Hyperosmolar Hyperglycaemic Non-Ketotic Coma (HONK)

Synonyms: Diabetic non-ketotic coma, Hyperosmolar non-ketotic state, Hyperosmolar hyperglycaemic state, Hyperosmolar Non-Ketotic Hyperglycaemia (HNKH)

See also: Coma, Diabetes and Intercurrent Illness, Management of Type 2 Diabetes Mellitus, Diabetic Ketoacidosis and Childhood Ketoacidosis.

This extreme metabolic derangement occurs through a combination of intercurrent illness, dehydration and an inability to take normal diabetic therapy due to the effect of illness. It is a potentially life-threatening emergency. HONK is characterised by severe hyperglycaemia with marked serum hyperosmolarity, without evidence of significant ketosis.

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.

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

• Annual incidence in the USA is estimated at 17.5 cases per 100,000 population,¹ slightly higher than for diabetic ketoacidosis.
• An audit of admissions to Birmingham General Hospital between 1971 and 1988, found 126 cases during this period, but gives no population-based incidence.³
• Up to a third of patients in some series did not have a history of diabetes.¹
• As the prevalence of type 2 diabetes mellitus rises inexorably in the general population, HONK is becoming an increasingly common community-based emergency.

Risk factors

• Can affect people of all ages, but is much commoner in older type 2 diabetics
• Nursing/rest home residents or those that live alone
• Dementia
• Sedative drugs
• Heat waves
• Propensity to infection, e.g. immunosuppressed, corticosteroid users
• Children with long-term steroid use and gastroenteritis are at increased risk²

Patients usually become very ill very quickly and in need of urgent assessment and treatment. HONK normally manifests as an extremely ill patient who, on initial assessment, shows signs of gross dehydration and focal or global neurological dysfunction.

Symptoms

• Patients usually notice early symptoms of generalised weakness, leg cramps or visual impairment.
• Nausea and vomiting may occur but this is much less so than for diabetic ketoacidosis.
• As the condition progresses patients may become bed-bound, confused and lethargic.
• Focal neurological symptoms such as weakness on one side or hemisensory abnormalities may develop and be easily confused with stroke.
• Seizures are present in up to 25% of cases;² they can be generalised, focal, movement-induced or myoclonic-jerk type.
• Despite the condition's name, coma is a relatively rare feature affecting only about 10% of those who present with the relevant metabolic abnormalities. Progression to coma represents severe disease.¹

Signs

• General Inspection: Patients usually appear ill and look exhausted if they are still conscious. There may be evidence of disorientation or confusion. Look for signs of self-neglect due to recent illness or long-standing inability to self-care. Signs of dehydration such as dry mouth, decreased skin turgor or sunken eyes may be visible on general inspection.
• Vital Signs: Tachycardia is common due to dehydration. Hypotension may be present due to severe fluid depletion or underlying sepsis/cardiac impairment. Postural hypotension is not a specific or sensitive sign due to its high background prevalence in the elderly population.¹ An increased respiratory rate may be found due to compensatory attempt to reduce metabolic acidosis. The temperature should ideally be measured using a rectal thermometer and may reveal pyrexia or hypothermia. Pulse oximeter measurement may show haemoglobin desaturation, in which case administer oxygen whilst conducting further assessment.
• Skin: A careful examination of the entire skin surface is needed, looking for rashes and localised sepsis (e.g. cellulitis or leg ulcers). Turgor will be reduced due to dehydration; in patients with infection the skin may feel warm and moist. Severe sepsis can lead to cold, dry mottled skin.
• Head: Check the eyes to see if they are sunken. Look in the mouth for dryness, check the pharynx for inflammation and perform auroscopy, looking for middle ear infection. A quick screening cranial nerve examination may reveal visual field deficits, nystagmus or other cranial nerve palsies.
• Neck: Check the lymph glands for enlargement and look for goitre due to thyrotoxicosis. Check for neck stiffness due to meningitis.
• Chest examination: May reveal evidence of pneumonia or acute respiratory distress syndrome (a potential complication of HONK).
• Cardiac examination: May reveal evidence of heart failure as the precipitant illness, or give reason to suspect myocardial infarction or infective endocarditis.
• Abdominal examination: Should look for signs of an acute abdomen. Paralytic ileus or gastroparesis may occur during the acute phase but usually settles when HONK is treated. Persisting signs of intestinal obstruction should prompt a search for an intra-abdominal cause for HONK. Consider rectal examination if there is reason to suspect GI bleeding, prostatitis or pelvic abscess. Women may need a pelvic examination/swab to exclude infection in the gynaecological tract.
• Neurological examination: Check orientation and higher cerebral functions. Kernig's test positive? Cranial nerves and limb tone, power, co-ordination, reflexes and sensation should be assessed.

• Once clinical picture is combined with initial investigation results, the diagnosis is usually clear. The range of precipitating conditions is vast (see table above).
• 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.
• Lactic acidosis or other causes of metabolic acidosis should be borne in mind, especially where there is a large anion gap (see below for calculation).

• Urinalysis shows marked glycosuria with normal or only slightly elevated ketones.
• Capillary glucose should be checked straight away and is usually markedly elevated at >30 mmol/l. Samples should also be sent for plasma glucose.
• 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

• Hypernatraemia is almost always present.
• Urea and creatinine are often elevated due to dehydration and pre-renal renal failure.
• Hyperkalaemia may be present.
  A variety of formulae exist for calculating corrected serum sodium and effective serum osmolarity (which are affected by very high glucose levels) in order to decide on appropriate electrolyte replacement regimens. Advice from a specialist in acute medicine/diabetology is recommended when interpreting or acting upon electrolyte results where plasma glucose is >40 mmol/l.
• Arterial blood gases usually show evidence of mild metabolic acidosis with pH < 7.30.
• The anion gap should be small at 10-12. Higher values indicate a possible alternative cause for metabolic acidosis. The anion gap should be calculated:
  

  Anion Gap = (Na mmol/l + K mmol/l) - (Cl mmol/l + HCO3)

• Creatine kinase and cardiac enzymes: Myocardial infarction and rhabdomyolysis can cause the syndrome or arise as a complication.
• 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, e.g. lumbar puncture for suspected meningitis.

Initial general measures:

• Resuscitation ABC: Check for and treat any problems with airway, breathing or circulation to buy time.
• Intubate and ventilate patients with deteriorating oxygen saturations (take senior-A&E/medical/anaesthetic advice).
• Obtain large-bore IV access (central line may be needed).
• Connect patient to ECG monitor, SaO2 monitor and BP monitor.
• Give oxygen if needed.
• Catheterise patient to obtain urine and monitor urine output.
• Consider passing NG tube if impaired consciousness and risk of aspiration.
• Arrange transfer to high dependency area as soon as feasible.
• Alert acute medical/diabetic team.

• Patients will require huge amounts of intravenous fluids. The overall fluid deficit is around 100-200 ml per kg, averaging about 9 litres of intravenous fluid.
• Initially give 1 litre of 0.9% NaCl over first hour.
• Shocked patients may benefit from colloid infusion and/or inotropic support in an intensive care setting.
• Further intravenous fluid regimens depend on the patient's response and continuing assessment of electrolytes:
  • Expert acute-medical/diabetology input is needed.
  • As a rough guide, if Na >155 mmol/l use 0.45% NaCl, otherwise give normal saline (0.9% NaCl).
  • It is important not to correct hypernatraemia too rapidly as it may precipitate cerebral oedema.
    Children are particularly prone to this complication of treatment and require careful planning of fluid replacement based on body mass and initial biochemistry.
• Glucose: When blood glucose levels are returning to near normal then dextrose infusion will need to be introduced to the regimen to prevent over-rapid fall in blood glucose, leading to hypoglycaemia.
• Potassium: Once insulin is given (the next most important arm of therapy), serum potassium can plummet from high to very low levels, as overall potassium depletion has occurred, despite its initial high blood concentration in the dehydrated patient.
• Insulin will cause an intracellular shift of potassium, so replacement potassium is usually given in intravenous fluids as soon as levels fall to between 3.5-5.0 mmol/l. This should be done under expert acute-medical supervision with regular electrolyte monitoring.
• Levels of phosphate, magnesium and calcium may also be monitored and replaced as appropriate (although trial data to show the efficacy of replacing these electrolytes is currently lacking).

Insulin therapy

• Aim to reduce glucose levels slowly, by approximately 3 mmol/hr.⁴
• Patients with HONK are often exquisitely sensitive to insulin and require much lower doses than in diabetic ketoacidosis (DKA).
• Fluid replacement must commence first; an initial insulin bolus of 0.15 U per kg may be given once infusions are under way.²
• Follow sliding scale below as a guide: Glucose must be monitored hourly and the regimen adjusted on an individual basis, depending on response.⁴

• Treat underlying cause if known.
• Antibiotics should not be used routinely but where there are reasonable grounds to suspect sepsis, such as elevated white cell count or a hypotensive patient, have a low threshold for their use.
• Review any medications the patient is taking and decide whether they should be discontinued pro-tem or permanently.
• Low-molecular weight heparin should be given routinely at prophylactic doses or as formal anticoagulation if there is a significant risk of thromboembolic disease.⁴

• Ischaemia or infarction affecting any organ, particularly myocardial infarction and brain (cerebral infarct)
• Thromboembolic disease, including deep vein thrombosis and pulmonary embolism
• Acute respiratory distress syndrome
• Disseminated intravascular coagulation
• Multi-organ failure
• Rhabdomyolysis
• Cerebral oedema (rare in adults, less so in children)
• Iatrogenic complications due to inexpert rehydration and electrolyte management; over-administration of insulin; fluid overload leading to cardiac failure

Mortality is 10-20%.¹

• Diabetic patients should be well educated about how to manage their condition, particularly when ill.
• Awareness in the medical profession that this is a possible presentation of diabetes may lead to earlier recognition of the problem.
• Patients who have suffered HONK should receive education and extra support to try and stop this dangerous situation from recurring.