eMedicine Specialties > Pediatrics: Surgery > Urology

Hemorrhagic Cystitis: Treatment & Medication

Author: Marcos Perez-Brayfield, MD, Consulting Staff, HIMA-San Pablo, San Juan, Puerto Rico
Coauthor(s): Andrew J Kirsch, MD, FAAP, FACS, Clinical Professor of Urology, Emory University School of Medicine, Children's Healthcare of Atlanta; President, Georgia Urology, PA
Contributor Information and Disclosures

Updated: Sep 18, 2009

Treatment

Medical Care

The best treatment of hemorrhagic cystitis (HC) is prevention, especially with cyclophosphamide-induced hemorrhagic cystitis. After hemorrhagic cystitis develops, the treatment is the same irrespective of the cause.

The first step in the treatment of hemorrhagic cystitis should be directed toward clot evacuation. Bladder outlet obstruction from clots can lead to urosepsis, bladder rupture, and renal failure. Clot evacuation can be performed by placing a wide-lumen bladder catheter at bedside. The bladder can be irrigated with water or sodium chloride solution. The use of water is preferable because water can help with clot lysis. Care must be taken to not overdistend the bladder and cause a perforation.

After clot evacuation, the patient should be vigorously hydrated using intravenous fluids to keep clots from reforming. If hematuria persists, a 3-way catheter can be inserted, and continuous bladder irrigation with saline can be started. All clots must be removed before continuous irrigation is started to avoid overdistention and potential bladder ruptures.

If clot evacuation is unsuccessful with this approach, the patient should undergo cystoscopy in the operating room with clot evacuation and fulguration of bleeding sites. Some have proposed the use of epsilon aminocaproic acid (Amicar). The problem with aminocaproic acid is that it creates large adhesive clots that are subsequently difficult to remove. With upper tract bleeding, clots due to aminocaproic acid can cause the loss of the respective renal unit, and use in pediatrics is not recommended.

When hematuria persists after the treatments described above, bladder irrigation can be performed with several astringent intravesical agents, including 1% silver nitrate or alum. Alum is an astringent that causes protein precipitation over bleeding sites. The systemic absorption is minimal, even in the presence of VUR. Alum irrigation tends to create large clots that can block the catheter, especially a pediatric-sized catheter. Aluminum levels must be monitored in patients with renal insufficiency because increased levels can cause encephalopathy and acidosis. Parenteral or intravesical prostaglandins are also used to treat hemorrhagic cystitis. Prostaglandins are cytoprotective and have both anti-inflammatory and vasoconstriction properties. They involve no coagulum formation and few side effects and are easy tolerated by the patients.

Formalin intravesical installations are reserved for severe and intractable hemorrhagic cystitis. It hydrolyzes proteins and coagulates superficial bladder mucosal tissue. The most critical factor in the effectiveness of formalin is its concentration. Installation is painful and requires general or regional anesthesia. The concentration used is 2.5-4% for 10-30 minutes. Intraoperative cystography is mandatory to rule out VUR because formalin contact with ureteral tissue leads to fibrosis, obstruction, and necrosis. In the presence of VUR, formalin can be used if occlusion balloon catheters are inserted in both ureters.

Antiviral agents should be added to bladder irrigation when a viral etiology is suspected or confirmed.

Surgical Care

In patients with refractory hemorrhagic cystitis, surgical intervention is warranted. These include percutaneous nephrostomy drainage, selective hypogastric artery embolization, temporary bladder exteriorization with packing of the bladder, ileal conduit diversion, cutaneous ureterostomy, and cystectomy. A few reports describe the use of hyperbaric oxygen, with some success in these difficult cases.^1,2

• Hyperbaric oxygen therapy
  • Few reports describe hyperbaric oxygen therapy in the pediatric population.
  • This is an alternative in patients with refractory hemorrhagic cystitis.
  • This treatment is better for radiation-induced hemorrhagic cystitis than for cyclophosphamide-induced hemorrhagic cystitis.
  • Treatment involves 100% oxygenation at 2 atm for 90 minutes 5 times per week. Treatment lasts an average of 40 sessions.
  • Contraindications include active cancer, active viral infection, pneumothorax, treatment with doxorubicin or cisplatin, and ear reconstruction.
• Nd:YAG laser therapy
  • Few reports describe Nd:YAG laser therapy in the pediatric population.
  • It is used for fulguration.
  • Patients may require several treatments.
  • Laser settings should be no higher than 20 W with a 2-second pulse mode to avoid deep penetration and possible bowel injury.
• Use of treatment pearls in pediatric patients
  • A catheter with decreased luminal size is needed because of the small urethra in pediatric patients.
  • Consider the use of a suprapubic tube.
  • Water irrigation is best with clot lysis.
  • The pediatric bladder is small; therefore, watch for overdistention, which can lead to rupture.
  • Always keep patients hydrated.
  • All clots must be removed before intravesical irrigations are started.
  • Do not hesitate to go to the operating room with pediatric patients.
  • Use caution with agents that create large clots.
  • If the bleeding cannot be controlled endoscopically, open cystostomy and temporary packing may be considered.
  • With an upper-tract bleed, use of aminocaproic acid is contraindicated.
  • Always perform cystography before formaldehyde therapy to rule out reflux or perforation.

Consultations

Treatment of the patient with hemorrhagic cystitis should be coordinated among urologists, oncologists, and pediatricians.

Diet

No specific diet is indicated.

Activity

Patients with active gross hematuria should limit their activities until it resolves. These patients are hospitalized and on bed rest during their therapeutic interventions.

Medication

Bladder irrigants

Various intravesical agents are used to treat hemorrhagic cystitis (HC). Ongoing assessment of treatment effectiveness is essential for a successful patient outcome. Changing to a different irrigation agent may be necessary.

Formaldehyde (Formalin)

Reserved for severe and intractable hemorrhagic cystitis. Hydrolyzes protein and coagulates superficial bladder mucosal tissue. Most critical factor is to administer proper solution (2.5-4% for 10-30 min). Make 4% solution by mixing buffered formalin 10% 200 mL with sterile water for irrigation 300 mL (total volume, 500 mL).

Alum

Indicated for bladder hemorrhage. Consists of aluminum potassium sulfate or aluminum ammonium sulfate and works as astringent that causes protein precipitation in interstitial spaces and cell membranes. Systemic absorption is minimal. May be administered if VUR present.

Silver nitrate

Used because of caustic, antiseptic, and astringent qualities. Mixed results observed.

Carboprost (Hemabate)

Various prostaglandins studied. Elicits cytoprotective, anti-inflammatory, and vasoconstriction properties and produces no coagulum.

Antidotes

Antidotes are used to manage poisoning and overdose, prevent toxic effects, or treat metabolic disorders in which toxic substances accrue. Mechanisms of action vary and include antagonism, toxin transformation, altered metabolism, chelation, and interactions with directed antibodies.

Mesna (Mesnex)

Also known as 2-mercaptoethane sulfonate. In kidney, mesna disulfide reduced to free mesna. Free mesna has thiol groups that react with acrolein, ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity. Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity. Also directly reacts with 4-hydroxy metabolites, inhibiting breakdown and release of acrolein.

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