מצב היפראוסמולרי היפרגליקמי

What is hyperosmolar hyperglycaemic state (HHS)?¹

Synonyms: hyperosmolar hyperglycaemic nonketotic coma, diabetic nonketotic coma, hyperosmolar nonketotic state, hyperosmolar nonketotic hyperglycaemia

ראו גם מאמרים נפרדים תרדמת, סוכרת ומחלה נלווית, Management of type 2 diabetes mellitus, חמצת קטוטית סוכרתית ו חמצת קטוטית בילדות.

Hyperosmolar hyperglycaemic state (HHS) is a life-threatening diabetic emergency consisting of severe hyperglycaemia, dehydration, and absence of significant ketoacidosis.²

Hyperosmolar hyperglycaemic state (HHS) occurs as a complication of type 2 diabetes. HHS is characterised by severe hyperglycaemia with marked serum hyperosmolarity, without evidence of significant ketosis. Previously known as HONK (hyperosmolar nonketotic coma), this condition was first described in the 1880s.³

A hyperosmolar hyperglycaemic state is a potentially life-threatening emergency.

Hyperosmolar hyperglycaemic state aetiology

Hyperglycaemia causes an osmotic diuresis with hyperosmolarity leading to an osmotic shift of water into the intravascular compartment, resulting in severe intracellular dehydration. Ketosis does not occur due to the presence of basal insulin secretion sufficient to prevent ketogenesis but insufficient to reduce blood glucose.

HHS is characterised by:

• Hypovolaemia.

• Marked hyperglycaemia (30 mmol/L or more) without significant hyperketonaemia (<3 mmol/L) or acidosis (pH>7.3, bicarbonate >15 mmol/L).

• Osmolality usually 320 mOsm/kg or more.

אפידמיולוגיה³

• The incidence of HHS is estimated to be approximately 1% of all diabetes-related hospital admissions in high income countries. It accounts for 26-40% of diabetes-related admissions in Africa (although there is a wide difference across Africa nations with one Nigerian study reporting that HHS made up 58% of all diabetes-related admissions).⁴

• It has been thought to most commonly present in adults between the ages of 40 and 60,³ but more recent studies suggest it is commoner in older age groups with the median age at presentation being 63 in a systematic review.⁴

• In the US, it is more commonly found in people of Black, Hispanic, and Native American ethnicities. However, this may simply be due to the higher rates of type 2 diabetes in these populations.

• In one study of patients admitted with hyperosmolar hyperglycaemic state, a third had not previously been diagnosed with diabetes. ⁵This finding has been replicated over other studies showing that HHS is the first presentation of diabetes in over 30% of patients worldwide and 44% in South America. ⁴

• Outcomes vary significantly across the globe with much poorer mortality rates in Africa than other parts of the world.⁴

HHS causative conditions

The following list is not exhaustive but covers the most common causes and those that may be easily overlooked.

Common and important causes of hyperosmolar hyperglycaemic state (HHS)⁶

Hyperosmolar hyperglycaemic state symptoms³

Typically patients initially present with polydipsia and polyuria. Weakness, malaise, and lethargy may also be described.

Patients usually appear dehydrated with increased skin turgor and dry mucous membranes.

Symptoms often relate to the underlying cause (for example, patients with an infective precipitant may have fever, sweating, tachycardia, and tachypnoea, whereas those with a cardiac or vascular precipitant may have chest pain, dizziness, palpitations, and headache).

Neurological signs are common and concerning. These include:

• חסר נוירולוגי מוקדי.

• Disturbance in visual acuity.

• Delirium.

• Coma.

Hyperosmolar hyperglycaemic state examination

• General inspection:

  • Patients usually appear ill and look exhausted.

  • There may be evidence of disorientation or confusion.

• מערכתי:

  • קרדיווסקולרי:

    • Tachycardia is common due to dehydration.

    • Hypotension may be present due to severe fluid depletion or underlying sepsis/cardiac impairment.

    • A weak or thready pulse may be found.

  • נשימתי:

    • An increased respiratory rate may be found due to a compensatory attempt to reduce metabolic acidosis.

    • Pulse oximeter measurement may show haemoglobin desaturation (in which case, administer oxygen whilst conducting further assessment).

  • עור:

    • Turgor will be reduced due to dehydration.

    • Delayed capillary refill is common.

    • Both of these signs may be masked by obesity so their absence should not necessarily be reassuring.

  • Genitourinary:

    • Reduced urine output.

  • Nervous:

    • חסר נוירולוגי מוקדי.

    • עייפות.

    • Reduced Glasgow coma score.

• Other examination:

  • Specific signs of the underlying cause may be seen. For example:

    • A rash may be present suggesting underlying אלח דם.

    • Kernig's or Brudzinski's signs may be positive suggesting underlying דלקת קרום המוח.

אבחנה מבדלת

• Once the clinical picture is combined with initial investigation results, the diagnosis is usually clear.

• Older patients often present with delirium when physically unwell and this is the major differential at first assessment. The same is true of an acute presentation of dementia.

• Some forms of acute poisoning or intentional overdose can produce metabolic derangement and should be considered as a cause, particularly where pre-existing diabetes is not established.

• חמצת לקטית or other causes of חמצת מטבולית should be borne in mind, especially where there is a large anion gap (see below for calculation).

חקירות

• Urinalysis shows marked glycosuria with normal or only slightly elevated ketones.

• Capillary glucose should be checked straightaway and is usually markedly elevated at >30 mmol/L. Samples should also be sent for plasma glucose.

• If the diagnosis is suspected in general practice, immediate admission should be arranged and further tests should take place in the acute setting.

• Glucose should be tested hourly to guard against precipitous drops and the associated cerebral oedema.³

• Serum osmolarity is usually >320 mmol/L (normal range is 290 ± 5 mmol/L). Osmolarity can be approximately calculated as: plasma osmolarity = 2 (Na mmol/L + K mmol/L) + urea mmol/L + glucose mmol/L.

• Renal function tests and electrolytes: dehydration and pre-renal acute kidney injury. Sodium and potassium levels are deranged. Sodium levels are often falsely low (pseudohyponatraemia) and potassium levels may be high or low.³

• Bicarbonate levels are often normal.³

• FBC, CRP.

• Blood cultures, urine cultures, and cultures from any other site of possible infection, including lumbar puncture if indicated.

• Arterial blood gases: pH is usually above 7.3. The anion gap is usually within the normal range (see the separate מאזן חומצה-בסיס ו חמצת מטבולית articles).

• Creatine kinase and cardiac enzymes: myocardial infarction and rhabdomyolysis can cause the syndrome or arise as a complication.

• ECG and CXR.

• Further investigations to detect the underlying cause should include urine, blood, and any other relevant cultures, and specific tests directed at detecting the most likely cause in a given case, where relevant to ongoing management - eg, lumbar puncture for suspected meningitis.

Hyperosmolar hyperglycaemic state treatment and management

Treatment goals include correction of dehydration, hyperglycaemia, and hyperosmolality, and electrolyte imbalance, as well as identification and treatment of any precipitating event.¹

Treatment should be managed by endocrinologists, intensive care teams or both.³ Detailed management can be found in Further Reading.⁷

Aggressive hydration with isotonic fluid with electrolyte replacement is standard practice to reduce the glucose levels. Using insulin infusions can result in a rapid drop in glucose levels, leading to cerebral oedema.

Other goals include the prevention of other potential complications, including arterial or venous thrombosis and foot ulceration.⁸

סיבוכים

Complications include:⁴

• Acute kidney injury (7.6%).

• Pulmonary oedema (4.8%).

• Acute coronary syndrome (3.9%).

Electrolyte abnormalities are common and frequent monitoring is required to avoid adverse events.³

Cerebral oedema is the most feared complication (as a result of rapid glucose lowering) but is rare in adults.³

תחזית

Whilst treatment and therefore mortality rates have significantly improved in higher income countries, overall mortality remains high from hyperosmolar hyperglycaemic state. Worldwide mortality is reported to be 21.1%, with a mortality rate of 40% across Africa, 18.1% in Asia, and 4.8% in North America.⁴

מניעה³

• People with diabetes should be well educated about how to manage their condition, particularly when ill.