Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) is characterized by the body producing too much antidiuretic hormone (ADH), or vasopressin. This excess hormone causes the kidneys to retain water, which subsequently dilutes the body’s sodium levels. The resulting low serum sodium concentration, known as hyponatremia, is the defining feature of SIADH and the primary target of treatment. The overall goal is to raise the serum sodium level slowly and safely to a healthy range (typically above 130 mEq/L) while addressing the underlying cause.
Initial Non-Drug Strategies
For individuals with mild or moderate hyponatremia without severe symptoms, the first approach is fluid restriction. This strategy directly counteracts water retention caused by excess ADH by limiting total fluid intake. A typical restriction involves limiting daily fluid consumption to 800 to 1000 milliliters per day, though some protocols suggest stricter limits.
Adherence to this low fluid volume can be challenging for patients, especially over the long term, making compliance difficult in an outpatient setting. The fluid limit must include all forms of liquid, such as water, coffee, soup, and juice, to be effective.
A secondary, non-pharmacological strategy is to increase the patient’s solute load, which encourages the kidneys to excrete more water. This is often achieved by increasing the dietary intake of salt or protein. The added solutes require a certain volume of water to be excreted, effectively helping to draw excess water out of the body.
High dietary salt intake can be supplemented with oral sodium chloride tablets. Similarly, a high-protein diet increases urea production, which acts as an osmotic agent within the kidney tubules. Increasing the solute load forces the body to excrete a larger volume of water to clear these waste products, reducing the dilutional effect on serum sodium.
Medications Used to Increase Sodium Levels
When fluid restriction alone fails to correct hyponatremia or if the condition is more persistent, pharmacological treatments are introduced to interfere with the ADH mechanism. One of the most effective and targeted groups of medications are the vasopressin receptor antagonists, often referred to as vaptans. These drugs work by blocking the V2 receptors in the renal collecting ducts, which are the sites where ADH normally acts.
By blocking the V2 receptors, vaptans prevent the movement of aquaporin-2 water channels to the kidney’s surface, which normally allows water reabsorption. This results in a selective excretion of water without significant electrolyte loss, a process known as “aquareisis.” An oral example is typically started at a low dose, such as 15 milligrams once daily, requiring careful monitoring to prevent an overly rapid rise in sodium levels.
Another pharmacological option is urea, which can be given orally to dramatically increase the solute load, particularly for cases resistant to fluid restriction. Urea functions as an effective osmotic diuretic, meaning it is filtered by the kidneys and pulls water along with it into the urine. Dosage typically ranges from 0.25 to 0.50 grams per kilogram of body weight per day. This treatment promotes significant water diuresis and is effective for increasing serum sodium concentration.
A third, older option is demeclocycline, a tetracycline derivative used off-label for SIADH. This antibiotic interferes with ADH action directly at the renal tubules, essentially inducing a form of drug-related diabetes insipidus. It works by impairing the normal signaling cascade within the kidney cells, reducing the expression of aquaporin-2 water channels. Due to its slow onset of action, which can take over a week, demeclocycline is not suitable for urgent treatment. Its use is also limited by potential side effects, including skin photosensitivity and nephrotoxicity.
Protocol for Severe Cases
The management of acute, severe hyponatremia accompanied by neurological symptoms (seizures, confusion, or coma) constitutes a medical emergency requiring immediate hospital care. The protocol involves the controlled intravenous administration of 3% hypertonic saline. This highly concentrated salt solution quickly raises the plasma sodium concentration, drawing excess water out of brain cells to relieve cerebral edema.
Initial treatment often involves administering the hypertonic saline in small, carefully calculated boluses, such as 100 milliliters over 15 minutes. The immediate goal is to achieve a rapid, but modest, increase in serum sodium of approximately 4 to 6 mEq/L within the first few hours, which is typically enough to resolve life-threatening symptoms. Serum sodium levels must be monitored frequently, often every two hours, to guide the infusion rate and prevent overcorrection.
The paramount concern during the correction of chronic hyponatremia is the prevention of Osmotic Demyelination Syndrome (ODS), a devastating neurological complication. ODS can occur if the serum sodium level is raised too quickly, causing irreversible damage to the myelin sheaths in the brain. To mitigate this risk, the total increase in serum sodium is strictly limited, generally not exceeding 8 to 10 mEq/L over the first 24 hours.
If the sodium level is rising too rapidly, clinicians may employ a strategy to deliberately lower the sodium concentration to maintain the safe rate. This can involve administering electrolyte-free water, such as a dextrose solution, alongside a drug like desmopressin. Desmopressin acts as a synthetic ADH, temporarily halting the kidneys’ ability to excrete water and thus helping to prevent the dangerous, unplanned overcorrection that can lead to ODS.