Question 25

A 45-year-old patient presented to the emergency department with a five-day history of nausea and vomiting and one day of slurred speech. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) was suspected due to sodium level of 110 mmol/l.

a) List five alternative differential diagnosis in this patient with severe hyponatremia, and a high urine sodium and osmolality? (25% marks)

b) Outline the management principles for the use of hypertonic saline (3% NaCl) in symptomatic acute hyponatremia and include the calculations in your answer. (50% marks)

c) List five risk factors for development of osmotic demyelination syndrome. (25% marks)

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College answer

Aim: To explore the candidate knowledge of SIADH and allow the candidate to display familiarity with the clinical use of 3% saline.
Key sources include: Paper 2009.1 Q14.4, 2017.2 Q5, CanMEDS Medical Expert.
Discussion. The successful candidate in part a was able to list differential diagnoses for severe hyponatraemia AND a high urinary sodium and osmolality as requested. Candidates scored less marks if they listed general causes of hyponatraemia.
Calculations were asked for in part b and candidates who provided an estimation of the sodium deficit and calculated the amount of 3% saline required to correct it scored highly. The expert pass commented on rates of administration, provided rationale behind the recommendations, and provided safe guidelines for sodium correction over 24 hours in the context of the acute symptomatology. Many candidates were unable to list five risk factors for part c. This may be due to a knowledge deficit or misreading of the question. Candidates are reminded to read the questions carefully and attempt to answer every question.


The college refer to Question 14.4 from the first paper of 2009, which asked about the calculation of a sodium deficit,  and Question 5 from the second paper of 2017, which was all about the use of hypertonic saline.


The lazy man's classification of sodium disturbances was basically designed to answer this sort of differential-generating exercise. The stem of the question gives you nausea vomiting and slurred speech, which might either indicate that the examiners wanted you to suspect hypovolemia, or to explain why the hypertonic saline is indicated (symptomatic hyponatremia), or to suggest that some sort of sinister intracranial horror is quietly lurking. so, the list of differentials would therefore incorporate:

  • Hypovolemic hyponatremia
  • Cerebral salt wasting
  • Mineralocorticoid deficiency
  • Hypothyroidism
  • Renal sodium loss, eg. renal failure


The question on the management principles for the use of hypertonic saline in this case contains a landmine, the word "acute" nestled in among all the other stem verbiage. This SAQ is specifically asking about the management of acute symptomatic hyponatremia, which requires emergency sodium replacement at a rate which is higher than what you would normally be comfortable with, to rapidly elevate the sodium to something like 115-120.

The management principles can be boiled down to this:

  • Generic guide to careful use of hypertonic saline:
    • Monitored environment, i.e. the ICU
    • 1:1 nursing (because patient is potentially going to become confused)
    • Ideally, central venous administration (hypertonic saline is a sclerosant)
    • Ideally, arterial line for monitoring (allows frequent samples to be taken)
    • Ideally, IDC to monitor urine output (to detect the rapid self-correction of volume that occurs with hypovolemic hyponatremia)
  • The next step is to rapidly correct the sodium ("acute symptomatic", etc): 
    • Aim for a 2-4% increase in sodium, so a sodium concentration of 115 or so
    • European guidelines (Spasovski et al, 2014) recommend 150ml of 3% saline over 20 minutes (followed by a sodium check) to derease the amount of maths involved, but this question clearly expects calculations, so: 
  • Calculation of sodium deficit using the Adrogué–Madias (A-M) formula, from this 1997 paper. The equation is 
    • Sodium deficit = 0.6 ×body weight × (desired concentration - current concentration)
    • The college did not give us a weight or the sex, but it clearly matters, as the multiplier of body weight is 0.6 for men and 0.5 for women (whose fraction of body water is smaller). Let's assume the patient is a 70kg woman. That would be 0.5 × 70 × (115-110) = 175 mmol of sodium.
    • 3% saline contains 516 mmol/L of sodium, so this would be about 339 ml of hyperonic saline.  
  • Rapid immediate correction can occur at a rate of about 2 mmol/hr, so that means you can run the 3% saline at about 135 ml/hr and correct the 5 mmol deficit over 2.5 hours.
  • Thereafter, slow replacement up to a total daily rise of 12 mmol/24 hr needs to occur
    • Frequent ABG or EUC sampling to control the rate of rise
    • Aim for a rate of rise no greater than 0.5 mmol/hour
    • Having already corrected 5 mmol of the 12, we only need to correct a further 7 mmol today, and we have 21.5 hours in which to do it
    • Thus, assuming we achieve 115 mmol/L with our rapid correction, the rest is  0.5 × 70 × (122-115) = 245 mmol deficit = 475 ml of 3% saline
    • This must infuse at 22 ml/hr (over 21.5 hrs)


Risk factors for osmotic demyelination include:

  • Alcoholism
  • Malnutrition
  • Other electrolyte disturbances (esp. hypokalemia)
  • Use of diuretics
  • Liver transplantation


Lee, Jennifer Ji Young, et al. "Management of hyponatremia.Canadian Medical Association Journal 186.8 (2014): E281-E286.

Lazaridis, Christos, et al. "High-Osmolarity Saline in Neurocritical Care: Systematic Review and Meta-Analysis*." Critical care medicine 41.5 (2013): 1353-1360.

R J Martin Central pontine and extrapontine myelinolysis: the osmotic demyelination syndromes J Neurol Neurosurg Psychiatry 2004;75:iii22-iii28 doi:10.1136/jnnp.2004.045906

Spasovski, Goce, et al. "Clinical practice guideline on diagnosis and treatment of hyponatraemia." European Journal of Endocrinology 170.3 (2014): G1-G47.

Adrogue, H. J., and N. E. Madias. "Aiding fluid prescription for the dysnatremias." Intensive care medicine 23 (1997): 309-316.