Page 7 - CUA Best Practice Report: Pediatric hemorrhagic cystitis

BPR: Pediatric hemorrhagic cystitis

two, or ≥3 fibrin glue applications in 60%, 17%, and 6% when resorting to this therapeutic option for children with
of patents, respectively. The procedure was well-tolerated HC (Level 3 evidence, Grade D recommendation).
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with no adverse events observed. Given the protocol rec-
ommended by Tirindelli et al, however, the 24 Fr nephro- Percutaneous nephrostomy tube (PNT)
scope will limit applicability in the pediatric population, as
most children younger than adolescents will not be able to Often considered a last resort stabilizing measure, urinary
accommodate this caliber in their urethra. diversion with bilateral percutaneous PNTs has become
Recommendation: Intravesical fibrin glue application is more a commonly used option in patients with HC refrac-
a promising treatment option in patients undergoing cys- tory to all conservative therapies whose next only option is
toscopy with clot evacuation, as it can be applied focally cystectomy. The theory behind diverting upper tract urine
or diffusely to hemorrhagic areas. Additional research is with nephrostomy tubes is that downstream persistent urine
needed to expand its applicability, as current recommenda- bathes the bladder in urokinase, the proteolytic enzyme
tions for large-caliber cystoscopes limits its use in children present in urine, which may contribute to persistent gross
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(Level 3 evidence, Grade C recommendation). hematuria. By removing this fibrinolytic activity, which
degrades beneficial fibrinogen and fibrin clots, clot forma-
Formalin tion in the bladder can be promoted so that the bladder
eventually becomes filled with clot and bleeding ceases.
As in adults, in severe cases of refractory HC, sclerotherapy Eventually, clamping trials of PNTs can be attempted, the
is a consideration in the pediatric population, but often a blood clot disintegrates, is passed per urethra, and the tubes
last resort prior to irreversible management options. The are ultimately removed. Lukasewycz et al reported on PNTs
proposed mechanism of action of formalin, much like its placed in children undergoing HSCT with HC refractory
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derivative formaldehyde, is to precipitate proteins by reduc- to conservative measures. Five of 11 had improvement
ing amino acids and fixing blood vessels, thus achieving within 30 days, and four of those five had complete response
hemostasis. Due to pain associated with bladder instilla- with the fifth passing of their disease. Two of the 11 were
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tion, general anesthesia is necessary whenever formalin is stabilized with the PNTs, one progressed and needed clot
instilled intravesically. Furthermore, prior to any consider- evacuation, and the remaining three passed of unrelated
ation of formalin instillation, patients must be evaluated for causes. The average time to stabilization was 12.4 days, and
vesicoureteral reflux (VUR) with a voiding cystourethrogram average duration of PNTs being in place was 8.8 weeks. No
due to potential for irreversible damage to the upper tracts long-term sequelae were reported.
with VUR. Should VUR be present, the ureteral orifices can Recommendation: Bilateral PNT urinary diversion is
be occluded during instillation with Fogarty catheters. Using a temporizing measure to allow the bladder to clot off,
traditional concentration of 4% formalin, Cheuk et al noted thus managing stable or unstable HC patients refractory
“satisfactory responses” in all five children with instillation to all other conservative and moderately invasive therapies
of the solution, an indwelling period of 10‒20 minutes, and short of performing irreversible surgical urinary diversion.
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then a washout. Four of the five children had improvement Persistent bladder spasms from blood clots may limit its
after one treatment, whereas the fifth needed three treatments tolerability in pediatric patients (Level 3 evidence, Grade
in two months to yield an adequate response. Other case C recommendation).
reports have documented success with lower concentrations,
such as 1% and 2%, though often with repeated courses of Treatment options for refractory, life-threatening HC
therapy needed. 21,54 Alternatively, cystotomy with application
of 4% formalin soaked swabs or endoscopic placement of
formalin soaked pledgets have also been reported in cases. Supraselective bilateral vesical artery embolization (SVAE)
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Silver nitrate irrigation has also been used to treat HC, but is
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notable for bladder fibrosis and contracture. Formalin and With progressive advances in interventional radiological
silver nitrate are, therefore, typically avoided or considered techniques, targeted embolization of bladder vasculature has
last-resort options due to their potential for bladder scarring added an additional tool to the urologist’s armamentarium for
and long-term compromise of bladder function. Especially management of the acutely ill HC patient refractory to prior
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in the pediatric population, significant consideration of long- conservative and invasive therapies. 25,56,57 Embolization is
term implications of therapy must be considered prior to employed using either gelatin sponge microparticles, gelfoam
pursuing these options. pledgets, or alcohol microspheres following angiography to
Recommendation: Although effective, the need for anes- identify the bilateral arterial vesical branch targets. Often
thesia with formalin instillation and the potential long-term SVAE is considered in patients with HC and hemorrhagic
compromise of bladder function must be heavily considered shock and massive blood product requirements, although it

CUAJ • November 2019 • Volume 13, Issue 11 E331