Hyponatremia in Emergency Medicine Treatment & Management

Hyponatremia is necessarily a hospital-based diagnosis, but patients may exhibit signs of severe neurologic dysfunction during prehospital evaluation and transport.

Address acute life-threatening conditions and initiate supportive care.

Establish reliable intravenous access and give supplemental oxygen to patients with lethargy or obtundation. In these patients, evaluate the possibility of hypoglycemia with a rapid glucose check. Administer intravenous glucose to hypoglycemic patients.

Administer standard prehospital anticonvulsant therapy to patients experiencing seizures. Seizures secondary to hyponatremia are unlikely to respond to this therapy, but it should be administered until a definitive diagnosis and therapy are available.

Intubate and initiate hyperventilation to reduce intracranial pressure in patients exhibiting signs of brainstem herniation (eg, obtundation; fixed, unilateral, dilated pupil; decerebrate or decorticate posturing) until a more definitive therapy can be initiated.

Avoid giving hypotonic intravenous fluids because they may exacerbate cerebral edema.

The ED evaluation of patients with hyponatremia includes determining the cause and the chronicity of the hyponatremic state in order to direct appropriate therapy. ^[25]

Acute hyponatremia is less common than chronic hyponatremia and typically is seen in patients with a history of sudden free water loading (eg, patients with psychogenic polydipsia, infants fed tap water or inappropriately diluted formula for 1-2 d, patients given hypotonic fluids in the postoperative period, a marathon runner drinking water without electrolyte supplementation).

Acute evolution of hyponatremia leaves little opportunity for compensatory extrusion of CNS intracellular solutes.

The ultimate danger for these patients is brainstem herniation when sodium levels fall below 120 mEq/L.

The therapeutic goal is to increase the serum sodium level rapidly by 4-6 mEq/L over the first 1-2 hours.

The source of free water must be identified and eliminated. In the non-hypotensive and non-dehydrated patient, a critical initial step is fluid restriction.

In patients with healthy renal function and mild to moderate symptoms, the serum sodium level may correct spontaneously without further intervention.

Patients with seizures, severe confusion, coma, or signs of brainstem herniation should receive hypertonic (3%) saline to rapidly correct the serum sodium level toward normal, but only enough to arrest the progression of symptoms. An increase in serum sodium level of 4-6 mEq/L is generally sufficient. Any further correction is potentially dangerous and must be avoided unless necessary to correct continued seizures or other severe CNS abnormality. If 3% hypertonic saline is not available, 8.4% sodium bicarbonate can be considered as an alternative for emergent sodium correction.

A Statement of the Third International Exercise-Associated Hyponatremia Consensus Development Conference provides the following guidelines for exercise-associated hyponatremia: ^{[26, 27]}

• Any athlete with exercise-associated hyponatremia (EAH) associated with signs or symptoms of encephalopathy should be immediately treated with an IV bolus or infusion of hypertonic saline (HTS) to acutely reduce brain edema, with additional IV boluses administered until there is clinical improvement.
• The dose and route of HTS administration should be based upon the severity of clinical symptoms and the available HTS formulations.
• The goal of IV HTS therapy is to stabilize the athlete for transfer to an advanced medical care facility.
• The use of IV HTS as the definitive treatment for acute hyponatremic encephalopathy is well validated, with the IV HTS bolus able to increase serum sodium levels 2-5 mmol/L, which decreases intracranial pressure and reduces symptoms.
• If the diagnosis of EAH is not confirmed, administration of HTS in small boluses is not associated with any negative consequences and serves as an excellent volume expander.

Chronic hyponatremia is more common than acute hyponatremia. Patients with mild symptoms and a serum sodium level of 125 mEq/L or less often have chronic hyponatremia. These patients lack any history of sudden free water loading.

Chronic hyponatremia must be managed with extreme care. Treatment of chronic hyponatremia has been associated with the development of the osmotic demyelination syndrome (also known as central pontine myelinolysis) characterized by focal demyelination in the pons and extrapontine areas associated with serious neurologic sequelae.

The pathophysiology of osmotic demyelination is controversial. Multiple cohort studies and 3 reviews of the literature suggest that the syndrome is caused by overly rapid correction or overcorrection of chronic hyponatremia. ^[28] Some investigators note that osmotic demyelination often develops when chronic hyponatremia is complicated by hypoxia and believe that osmotic demyelination may be a form of hypoxic encephalopathy associated with hyponatremia and not a complication of therapy. ^[29] Until further data are available, management should include meticulous attention to adequate oxygenation and a gradual increase in serum sodium level to 120-125 mEq/L. Serum sodium level should not be allowed to reach normal levels or hypernatremic levels within the first 48 hours.

Symptoms of osmotic demyelination (eg, dysarthria, dysphagia, seizures, altered mental status, quadriparesis, hypotension) typically begin 1-5 days after correction of serum sodium level. ^[30]

The condition is typically irreversible and often devastating. Slow, cautious correction of serum sodium level and maintenance of adequate oxygenation in these patients is important.

Patients with hypokalemia, female gender, or history of alcoholism or liver transplant seem to be particularly prone to develop osmotic demyelination. ^[31] Exercise extreme caution in treating hyponatremia in these subgroups.

To minimize the risk of osmotic demyelination, older literature recommended correction of sodium in chronic hyponatremia at a rate no greater than 10-12 mEq/L in the first 24 hours. However, newer guidelines recommend a maximum of 8 mEq/L in the first 24 hours, with a maximum of 6 mEq/L for patients at high risk of osmotic demyelination. The authors will use the safer margin as our recommendation. ^[28]

Patients with chronic hyponatremia and severe symptoms (eg, severe confusion, coma, seizures) should receive hypertonic saline, but only enough to raise the serum sodium level by 4-6 mEq/L and to arrest seizure activity. After this, we recommend no further correction of the sodium for the first 24 hours. Reports suggest that therapeutic relowering of the serum sodium level with hypotonic fluids and desmopressin (DDAVP) may help avert neurologic sequelae in patients whose chronic hyponatremia is inadvertently corrected too quickly. ^[32]

In treating patients with chronic hyponatremia and mild to moderate symptoms, consider the cause of the hyponatremic state. Patients are classified as having hypovolemic, euvolemic, or hypervolemic hyponatremia based on historical clues and physical examination. Regardless of the therapeutic approach, serum sodium must be monitored closely and corrected no faster than 6 mEq/L in the first 24 hours.

Patients with hypovolemic hyponatremia who are hypotensive and have signs of decreased end-organ perfusion may need IV fluid volume repletion in addition to sodium correction. Careful treatment with isotonic saline may be considered, but monitor serum sodium levels frequently to ensure that the serum sodium level increases slowly, with a maximum rise of 6 mEq/L in the first 24 hours. Be aware that as isotonic saline is given, large-volume diuresis of dilute urine may occur, causing overcorrection of sodium. As such, some practitioners will give low-dose (1-2 μg) DDAVP, continued every 6-8 hours, before administering IV fluids, thereby proactively decreasing urine output and preventing the overcorrection of sodium. ^{[21, 33]}

Patients with hypervolemic hyponatremia have increased total body sodium stores. Treatment consists of sodium and water restriction and attention to the underlying cause. The vasopressin receptor antagonists conivaptan (Vaprisol) and tolvaptan (Samsca) are now approved for use in hospitalized patients with hypervolemic hyponatremia, though clinical experience is scant. ^[34]

In April 2013, the FDA limited use of tolvaptan to no more than 30 days and indicated that it should not be used in patients with underlying liver disease. This decision was based on reports of liver injury, including those potentially leading to liver transplant or death. ^[35]

Euvolemic hyponatremia implies normal sodium stores and a total body excess of free water. Treatment consists of free water restriction and correction of the underlying condition. AVP (vasopressin) receptor antagonists (eg, conivaptan, tolvaptan) showed promise as effective and well-tolerated intravenous therapy for SIADH. ^[36] However, their mechanism of action poses a risk of overcorrection, as they lead to uncontrolled free water excretion; this risk of overcorrection led to European guidelines recommending against the use of AVP receptor antagonists in SIADH. ^[37] As a result, we do not recommend their employment in the emergency department.

Special consideration must be given to patients with concomitant hypokalemia and hyponatremia. With potassium repletion, intracellular shifts cause plasma sodium to increase. Consequently, the potassium repletion must be taken into account as patients undergo hypertonic saline therapy, and appropriate downward adjustment of the hypertonic saline dosage should be made. ^[38]

Admit patients with severely symptomatic hyponatremia manifested by coma, recurrent seizures, or evidence of brainstem dysfunction to an ICU and monitor serum sodium levels closely.

Admit patients with a propensity toward inappropriate free water ingestion to a unit where free water access is restricted. Clozapine appears to be effective in the long-term treatment of schizophrenic patients with compulsive water drinking.

Discontinue medications known to be associated with hyponatremia. Thiazide diuretics are a well-known cause of profound hyponatremia, especially in elderly patients, and should be discontinued in all admitted patients.