What are the management options for hemorrhagic cystitis?

Management of Hemorrhagic Cystitis

Hemorrhagic cystitis should be managed with a stepwise approach starting with hydration and mesna for prevention, followed by conservative measures for mild cases, and progressing to more invasive interventions for severe or refractory cases.

Prevention Strategies

Chemotherapy-Induced Hemorrhagic Cystitis

• Mesna administration is essential when using cyclophosphamide or ifosfamide to prevent hemorrhagic cystitis by binding to the toxic metabolite acrolein 1
• For ifosfamide, mesna should be administered as an IV bolus at 20% of the ifosfamide dose at the time of administration, followed by oral mesna at 40% of the ifosfamide dose at 2 and 6 hours after each ifosfamide dose 1
• Adequate hydration (2-3 L in 24 hours) is crucial to dilute toxic metabolites in the urine 2
• Patients should be instructed to urinate frequently, especially upon waking, to prevent acrolein from inducing hemorrhagic cystitis 1
• Forced diuresis with >8 glasses of water daily and monthly monitoring of urine for red blood cells is recommended for patients on cyclophosphamide 1

Diagnostic Approach

• Obtain a focused medical history and perform a complete physical examination, including digital rectal examination to rule out other causes of hematuria 1
• Check vital signs, hemoglobin, hematocrit, and coagulation parameters to evaluate bleeding severity 1
• For severe bleeding, blood typing and cross-matching should be performed 1
• Imaging investigations (CT, MRI, or ultrasound) should be considered if there is suspicion of concomitant anorectal diseases 1
• Urine analysis and culture should be performed to rule out infection as a cause 1

Treatment Algorithm

Mild to Moderate Hemorrhagic Cystitis

• Hydration with forced diuresis (as clinically warranted) and frequent bladder emptying to reduce bladder toxicity 1
• Non-steroidal anti-inflammatory drugs for pain management 1
• Anticholinergic agents such as oxybutynin for urinary symptoms 1
• Analgesics such as phenazopyridine for symptomatic relief 1

Moderate to Severe Hemorrhagic Cystitis

• Continuous bladder irrigation with isotonic saline to prevent clot formation 3
• Clot evacuation in cases of urinary retention 3
• Transurethral fulguration for localized bleeding sites 3
• Botulinum toxin A injection into the detrusor muscle when drug therapy is ineffective 1

Severe or Refractory Hemorrhagic Cystitis

• Intravesical instillations of astringent agents 3
• Hyperbaric oxygen therapy which has shown efficacy in radiation-induced hemorrhagic cystitis 4, 3
• Transarterial embolization or surgical ligation of vesical arteries in emergency cases 3
• Urinary diversion with or without cystectomy in rare refractory cases 3

Special Considerations

Radiation-Induced Hemorrhagic Cystitis

• Occurs in approximately 5-10% of patients receiving pelvic radiation 3
• May present as a late complication, requiring long-term monitoring 3
• Hyperbaric oxygen therapy has demonstrated efficacy in this specific etiology 4

Cyclophosphamide-Induced Hemorrhagic Cystitis

• Risk increases with higher doses and longer duration of therapy 5
• Mesna plus saline diuresis is recommended to decrease urothelial toxicity associated with high-dose cyclophosphamide in stem-cell transplantation 1

Monitoring Recommendations

• Monitor urine output and appearance for signs of hematuria 2
• Regular assessment of renal function, especially in patients with pre-existing renal impairment 2
• Monitor for signs of infection, as hemorrhagic cystitis can predispose to urinary tract infections 1
• In patients on cyclophosphamide, monthly monitoring of urine for red blood cells or other abnormalities 1

Common Pitfalls and Caveats

• Failure to provide adequate hydration before, during, and after cyclophosphamide administration 5
• Delayed recognition and treatment of hemorrhagic cystitis can lead to significant morbidity 6
• Patients who vomit within 2 hours of taking oral mesna should repeat the dose or receive IV mesna 1
• Conservative management is preferred for intracystic hemorrhage, and interventions such as aspiration or laparoscopic procedures should be avoided during active hemorrhage 1
• Steroids should be avoided for prevention of gastrointestinal symptoms in patients receiving TIL therapy to prevent possible adverse effects on the infused TIL 1