hour if already commenced.

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Resolution of HHS

First 24 hours
Biochemistry is unlikely to have normalised and expect osmolality and sodium levels to be elevated at 24 hours

• Continue IV fluid replacement and IV insulin and adjust rates of infusion according to osmolality, sodium and glucose levels (as mentioned above)
• Commence 5% or 10% glucose at 125ml/hour if CBG <14mmol/l
• Adjust insulin infusion rate by increments or decrements of 1unit/hour to maintain glucose 10-15mmol/l
• Assess for complications of treatment e.g fluid overload, cerebral oedema, central pontine myelinolysis.

Day 1 to Day 3
There should be a steady improvement in the patient’s condition, beginning to eat and drink and biochemistry normalising.

• Continue IV fluid until eating and drinking normally.
• Swap to variable rate insulin infusion if not eating and drinking.
• Commence appropriate subcutaneous insulin regime and oral agent (following advice from diabetes team) when biochemically stable and eating and drinking.
• Encourage early mobilisation.
• Daily renal function.
• Continue to assess for signs of fluid overload, cerebral oedema etc.
• Daily foot checks

Follow up

• Ensure review by diabetes team and education prior to discharge and confirm outpatient follow up in diabetes centre arranged.
• Most patients will require subcutaneous insulin, however newly diagnosed patients or those previously well controlled on oral hypoglycaemic agents may be switched from insulin to appropriate oral agents after a period of stability ( weeks to months)

Referrals
The Inpatient Diabetes Team (IDT) needs to be informed.
The on-call Diabetes registrar needs to be contacted on bleep 4710

Appendices

1. See HHS Treatment Summary Algorithm Quick Reference Guide
2. See HHS Troubleshoot Flowchart
3. See See HHS Prescription Chart