What are the causes and symptoms of hyponatremia?

From the Guidelines

Hyponatremia is a condition characterized by abnormally low sodium levels in the blood, specifically below 135 mEq/L, and its causes include excessive water intake, certain medications, medical conditions like heart failure, kidney disease, liver cirrhosis, and SIADH, hormonal disorders, and excessive sweating or diarrhea causing electrolyte imbalances. The symptoms of hyponatremia vary based on severity and how quickly sodium levels drop, ranging from mild symptoms such as nausea, headache, confusion, and fatigue to severe symptoms like muscle weakness, cramps, irritability, and decreased consciousness, and even life-threatening complications like seizures, coma, and death due to brain swelling 1.

Causes of Hyponatremia

• Excessive water intake
• Certain medications (such as diuretics, antidepressants, and anticonvulsants)
• Medical conditions (like heart failure, kidney disease, liver cirrhosis, and SIADH)
• Hormonal disorders (including adrenal insufficiency and hypothyroidism)
• Excessive sweating or diarrhea causing electrolyte imbalances

Symptoms of Hyponatremia

• Mild hyponatremia: nausea, headache, confusion, and fatigue
• Moderate hyponatremia: muscle weakness, cramps, irritability, and decreased consciousness
• Severe hyponatremia: seizures, coma, and even death due to brain swelling The treatment of hyponatremia depends on the underlying cause and severity, ranging from fluid restriction for mild cases to intravenous sodium solutions for severe symptoms, and correcting sodium levels too quickly can cause osmotic demyelination syndrome, a serious neurological complication, so medical supervision is essential when treating hyponatremia 1. According to the most recent guidelines, for patients with cirrhosis and ascites, treatment of hyponatremia should be based on etiology, chronicity, severity, and urgency, and patients with acute hyponatremia can have hyponatremia corrected rapidly, while patients with chronic hyponatremia require more gradual and measured correction to avoid overcorrection and mitigate the risk of osmotic demyelination syndrome (ODS) 1.

From the FDA Drug Label

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 causes of hyponatremia mentioned in the study include:

• Heart failure
• Liver cirrhosis
• Syndrome of inappropriate antidiuretic hormone (SIADH)
• Other underlying causes

The study does not explicitly mention the symptoms of hyponatremia. 2

From the Research

Causes of Hyponatremia

• Hyponatremia can result from various causes, including water retention, certain medications, excessive alcohol consumption, very low-salt diets, and excessive free water intake during exercise 3.
• It can also be caused by primary vasopressin excess, leading to the syndrome of inappropriate antidiuresis (SIAD), or secondary vasopressin stimulation, involving a baroreceptor mechanism, often found in liver cirrhosis, cardiac failure, and volume contraction 4.
• Diuretics, particularly thiazide diuretics, are a common cause of severe hyponatremia 5.
• Hyponatremia is common in patients with cirrhosis and portal hypertension, characterized by excessive renal retention of water relative to sodium due to reduced solute-free water clearance, with the primary cause being increased release of arginine vasopressin 6.

Symptoms of Hyponatremia

• Symptoms of hyponatremia can range from mild and nonspecific, such as weakness, nausea, headache, and mild neurocognitive deficits, to severe and life-threatening, including delirium, confusion, impaired consciousness, ataxia, seizures, and brain herniation 7, 3.
• The severity of symptoms depends on the rapidity of development, duration, and severity of hyponatremia 7.
• Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 7.
• Severe symptoms of hyponatremia, such as somnolence, obtundation, coma, seizures, or cardiorespiratory distress, are a medical emergency and require immediate treatment 7, 3.

Classification and Treatment of Hyponatremia

• Hyponatremia can be classified into three categories based on fluid volume status: hypovolemic, euvolemic, and hypervolemic 7, 3.
• Treatment of hyponatremia depends on the underlying cause and the severity of symptoms, and may involve fluid restriction, normal saline infusions, salt tablets, intravenous vaptans, or hypertonic saline 7, 3, 6, 4.
• In cases of severely symptomatic hyponatremia, bolus hypertonic saline may be used to rapidly correct the serum sodium level, but the correction limit should not exceed 10 mEq/L within the first 24 hours to avoid osmotic demyelination syndrome 7, 3.