Recommendations
Urgent
Consider a diagnosis of hyperosmolar hyperglycaemic state (HHS) in any patient who is unwell and has a raised blood glucose. There are no specific diagnostic criteria for HHS, but the following may be used to differentiate HHS from other hyperglycaemic states such as diabetic ketoacidosis (see Diabetic ketoacidosis):[2][6]
Hypovolaemia
Marked hyperglycaemia (≥30 mmol/L [≥540 mg/dL]) without significant hyperketonaemia (ketones ≤3 mmol/L) or significant acidosis (pH ≥7.3, bicarbonate ≥15 mmol/L [≥15 mEq/L])
High serum osmolality (usually ≥320 mOsm/kg [≥320 mmol/kg]).
Identify and treat any underlying cause.[6]
Common causes include myocardial infarction, sepsis, and stroke.[9]
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.
Key Recommendations
Be aware that some patients may present with mixed HHS and diabetic ketoacidosis (DKA).[2][6]
HHS usually develops over days to weeks; common features include:[6][46]
Dehydration
Acute cognitive impairment
Polyuria, polydipsia, and weight loss
Weakness
Signs of the underlying cause.
Common causes include myocardial infarction, sepsis, and stroke.[9]
Check the patient’s feet for new ulceration or infection.[2][6][47]
Always order the following investigations:[6]
Blood glucose
Blood ketones
Venous blood gas
Serum osmolality
Urea, creatinine, and electrolytes
Full blood count
Blood cultures
ECG
Chest x-ray.
Consider other investigations (e.g., CRP) based on the individual clinical presentation and to determine the underlying cause of HHS.
Consider a diagnosis of HHS in any patient who is unwell and has a raised blood glucose. There are no specific diagnostic criteria for HHS, but the following may be used to differentiate HHS from other hyperglycaemic states such as DKA (see Diabetic ketoacidosis):[6]
Hypovolaemia
Marked hyperglycaemia (≥30 mmol/L [≥540 mg/dL]) without significant hyperketonaemia (ketones ≤3 mmol/L) or significant acidosis (pH ≥7.3, bicarbonate ≥15 mmol/L [≥15 mEq/L])[2]
High serum osmolality (usually ≥320 mOsm/kg [≥320 mmol/kg]).
There may be gradual onset (over days to weeks) of:[6][46]
Dehydration
Polyuria
The patient may, however, present with oliguria if they are very dehydrated
Polydipsia
Weakness
Acute cognitive impairment
Seizures
These may be generalised, focal, myoclonic jerking, or may be movement induced.[3]
Other clinical features include:
Weight loss
Nausea and vomiting
Abdominal pain
May be due to HHS or to an acute intra-abdominal precipitating cause (e.g., pancreatitis).
Abdominal pain is uncommon in HHS, however; suspect DKA if there is no obvious cause for the pain.[1]
Practical tip
In practice, patients presenting with HHS are typically older and usually have known type 2 diabetes, which they find difficult to manage, as well as other significant comorbidities, such as heart failure. However, HHS is now being seen in younger adults (and even in children/teenagers), often as the initial presentation of type 2 diabetes.[6]
Be aware that some patients may present with mixed HHS and DKA.[2][6]
Ask about possible causes of HHS. These are:
Infection
Inadequate insulin or oral antidiabetic therapy
In practice, look out for patients with worsening glycaemic control.
Risk factors for hyperglycaemia (e.g., corticosteroids or antipsychotic drugs)[9][24][32][33]
In practice, HHS secondary to corticosteroids is commonly seen in patients who develop HHS during admission to hospital.
Acute illness
Common causes include myocardial infarction, sepsis, and stroke.[9]
Be aware that patients with stroke are at increased risk of dehydration (and subsequent HHS) due to difficulty drinking because of limb weakness or dysphagia.
Evidence: Precipitating causes
HHS most commonly occurs in older people with type 2 diabetes and comorbidities. Infection is the most common precipitating factor.
People with HHS are generally older than people with DKA.[9]
A retrospective chart review study found patients with diabetic acidosis were younger (n=134, mean age 33 years) while patients with HHS were significantly older (n=278, mean age 63 years).[48]
However, HHS does also occur in young adults and even children.[13][49][50]
Infection represents the commonest precipitating cause of HHS with the most common being pneumonia (40% to 60%) and urinary tract infection (5% to 16%).[3][9][17]
Other precipitating factors of HHS include:
Severe dehydration caused by underlying medical illness (e.g., stroke, myocardial infarction, trauma) due to the release of counterregulatory hormones and/or reduced water intake[1][9][11]
Medications including glucocorticoids, thiazide diuretics, phenytoin, beta-blockers, and atypical antipsychotics[9][24]
Poor compliance with insulin treatment and previously undiagnosed diabetes.[25][48]
One study looking at predisposing factors compared 135 people with HHS with 135 age-matched controls with diabetes. The authors did a multivariate analysis and found female sex, newly diagnosed diabetes, and acute infection to be the only three independent predictors of HHS.[51]
Look for signs of hypovolaemia:
Hypotension (systolic blood pressure <90 mmHg)
Tachycardia
Poor skin turgor
Dry mucous membranes.
Record the patient’s GCS or AVPU.
Involve senior or critical care support if GCS is <12 or AVPU is abnormal. [ Glasgow Coma Scale Opens in new window ]
Cognitive impairment is common and can range from disorientation and lethargy to coma.[11] This may be due to cerebral oedema in severe cases, significant electrolyte disturbances, changes in osmolality, dehydration, infection and sepsis, hypoglycaemia during treatment, or renal failure.[6]
Assess for focal neurological signs such as hemianopia and hemiparesis.[11]
Measure the patient’s temperature.
Patients may be normothermic or hypothermic primarily because of peripheral vasodilation, even if there is concurrent infection.[11]
Severe hypothermia is associated with a poor prognosis.[11]
Involve senior or critical care support if the patient is hypothermic.[6]
Check the patient’s feet to look for new ulceration or infection.[2][47]
Assume the patient is at high risk of foot ulceration or infection if they are too confused or sleepy to cooperate with assessment.[6]
Order a foot x-ray if the patient has a foot ulcer and you suspect osteomyelitis. See Osteomyelitis.
Practical tip
Check the feet for loss of protective sensation in any patient with diabetes.
Follow your local guidelines, but a quick, simple test is the Ipswich Touch Test©️, which involves lightly touching/resting the tip of the index finger for 1 to 2 seconds on the tips of the first, third, and fifth toes.[52]
If your patient is unable to feel at two or more of these six sites, they have reduced protective sensation.
If your patient has reduced sensation, they are at high risk of pressure ulceration. Inform the nursing staff and provide pressure-relieving devices.
A daily heel check for signs of pressure trauma should be done by nursing or healthcare assistant staff.
There is a debate about whether compression stockings should be used in people with diabetes. Do not use them if there is vascular disease.
Always order
Blood glucose
Blood glucose is high; usually ≥30 mmol/L (≥540 mg/dL).[6]
The Joint British Diabetes Societies (JBDS) guideline recommends hourly monitoring of blood glucose for the first 24 hours to measure the patient’s response to treatment.[6]
Blood ketones
Use the blood ketone concentration to help distinguish HHS from DKA. There is usually no significant ketonaemia (ketones are usually ≤3 mmol/L) in patients with HHS.[6]
Venous blood gas
Check the lactate level and pH.[6]
A mild acidosis (pH >7.3, bicarbonate >15 mmol/L [>15 mEq/L]) may be present due to renal impairment secondary to dehydration.[6]
Lactic acidosis may be present due to sepsis.[6]
Use a venous blood gas to monitor the patient’s biochemical progress (urea, electrolytes, glucose, serum osmolality, bicarbonate).[6]
Only perform an arterial blood gas if an accurate measurement of oxygen is required.[6]
How to obtain an arterial blood sample from the radial artery.
Serum osmolality
Calculate the serum osmolality; this is usually ≥320 mOsm/kg ( ≥320 mmol/kg) in patients with HHS.[6] [ Osmolality Estimator (serum) Opens in new window ]
The Joint British Diabetes Societies (JBDS) guideline recommends monitoring serum osmolality to measure the patient’s response to treatment as follows:[6]
Hourly for the first 6 hours
Every 2 hours from 6 to 12 hours as long as serum osmolality is falling at 3 to 8 mOsm/kg/hour (3-8 mmol/kg/hour)
Every 4 hours after 12 hours if serum osmolality continues to improve.
Bear in mind, however, that in practice measurement of serum osmolality to monitor the patient's response to treatment may not be commonly used; check your local protocol. As an alternative, reduce monitoring of sodium, potassium, and urea to every 2 hours after 6 hours if these are improving.
Urea, electrolytes, and creatinine
Co-existing renal failure is common.[6]
In practice, always measure serum, rather than urine, electrolytes.
Hypokalaemia is common. However, hyperkalaemia may be present if there is significant acute kidney injury.[6]
Practical tip
Be aware that patients taking a diuretic may have severe hypokalaemia.[6]
Hypernatraemia or hyponatraemia may be present.
Hypernatraemia indicates severe dehydration.[1]
Hyponatraemia is mostly dilutional if the blood glucose is ≥30 mmol/L (≥540 mg/dL) and will normalise as the blood glucose is corrected.[6]
The Joint British Diabetes Societies (JBDS) guideline recommends monitoring sodium, potassium, and urea to measure the patient’s response to treatment as follows:[6]
Hourly for the first 6 hours
Every 2 hours from 6 to 12 hours as long as serum osmolality is falling at 3 to 8 mOsm/kg/hour (3-8 mmol/kg/hour)
Every 4 hours after 12 hours if they continue to improve.
Practical tip
A rise in the sodium level is inevitable once intravenous fluids are started (without insulin) as they will lower blood glucose which will reduce osmolality, causing a shift of water into the intracellular space.[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.
As an alternative, reduce monitoring of sodium, potassium, and urea to every 2 hours after 6 hours if these are improving.
Hypophosphataemia and hypomagnesaemia are common.[6]
Full blood count
Leukocytosis is common in HHS and correlates with blood ketone levels.[11]
However, leukocytosis more than 25 × 10⁹/L (25,000/microlitre) may indicate infection and requires further investigation.[11]
ECG
Use to look for cardiac precipitants of HHS such as myocardial infarction (MI), or consequences of HHS such as hypovolaemia, which could precipitate MI, or electrolyte abnormalities, which could cause arrhythmias.
Findings may include abnormal T or Q waves or ST segment changes.[53]
Look for cardiac effects of electrolyte abnormalities.
How to record an ECG. Demonstrates placement of chest and limb electrodes.
Consider ordering
Urinalysis
Look for signs of a urinary tract infection.
There is usually no significant ketonuria (ketones <2+ on urinalysis). Use the result to help distinguish HHS from DKA.[6]
Cardiac enzymes
Order troponin T or I if you suspect myocardial infarction as a precipitant.[56]
Chest x-ray
Order if the patient has reduced oxygen saturations.
Signs of pulmonary oedema are pleural effusions, interstitial and alveolar oedema, prominent superior vena cava, Kerley B lines, and dilated upper lobe blood vessels.[57]
Consolidation occurs in pneumonia.
Liver function tests
Use to screen for an underlying hepatic precipitant of HHS. Abnormal LFTs indicate underlying liver disease (e.g., non-alcoholic fatty liver disease or congestive heart failure).[58]
C-reactive protein
Order if you suspect infection as a precipitant.
Blood, urine, and sputum cultures
Order these if there are signs of infection.
The most common causes are pneumonia and urinary tract infection.[3][9][17]
How to take a venous blood sample from the antecubital fossa using a vacuum needle.
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