A 72-year-old woman, previously well apart from mild hypertension, has been admitted comatose to Accident and Emergency (A&E). She has a normal blood glucose level but her serum sodium is 112mmol/L.

What is your clinical approach to this clinical presentation?

In a comatose patient always check blood glucose level at the bedside before proceeding any further, even if there appears to be another explanation for the coma. Untreated hypoglycaemia can result in serious neurological sequelae and is easily corrected with 25 or 50% dextrose.

The first priorty is clearly to ensure safe management of the unconscious patient ( we will discuss this in detail in our next scenario), the next is to consider the broad differential diagnosis of hyponatremia. It is likely that the two problems are related( coma and hyponatremia), but this is not certain.

Obtaining a history from accompanying person if possible is vital.

Given the wide differential of both coma and hyponatraemia directed questions should be guided by your initial clinical observations.

Questions relating to coma:

Who found her?

What where the circumstances?

When was she last seen before that, and did she appear to be well?

Is there any possibility that she has taken an overdose?

A neurological history is clearly of prime importance in someone who is comatose, since a neurological problem could cause coma in its own right, or in this case via hyponatremia induced by syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Ask about:

-head injury

-fluctuating consciousness-suggestive of subdural hematoma

-headaches-especially with feature of raised intracranial pressure

-symptons suggestive of meningeal irritation-neck stiffness, photophobia.

Questions relating to the hyponatremia: 

Features of malignancy - wieght loss, unexplained fever, night sweats, pruritis.

Could this woman have lung cancer complicated by SIADH? (most likely in smoker, ask about previous and past)

Have there been features of lung cancer (e.g.cough,haemoptysis,dyspnoes,pleuritic chest pain), or symptons of pulmonary inflammation(e.g. purulent cough, dypsnoea)?

Fluid loss and fluid intake- diarrhoea or vomitting, drink  (what, and how much)  Psychogenic poldipsia is extremely unlikely in a woman of this age, most commonly being seen in a young psychiatric patients when excessive intake is frequently concealed.

Drug history - diuretics are a very common cause of hyponatraemia and this woman has hypertension. Enquire about drugs associated with SIADH (antidepressants-tricyclics,SSRIs, carbamezapine,chlorpropamide, phenothiazines-chlorpromazine, vincristine, cyclophosphamide,ecstasy.),  angiotensin converting enzyme inhibitors, exogenous steroids and nephrotoxins.

Other aspects -  cardiac, renal or liver failure or nephrotic syndrome.

Possible endocrine cause of hyponatraemia? Ask about the following:

- hypothyroidism

- weight gain, cold intolerance, constipation.

- hypopituitarism

- enquire specifically about symptons of hypogonadism,hypothyroidism and hypoadrenalism.

- Addison’s disease-unexplained hyponatremia in a comatose patient should prompt immediate consideration of hypoadrenalism.

- porphyria-abdominal pain, neuropathy and preceding psychiatric illness in a young patient are important clues to the diagnosis.

Examination

In a comatose patient the immediate priorties are:

- check airway, breathing, circulation:insert oropharangeal tube if tolerated.

- check Glasgow Coma scale score. ( We consider details of examination and mangement of a comatose patient  in our next scenario)

In this case, pursue the cause of hyponatremia as follows:

Check fluid status( discussed below)

Look specifically for:

-pyrexia-infection/inflammation

-clubbing-malignacy or pyogenis lung disease

-lymphadenopathy-malignancy

-Horner’syndrome-Pancoast’s tumour

-buccal/palmer/generalized pigmentation - Addison’s disease

-myxoedamatous features - hypothyroidism

-diminished body hair - hypopituitarism.

Other things to consider in a full physical examination:

- cardiac - is there evidence of heart failure?

- respiratory - look for signs of collapse/consolidation and bronchioectasis

- abdominal check for features of chronic liver disease or hepatomegaly

- neurological-look for neck stiffness, photophobia,papilloedma or any focal neurological deficits.

Discussion

There are many causes of hyponatremia but it best to classify them according to volume status: (hypovolemic, normovolemic and hypervolemic)

Hypovolaemic- the most reliable sign are a low jugular venous pressure and postural hypotension  ( difficult to assess the later in a comatose patient as may require standing and recumbent  blood pressures)

Normovolaemic

Hypervolaemic- look for raised jugular venous pressure, gallop rhythm, pulmonary oedema, peripheral oedema.

For example is our patient hypovolaemic?

 

     If YES                                                                                                             If    NO                                                                               

         V                                                                                                                            V

     Is urine sodium >220mmols/L                                                         Does the patient have signs of    

                                                                                                                       oedema?                  

          Yes                                             If No                                   No                                                                     Yes

           V                                                     V                               (normovolaemic)                                                (hypervolaemic)   

Sodium and water are being           Sodium and water                        V                                                                              V  

lost through the kidneys.                  are being lost                     Is urine osomlality                                             . Primary                                                                                                                                                                                                                               polydipsia

                                                             elsewhere.                        >500mmol/kg?                                                     . Nephrotic                                                                                                                                                                                                                            syndrome

 .Addison's Disease                           . Diahorrea                                                                                                     .Cardiac failure                           

 .Renal failure                                    and or / vomitting                  Yes                                                          . Cirrhosis    

 -Diuretic stage ATN                         . Fistula                                SIADH                                                           . Renal failure

 -Chronic pyelonephritis,                 . Burns                                                                          

 -analgesic nephropathy,                 . Villous                                       No

 -polycystic kidneys                            adenoma(rectum)                 . Water overload

 -nephrocalcinosis,                          . Small bowel obstruction      . Excess 5% Dextose

 -medullary cystic disease               . Pancreatitis                             .Severe hypothyroidism

 .Diuretics (especially thiazides)       . Trauma                                  . Glucorticoid deficiency

 .Osmolar diuresis                           . Cystic fibrosis                        

 (high glucose; high urea)                 . Heat exposure                        

                                                           . Endurance                              

                                                           sporting events

 

 

Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Diagnosis requires presence of all following criteria:

- Plasma hypo-osmolarity proportional to hyponatraemia.

-Urine osmolarity >plasma osmolarity.

-Persistent renal sodium excretion of around 50-70mmol/l.

-Normal renal, thyroid and adrenal function.

(Recent information on an SIADH-like clinical picture,  termed "nephrogenic syndrome of inappropriate antidiuresis." has been described...CLICK HERE for the abstract.)

Management of hyponatremia

No treatment for mild hyponatraemia is usually needed. Correct underlying cause (eg stop thiazide).

In symptomatic or severe form:

Hypovolaemic – volume replacement with isotonic saline (may need intravascular volume expanders to raise blood pressure).

Normovolaemic – fluid restriction to 500ml/24 hours first line to achieve 130mmol/l. If inadequate, induction of partial nephrogenic diabetes inspidus with demeclocycline (takes 2 weeks to reach maximum effect). Alternatively furosemide + oral sodium chloride 3g daily.

Hypervolaemic – furosemide +/- ACE inhibitors +/- water restriction to <1l/24 hours.

NB: whatever the cause, chronic, severe hyponatraemia (Na+ <120mmol/l for more than 3 days) must be corrected slowly, i.e. at no more than 0.5mmol/l/hour. Avoid an infusion of hypertonic saline if possible (seek expert help) - but if essential, increase serum sodium by <0.5mmol/l/hour (10mmol/l/24 hours) and stop infusion at 120mmol/l.

CLICK HERE for a set of guidelines on correction of hyponatremia.

 

If the hyponatraemia has only occured in the last 3 days and is causing acute symptoms (with drowsiness, convulsions or coma) it can be corrected more quickly - increase serum sodium by 2mmol/l/hour but stop at 120mmol/l. This condition is usually caused by giving large quantities of 5% dextrose infusion.

 

Complications Too rapid correction of serum sodium can cause central pontine myelinolysis (also known as osmotic demyelination syndrome). [ Which may present as a locked- in syndome, click on the phrase for a detailed but simple discussion of the topic. ]Caused by large shifts of intracellular water occurring outside the brainstem as well as in the pons. Always associated with rapid correction to normal levels (therefore stop at 120mmol/l and allow more gradual correction from then on). Symptoms occur 2-4 days later typically with quadriplegia and pseudobulbar palsy but can take the form of mutism with paralysis ('locked in' syndrome).

 

References

1.Oxford textbook of Medicine, water and electrolyte metabolism    

 2.Medical Masterclass, Endocrinology section1.1