Assessing the severeness of hyponatraemia is based on both symptoms and the concentration of sodium in the plasma.
The plasma sodium concentration should be checked from all acutely ill patients. In hyponatraemia, the concentration of sodium in the plasma decreases below 135 mmol/l, and in a severe condition the concentration decreases below 120 mmol/l.
In order to assess the symptoms and the risk of developing complications resulting from the treatment, the objective is to differentiate between acute, clearly symptomatic hyponatraemia that has developed rapidly (< 48 hours) and chronic hyponatraemia that has developed slowly over several days, weeks or even months. If the duration of the condition cannot be inferred, hyponatraemia is considered chronic.
The manifestations of acute hyponatraemia are progressive central nervous system symptoms (confusion, vomiting, seizures, unconsciousness), whereas the symptoms of chronic hyponatraemia can be very slight and more generalised (e.g. lethargy, falls, gait disturbances, muscular weakness, muscle cramps, impairment of attention).
The urgency of treatment is always determined by the patient's symptoms as well as the degree and duration of hyponatraemia.
In most cases, hyponatraemia is caused by excessive body water, which dilutes the sodium concentration in the extracellular fluid and plasma. The phenomenon results from conditions or drugs that increase the secretion of the antidiuretic hormone (ADH) or inhibit water diuresis in other ways (syndrome of inappropriate antidiuresis, SIAD).
The possibility of cortisol deficiency should be kept in mind.
Sodium depletion is far from being a common cause of hyponatraemia, but it is clinically fairly easy to identify.
Plasma copeptin, urate, urea as considered necessary
Symptoms
The spectrum of symptoms correlates well with the rate and magnitude of the decrease in sodium concentration. Consider the possible acute worsening of chronic hyponatraemia (acute-on-chronic).
Rapidly developed acute hyponatraemia (water intoxication) may cause seizures and unconsciousness in a totally healthy person.
Slowly developed hyponatraemia may have surprisingly few symptoms.
Fatigue
”Feeling odd”
Asthenia
Falls
Gait disturbances
Slowing down
Impairment in attention
The neurological symptoms of chronic hyponatraemia do not generally emerge uuntil the plasma sodium concentration decreases below 120 mmol/l.
Drowsiness
Headache
Confusion
Seizures
Unconsciousness
Causes and evaluation
Hyperglycaemia and iatrogenic administration of mannitol are associated with isotonic or hypertonic hyponatraemia which does not cause symptoms and is reversed with the secretion or metabolism of these effective osmoles.
In association with other hyponatraemic conditions, plasma osmolality is decreased which means that there is hypotonic hyponatraemia. Its subtypes are dilutional hyponatremia, sodium depletion and hyponatraemia associated with oedematous disorders.
The concentration of plasma sodium becomes diluted if water intake occurs at a higher rate than water can be excreted (water accumulates in the body without oedema formation and is mainly contained within the cells). This is the most common mechanism of hyponatraemia (diagnostic tips: normal blood pressure, no salt craving or oedema and normal jugular venous pressure, JVP, or mild findings of hypervolaemia).
Nausea and pain associated with excessive hydration
Thiazides
True deficiency of glucocorticoids and severe hypothyroidism
Drugs that either increase the secretion of ADH or potentiate its effect (e.g. SSRIs, tricyclic antidepressants, opioids, antiepileptics, metoclopramide)
Syndrome of inappropriate ADH secretion (SIADH) associated with tumours (small cell lung cancer), CNS diseases (encephalitis, head injury, subarachnoid haemorrhage) or lung disease (pneumonia, tuberculosis, positive pressure ventilation)
Decreased dietary intake of salt due to a diet exceptionally poor in sodium (”tea and toast” phenomenon) or beer used as the primary source of nutrition (beer potomania)
Hyponatraemia associated with oedematous disorders
Close monitoring of the fluid balance, haemodynamic state and weight
Are there signs of sodium depletion?
Salt craving, hypotension, orthostatic hypotension, pigmentation in Addison's disease
Does the patient have heart failure, liver cirrhosis or nephrosis?
Does the patient have oedema, increased JVP, ascites or hypotension due to the decreased effective circulating plasma volume?
Are there clinical signs of
glucocorticoid deficiency (weight loss, loss of appetite, asthenia, lethargy)
severe hypothyroidism?
Does the patient use diuretics (combination products must be borne in mind) or other medication that may lead to reduced water diuresis (see above)?
What are the patient's drinking habits?
The causes of hyponatraemia may be categorized on the basis of urine osmolality and sodium concentration determined from a single urine sample as well as of clinical findings (blood pressure, swellings); see flowchart 1. The reference ranges presented in the chart are indicative only.
The treatment of hyponatraemia has four main aims:
to prevent decrease of the plasma sodium concentration
to decrease/improve the symptoms of hyponatraemia
to decrease the intracranial pressure in patients at risk of brain herniation
to avoid too rapid a correction of plasma sodium concentration (and thus the risk of osmotic demyelination).
The urgency of treatment is determined by the symptoms as well as the degree and duration of hyponatraemia.
The treatment of hypokalaemia and avoidance of drugs which aggravate hyponatraemia should be remembered.
The objective of the treatment is 5 mmol/l/24 h increase of plasma sodium, except in the case of severe symptoms max. 8 mmol/l/24 h, until plasma sodium is > 130 mmol/l (and usually the active treatment of hyponatraemia may be discontinued). The correction of hyperacute hyponatraemia may be carried out faster.
If the symptoms do not improve when the plasma sodium has increased 5 mmol/l or the plasma sodium is 130 mmol/l, other causes of the symptoms should be searched for.
Urgent management is indicated because of severe symptoms if the patient convulses or if the patient's level of consciousness has clearly deteriorated signifying cerebral oedema.
Hypertonic 3%sodium chloride should be started as an infusion at the rate of 150 ml/20 min.
A 3% sodium chloride fluid is prepared by removing 45 ml of fluid from a 500 ml NaCl 0.9 solution bag and adding the same amount (45 ml) of sodium chloride concentrate (235 mg/ml NaCl which has 4 mmol/ml sodium). The sodium concentration of the ready solution is around 500 mmol/l. If the strength of the locally available NaCl solution differs from the aforementioned value, adjust the amounts accordingly.
The plasma sodium concentration is checked after the infusion and then hourly. The infusion should be repeated when needed until the plasma sodium has increased 5 mmol/l from the baseline or when severe symptoms subside.
Urine output is carefully monitored; increase to the level > 100 ml/h is predictive of negative fluid balance and too rapid an increase of sodium concentration.
Infusion is stopped immediately if the plasma sodium concentration has increased as per the limits described above or symptoms improve or urine output shows marked increase. The objective is to limit the increase of the plasma sodium concentration to max. 8 mmol/l/24 t.
A too rapid correction may be associated with cerebral osmotic demyelination, for which no specific treatment exists. Particular predisposing risk factors are alcoholism, hypokalaemia, undernutrition and hypoxaemia. When symptoms occur, the plasma natrium concentration should be decreased in a controlled manner.
As the treatment of hypovolaemic hyponatraemia, NaCl 0.9% solution should be infused according to the individual assessment of the situation.
In sodium depletion, or in suspicion of it (urine sodium < 30 mmol/l), treatment should be started with a slow infusion (150 ml/hour) of physiological sodium chloride or oral hydration and salt supplement.
The patient's diuretic should be stopped and possible hypokalaemia corrected.
Mildly symptomatic or chronic eu- and hypervolaemic hyponatraemia does not require urgent management and is treated according to the underlying disorder.
Any medication causing hyponatraemia should be stopped.
In hyponatraemia associated with oedematous disorders, the treatment should focus on the underlying disease (heart failure, liver cirrhosis or nephrotic syndrome).
There is no need to correct mild (Na ≥ 130 mmol/l) and asymptomatic drug-induced (e.g. antiepileptics) hyponatraemia as long as the patient has been advised to avoid excessive fluid intake that could acutely worsen hyponatraemia.
In rare severe hypothyroidism, thyroxine will correct hyponatraemia.
Hyponatraemia caused by excessive fluid intake or SIADH is treated by focusing on the underlying disease and restricting fluid intake (initially < 800-1 000 ml/day). The oral use of osmotically active urea with the dose of 0.25-0.50 g/kg/day has also been beneficial.
In the treatment of hyponatraemia associated with SIADH or oedematous disorders (e.g. heart failure), the status and indications of ADH antagonist (tolvaptan, initial dose 3.25-7.5 mg/day) are not established. When the therapy is started, restriction of fluid intake is ended. The use of demeclocycline or lithium is not recommended.
Irrespective of the treatment method, and if necessary, a too rapid increase in sodium concentration (plasma sodium increases over 8 mmol/l within 24 h) has to be corrected by infusion of hypotonic fluids; for example by infusion of 5% glucose solution at a rate matching the diuresis of the previous hour. Also desmopressin (e.g. 0.1-1 µg single dose intravenously) has been used for this purpose at a monitoring ward, although for the time being there is no information available on the benefits and optimal dosage.
References
Fenske W, Maier SK, Blechschmidt A et al. Utility and limitations of the traditional diagnostic approach to hyponatremia: a diagnostic study. Am J Med 2010;123(7):652-7. [PubMed]
Spasovski G, Vanholder R, Allolio B et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol 2014;170(3):G1-47. [PubMed]
Sterns RH. Disorders of plasma sodium. N Engl J Med 2015;372(13):1269. [PubMed]
Palmer BF, Clegg DJ. Electrolyte Disturbances in Patients with Chronic Alcohol-Use Disorder. N Engl J Med 2017;377(14):1368-1377. [PubMed]