How to manage hyponatremia in a patient taking lisinopril (angiotensin-converting enzyme inhibitor)?

Management of Sodium 135 mEq/L in a Patient on Lisinopril

Continue lisinopril without modification and monitor sodium levels, as a serum sodium of 135 mEq/L represents the lower limit of normal and does not require intervention in an asymptomatic patient. 1, 2

Assessment of Current Sodium Level

• A sodium level of 135 mEq/L is at the threshold of hyponatremia (defined as <135 mEq/L) but is not clinically significant in most cases 2, 3
• Mild hyponatremia (130-134 mEq/L) is generally asymptomatic and does not require active treatment unless the patient has symptoms or underlying conditions that increase risk 2, 3
• Even mild hyponatremia can be associated with cognitive impairment, gait disturbances, and increased fall risk in some populations, but this typically occurs at levels below 130 mEq/L 2

ACE Inhibitor Considerations

• The FDA-approved lisinopril label recommends a starting dose of 2.5 mg once daily in patients with heart failure and hyponatremia (serum sodium <130 mEq/L), but does not mandate discontinuation at sodium levels of 135 mEq/L 1
• ACE inhibitors can cause hyponatremia through multiple mechanisms, but this is uncommon and typically occurs with other contributing factors 4
• In the PARADIGM-HF trial context, patients with heart failure on ACE inhibitors were successfully managed with careful monitoring even when sodium levels were borderline 5

Management Algorithm

For sodium 135 mEq/L (borderline normal):

• Continue current lisinopril dose without modification 1
• Check serum sodium, potassium, and creatinine in 1-2 weeks 5
• Assess for symptoms of hyponatremia (nausea, headache, confusion, weakness) 2, 3
• Review medication list for other drugs that may contribute to hyponatremia (diuretics, NSAIDs, SSRIs) 5, 3

If sodium drops to 130-134 mEq/L on repeat testing:

• Continue lisinopril but increase monitoring frequency 5
• Evaluate volume status (orthostatic vital signs, mucous membranes, skin turgor, edema) 6
• Check urine sodium and osmolality to determine etiology 6, 3
• Consider reducing or temporarily holding diuretics if patient is on them 5, 6

If sodium drops below 130 mEq/L:

• Temporarily reduce lisinopril dose by 50% or hold 1
• Perform comprehensive workup including thyroid function, cortisol, and assessment for SIADH 6, 3
• Implement treatment based on volume status and symptom severity 6, 2

Monitoring Parameters

• Recheck electrolytes (sodium, potassium, chloride), creatinine, and BUN in 1-2 weeks after any dose adjustment 5
• At 3 months, then every 6 months if stable 5
• More frequent monitoring if patient develops symptoms or has additional risk factors (advanced age, concurrent diuretic use, low salt intake) 5, 3

Common Pitfalls to Avoid

• Do not discontinue lisinopril for a sodium of 135 mEq/L, as this represents borderline normal and the cardiovascular benefits of ACE inhibition outweigh the minimal risk at this level 5, 1
• Avoid adding potassium-sparing diuretics during ACE inhibitor therapy without careful monitoring, as this increases hyperkalemia risk 5
• Do not ignore even mild hyponatremia (130-135 mEq/L) as clinically insignificant—it requires monitoring even if not requiring active treatment 6, 2
• Avoid NSAIDs, which can worsen both renal function and hyponatremia in patients on ACE inhibitors 5
• Do not implement fluid restriction at sodium levels of 135 mEq/L unless there is clear evidence of hypervolemic hyponatremia 6

When to Refer for Specialist Care

• Serum sodium persistently <130 mEq/L despite conservative management 5
• Serum creatinine >150 µmol/L (approximately 1.7 mg/dL) 5
• Systolic blood pressure <100 mmHg 5
• Severe heart failure requiring GDMT optimization 5