From the Guidelines
Hypernatremia and hyponatremia are disorders of sodium balance that require prompt recognition and treatment, with the goal of minimizing morbidity, mortality, and improving quality of life. Hypernatremia occurs when serum sodium exceeds 145 mEq/L, resulting from either water loss exceeding sodium loss or excessive sodium intake. Common causes include inadequate water intake (especially in elderly or disabled patients), diabetes insipidus, excessive sweating, severe diarrhea, and iatrogenic causes like hypertonic saline administration. Diagnosis relies on serum sodium measurement, assessment of volume status, and urine osmolality. Treatment focuses on addressing the underlying cause while carefully correcting sodium levels with hypotonic fluids (typically 0.45% saline or 5% dextrose in water) at a rate not exceeding 10-12 mEq/L per day to prevent cerebral edema 1.
Pathophysiology and Etiology
Hyponatremia, defined as serum sodium below 135 mEq/L, can be hypovolemic (from fluid losses), euvolemic (SIADH, hypothyroidism, adrenal insufficiency), or hypervolemic (heart failure, cirrhosis, nephrotic syndrome). The pathophysiology of hyponatremia involves an imbalance between water and sodium, leading to an excess of water relative to sodium in the body. This can result from various etiologies, including but not limited to, heart failure, liver cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion (SIADH) 1.
Diagnostic Tests
Diagnostic workup includes serum and urine sodium, osmolality, thyroid and adrenal function tests, and volume status assessment. These tests help determine the underlying cause of the sodium imbalance, which is crucial for guiding treatment. For instance, in patients with cirrhosis, the diagnosis and management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome are critical in the context of hyponatremia 1.
Treatment
Treatment depends on the severity and type of hyponatremia. Severe symptomatic hyponatremia may require 3% hypertonic saline (100-150 mL over 10-20 minutes, repeatable up to 3 times if needed), while chronic cases require fluid restriction (800-1000 mL/day), salt tablets, or vasopressin receptor antagonists like tolvaptan (starting at 15 mg daily). In patients with cirrhosis, the management of hyponatremia involves water restriction, cessation of diuretics, and in some cases, the use of vasopressin receptor antagonists or hypertonic saline for severe cases 1. Correction should not exceed 8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome.
Complications
Complications of hypernatremia include cerebral hemorrhage, seizures, and death, while hyponatremia can lead to cerebral edema, seizures, coma, and osmotic demyelination syndrome if corrected too rapidly. Hyponatremia is also associated with a poorer prognosis in patients with liver cirrhosis and ascites, including an increased risk of refractory ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and death 1. The MELD-Na score, which incorporates the sodium level into the Model for End-Stage Liver Disease (MELD) score, is used to determine the prognosis of end-stage cirrhosis and prioritize liver transplant candidates.
Key Considerations
- The goal of treatment is to correct sodium levels while minimizing the risk of complications, such as osmotic demyelination syndrome in hyponatremia.
- Fluid restriction and the use of vasopressin receptor antagonists are key components of the management of hyponatremia in certain contexts, such as cirrhosis.
- The rate of correction of sodium levels is critical, with a recommended maximum correction rate of 8-10 mEq/L per 24 hours to prevent osmotic demyelination syndrome.
- Multidisciplinary care is essential, especially in complex cases such as those involving liver cirrhosis and ascites, to mitigate the risk of complications and improve outcomes.
From the FDA Drug Label
14 CLINICAL STUDIES 14. 1 Hyponatremia In two double-blind, placebo-controlled, multi-center studies (SALT-1 and SALT-2), a total of 424 patients with euvolemic or hypervolemic hyponatremia (serum sodium <135 mEq/L) resulting from a variety of underlying causes (heart failure, liver cirrhosis, syndrome of inappropriate antidiuretic hormone [SIADH] and others) were treated for 30 days with tolvaptan or placebo, then followed for an additional 7 days after withdrawal.
The pathophysiology and etiology/risk factors of hyponatremia are not directly addressed in the provided text, but it mentions that the patients had euvolemic or hypervolemic hyponatremia resulting from various underlying causes such as:
- Heart failure
- Liver cirrhosis
- Syndrome of inappropriate antidiuretic hormone (SIADH)
- Others
The diagnostic tests used in the study included:
- Serum sodium concentration measurements
The treatment used in the study was:
- Tolvaptan (15 mg/day to 60 mg/day)
- Placebo
- Fluid restriction (defined as daily fluid intake of ≤1.0 liter/day) as clinically indicated
The complications of hyponatremia are not directly addressed in the provided text, but it mentions that the patients were excluded if they had:
- Acute and transient hyponatremia associated with head trauma or postoperative state
- Hyponatremia due to primary polydipsia, uncontrolled adrenal insufficiency, or uncontrolled hypothyroidism
Hypernatremia is not mentioned in the provided text. 2
From the Research
Hypernatremia and Hyponatremia Overview
- Hypernatremia is a common electrolyte disorder that reflects an imbalance in the water balance of the body, often resulting from an increased loss of free water compared to sodium excretion 3.
- Hyponatremia is a condition where the serum sodium level is less than 135 mmol/L, and its symptoms are highly dependent on its acuteness and cause 4.
Pathophysiology
- Hypernatremia is characterized by a central nervous system dysfunction (confusion, coma) and pronounced thirst (in awake patients) 3.
- Hyponatremia can cause confusion, lethargy, seizures, or frank coma due to brain edema, especially in severe acute cases (serum sodium less than 125 mEq/l) 4.
Etiology/Risk Factors
- Hypernatremia can result from an increased loss of free water compared to sodium excretion, and is rarely based on excessive sodium intake 3.
- Hyponatremia can occur in malnourished alcoholic patients, who may represent a special case with possible dangers of central pontine myelinolysis if a very low serum sodium is corrected acutely to normonatremic or hypernatremic levels 4.
Diagnostic Tests
- The diagnosis of hypernatremia involves determining the extracellular volume status, measuring urine sodium levels, urine volume and osmolality, and checking ongoing urinary electrolyte free water clearance 5.
- The diagnosis of hyponatremia involves measuring serum sodium levels and assessing the patient's volume status and osmolality of urine 4.
Treatment
- The treatment of hypernatremia involves replacing the (absolute or relative) loss of free water by hypotonic infusions, or in case of diabetes insipidus, by application of Desmopressin (Minirin) 3.
- The treatment of hyponatremia involves correcting the serum sodium level to 125-130 mEq/l at a rate of 1.5-2.0 mEq/l/h, and may require careful consideration of the underlying cause and the patient's volume status 4.
- For acute hypernatremia (< 24 hours), hemodialysis is an effective option to rapidly normalize the serum sodium levels 3.
- Preexisting hypernatremia (>48h) should not be reduced by more than 8-10 mmol/l/day to avoid osmotic demyelination syndrome 3.
Complications
- Rapid correction of hypernatremia is not associated with a higher risk for mortality, seizure, alteration of consciousness, and/or cerebral edema in critically ill adult patients with either admission or hospital-acquired hypernatremia 6.
- Hyponatremia carries a high mortality rate and risk of irreversible brain damage if therapy is delayed 4.
- Central pontine myelinolysis is a possible complication of rapid correction of hyponatremia in malnourished alcoholic patients 4.