An elderly male with hypertension and diabetes on lisinopril and amlodipine presents with fatigue; labs show low serum sodium, high potassium, and high calcium. Which electrolyte disturbance is most likely responsible for his fatigue?

Hyponatremia is the Primary Cause of This Patient's Fatigue

In this elderly male with hypertension and diabetes on lisinopril and amlodipine presenting with fatigue, low sodium, high potassium, and high calcium, the hyponatremia is the most likely culprit for his symptoms and requires immediate attention.

Clinical Reasoning and Prioritization

Why Hyponatremia is the Primary Concern

• Hyponatremia is the most common electrolyte disorder, affecting approximately 5% of adults and 35% of hospitalized patients, and even mild hyponatremia is associated with increased hospital stay and mortality 1
• Symptoms of hyponatremia range from mild and nonspecific (such as weakness, fatigue, or nausea) to severe and life-threatening, with symptom severity depending on the rapidity of development, duration, and severity 1
• Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 1
• In heart failure patients (which this patient may have given his medication regimen), development of hyponatremia is often a sign of disease progression and is associated with impaired survival 2

Medication-Induced Hyponatremia

• Lisinopril (an ACE inhibitor) can cause hyponatremia through multiple mechanisms, including impaired free water excretion and syndrome of inappropriate antidiuresis 3
• Thiazide-like diuretics can induce hyponatremia as a side effect with diverse symptoms and variable onset, and when initiating these agents, it is essential to be vigilant for hyponatremia 4
• Loop diuretics can exacerbate existing hyponatremia, and thiazide diuretics can further deplete potassium levels and worsen hyponatremia 2

Why Hyperkalemia is Less Likely the Cause

• While hyperkalemia can cause fatigue and muscle weakness, the patient is on lisinopril, which typically causes hyperkalemia rather than being caused by it 3
• The hyperkalemia in this case is likely medication-induced (lisinopril) rather than the primary pathology causing symptoms 5
• Patients with cardiac disease should maintain potassium levels between 4.0-5.0 mEq/L, as both hypokalemia and hyperkalemia can adversely affect cardiac excitability and conduction 2

Why Hypercalcemia is Less Likely the Cause

• While hypercalcemia can cause fatigue, the combination of low sodium with high calcium suggests a more complex picture where hyponatremia is the dominant electrolyte abnormality 1
• The patient's medication regimen (lisinopril and amlodipine) is more directly associated with sodium and potassium disturbances than calcium abnormalities 3

Immediate Management Algorithm

Step 1: Assess Severity and Volume Status

• Categorize the patient according to fluid volume status (hypovolemic, euvolemic, or hypervolemic hyponatremia) to guide treatment 1
• Short-term changes in fluid status are best assessed by measuring changes in body weight 2
• Check serum osmolality, urine osmolality, and urine sodium to determine the etiology of hyponatremia 6

Step 2: Medication Review and Adjustment

• Discontinue or reduce lisinopril temporarily if hyponatremia is severe, as ACE inhibitors can impair free water excretion 3
• Review all medications for potential contributors to hyponatremia, including any diuretics 4
• Worsening renal function may require adjustment of diuretic doses and renin-angiotensin-aldosterone system antagonists 2

Step 3: Address Hyperkalemia Concurrently

• For patients with hyperkalemia on RAAS inhibitors, maintain the RAAS inhibitor using newer potassium binders if needed, targeting potassium levels of 4.0-5.0 mEq/L 2
• Regular monitoring of serum sodium and potassium is essential, as both abnormalities can adversely affect cardiac excitability and conduction 2

Step 4: Symptomatic Treatment

• For most patients, the approach to managing hyponatremia should consist of treating the underlying cause 1
• Urea and vaptans can be effective treatments for syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects 1
• Severely symptomatic hyponatremia (with signs of somnolence, obtundation, coma, seizures, or cardiorespiratory distress) is a medical emergency requiring hypertonic saline 1

Critical Pitfalls to Avoid

• Do not aggressively correct chronic hyponatremia too rapidly, as overly rapid correction may cause osmotic demyelination, a rare but severe neurological condition that can result in parkinsonism, quadriparesis, or death 1
• US and European guidelines recommend treating severely symptomatic hyponatremia with bolus hypertonic saline to increase serum sodium by 4-6 mEq/L within 1-2 hours but by no more than 10 mEq/L within the first 24 hours 1
• Do not assume the hyperkalemia is the primary problem without first addressing the hyponatremia, as the medication regimen suggests ACE inhibitor-induced hyperkalemia is secondary 3
• Failing to monitor both sodium and potassium levels regularly can lead to serious complications, as both abnormalities increase mortality risk 2

Monitoring Protocol

• Management in the ICU facilitates frequent laboratory draws and allows close monitoring of the patient's mentation as well as quantification of urine output 6
• Determination of the etiology of chronic hyponatremia requires analysis of serum osmolality, volume status, and urine osmolality and sodium level 6
• Therapeutic measures to lower the serum sodium level should be undertaken if the rate increases too rapidly during correction 6