At no stage has the college ever asked about hypernatremia specifically, but it appears as a garnish to the following SAQs:

Oh's Manual coverage of hypernatremia is limited to half of page 954 from Finfer and Delaney's fluid and electrolyte chapter, which references only one paper (Adrogué and Madias, 2000). Of this half-page, the majority is taken up by a Blue Box, which classifies causes of hypernatremia into water loss and salt gain. Unfortunately, in the "salt gain" category there is only one entry: "Hypertonic, saline or sodium bicarbonate". The other category is sufficiently diverse to merit a long unordered list:

Causes of  Hypernatremia

Renal water loss

  • Glucosuria
  • Mannitol
  • Urea therapy
  • Loop diuretics
  • Post obstructive diuresis
  • Hyperaldosteronism

Extrarenal water loss

  • Dehydration by exposure
  • Burns
  • Gastric losses
  • Diarrhoea

Salt gain

  • Infusion of sodium-rich fluids of some sort (eg. hypertonic saline)
  • Ingestion of sea water
  • Salt pica

Nephrogenic DI

  • Hypercalcemia
  • hypokalemia
  • Lithium
  • Pyelonephritis
  • Medullary sponge kidney
  • Multiple myeloma
  • Amyloid
  • Sarcoid

Central DI

  • Traumatic brain injury
  • Pituitary tumour
  • Meningitis
  • Encephalitis
  • Tuberculosis
  • Sarcoidosis
  • Idiopathic

Generally, adverse effects of hypernatremia develop at sodium concentrations in excess of 155-160 mmol/L

  • Increased temperature
  • Restlessness
  • Irritability
  • Confusion
  • Drowsyness
  • Coma
  • Seizures
  • Subarachnoid haemorrhage (due to brain shrinkage and vascular rupture) 

Rapid rehydration may give rise to cerebral oedema, and this is the main risk in starting any sort of corrective therapy. If the hypernatremia developed over hours, reducing the sodium concentration by 1mmol/hr is appropriate. Just as in the correction of hyponatremia, a daily decrease of 10mmol/L of sodium is a sensible goal.

Central and nephrogenic diabetes insipidus

Question 2 from the first paper of 2023 asked the candidates to discriminate between these two forms of DI. The only controversy here would have to be the position of gestational DI, which is not "central" per se, but which does not fit the nephrogenic description either. It is a depletion of vasopressin which results from the overexpression of placental enzymes, and so produces a depletion of the hormone which is functionally indistinguishable from the situation where the pituitary fails to secrete it.

Heading Central DI Nephrogenic DI
  • Inadequate release of vasopressin
  • Inadequate renal response to vasopressin
  • Stroke or ICH (eg. SAH, pituitary apoplexy)
  • Meningitis
  • Neoplasm (eg. mets or pituitary adenoma)
  • Trauma (eg. TBI, base of skull fracture)
  • Gestational (placental vasopressinase)
  • Idiopathic congenital and autoimmune forms account for ~ 50%
  • Drug-induced:
    • Lithium
    • Foscarnet
    • Clozapine
    • Amphotericin
  • Congenital (eg. aquaporin-2 gene mutation)
  • Post-obstructive
  • Hypercalcemia
  • Hypokalemia
  • Polydipsia
  • Polyuria
  • Hypernatremia
  • Plus whatever features are characteristic of the primary pathology (eg. the diplopia of a pituitary adenoma)

Diagnosis of DI:

  • Paired serum and urine osmolality (urine expected to be low, serum expected to be high)
  • Serum sodium
  • Water deprivation test, or the alternative hypertonic saline infusion test (to exclude primary polydipsia)

Discrimination between different causes of DI:

  • Measurement of plasma vasopressin (depressed in central DI)
  • Measurement of plasma copeptin (depressed in central DI)
  • DDAVP challenge (no effect in nephrogenic DI)
  • DDAVP (desmopressin) IV, s/c, orally, or intranasally
  • Free water or 5% dextrose to correct water deficit
  • Cease causative drug
  • Low sodium diet
  • Thiazide diuretics
  • Amiloride
  • Indomethacin

Calculating the free water deficit

Water is often what's missing from the patient's body fluid compartments, and therefore it is fair to say that at some stage the college may expect their candidates to calculate the water deficit. There are several similar-looking equations available.

A conventional equation quoted by  Cheuvront et al (2013) is as follows:

Water deficit = total body water × (1- [140 ÷ serum sodium])

Because the calculation of total body water is usually (body mass × 0.6), the equation is often rewritten as:

Water deficit = 0.6 × body mass × (1- [140 ÷ serum sodium])

Cheuvront et al actually offer seven variations of this equation, which include a proposed correction for unknown body mass, a total body water estimate from body composition, one which uses the actual plasma sodium, one which substitutes plasma osmolality for sodium, and so on. To cut a long story short, they all suck equally, in terms of being unable to accurately predict water losses in dehydrated volunteers.

Adrogué and Madias (2000) quote the same equation, recommend against its use, and suggest a refinement to it:

 Adrogué and Madias equation

Thus, a 70kg male with a serum sodium of 160 will enjoy a 3mmol/L decrease in his serum sodium after receiving 1000ml of 5% dextrose with 30mmol of KCl in it.

LITFL  rearrange things slightly: 

Free water deficit = Total body water x (serum Na-140)/ (140)

where the total body water is 50%, not 60%. Cadogan did not reference this, but it resembles the equation given by MDCalc:

Free water deficit = % total body water, fraction × weight, kg × (current Na / ideal Na – 1)

where % total body water (TBW) is:

  • Adult male: 60% (i.e., use 0.6 in the equation)
  • Adult female: 50% (0.5)
  • Elderly male: 50% (0.5)
  • Elderly female: 45% (0.45)
  • Child: 60% (0.6)

MDCalc referenced Barsoum & Levine (2002) for this, weirdly selecting only one of the three equations offered by the authors, and not even the one they recommended. Another equation offered by these authors was:

Water deficit = total body water - (total body water  × serum sodium / 140)

If one were to obsess over these matters, one would enter these equations into a spreadsheet and demonstrate that with identical variables, mathematically the results differ only by 1L of estimated water deficit:

Author water fraction body mass (kg) serum sodium (mmol/L) ideal sodium (140 mmol/L) water deficit (L)
Cheuvront et al 0.6 70 160 140 5.25
LITFL 0.5 70 160 140 5
MDcalc 0.6 70 160 140 6
Barsoum & Levine 0.6 70 160 140 -6

So, in summary, it does not matter which equation you use, and in the grand scheme of things it must be acknowledged that the calculation of a water deficit is a purely self-indulgent exercise in biochemical nerdsmanship, given the well-established inaccuracy of all the equations. In reality, nobody would prescribe 6000ml of 5% dextrose and walk away without any intention of reassessing the sodium or re-examining the patient. Unfortubately, as the college examiners have never used any of these calculations in an SAQ, we do not know what the CICM Officical Scrabble Dictionary free water deficit equation is.


Adrogué, Horacio J., and Nicolaos E. Madias. "Hypernatremia." New England Journal of Medicine 342.20 (2000): 1493-1499.

Cheuvront, Samuel N., et al. "Water-deficit equation: systematic analysis and improvement" The American journal of clinical nutrition 97.1 (2012): 79-85.

Barsoum, Noha R., and Barton S. Levine. "Current prescriptions for the correction of hyponatraemia and hypernatraemia: are they too simple?." Nephrology Dialysis Transplantation 17.7 (2002): 1176-1180.

Makaryus, Amgad N., and Samy I. McFarlane. "Diabetes insipidus: diagnosis and treatment of a complex disease." Cleveland Clinic journal of medicine 73.1 (2006): 65.

Bendz, Hans, and Mattias Aurell. "Drug-induced diabetes insipidus: incidence, prevention and management." Drug safety 21.6 (1999): 449-456.

Christ-Crain, Mirjam, et al. "Diabetes insipidus." Nature reviews Disease primers 5.1 (2019): 54.

Pivonello, Rosario, et al. "Central diabetes insipidus and autoimmunity: relationship between the occurrence of antibodies to arginine vasopressin-secreting cells and clinical, immunological, and radiological features in a large cohort of patients with central diabetes insipidus of known and unknown etiology." The Journal of Clinical Endocrinology & Metabolism 88.4 (2003): 1629-1636.

Ananthakrishnan, Sonia. "Gestational diabetes insipidus: diagnosis and management." Best Practice & Research Clinical Endocrinology & Metabolism 34.5 (2020): 101384.

Khositseth, Sookkasem, et al. "Hypercalcemia induces targeted autophagic degradation of aquaporin-2 at the onset of nephrogenic diabetes insipidus.Kidney international 91.5 (2017): 1070-1087.

Khositseth, Sookkasem, et al. "Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus." Scientific reports 5.1 (2015): 18311.