In a 57‑year‑old man with influenza who is taking olmesartan, furosemide and hydrochlorothiazide and now has a serum sodium of 122 mmol/L, what is the most likely cause of the hyponatremia and what is the appropriate initial management?

Hyponatremia in a Patient on Multiple Diuretics with Influenza

Most Likely Cause and Immediate Action

The most likely cause is thiazide-induced hyponatremia from HCTZ, and you must stop the HCTZ immediately. 1, 2

While this patient is taking three medications that affect sodium balance (olmesartan, furosemide, HCTZ), thiazide diuretics are the most common diuretic cause of severe hyponatremia, with HCTZ being particularly notorious for causing serum sodium levels in the 120s range. 1, 2 Importantly, ongoing furosemide use is actually inversely correlated with hospitalization for hyponatremia, suggesting a protective effect rather than a causative one. 3

Diagnostic Algorithm

Step 1: Assess Volume Status and Symptoms

• Check for neurologic symptoms: confusion, lethargy, seizures, or altered mental status require urgent 3% saline. 4
• Examine for volume depletion: orthostatic hypotension, tachycardia, decreased skin turgor, dry mucous membranes. 5
• Look for signs of fluid overload: peripheral edema, pulmonary crackles, elevated JVP (less likely given sodium of 122). 5

Step 2: Order Immediate Laboratory Tests

• Serum osmolality (should be low, <280 mOsm/kg, confirming hypotonic hyponatremia). 4
• Urine osmolality (inappropriately concentrated, >100 mOsm/kg, suggests SIADH or thiazide effect). 4
• Urine sodium (>40 mEq/L indicates renal sodium wasting from diuretics or SIADH). 4
• Serum potassium (often low with thiazides, contributing to hyponatremia). 1
• Serum creatinine and BUN (assess renal function and volume status). 6

Step 3: Distinguish Between Causes

Thiazide-induced hyponatremia (HCTZ) is most likely because:

• Thiazides cause severe hyponatremia (sodium 120s) far more commonly than loop diuretics. 1, 2
• The patient has been on HCTZ chronically, and thiazide-associated hyponatremia can develop after months or years of use. 1
• Furosemide use is actually protective against hyponatremia in ongoing therapy. 3

Influenza-associated SIADH is a secondary consideration:

• Influenza can cause SIADH, but this is less commonly reported than thiazide-induced hyponatremia. 7
• SIADH presents with euvolemia, urine osmolality >100 mOsm/kg, urine sodium >40 mEq/L, and normal renal/adrenal/thyroid function. 4, 7

Olmesartan contribution:

• ARBs like olmesartan can contribute to hyponatremia through volume depletion or SIADH-like effects, but this is less common than thiazide-induced hyponatremia. 5

Initial Management Protocol

Immediate Actions (First 24 Hours)

1. Stop HCTZ immediately – this is the single most important intervention. 1, 2

2. Assess symptom severity and treat accordingly:

• If symptomatic (confusion, seizures, severe lethargy): Give 3% hypertonic saline at 1–2 mL/kg/hour to raise sodium by 1–2 mmol/L per hour until symptoms resolve. 4
• Target correction: Maximum 12 mmol/L in 24 hours or 18 mmol/L in 48 hours to avoid osmotic demyelination syndrome. 4
• If asymptomatic or mildly symptomatic: Fluid restriction to <1 L/day and monitor closely. 5, 4

3. Replete potassium aggressively:

• Hypokalemia exacerbates hyponatremia through osmotic inactivation of sodium. 1
• Target potassium >4.0 mEq/L with oral or IV potassium chloride. 6, 1

4. Continue furosemide at current dose:

• Furosemide does not cause hyponatremia in ongoing use and may actually help by promoting free water excretion. 3
• Do not stop furosemide unless the patient develops marked hypovolemia or hypotension (SBP <90 mmHg). 8, 9

5. Hold or reduce olmesartan temporarily:

• If the patient is hypovolemic or hypotensive, hold olmesartan until volume status normalizes. 5
• If euvolemic and normotensive, continue olmesartan but monitor closely. 5

Monitoring Requirements

• Check serum sodium every 4–6 hours during active correction if symptomatic. 4
• Check serum sodium daily if asymptomatic and managing with fluid restriction. 4
• Monitor potassium, creatinine, and BUN every 1–2 days initially, then every 3–7 days. 8, 6
• Reassess volume status daily: weight, orthostatic vitals, physical exam. 8

Common Pitfalls to Avoid

1. Do not assume furosemide is the culprit:

• Loop diuretics like furosemide are protective against hyponatremia in ongoing use. 3
• Stopping furosemide may worsen fluid overload if the patient has underlying heart failure or cirrhosis. 5, 8

2. Do not correct sodium too rapidly:

• Overcorrection (>12 mmol/L in 24 hours) risks osmotic demyelination syndrome, which is irreversible. 4
• If sodium rises too quickly, consider giving desmopressin and free water to slow correction. 4

3. Do not forget to check for influenza-associated SIADH:

• If hyponatremia persists after stopping HCTZ and repleting potassium, consider SIADH from influenza. 7
• Treat influenza with antivirals (oseltamivir) if within 48 hours of symptom onset. 7

4. Do not restart HCTZ:

• Thiazide-induced hyponatremia has a high recurrence rate if the drug is restarted. 1, 2
• Switch to a different antihypertensive class (e.g., amlodipine, metoprolol) once sodium normalizes. 1

Long-Term Management

• Avoid thiazide diuretics permanently in this patient. 1, 2
• Continue furosemide if needed for volume management (heart failure, cirrhosis). 8, 3
• Monitor sodium monthly for the first 3 months after stopping HCTZ, then every 3–6 months. 6
• Educate the patient to avoid excessive free water intake and to report symptoms of hyponatremia (confusion, weakness, nausea). 6