Oh sugar!

Labs and Lytes 031

Author: David Humphreys
Reviewer: Sarah Yong

A 66-year-old man was found by a neighbour lying face down on the grass outside his home. He was in a confused and disoriented state. An ambulance was called.

On presentation to the emergency department these biochemistry results were obtained from a venous sample:

Sodium (mmol/L) 142 (135-145)
Potassium (mmol/L) 7.4 (3.5-5.2)
Chloride (mmol/L) 101 (95-110)
Bicarbonate (mmol/L) 11 (22-32)
Urea (mmol/L) 34.9 (4-9)
Creatinine (umol/L) 390 (60-110)
Glucose (mmol/L) 71.3 (3.5-7.7)

NB. reference ranges also shown in brackets in the right-hand column.

Q1. Are you happy with this patient’s serum sodium concentration?


Serum sodium is likely significantly elevated (beyond the reported value) but masked by the osmotic effect of the severe hyperglycaemia.

Due to the water shift provoked by severe hyperglycaemia, serum sodium does not initially appear as high as would be expected for the actual degree of total body dehydration (i.e. dilutional or pseudo-hyponatraemia).

Q2. What is the ‘corrected’ sodium concentration?

Approximately 166 mmol/L.

An appreciation of the serum sodium concentration that would be present but for the hyperglycaemia-driven fluid shift can be estimated using this formula:

Measured serum sodium + 1/3 x blood glucose (mmol/L)

Therefore in this patient:

142 + (1/3 x 71) = 142 + 23.7 = 165.7

In addition, the patient’s initial serum osmolality was measured at 427 mosm/kg (ref. 275-300).

Q3. What is the diagnosis and its pathophysiology?

Hyperosmolar hyperglycaemic state (HHS), due to relative insulin deficiency.

Hyperosmolar hyperglycaemic state (HHS) is one of the most severe acute metabolic complications of diabetes. Mortality rates have been reported at 5-20%. HHS is typically characterised by severe hyperglycaemia, hyperosmolarity, dehydration (due to osmotic diuresis) and change in mental state, in the absence of significant ketoacidosis.

In HHS there is a relative insulin deficiency, limiting peripheral glucose uptake, but sufficient to prevent lipolysis and subsequent ketone production.

You could argue, though, that HHS isn’t really a diagnosis — we still need to go looking for the underlying cause!

Q4. What are likely precipitants of this condition?

Underlying precipitating events should be always be considered, including:

  • Acute infection (e.g. LRTI, UTI)
  • Other acute illness (AMI, CVA, pancreatitis, etc)
  • Discontinuation of or inadequate insulin therapy
  • Compromised fluid intake due to underlying medical conditions
  • Excessive fluid losses resulting in dehydration (e.g. gastroenteritis)
  • Drugs that affect carbohydrate metabolism (e.g. glucocorticoids, higher dose thiazide diuretics)
  • Psychological or psychiatric illness (including dementia)

Consideration of ‘unmeasured osmoles’ should also be included here, if there is a significant gap between the measured osmolality and estimated osmolarity.

Q5. What principles will guide your treatment of this patient?

The principles of HHS treatment are:

  1. Rehydration: replacement of fluid losses
  2. Lowering serum glucose
  3. Monitoring and correcting  sodium
  4. Monitoring and correcting potassium
  5. Avoiding potential complications
  6. Investigation and management of precipitating factors

Management of HHS should proceed more slowly than is typical for diabetic ketoacidosis (DKA), aiming to restore volume state and establish normoglycaemia over days rather than hours. Serial clinical evaluation and monitoring of pH, UECs, glucose, and calculated omsolality is critical.

1. Rehydration

  • Fluid losses can be profound, from 100-220 mL/kg (6-13 litres in a 60kg patient)
  • Aim to replace 50% of the estimated deficit within the first 12 hours, and the remainder over the ensuing 36 hours (NB. local protocols may vary)
  • Rapid complete saline rehydration should be avoided as this can provoke hypo-osmolality and cerebral oedema

2. Lowering serum glucose

  • Most of the initial fall in blood glucose is due to rehydration, not insulin action, and relates to the shift of water back into the interstitial space
  • Commence insulin therapy after fluid resuscitation is underway and serum potassium is above 3.5 mmol/L, as serum potassium is likely to decrease
  • Commence dextrose when serum glucose decrease to 15mmol/L, to continue replenishment of total body water whilst preventing hypoglycaemia

3. Monitoring and correcting sodium

  • An initial (rebound) rise in serum sodium concentration can be expected during treatment as blood glucose falls
  • The rate of decrease in serum sodium concentration should generally not exceed 10 mmol/L in 24 hours to prevent osmotic demyelination as a complication

4. Monitoring and correcting potassium

  • Total potassium deficit is common due to increased urinary losses (due to glucose osmotic diuresis) and the effects of insulin and fluid therapy
  • Careful monitoring including telemetry, and timely administration of potassium replacement is essential

5. Avoiding potential complications, including:

  • Cardiovascular instability due to volume depletion
  • Thromboembolic complications due to low circulating and viscous blood flow (e.g. stroke, myocardial infarction, and venous thromboembolism)
  • Non-cardiogenic pulmonary oedema may occur, due to excessive fluid resuscitation (especially older patients)
  • Osmotic demyelination from rapid correction of serum sodium

6. Investigation and management of precipitating factors

  • As above


  • UpToDate Online: Kitabchi AE et al. Diabetic ketoacidosis and hyperosmolar hyperglycaemic state in adults: clinical features, evaluation, and diagnosis. July 2014. [Accessed online February 2016]
  • UpToDate Online: Kitabchi AE et al. Diabetic ketoacidosis and hyperosmolar hyperglycaemic state in adults: treatment. December 2015. [Accessed online February 2016]
  • Local guidelines, e.g.: Wyatt S et al. Alfred Health guideline: Management of hyperosmolar hyperglycaemic state in adults. Alfred Health intranet. June 2014. [Accessed online February 2016]
  • LITFL: Hyperosmotic Hyperglycaemic Syndrome (HHS), see: https://lifeinthefastlane.com/ccc/hyperosmotic-hyperglycaemic-syndrome-hhs/
  • LITFL: Treatment of HHS/DKA, see: https://lifeinthefastlane.com/treatment-of-hhs-dka/

All case-based scenarios on INTENSIVE are fictional. They may include realistic non-identifiable clinical data and are derived from learning points taken from clinical practice. Clinical details are not those of any particular person; they are created to add educational value to the scenarios.

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