Altered Mentation and Hyponatremia

Today's case was of a  man with a previous history of lung cancer and brain metastasis, a primary psychotic disorder, and COPD who presented with a subacute alteration in his mental status characterized by some delusional thoughts.

There were a lot of valuable learning points:

-We discussed a differential diagnosis and approach to altered mentation.  This will come up continuously when seeing ward patients or admitting from the ED.  Broad categories include drugs (illicits, narcotics, alcohol, CNS depressants, withdrawal), infections (meningitis is the most concerning), metabolic derangements (acidemia, hypercalcemia, B12 deficiency, thyroid disease), and structural derangements (intracranial hemorrhage, mass effect, etc).  In most cases, it is a good idea to obtain some form of neuroimaging, and some bloodwork (CBC, lytes, calcium profile, liver enzymes) +/- an arterial blood gas for acidemia.

-Delirium is something that we see frequently in medicine. Delirium is an acute change in mental status characterized by a fluctuating course, disordered thought, and agitation or depressed level of consciousness.  It has a very wide differential diagnosis, and can be caused by quite a number of things.  The typical treatment of delirium is fixing the underlying cause which can vary quite substantially depending on what it is.  Around 20% of the time, no definitive cause is found for the delirium. Delirium is independently associated with higher risk of poor outcomes from hospitalization, suggesting that it should be treated as a medical emergency on that basis.  In the case of our patient, it is less clear whether there is also some component of disordered thought and delusions on the basis of his psychiatric disorder as well.

-Hyponatremia is a common problem in hospitalized patients.  Think of hyponatremia as a water disorder rather than a sodium disorder.  Essentially there is too much free water for the amount of sodium in the body.

-Why do we care so much about hyponatremia? There are a couple of reasons.  Acutely, hyponatremia can produce alterations in mental status and seizures a result of cerebral edema (too much water outside brain cells, osmotic shift of water into brain cells, cerebral edema, raised intracranial pressure, seizure).  The other component that we care about is overcorrection of hyponatremia which can lead to osmotic demyelination syndrome (previously central pontine myelinolysis).  For those who have never seen this complication, it is a devastating injury to the brainstem that can result in “locked-in” syndrome (only able to move eyes).  Risk factors include low muscle mass (cirrhotic, malnourished), hypokalemia, and female sex.  The classic teaching recommended not increasing the sodium by more than 10mmol/L in a 24 hour period, but nephrologists are now stratifying patients by their risk for ODS, and recommending more conservative correction for those at higher risk.

-There are a lot of ‘approach to hyponatremia’ documents out there but I will try to give you a simplified one that I use.  Firstly, there are only THREE mechanisms that can produce hyponatremia:

(1) – free water is unable to be excreted by the kidney leading to an elevated water:sodium ratio in the body (this is the case in extreme renal failure).

(2) – Antidiuretic hormone is turned on, and is the only mechanism that separates salt from water retention. With this on, water is preferentially reabsorbed by kidneys leading to an increased water:sodium ratio in the body.

(3) – there is insufficient solute to excrete the free water.  Our kidneys can only dilute urine down to around 50 mOsm/L meaning that guzzling free water and eating things without any solute (sodium, proteins, etc.) will invariably lead to, you guessed it, an increased water:sodium ratio in the body.

-As far as an approach goes, I like to think of things this way:

(1) – is the hyponatremia real? (check the serum osmolality). Things that can cause hyperosmolar or euosmolar hyponatremia are elevated paraproteins, lipids, glucose, etc.

(2) – Now that it’s real, is it symptomatic? (i.e. is the patient seizing)

If it’s symptomatic, the treatment should be to rapidly correct the sodium by 1-2mmol/L until the patient stops seizing.  This is done in ICU’s with 200cc of 3% NaCl solution rapidly infused.

(3) – Now that it’s real, and asymptomatic, is it acute or chronic?  Most of the time you won’t know whether it’s acute or chronic because people don’t get their labs checked at home.  That said, acute hyponatremia can be corrected acutely without risk of ODS.  Chronic hyponatremia (48-72h) must be corrected slowly to avoid ODS.

(4) – Now that it’s real, asymptomatic, and chronic, what is the patient’s volume status?  What volume status is the kidney seeing?  Ordering the urine lytes answers the second question (if the kidney is seeing low volume, the urine sodium will be under 20).  Diuretics will interfere with this.  The rest of your physical exam answers the first question.  Many people will order urine osmolality as well.  This tells you whether ADH is acting or not (it is high if ADH is acting).  An example of hyponatremia when ADH is not acting would be psychogenic polydipsia, or insufficient solute intake.

From here, it’s helpful to break things down into causes by volume.  Hypovolemia causes ADH to be released to maintain plasma volume.  This is not because extracellular water stays intravascular, but because ADH acts as a potent vasoconstrictor to maintain systemic vascular resistance.  So patients with diarrhea, vomiting, sepsis, etc. may have appropriate ADH on board.

Hypervolemic patients like CHF, cirrhotic, or nephrotic syndrome patients are hypovolemic from a renal perspective, meaning that their kidneys behave like the first group.  Treatment of their underlying problem may resolve the hyponatremia.

The euvolemic group has a lot of causes: hypothyroidism, adrenal insufficiency, medications (diuretics, antiepileptics, SSRI’s), “tea and toasters”, psychogenic polydipsia, and the ever-famous SIADH (syndrome of inappropriate antidiuretic hormone).

SIADH occurs for a number of reasons: lung pathology, tumours, CNS disease, pain, nausea, etc.

So based on the above, you can see that the treatment varies widely.  If you give someone with SIADH normal saline, their sodium may go down because that potent ADH will reabsorb all the water, and allow excretion of all the sodium. On the contrary, someone with hypovolemic hyponatremia will correct their sodium rapidly because the saline restores intravascular volume, leading to a shutoff of their ADH release, and a water diuresis.  That’s why we sometimes give salt cubes, or urea, to patients with low solute intake – it drags out some of the excess water and increases the capacity for free water excretion.

Further Reading:

Ellison, D. H., & Berl, T. (2007). The syndrome of inappropriate antidiuresis. New England Journal of Medicine, 356(20), 2064-2072.

Spasovski, G., Vanholder, R., Allolio, B., Annane, D., Ball, S., Bichet, D., ... & Nagler, E. (2014). Clinical practice guideline on diagnosis and treatment of hyponatraemia. European journal of endocrinology, 170(3), G1-G47.