There’s a lady in Resus, she’s 46, she’s got a history of mental health problems.  Her husband tells you she’s been gradually more lethargic over the last few days.  He called the ambulance today because he found her on the sofa in the morning mumbling incoherently.  Her observations are okay.  Her ABC’s are okay, she’s got a normal glucose, but when you go to move her arm to cannulate you notice she’s rigid.  Hypertonic all over.  You do what you can of a neuro exam and find she’s got globally increased reflexes.  Her pupils are fine.  VBG is okay acid base wise but her Na is 154.

Now as we said last week.  Sodium is important, and it’s ubiquitous.  We need it for everything, and every single one of our cells uses a lot of energy to maintain a sodium concentration of between 135-145mmol/l.  When things go wrong with sodium homeostasis, things are very wrong indeed.  Mortality rates are higher for hypernatraemia than hyponatraemia ranging from 45-60% for all patient groups, and can be as high as 80% in the elderly.  Thankfully it is less common than hyponatraemia, and we most often see it in patients as they enter their last phase of life, this adds an ethical dimension to treatment that I’m not going to talk about here (maybe another day).

Features of severe hypernatraemia are hyperthermia, delirium, seizures, and coma.  Patients with milder symptoms can sometimes present with delirium or changes in mental status.  Patients might have features of underlying disease processes (such as Conns or Cushings).

Hypernatreamia is usually caused by combined electrolyte and water loss, it’s just that the water loss is in excess of the electrolyte loss, and is coupled with an inability to replace water via the thirst response (people with low GCS, dementia, mental health problems).  The trick is working out where the water is being lost from.

Net water loss from kidneys

Diabetes insipidus can be neurogenic, or nephrogenic.  Neurogenic is usually due to traumatic brain injury, space occupying lesions or infections.  Nephrogenic can be caused by general renal dysfunction, or electrolyte abnormalities such as hypercalcaemia or hypokalaemia, or HHS.

Net water loss from other sources:

The commonest drug cause of hypernatraemia is Lithium, though other drugs such as amphotericin, diuretics and vasopressin analgoues (demeclocycline) can also contribute to or cause it.  Lithium actually inhibits a protein called GSK3 which is part of how renal cells’ respond to vasopressin.  Colchicine, gentamicin, and rifampicin can also cause diabetes insipidus.  Unreplaced loss from the respiratory system, sweating, burns, GI tract (D+V) or any type of fistulae can also be implicated.

Hypernatraemia from sodium gain

Feeding, or increased oral salt intake (this usually needs to be massive, or Iatrogenic).  Sea water ingestion, hyptertonic enemas, or dialysis.  Primary hyperaldosteronism (Conns), or Cushings syndrome can also cause excess sodium re-absorption.



As with hyponatraemia the symptoms are vague and wide ranging.  Treatment depends on the speed of onset with those with a rapid onset (<48 hours) likely to have more severe symptoms.

Assessment of volume status again here is key, because disorders of sodium metabolism are also disorders of WATER.

Hypovolaemic hypernatraemia – patients have signs of hypovolaemia, plus a high sodium!  If you check a urinary sodium and it is low it suggests that the the loss of Na is coming from somewhere other than the kidneys (normally GI tract).  The Na in these cases is usually elevated at 150-170mmol/L.  I think this is the most common class of hypernatraemia.

Euvolaemic hypernatraemia – can be caused by either renal or extra-renal loss of water without loss of Na.  These patients usually have an inability to respond to thirst, or one of the diabetes insipiduses? Inspidies?  Urine osmolality will be lower than plasma osmolality in patients with renal losses of water.  Serum Na in these cases is usually higher >170mmol/L.

Hypernatreamia with hypervolaemia – least common, these patients have normally been given more Na+ than they need (hypertonic solutions either NG, IV) OR they may have conditions which compound this such as renal or liver dysfunction.  People in this category have sky high sodiums >190mmol/L.

Acute Ix strategy – send urine and plasma for electrolytes and osmolality.

Urine osmolality

Lower than plasma or <300

[very dilute]

Normal 400-800 High >800

[super concentrated]

Central or nephrogenic diabetes insipidus


Incomplete Central or nephrogenic diabetes insipidus



Lots of water loss (and your patient has just run out of free H20)


Total Na+ gain


Extra-renal losses, D+V, burns etc

The mainstay of emergency treatment is infusion of the right amount of normal saline to bring the sodium back down.  You want to do this slowly in chronic hypernatreamia (drop the Na by no more than 10mmol/day).  I think this is why Normal Saline is suggested in the emergency phase rather than 5% Dextrose.

Most sources suggest we calculate the water deficit, and replace the lost fluid (after initial resuscitation fluids) over 24-48 hours with oral or 5% dextrose.  The formulae are similar but I encountered 3 different ones in the 3 sources I used (BMJ best evidence, Life in the Fast Lane, Mushin article).  Most of them changed either B or the way you calculate the Na excess.  The one below is from BMJ best evidence I found it the easiest to actually use (for me).

Deficit = A x B x ([Serum Na/140]-1)

A = is their weight

B = % water (0.6 for men, 0.4 for women)


Patients with hypervolaemic hypernatraemia might require that dirtiest of treatments;  fluid AND diuretics, as by expanding their intravascular volume with IV fluid you will downregulate vasopressin excretion further, compounding the problem.  This group of patients might benefit from dialysis to remove the volume and improve the sodium (carefully).

Once we’ve corrected this (and unless your bed-state is really really bad) most patients will be out of your department but further diagnostic tests may be done to confirm the cause.

Tests that may be required:

Plasma Aldosterone:Renin ratio: a high PCA:PRA ratio supports the diagnosis of Conns.  The ratio should be >1000 and a random aldosterone level should be >250pmol/L. (requires patient to be K+ replete, and have all diuretics and antihypertensives stopped for a few weeks beforehand  ).  If you get an equivocal result you might need to get a saline infusion test for hyperaldosteronism (this is an outpatient thing).

Dexamethasone suppression test (Cushings).  Patient takes 1mg dexamethasone at 23:00 and at 09:00 has blood taken for plasma cortisol.  A positive result is <50nmol/L.

Water deprivation test (for euvolaemic hypernatraemias)

When everything is back to normal.  Water restriction starts in the early morning, with baseline vasopressin level, with hourly Na checks.  Once the sodium is >148mmol/L another vaspopressin level should be taken.  At this point DDAVP (vasopressin agonist) should be given.  Patients with nephrogenic DI fail to respond to DDAVP, and their urine osmolality increases by <50% or <150mOsm/kg from baseline pointing to another cause.

CT or MRI head for cranial DI

CT or MRI adrenals for primary aldosteronism.


So just like our hyponatraemia patients, hypernatraemia patients need a serum and urine electrolytes and osmolality.  We need to decide on their volume status.  We need to resuscitate if required with normal saline, or replace slowly with 5% dextrose.  It is possible to calculate their fluid requirements and we should do this too.  In some circumstances we might even need to infuse 5% dextrose while giving diuretics.

The key question to answer is “Where has all the water gone?”


Hypovolaemic Euvolemic Hypervolaemic


Renal Losses

Renal failure


Post-obstructive diuresis


Non Renal Losses (urinary sodium low)




Failure to drink (psychological, behavioral, inability)


Nephrogenic DI

Drugs, AKI, Electrolytes


Neurogenic DI



Failure to drink (psychological, behavioral, inability)


Iatrogenic infusion/feeding of high Na fluid


Co-existing renal or liver dysfunction



Primary Aldosteronism

Resuscitate with Normal Saline


Calculate deficit and replace losses with 5% dextrose over 48 hours.


Aim for <10mmol/day increase in Na

Calculate deficit and replace losses with 5% dextrose over 48 hours.


Aim for <10mmol/day increase in Na

Calculate deficit, replace any losses carefully to avoid worsening overload using 5% dextrose.


Use IV Furosemide


Aim for <10mmol/day increase in Na

PS if you are wondering about that lady, she ended up having neuroleptic malignant syndrome plus a partial neurogenic diabetes insipidus from mass effect from maxillary bone osteomyelitis.  You know, one of those simple diagnoses…



BMJ best practice Hypernatraemia ( Accessed 24/11/2016

Mushin, A, Mount D Diagnosis and Treatment of Hypernatraemia.  Best Practive and Research Clinical Endocrinology and Metabolism 30;2 March 2016 189-203.  [paywall]

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