Alkylating Agent Cystitis

Introduction

Alkylating agent–induced cystitis is a serious urological complication that occurs most commonly with chemotherapy drugs such as cyclophosphamide and ifosfamide. These agents are metabolized into toxic byproducts—particularly acrolein—that accumulate in the bladder, leading to irritation, inflammation, and hemorrhagic cystitis. If untreated, this condition can result in significant morbidity, including hematuria, bladder fibrosis, and impaired urinary function. Early recognition and proactive management are critical to reducing complications and improving patient outcomes.

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Treatment Options

1. Mesna (2-mercaptoethane sulfonate sodium)

• Mechanism: Binds and detoxifies acrolein in the urinary tract.

• Dose: Administered intravenously or orally alongside cyclophosphamide/ifosfamide.

  • Typical regimen: 20% of the chemotherapeutic dose given IV at the same time, then repeated at 4 and 8 hours after chemotherapy.

• Role: Standard prophylaxis against hemorrhagic cystitis in patients receiving high-dose alkylating agents.

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2. Aggressive Hydration and Forced Diuresis

• Mechanism: Dilutes urinary metabolites and increases urine flow, reducing bladder exposure to toxins.

• Implementation:

  • IV fluids (e.g., normal saline) to maintain urine output ≥100 mL/hour.

  • Use of diuretics (e.g., furosemide, mannitol) in selected cases to ensure adequate diuresis.

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3. Bladder Irrigation

• Method: Continuous bladder irrigation with sterile saline via a three-way Foley catheter.

• Indication: Used when hemorrhagic cystitis is present to prevent clot formation and tamponade.

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4. Pharmacologic and Supportive Therapies

• Analgesics & Antispasmodics: For pain and urinary urgency.

• Intravesical Treatments (for severe hemorrhagic cystitis):

  • Alum irrigation (1% solution) – helps control bleeding.

  • Prostaglandin instillations – for refractory bleeding.

  • Silver nitrate or formalin (reserved for resistant cases due to toxicity).

• Hyperbaric Oxygen Therapy: In selected refractory cases, to enhance healing of bladder mucosa.

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5. Treatment of Severe/Refractory Cases

• Endoscopic clot evacuation: To relieve obstruction.

• Surgical options (rare): Urinary diversion or cystectomy in life-threatening or intractable hemorrhagic cystitis.

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Key Considerations

• Prevention is paramount: Prophylaxis with mesna and hydration is more effective than managing established cystitis.

• Close monitoring: Patients should be observed for hematuria, dysuria, or urinary frequency during and after chemotherapy.

• Individualization: Treatment intensity depends on severity, ranging from conservative measures (hydration, mesna) to invasive procedures in refractory cases.