Patients with any symptoms of haemorrhagic cystitis should be referred to a medical officer for management.
The aim of prevention is to reduce the risk of damage to the bladder mucosa. Increased fluid input dilutes the concentration of acrolein while increased voiding reduces the duration of exposure.rrrr
Some commonly used preventative measures include:rrrrrr
- intravenous or oral hydration
- concurrent administration of mesna (see below)
- frequent voiding
- continuous bladder irrigation
- administration of diuretics such as frusemide if urine production declines (<100 mL/m2/hr)
- maintenance of urine output minimum of >100 mL/hr.
Mesna interacts with the urotoxic metabolite acrolein to reduce the incidence of cyclophosphamide and ifosfamide induced haemorrhagic cystitis. Mesna is rapidly cleared by the kidneys and does not reduce the anti-tumour effect of cyclophosphamide or ifosfamide and can be given orally or intravenously, either as a bolus injection or continuous infusion.r
It is important that mesna is present in the bladder at the time of chemotherapy administration in order to be effective. Mesna therapy should continue for the duration of the chemotherapy and for up to 12 to 24 hours post administration. This allows for the concentration of the urotoxic metabolites to fall to non-toxic levels.r
Various mesna dosages have been used, and harmonised dosages and methods of administration have not been established. In 2008, ASCO updated their guideline recommendations for administration of mesna with ifosfamide; note that there have been no randomised controlled trials identified since the publication of the 2002 guidelines.r
Use of mesna with ifosfamider
As there are numerous mesna dose variations stated in the literature, a consensus decision was made by the eviQ Haematology Reference Committee in 2013 to have equal doses of mesna and ifosfamide on eviQ. The 1:1 ratio has been adopted from clinical practice.
Standard dose ifosfamide (< 2.5 g/m2/day) short infusion:
- daily dose of IV mesna is calculated to equal 60% of the daily ifosfamide dose, administered as three IV bolus doses to be given 15 minutes before and 4 and 8 hours after each dose of ifosfamide.
Standard dose ifosfamide (< 2.5 g/m2/day) continuous infusion:
- mesna IV bolus dose equal to 20% of the daily ifosfamide dose to be given with ifosfamide
- followed by a continuous infusion of mesna equal to 40% of the daily ifosfamide dose, during and for 12 to 24 hours after completion of ifosfamide infusion.
High dose ifosfamide (> 2.5 g/m2/day) infusion:
- there is insufficient evidence to recommend a dose of mesna
- given the longer half life of ifosfamide with higher dose therapy, more frequent and prolonged mesna dosage regimens may be necessary.
- the oral dose of mesna is twice the IV dose of mesna
- administration of oral mesna as an initial dose is not recommended. An IV bolus dose of mesna equal to 20% of the daily ifosfamide at the time of ifosfamide administration is recommended. Administer oral mesna 2 and 6 hours after the completion of the ifosfamide infusion, at a dose equal to 40% of the daily ifosfamide dose. The total daily dose of mesna is equal to 100% of the ifosfamide dose
- the protective effect of administering a combination of IV and oral mesna appears to be equivalent to intravenous mesna aloner
- patients who vomit within 2 hours of taking oral mesna should repeat the dose or receive IV mesna.
Use of mesna with cyclophosphamide
Although, most centres use mesna as a prophylaxis for high-dose cyclophosphamide (doses of 50 mg/kg or 2 g/m2 ) based regimens, studies have shown that this drug does not offer additional benefits if hydration and diuresis are adequate.r The recommended daily dose for hyper-hydration is 3 L/m2 in a 24 hour period. Individual patient clinical needs and preferences should be taken into account.r
The use of hyper-hydration alone or mesna with hyper-hydration is recommended to decrease the incidence of urothelial toxicity associated with high-dose cyclophosphamide.r If used, the daily dose of mesna should be 1.0-1.5 x the daily dose of cyclophosphamide and administered intravenously.r
Treatment of established HC varies, is dependent on severity, and should be individualised for each patient.r There are numerous treatment modalities reported however there is no evidence based standardised approach. Ensure you follow the health facility’s policies and procedures.
Mild HC is transient and will generally resolve with supportive treatment including hydration and pain relief.
Moderate to severe HC may require more interventional approach dependent on the severity and refractoriness of symptoms.
Prior to commencing treatment, bacterial, fungal, viral and parasitic infections need to be excluded. In the case of infection, appropriate antibacterial, antifungal, antiviral and antiparasitic agents should be administered. Late onset viral HC will require treatment of the underlying infection as well as symptom management.r
Treatment options may include:rrrrrr
- discontinuation of the treatment/medication
- continuous bladder irrigation
- blood transfusions as required
- platelet transfusions as required.
Other measures for treatment of severe HC which have been reported in the literature include:rrrrrrr
- surgical treatment - cystoscopy with clot evacuation and/or suprapubic catheterisation
- systemic treatment - hyperbaric oxygen (HBO)
- local treatment - intravesical therapy e.g. prostaglandins, sodium hyaluronate, growth factors, alum, oestrogen, cidofovir, sodium pentosan polysulphate, phenol, vasopressin, steroids, amifostine.