Endocrinology
Question 53 of 180
A 78 year old man is brought into the Emergency Department by his carers. They describe 2 days of increased thirst and urination, alongside increased confusion. He has a history of type 2 diabetes. His blood results are:
- Haemoglobin: 135 g/L
- White cell count: 13.2 x 109/L
- Platelets: 435 x 109/L
- Sodium: 145 mmol/L
- Urea: 25 mmol/L
- Creatinine: 170 μmol/L
- Glucose: 32 mmol/L
You suspect a hyperglycaemic hyperosmolar state. What is the calculated osmolality?
Answer:
Calculated osmolality = [2Na + Glucose + Urea] =[(2 x 145) + 32 + 25] = 347 mOsm/kg (N.B. normal serum osmolality is 275 – 295 mOsm/kg).Hyperosmolar Hyperglycaemic State
Endocrinology
Last Updated: 21st February 2023
The hyperglycaemic hyperosmolar state (HHS) occurs most commonly in older people with type 2 diabetes. HHS is different from diabetic ketoacidosis (DKA) and treatment requires a different approach. Whilst DKA presents within hours of onset, HHS comes on over many days, and consequently the dehydration and metabolic disturbances are more extreme.
HHS is characterised by:
- Marked hyperglycaemia (glucose > 30 mmol/L or more)
- Hyperosmolality (effective serum osmolality > 320 mOsm/kg)
- Hypovolaemia
- In absence of significant ketonaemia (ketones < 3 mmol/L) or acidosis (pH > 7.3 and bicarbonate > 15 mmol/L)
Clinical features
Presents with polyuria, polydipsia, weakness, weight loss, tachycardia, dry mucous membranes, poor skin turgor, hypotension, and, in severe cases, shock.
Acute cognitive impairment (lethargy, disorientation, stupor) is common with osmolalities over 330 mosmol/kg.
Complications
- Hypothermia
- Myocardial infarction
- Stroke
- Peripheral arterial thrombosis
- Seizures
- Cerebral oedema
- Central pontine myelinolysis (CPM)
- Venous thromboembolism
- Foot ulceration
Management
- Fluid replacement
- Rapid changes in osmolality may be harmful. Use intravenous (IV) 0.9% sodium chloride solution as the principle fluid to restore circulating volume and reverse dehydration. Isotonic 0.9% sodium chloride solution is already relatively hypotonic compared to the serum in someone with HHS.
- Measurement or calculation of osmolality should be undertaken every hour initially and the rate of fluid replacement adjusted to ensure a positive fluid balance sufficient to promote a gradual decline in osmolality.
- Fluid replacement alone (without insulin) will lower blood glucose which will reduce osmolality causing a shift of water into the intracellular space. This inevitably results in a rise in serum sodium (a fall in blood glucose of 5.5 mmol/L will result in a 2.4 mmol/L rise in sodium).
- This is not necessarily an indication to give hypotonic solutions. Isotonic 0.9% sodium chloride solution is already relatively hypotonic compared to the serum in someone with HHS.
- Rising sodium is only a concern if the osmolality is NOT declining concurrently. Rapid changes must be avoided – a safe rate of fall of plasma glucose of between 4 and 6 mmol/hr is recommended. If the inevitable rise in serum Na+ is much greater than 2.4 mmol/L for each 5.5 mmol/L fall in blood glucose this would suggest insufficient fluid replacement. Thereafter, the rate of fall of plasma sodium should not exceed 10 mmol/L in 24 hours.
- The aim of treatment should be to replace approximately 50% of estimated fluid loss within the first 12 hours and the remainder in the following 12 hours though this will in part be determined by the initial severity, degree of renal impairment and co-morbidities such as heart failure, which may limit the speed of correction.
- Ideally patients will recover quickly enough to replace the water deficit themselves by taking fluids orally. However, if the osmolality is no longer declining despite adequate fluid replacement with 0.9% sodium chloride solution AND an adequate rate of fall of plasma glucose is not being achieved then 0.45% sodium chloride solution should be substituted.
- Insulin therapy
- Insulin treatment prior to adequate fluid replacement may result in cardiovascular collapse as water moves out of the intravascular space, with a resulting decline in intravascular volume (a consequence of insulin-mediated glucose uptake and a diuresis from urinary glucose excretion).
- Low dose IV insulin (0.05 units/kg/hr) should only be commenced once the blood glucose is no longer falling with IV fluids alone OR immediately if there is significant ketonaemia (3β-hydroxybutyrate greater than 1 mmol/L or urine ketones greater than 2+), as this indicates relative hypoinsulinaemia.
- A fall of glucose at a rate of up to 5 mmol/L per hour is ideal and once the blood glucose has ceased to fall following initial fluid resuscitation, reassessment of fluid intake and evaluation of renal function must be undertaken. Insulin may be started at this point, or, if already in place, the infusion rate increased by 1 unit/hr.
- Electrolyte replacement
- Patients with HHS are potassium deplete but less acidotic than those with DKA so potassium shifts are less pronounced, the dose of insulin is lower, and there is often coexisting renal failure. Hyperkalaemia can be present with acute kidney injury and patients on diuretics may be profoundly hypokalaemic. Potassium should be replaced or omitted as required.
- Hypophosphataemia and hypomagnesaemia are common in HHS. As with the management of DKA there is no evidence of benefit of treatment with phosphate infusion. However, these patients are often elderly and may be malnourished, and the refeeding syndrome could be precipitated once the person begins to eat. If hypophosphataemia persists beyond the acute phase of treatment of HHS, oral or IV replacement should be considered.
- Magnesium replacement has also not been shown to be beneficial so should only be considered if the patient is symptomatic or has symptomatic hypocalcaemia.
- General principles
- A target blood glucose of between 10 and 15 mmol/L is a reasonable goal. Complete normalisation of electrolytes and osmolality may take up to 72 hours.
- The patient should be encouraged to drink as soon as it is safe to do so and an accurate fluid balance chart should be maintained until IV fluids are no longer required.
- Assessment for complications of treatment e.g. fluid overload, cerebral oedema or central pontine myelinolysis (as indicated by a deteriorating conscious level) must be undertaken frequently (every 1-2 hours).
- Underlying precipitants must be identified and treated. An infective source should be sought on clinical history and examination and C-reactive protein may be helpful.
- Patients in HHS have an increased risk of arterial and venous thromboembolism. All patients should receive prophylactic low molecular weight heparin (LMWH) for the full duration of admission unless contraindicated.
- All patients should be assumed to be at high risk of foot ulceration if obtunded or uncooperative - the heels should be appropriately protected and daily foot checks undertaken.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
