1. Introduction to SIADH

SIADH is the leading cause of euvolemic hypotonic hyponatremia in hospitalized patients, driven by inappropriate ADH release. Even mild chronic hyponatremia increases morbidity and mortality.

• Definition: Non-osmotic ADH (AVP) secretion leads to impaired free water excretion, resulting in dilutional hyponatremia in a euvolemic patient.
• Epidemiology: It is the most frequent cause of hypotonic hyponatremia in the ICU and is commonly associated with malignancy, CNS and pulmonary diseases, and polypharmacy.

2. ADH Regulation and Pathophysiology

Under normal conditions, AVP release is tightly controlled by plasma osmolality and volume. In SIADH, non-osmotic stimuli override this regulation, causing persistent V2-receptor activation and water retention.

A. Normal ADH (AVP) Axis

The normal regulation involves hypothalamic osmoreceptors sensing plasma osmolality. When osmolality rises or blood volume drops, the posterior pituitary releases AVP. AVP then acts on V2 receptors in the renal collecting ducts, promoting aquaporin-2 channel insertion, which leads to water reabsorption.

B. Pathophysiology in SIADH

In SIADH, AVP release is uncoupled from osmotic control. Non-osmotic triggers such as baroreceptor activation (due to hypotension or mechanical ventilation), pain, nausea, stress, or cytokines can stimulate AVP release. In some cases, AVP is produced ectopically (e.g., by tumors). This persistent AVP elevation, despite low plasma osmolality, leads to continuous water reabsorption. Consequently, urine osmolality remains inappropriately high (>100 mOsm/kg) and urine sodium concentration is typically elevated (>30 mmol/L, assuming normal salt intake), reflecting a state of free water retention and dilutional hyponatremia.

3. Etiologies of SIADH in the ICU

SIADH in critically ill patients is often multifactorial. Major categories include paraneoplastic ADH release, CNS insults, pulmonary disease, and certain medications.

4. Clinical Manifestations

The severity and tempo of hyponatremia determine symptoms. Acute drops cause cerebral edema and neurologic emergencies, while chronic decline results in adaptive cerebral changes and more subtle deficits.

5. Risk Factors and Predisposing Conditions

The risk of developing SIADH is amplified by a combination of preexisting diseases, acute stressors common in the ICU setting, and iatrogenic factors. A multifactorial assessment is essential for identifying patients at risk.

• Underlying Chronic Conditions:
  • Known malignancies, especially small cell lung cancer
  • History of CNS tumors, trauma, or surgery
  • Chronic pulmonary diseases (e.g., COPD, tuberculosis)
  • Previous episodes of SIADH
• ICU Triggers:
  • Mechanical ventilation (especially with positive end-expiratory pressure – PEEP)
  • Postoperative state (pain, stress, nausea, non-osmotic ADH release)
  • Sepsis and severe inflammatory states
  • Significant pain or nausea from any cause
  • Major surgery or trauma
• Iatrogenic Contributors:
  • Administration of hypotonic fluids (e.g., D5W, 0.45% NaCl) in susceptible individuals
  • Use of ADH‐stimulating drugs or drugs that potentiate ADH effect (see Etiologies table)
  • High doses of opioids

6. Summary and Clinical Pearls

SIADH is characterized by euvolemic, hypotonic hyponatremia resulting from inappropriately high antidiuretic hormone (AVP) activity, leading to impaired water excretion.

Diagnostic Criteria (Bartter & Schwartz, adapted)

The diagnosis of SIADH generally requires the following criteria to be met:

1. Serum osmolality <275 mOsm/kg H₂O.
2. Urine osmolality >100 mOsm/kg H₂O (in the presence of serum hypo-osmolality).
3. Urine sodium concentration >30 mmol/L (with normal dietary salt and water intake).
4. Clinical euvolemia (absence of signs of hypovolemia like orthostasis or tachycardia, and absence of signs of hypervolemia like edema or ascites).
5. Exclusion of other potential causes of hyponatremia, particularly hypothyroidism, adrenal insufficiency (secondary hypocortisolism), and significant renal dysfunction or diuretic use.

Key Management Implications

Effective management hinges on accurate volume status assessment, a comprehensive review of medications to identify potential culprits, and targeted therapy aimed at correcting hyponatremia safely and addressing the underlying cause of SIADH.