How to manage a patient with hyponatremia and polycythemia after recently starting chlorthalidone (thiazide-like diuretic) and losartan (angiotensin II receptor antagonist)?

Management of Hyponatremia and Polycythemia in a Patient on Chlorthalidone and Losartan

The patient's hyponatremia (Na 125 mEq/L) and polycythemia (Hgb 19.1) are likely medication-induced adverse effects that require immediate discontinuation of chlorthalidone and possibly losartan, with careful fluid management and electrolyte monitoring.

Medication-Induced Hyponatremia

• Thiazide and thiazide-like diuretics (such as chlorthalidone) are common causes of hyponatremia, with chlorthalidone carrying a 31% higher risk of hyponatremia compared to hydrochlorothiazide (HR 1.31; 95% CI, 1.16-1.47) 1
• Losartan can also contribute to hyponatremia, especially in elderly patients with type 2 diabetes, as documented in case reports 2
• The combination of these two medications likely has an additive effect on sodium levels through different mechanisms 3

Assessment and Initial Management

For Hyponatremia (Na 125 mEq/L):

• Discontinue chlorthalidone immediately as it is the most likely primary cause of hyponatremia 1
• Consider discontinuing losartan temporarily until sodium levels normalize 2
• Assess for symptoms of hyponatremia (cognitive impairment, gait disturbances, seizures, altered mental status) 4
• Determine volume status to guide management approach (hypovolemic, euvolemic, or hypervolemic) 4
• Check urine osmolality and sodium to help determine the cause 3
• Monitor serum potassium levels as hypokalemia often accompanies thiazide-induced hyponatremia 3

For Polycythemia (Hgb 19.1):

• The elevated hemoglobin is likely due to hemoconcentration from diuretic-induced volume depletion 1
• This should resolve with proper fluid management and discontinuation of chlorthalidone 1

Treatment Algorithm

If Asymptomatic or Mildly Symptomatic:

1. Discontinue chlorthalidone and consider holding losartan 3, 2
2. Implement fluid restriction only if the patient is hypervolemic 3
3. Monitor serum sodium levels every 4-6 hours initially 5
4. Correct sodium gradually at a rate not exceeding 8-10 mEq/L in 24 hours to avoid osmotic demyelination syndrome 4, 6

If Severely Symptomatic (seizures, altered mental status):

1. Administer hypertonic (3%) saline as bolus therapy to increase serum sodium by 4-6 mEq/L within 1-2 hours 4
2. Do not exceed correction of 10 mEq/L in the first 24 hours 4
3. Consider vasopressin antagonists (tolvaptan or conivaptan) for persistent severe hyponatremia with cognitive symptoms despite water restriction 3

Special Considerations

• Rapid correction of chronic hyponatremia can lead to osmotic demyelination syndrome (central pontine myelinolysis), which can cause permanent neurological damage including parkinsonism, quadriplegia, or death 4, 6
• Thiazide-induced hyponatremia typically resolves within 48-72 hours after drug discontinuation 1
• For hypertension management after resolution, consider alternative antihypertensive agents with lower risk of electrolyte disturbances 1

Monitoring and Follow-up

• Monitor serum electrolytes (sodium, potassium) daily until stable 3
• Check renal function as chlorthalidone is associated with a 37% higher risk of acute renal failure (HR 1.37; 95% CI, 1.15-1.63) 1
• Monitor hemoglobin levels until polycythemia resolves 1
• Once sodium levels normalize, carefully reintroduce alternative antihypertensive medications 3

Prevention of Recurrence

• Avoid thiazide and thiazide-like diuretics in this patient in the future 1
• If ARB therapy is required, monitor sodium levels closely, especially in the first few months of treatment 2
• Consider calcium channel blockers or ACE inhibitors as alternative antihypertensive agents 1
• Educate the patient about symptoms of hyponatremia and when to seek medical attention 4