Viva 3

A 45 year old male weighing 75kg presents to the Emergency Department with nausea and vomiting and is tolerant of fluids only. He has progressive weakness and is unable to walk and dress.  Initial observations are a systolic blood pressure of 90 mmHg, pulse 95 beats per minute, respiratory rate 18 breaths per min and tympanic temperature  of  37.4 C.   An abdominal examination reveals  a  soft  abdomen with no tenderness and no organomegaly.

His initial blood tests are as shown below and you are asked to provide assistance.




137 - 146




3.7 - 5.0

Bicarbonate 27 mmol/L 22.0 - 26.0




98 - 108




3.0 - 8.5




60 - 120




3.0 - 8.0




2.0 - 18.0




34 - 46




2.1 - 2.6




0.7 - 0.96




0.8 - 1.5

What are the key biochemical abnormalities?

This patient has some substantial problems:

  • Severe hyponatremia
  • Hypokalemia
  • Hypomagnesemia
  • Hypophosphataemia
  • Slightly raised urea
What investigations will you ask for?
  • Serum osmolality
  • Urine osmolality
  • Urine sodium

Also plausible:

  • LFTs
  • TTE
  • 24 hr urinary protein collection
  • TFTs
  • Serum cortisol
  • Short synacthen test
  • ABG
What is the relevance of the serum osmolality?
  • It discriminates between different classifications of hpyonatremai
  • The possible variants arre
    • Hypo-osmolar
    • Isoosmolar
    • Hyperosomolar
What would a high or normal serum osmolality suggest?
  • Hyperosmolar hypernatremia:
    • Hyperglycaemia
    • Mannitol use
    • Alcohol intoxication
  • Isoosmolar hyponatremia:
    • Massively raised triglycerides
    • Hyperproteinaemia
What examination findings will you specifically look for?
  • Volume status seems like an important element:
    • Features of dehydration
    • Features of oedema
  • Also:
    • Features of heart failure
    • Features of hypothyroidism
    • Features of Addison's disease
The patient appears euvolaemic and has no clinical features of heart failure.
  • Serum osmolality is 240.
  • Urine osmolality is 450.
  • Urine sodium is 44 mmol/L.
What do these findings suggest?
Prompt: what are your differentials?

The patient probably has euvolaemic hyponatremia. The high urinary sodium suggests the following differentials:

  • hypothyroidism
  • hypoadrenalism
  • Glucocorticoid deficiency
What additional history will you ask for?

The trainee should use some additional history data to ask questions which help discriminate SIADH from the other differentials

The following bits of historical information are important:

  • Medication history (diuretics, steroids, drugs which cause SIADH eg. SSRIs)
  • Fluid chart (has somebody been mindlessly charting dextrose)
  • Psychosocial history (is psychogenic polydipsia even a possibility; are they on a weird diet)
  • Alcohol history (liver disease, cirrhosis, beer potomania)
  • Oedema history (Ascites worse recently? Sleep on twenty pillows?)
  • Trauma history (cerebral salt wasting, pituitary injury)
  • Urine output (massive diuresis of HONK or ATN recovery phase, or oliguria or chronic renal failure)
  • Recent procedures: TURP, contrast CT, recent surgery, etc.
The patient gives a history of starting an SSRI eight weeks ago. The endocrinologist agrees that this is likely SIADH. What is the definition of SIADH, and how do you confirm the diagnosis?

 The diagnostic criteria for SIADH are:

  • Hypoosmolar hyponatremia
  • Urine osmolality greater than plasma osmolality
  • Urine sodium excretion greater than 20mmol/L
  • Normal renal, hepatic, cardiac, pituitary, adrenal and thyroid function
  • Absence of hypotension, hypovolemia, oedema and ADH-influencing drugs
  • Hyponatremia corrects with water restriction
What are the causes of SIADH?

Numerous causes could be spouted by the well prepared candidate:

Non-Drug-Related Causes of SIADH

Ectopic ADH production

  • Small cell lung cancer
  • Leukaemia
  • Lymphoma
  • Thymoma
  • Neuroendocrine tumours
  • Pancreatic adenocarcinoma

CNS disorders

  • Cerebral trauma
  • Brain tumour (primary or secondary)
  • Meningitis or encephalitis
  • Brain abscess
  • Subarachnoid haemorrhage
  • Acute intermittent porphyria
  • Guillain–Barré syndrome
  • SLE

Pulmonary diseases

  • Pneumonia
  • Tuberculosis
  • Lung abscess

Drugs Associated with SIADH

  • carbamazepine
  • cyclophosphamide
  • phenothiazines
  • SSRIs
  • nicotine
  • tricyclics
  • vinca alkaloids eg. vincristine
  • interferon
  • cisplatin
  • MDMA
  • amiodarone
  • ciprofloxacin
  • sodium valproate
  • NSAIDs
  • Thiazides
What is your normal approach to the management of SIADH?
Prompt: What pharmacological options are there?
Therapy Benefits Drawbacks
Fluid restriction Simple, easily implemented

Minimal cost

Can be useful in patients with urine osmolality <400–600 mosmol/kg
Minimally effective and requires several days to achieve correction

Hard for patients to remain compliant
Demeclocycline Effective in raising serum sodium Slow response

Potentially nephrotoxic

Loop diuretics with or without salt supplementation May allow relaxation of fluid restriction and decreases urine-concentrating ability Requires careful titration and monitoring

Risk for other electrolyte abnormalities
Urea Effective and inexpensive Palatability

Limited availability
Hypertonic (3%) saline Effective for severe acute and symptomatic chronic hyponatremia Risk of overly rapid correction

Requires careful, intensive monitoring
Vasopressin receptor antagonists Targets excessive arginine vasopressin

Safe and effective

Predictable rise in sodium values

No risk for concomitant electrolyte disorders

Induces polyuria

Requires close monitoring of serum sodium at initiation with inpatient admission
Lithium It is known to interfere with the effect of ADH on the collecting duct, thereby causing nephrogenic Affect change and weight gain
What features might give you the impression that fluid restriction by itself is not going to work?
  • High urine osmolality
  • Low urine output
  • Sum of urinary sodium and potassium concentrations exceeds the serum sodium concentration
  • After 2 days of fluid restriction, the sodium concentration has failed to increase by more than 2 mmol/L
The endocrinologist insists on a hypertonic saline infusion.  What is the  rationale for hypertonic saline in this scenario?
  • Sometimes, fluid restriction or other conservative measures may not be enough
  • Severe prolonged hyponatremia is not without consequences
  • Hyponatremia may have life-threatening symptoms (such as coma and seizures), for which sodium replacement is the only sensible solution.
  • Symptomatic hyponatremia should be managed with the infusion of hypertonic saline, so as to contribute sodium without contributing volume.
What are the indications for hypertonic saline in hyponatremia? How would you administer it?|

The recent European guidelines (Spasovski et al, 2014) recommend to raise the sodium level by 2-4% over 30 minutes if the patient is symptomatic, i.e. confused or having seizures.

Hyponatremia with severe symptoms, irrespective of chronicity

  • 150 ml 3% hypertonic over 20 min
  • check serum sodium after 20 min while repeating an infusion of 150 ml 3% hypertonic saline for the next 20 min
  • Continue  until a target of 5 mmol/l increase in serum sodium concentration is achieve

Chronic hyponatremia without severe symptoms, and due to SIADH:

  • Fluid restriction is first line treatment
  • oral urea or salt tablets with loop diuretics may be used as second line
What dose of sodium will you give in the first 24 hours? i.e. how will you calculate the sodium deficit, and what are your outcome targets?
  • Sodium deficit = 0.6 ×body weight × (desired concentration - current concentration)
  • A 70kg person  will require about 10ml (34mmol) of 20% saline for every 1mmol rise in sodium
  • A sensible safe rate of replacement is about 4-5ml/hr of 20% saline for the first 24 hours.
  • That would be about 25-35 ml/hr of 3% saline, if that is all you have available.
The endocrinologist expresses concern about osmotic demyelination syndrome. What is this  syndrome?

This is the major danger of correcting sodium too quickly.

A few points:

  • The pons is not unique and you can myelinolyse anywhere there is myelin (Martin, 2004)
  • Sodium is not unique and osmotic demyelination can occur in a variety of other scenarios, eg. with large changes in urea or glucose. .However, it is for some reason rare in diabetes and dialysis, in spite of the comparatively massive osmotic shifts.
  • You don't need to give hypertonic saline to demyelinate the pons: you can do that with rapid autocorrection, eg. when you cease the drug that was causing the SIADH.
What are the risk factors for osmotic demyelination syndrome?
  • Alcoholism
  • Malnutrition
  • Other electrolyte disturbances (esp. hypokalemia)
  • Use of diuretics
  • Liver transplantation

Almost all patients who develop osmotic demyelination presented with a sodium of under 120, which means that this should probably be the threshold for concern. Of those who develop it at a sodium of over 120, the majority of cases are in patients undergoing liver transplantation.

What are the clinical manifestations of osmotic demyelination syndrome?
  • Dysarthria
  • Dysphagia
  • Flaccid paraparesis or quadriparesis
  • Behavioural disturbance, resembling delirium
  • Lethargy
  • Coma, obtundation
  • A "locked in" state
  • Seizures

Disclaimer: the viva stem above may be an original CICM stem, acquired from their publicly available past papers. Or, perhaps it is a slightly altered version of the original CICM stem. Or, it is a completely original viva stem, concocted by the monstrously amoral author of Deranged Physiology for nothing more than his own personal amusement. In either case, because the college do not make the main viva text or marking criteria available, almost everything here has been confabulated. It might sound like a plausible viva and it could be used for the purpose of practice, but all should be aware that it does not represent the "true" canonical CICM viva station.