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Electrolyte Depletion Following Combination Diuretic Therapy

Published

October 17, 2025

Patient Background:

David is a 74-year-old male with a past medical history of chronic systolic heart failure, hypertension, and type 2 diabetes mellitus. His long-term medications included carvedilol, sacubitril/valsartan, furosemide, and spironolactonewhich had maintained him in a clinically stable condition.

Clinical Presentation:

Recently, David developed worsening bilateral lower extremity edema and dyspnea on exertion. In response to persistent fluid overload, his provider intensified diuretic therapy by adding metolazone 2.5 mg once daily, to be taken 30 minutes before furosemide.

Within ten days, David presented to the emergency department with generalized weakness, fatigue, and mild confusion. Laboratory findings revealed severe hypokalemia (K⁺ 2.3 mEq/L) and hypomagnesemia (Mg²⁺ 1.2 mg/dL), necessitating intravenous electrolyte replacement and hospital admission for cardiac and electrolyte monitoring. Chart review indicated that his last potassium check had been more than one month prior to metolazone initiation.

Clinical Issue Identified:

The concurrent use of metolazone (a thiazide-like diuretic) and furosemide (a loop diuretic) can produce a potent synergistic diuretic effect, particularly beneficial in resistant fluid overload associated with heart failure. However, this synergy is a double-edged sword, as it also markedly increases urinary loss of sodium, potassium, and magnesium, predisposing patients to severe electrolyte depletion.

In this case, the combination led to clinically significant hypokalemia and hypomagnesemia, resulting in neuromuscular symptoms and a preventable hospital admission.

Pharmacist Intervention and Management Plan:

Immediate Management:

  • Administer intravenous potassium and magnesium to correct acute electrolyte disturbances.
  • Continuous cardiac monitoring during correction due to the risk of arrhythmia.

Medication Review and Adjustment:

  • Hold metolazone temporarily until electrolyte stability is achieved.
  • Consider restarting at a reduced frequency (e.g., 2.5 mg two to three times per week) rather than daily, if clinically indicated.
  • Maintain spironolactone for its potassium-sparing effects but monitor closely for hyperkalemia once supplementation is initiated.

Monitoring and Laboratory Follow-Up:

  • Recheck electrolytes (Na⁺, K⁺, Mg²⁺) and renal function within 2–3 days after initiating or adjusting metolazone therapy.
  • Continue periodic monitoring at least weekly during the titration phase, then monthly once stable.
  • Establish clear monitoring protocols for future adjustments.

Supplementation and Supportive Measures:

  • Consider prophylactic oral potassium supplementation (e.g., KCl 20 mEq/day) when initiating metolazone, especially if baseline K⁺ <4.0 mEq/L.
  • Encourage dietary sources of potassium and magnesium, unless contraindicated.

Education and Communication:

  • Educate the patient and caregivers on symptoms of electrolyte imbalance (muscle cramps, weakness, palpitations, confusion).
  • Communicate with the prescriber regarding dose frequency modification and monitoring intervals.
  • Reinforce the importance of regular laboratory checks in elderly patients with heart failure receiving combination diuretic therapy.

Clinical Rationale and Ramifications:

This case highlights a common but preventable adverse event associated with aggressive diuretic therapy in older adults. The synergistic action of metolazone and loop diuretics can be therapeutically valuable for managing refractory edema, but without careful dose titration and close electrolyte monitoring, patients face a high risk of severe hypokalemia, hypomagnesemia, dehydration, and cardiac arrhythmias.

In David case, failure to recheck serum electrolytes soon after initiating metolazone resulted in a hospitalization that could have been avoided with more cautious dosing and proactive monitoring.

The pharmacist’s intervention—through recommending dose frequency reduction, routine lab monitoring, and preventive supplementation—is essential to prevent recurrence and enhance patient safety.

This case reinforces the importance of individualized diuretic therapy in elderly heart failure patients, where efficacy must always be balanced against electrolyte and hemodynamic stability.