What are the guidelines for managing hemorrhagic cystitis?

From the Guidelines

Management of hemorrhagic cystitis involves a stepwise approach based on severity, with initial treatment focusing on conservative measures including adequate hydration and pain management, as recommended by the most recent guidelines 1.

Initial Treatment

• Increasing fluid intake to 2-3 liters daily is recommended for mild cases.
• Continuous bladder irrigation with normal saline via a three-way Foley catheter should be implemented to prevent clot formation if bleeding persists.

Pharmacological Interventions

• Intravesical instillations of alum (1% solution, 50-100 ml instilled for 15-60 minutes) can be used as an astringent to reduce bleeding.
• Aminocaproic acid (Amicar) can be administered orally (4-5 g initially, then 1 g every hour) or intravenously to inhibit fibrinolysis.

Severe Cases

• Intravesical formalin (1-10% solution) may be used, though it requires anesthesia due to pain.
• Hyperbaric oxygen therapy (100% oxygen at 2.0 atmospheres for 90-minute sessions) promotes healing by increasing tissue oxygenation.

Refractory Cases

• Selective arterial embolization of the vesical arteries or surgical options such as cystectomy with urinary diversion may be considered. The underlying cause of hemorrhagic cystitis—whether radiation-induced, chemotherapy-related (particularly cyclophosphamide or ifosfamide), viral (BK virus, adenovirus), or bacterial—should be addressed simultaneously to prevent recurrence and promote healing of the bladder mucosa, as supported by previous studies 1.

From the FDA Drug Label

Hemorrhagic cystitis, pyelitis, ureteritis, and hematuria have been reported with cyclophosphamide. Medical and/or surgical supportive treatment may be required to treat protracted cases of severe hemorrhagic cystitis. Discontinue cyclophosphamide therapy in case of severe hemorrhagic cystitis Urotoxicity (bladder ulceration, necrosis, fibrosis, contracture and secondary cancer) may require interruption of cyclophosphamide treatment or cystectomy. Urotoxicity can be fatal. Urotoxicity can occur with short-term or long-term use of cyclophosphamide. Before starting treatment, exclude or correct any urinary tract obstructions [see Contraindications (4)] Urinary sediment should be checked regularly for the presence of erythrocytes and other signs of urotoxicity and/or nephrotoxicity. Cyclophosphamide should be used with caution, if at all, in patients with active urinary tract infections. Aggressive hydration with forced diuresis and frequent bladder emptying can reduce the frequency and severity of bladder toxicity. Mesna has been used to prevent severe bladder toxicity.

The guidelines for managing hemorrhagic cystitis include:

• Discontinuing cyclophosphamide therapy in case of severe hemorrhagic cystitis
• Using medical and/or surgical supportive treatment to manage protracted cases
• Interrupting cyclophosphamide treatment or performing cystectomy in cases of urotoxicity
• Excluding or correcting urinary tract obstructions before starting treatment
• Checking urinary sediment regularly for signs of urotoxicity and/or nephrotoxicity
• Using aggressive hydration with forced diuresis and frequent bladder emptying to reduce bladder toxicity
• Considering the use of Mesna to prevent severe bladder toxicity 2.

From the Research

Guidelines for Managing Hemorrhagic Cystitis

The management of hemorrhagic cystitis can be challenging and depends on the underlying cause and severity of the condition. The following are some guidelines for managing hemorrhagic cystitis:

• Diagnosis and Treatment Options: A review of the literature reveals that hemorrhagic cystitis can be caused by various factors, including infection, chemical exposure, malignancy, nephropathy, trauma, radiation therapy, and idiopathic etiology 3. The treatment options range from conservative strategies, such as bladder fulguration and continuous irrigation, to more extreme and morbid therapies, such as intravesical instillations, embolization, and urinary diversion.
• Hyperbaric Oxygen Therapy: Hyperbaric oxygen therapy (HBOT) has been shown to be effective in treating cyclophosphamide-induced hemorrhagic cystitis 4. HBOT reduces inflammation, stimulates neoangiogenesis, maintains tissue oxygenation, and heals tissue hypoxia and radio necrosis.
• Radiation-Induced Hemorrhagic Cystitis: The management of radiation-induced hemorrhagic cystitis is challenging, and there is no consensus on the primary approach to management beyond symptomatic measures 5. However, hyperbaric oxygen therapy has been shown to be a well-tolerated and effective first-line treatment.
• Formalin Treatment: Formalin treatment has been used to manage intractable hemorrhagic cystitis, particularly in cases where other treatments have failed 6. However, it is associated with complications, and the use of dilutions of 4% or less is recommended to minimize these complications.
• Stepwise Treatment Approach: A stepwise treatment approach is recommended, taking into account the severity of bleeding and the underlying cause of the condition 3. This approach may involve conservative strategies, such as bladder fulguration and continuous irrigation, followed by more invasive therapies, such as intravesical instillations, embolization, and urinary diversion, if necessary.