The management of hyponatremia requires an approach that identifies the underlying cause of the electrolyte disorder. One approach to this involves the sequential assessment of serum osmolality, urine osmolality, volume status and urinary [Na+].

 

 

Sodium is the predominant solute in the extracellular fluid compartment and, as such, the primary determinant of serum osmolality. A decrease in serum [Na+] (i.e., hyponatremia) generally, but not always, reflects a state of hypo-osmolality. The presence of an increased concentration of solutes that do not cross the cell membrane (such as glucose, mannitol or glycine) can lead to the development of translocational hyponatremia as a result of the movement of water from the cells to the extracellular space. Such patients can have normal, or even high, serum osmolality. Another setting in which hyponatremia is associated with a normal serum hypo-osmolality occurs in the presence of high levels of lipids or proteins.

 

This is designated as pseudohyponatremia and is the result of the increased proportion of serum volume taken up by these substances. The serum osmolality remains normal in pseudohyponatremia and can be used to eliminate this diagnosis.

 

 

Once the presence of hypotonicity has been established, the urinary osmolality may be used to differentiate between patients who do and do not have a disorder in the renal diluting mechanism. A urine osmolality below 100 mOsm/kg reflects a normal diluting mechanism, the hyponatremia resulting from a level of water intake that exceeds normal urinary diluting capacity (psychogenic polydipsia). This can also be observed in infants fed dilute formula and patients with a low solute intake. In contrast, a urine osmolality exceeding 100 mOsm/kg reflects impairment to the renal diluting mechanism at a time when the urine should be maximally dilute in the setting of serum hypotonicity; this most commonly is a consequence of persistent vasopressin in the circulation.

 

 

 

In patients whose urine osmolality is greater than 100 mOsm/kg, assessment of volume status is necessary to identify the underlying etiology of the hyponatremia. In hypovolemic patients with hyponatremia, urinary [Na+] greater than 20 mmol/L is indicative of renal sodium losses, whereas a urinary [Na+] below 20 mmol/L reflects extra renal sodium losses. Patients with hypervolemic hyponatremia (due to heart failure, cirrhosis and nephrotic syndrome) characteristically also have a sodium retaining disorder in addition to the water retention reflected in the decrement of sodium serum. Thus, their urinary sodium is <20 mmol/L. Less commonly, hypervolemic hyponatremia is seen in patients with advanced renal failure who cannot conserve sodium, and therefore may have a urinary [Na+] >20 mmol/L. In euvolemic hyponatremia there is an excess of total body water relative to a normal amount of total body sodium. These patients characteristically have a urinary sodium >20 mmol/L, as this reflects their sodium intake.

 

 

 

Hyponatremia is classified according to serum osmolality:

 

Hypotonic hyponatremia is further classified according to extracellular fluid volume status:

 

 

SIAD is a diagnosis of exclusion. It fits the category of hyponatremia with a urine osmolality >100 mOsm/kg, urine sodium concentration ≥30 mmol/L and normal extracellular fluid volume, but formal diagnosis requires exclusion of other possible causes of hyponatremia. One such possible cause is adrenal insufficiency. Hyponatremia due to hypothyroidism is very rare other than in myxoedema coma, when there is also a decrease in cardiac output and glomerular filtration rate.

 

 

Supplemental criteria

 

 

Malignant disease. Carcinoma of lung, orophraynx, gastrointestinal tract, genitourinary tract, lymphoma, sarcoma and neuroblatoma.

 

Pulmonary disorder. Infection (bacterial pneumonia, viral pneumonia, tuberculosis, aspergillosis, pulmonary abscess, asthma and cystic fibrosis).

 

Disorder of central nervous system. Infection (meningitis, encephalitis, brain abscess, AIDS, malaria), vascular and masses (brain tumor, head trauma, stroke, subdural hematoma and subarachnoid hemorrhage), Guillain–Barré syndrome, multiple sclerosis, hydrocephalus and cavernous sinus thrombosis.

• Antidepressants (SSRIs, tricyclic antidepressant, MAOI and venlafaxine)
   
• Anticonvulsants (carbamazepine, oxcarbazepine, sodium valproate, lamotrigine)
   
• Antipsychotics (phenothiazides, butyrophenones)
   
• Anticancer (ifosfamide, melphalan, cyclophosphamide, methotrexate and pentostatin)
   
• Vasopressin analogues (desmopressin, oxytocin, terlipressin and vasopressin)
   
• Miscellaneous (opiates, levamisole, interferon, NSAIDs, clofibrate, nicotine, amiodarone and proton pump inhibitors)
   

Approach to Hyponatremia

• Vomiting
   
• Diarrhea
   
• Third space
   
• Burn
   
• Pancreatitis
   
• Traumatic

• Diuretic excess
   
• Minerlocortical deficiency
   
• Salt-losing nephropathy
   
• Bicarbonaturia
   
• Renal tubular acidosis
   
• Ketonuria

Management

 

The key to effective management of hyponatremia is establishing the type and its cause so that the cause can be removed, if possible, and the management will be appropriate. The treatment of hyponatremia is determined by three major factors: severity of hyponatremia, that is, the presence or absence of severe central nervous system (CNS) symptoms such as lethargy, delirium, seizure, and coma; onset of hyponatremia, acute or chronic; and volume status.

 

 

The correct treatment of hyponatremia in acute illness depends first and foremost on the correct diagnosis.

Unfortunately, occasionally a physician believes that all types of hyponatremia means a decrease in total body sodium concentration and therefore the treatment is isotonic saline administration. Only hypovolemic hyponatremia is appropriately treated by volume expansion with isotonic saline. Therefore, when hypovolemic hyponatremia is the suspected diagnosis, a trial of volume expansion with isotonic saline is certainly appropriate.

 

 

Acute symptomatic hyponatremia can be a very serious clinical situation. In hyponatremia, the water equilibrates across the brain cell membrane and leads to cell swelling. Acute hyponatremia can lead to severe brain swelling, herniation and cardiopulmonary arrest. There are, however, adaptive changes that occur in the brain over time. Within the first 1–3 hours, extracellular fluid moves into the cerebrospinal fluid and then into circulation. A slower process of adaptation then occurs in which brain cells extrude potassium and organic solutes, thereby decreasing intracellular osmolality and reducing brain edema as water moves out of cells. In acute hyponatremia with neurological symptoms, the treatment of choice is 3% hypertonic saline at 100 ml/h. For each 100 mL of 3% hypertonic saline, the serum sodium concentration will increase by approximately 2 mEq/L. The duration of hypertonic saline treatment of acute symptomatic hyponatremia should be based on the improvement in the patient’s symptoms and signs. Patients with acute hyponatremia may be lethargic, disoriented, agitated and have anorexia and nausea. Physical findings include abnormal sensorium, pathological reflexes, Cheyne–Stokes respiration, hypothermia and seizures. In case of severe symptoms, such as seizures, obtundation and coma, 3% sodium chloride may be infused at 4–6 mL/kg/h. A loop diuretic, for example, furosemide, may be added to this treatment, as it may cause hypotonic urine. Urinary electrolytes, however, should be replaced to avoid extracellular fluid volume (ECFV) depletion and electrolyte disturbances such as decreased plasma potassium, magnesium and calcium. The consensus is that correction of hyponatremia should be limited to less than 12 mEq/L in 24 hours and less than 18 mEq/L in 48 hours. There are high-risk patients, however, with severe malnutrition, alcoholism or advanced liver disease in whom the rate of correction of hyponatremia should be below these limits. Patients with too rapid correction of hyponatremia develop osmotic demyelination syndrome (central pontine myelinosis).The patients demonstrate improved neurological symptoms initially, but one to several days later, new and progressive neurological symptoms emerge and can lead to permanent neurological deficits or even death.