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Intravesical Instillations for SCI-Related Detrusor Overactivity

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Intravesical instillations are intended as a means for increasing bladder capacity, lowering pressures, and decreasing incontinence, with the potential for decreased systemic side effects compared to oral medications. Capsaicin and resiniferotoxin have been discussed above in toxins. Other medications used as intravesical installations are anticholinergics such as oxybutynin and propantheline which are presented below. Most of these protocols consist of dissolving the medication in a liquid solution and instilling the medication after emptying the bladder by IC, then leaving it in place until the next scheduled intermittent catherization.

Discussion

George et al. (2007) described results of a double-blind crossover (6 day washout) trial comparing propantheline (15mg) and oxybutynin (5mg) solutions (10ml) for thrice daily intravesical instillation in 18 individuals with SCI that managed their neurogenic bladder dysfunction with clean IC. Capsaicin was also included as a comparator but because instillation required local anesthesia to prevent hyperreflexia, CAP treatment could not be blinded. Although the study suggests that all of the intravesical agents exhibited effective attributes as adjuvant treatments, more subjects demonstrated improvement with propantheline (vs. oxybutynin) for residual volume, detrusor leak point pressure and clean IC volume. However, there was a significant worsening of leak frequency (p=0.039) for propantheline versus oxybutynin. Conversely, the pre-post CAP results revealed significant improvement for leak volume and leak frequency and significant worsening for residual volume and cystometric capacity. Two of the individuals with the oxybutynin instillations developed systemic side effects (e.g., dry mouth) typical of those on oral oxybutynin. Two individuals experienced autonomic dysreflexia following CAP instillation.

Vaidyananthan et al. (1998) reported a pre-post trial (n=7) for which individuals originally managed by condom catheterization were switched to IC. Oral oxybutynin was provided to five study participants to overcome mild to moderate urine leakage between intermittent catheterizations. As a result of unacceptable side effects, oral oxybutynin was replaced with intravesical instillation to overcome the unaceptable side effects of the oral formulation. However, despite daytime continence, reduced UTI frequency and cessation of dry mouth, three of the five study participants reported continued nocturnal leaking 1-2 times per week when IC was accompanied by intravesical instillation. In all seven individuals, QoL scores were mixed with IC alone but showed a definite improvement when oxybutynin was added.

Ersoz et al. (2010) studied individuals who used indwelling catheters and were treated simultaneously with oral and intravesical oxybutynin. With this combination treatment, significantly improved bladder volumes were reported, however, 52.6% of individuals were lost to attrition and reports of difficulty with intravesical instillation of oxybutynin were common.

Haferkamp et al. (2000) studied the addition of intravesical oxybutynin instillation in indviduals who performed IC five times daily and who were not adequately treated with oral anticholinergic medication (n=15) and/or experienced intolerable side effects from the oral medication (n=13). Four additional pediatric participants were included who had difficulty swallowing oxybutynin tablets. Of the 32 participants with SCI and neurogenic bladder function, twenty-one became continent with a standard dosage (0.3-0.7mg/kg/day) and eleven required a higher dosage (0.9mg/kg/day). Two participants treated with the higher dose complained of constipation and dryness of the mouth; none of the participants withdrew from treatment.

Intravesical oxybutynin (15mg TID) treatment was combined with oral treatment (5 mg four times daily) in a group of 25 individuals with SCI that had detrusor storage pressures greater than 40cm H2O (n=21) or persistent autonomic dysregulation (n=5) for at least 3 months (Pannek et al. 2000). All participants performed clean IC and 8 of 25 participants also received desipramine treatment. Although detrusor storage pressure responded well and no participants discontinued treatment as a result of side effects, autonomic dysregulation was not resolved with the combination treatment. This study reported that surgical intervention for detrusor hyperreflexia was avoided in 80% of individuals as a result of combination treatment with intravesical and oral oxybutynin. When combined therapy proved successful, a structured reduction of oral oxybutynin was undertaken in 11 of 25 participants and this likely contributed to the lack of side effects reported in this study.

Intravesical instillation of oxybutynin (5 mg suspended in 10 ml water) combined with clean IC was reported to increase bladder capacity in a group of 12 individuals (SCI n=8) with neurogenic bladder dysfunction (Prasad & Vaidyanathan 1993). Six to 12 months of follow-up revealed significantly improved maximum cystometric capacity and vesical compliance (both p<0.001) and decreased clean IC frequency (p<0.05). Notably, no local or systemic side effects were reported.

Szollar & Lee (1996) also reported significantly decreased leak point pressure and improved mean bladder capacity and mean volume at first contraction, for 10 of 13 individuals (including an initial non-responder) with SCI treated with intravesical oxybutynin (5 mg diluted in 30 ml saline, tid for 3 months). Participants were selected if they practiced clean IC but were intolerant to 5 mg TID oral oxybutynin. After 3 months of treatment, no local or systemic side effects were reported. An initial non-responder continued to experience incontinence after augmentation cystoplasty but did eventually respond positively to oxybutynin instillation post-operatively.

In contrast, Singh and Thomas (1995) presented a pre-post study with oxybutynin instillations (10 mg) in 6 male participants with SCI who had Brindley anterior root stimulators implanted and who failed to demonstrate significant improvements in peak detrusor pressure during voiding and peak flow rate. During implantation of the Brindley anterior root stimulator, sacral dorsal rhizotomies are performed. Considering oxybutynin’s effectiveness in individuals who manage their neurogenic bladder dysfunction with catheterization; the lack of efficacy in the above study could be attributable to the absence of an intact sacral arc and therefore may provide additional insight into the mechanism of action for oxybutynin.

Conclusions

There is level 2 evidence (from one RCT; George et al. 2007) advocating for propantheline and oxybutynin intravesical instillation as adjuvant therapy for neuropathic bladder dysfunction managed with clean intermittent catheterization; with propantheline being superior in more cystometric parameters,.

There is level 4 evidence (from a pre-post study; George et al. 2007) supporting the use of capsaicin intravesical instillation in reducing leak volume and frequency. However, this study also revealed that capsaicin intravesical instillation increased residual volume and decreased cystometric capacity, and can induce hyperreflexia in individuals with SCI and neurogenic bladder dysfunction.

There is level 4 evidence (from three pre-post studies; Vaidyanathan et al. 1998; Szollar & Lee 1996; Parsad & Vaidyannathan 1993) that intermittent catheterization combined with intravesical oxybutynin instillation is effective for the treatment of neuropathic bladder dysfunction following SCI.

There is level 4 evidence (from three pre-post studies; Haferkamp et al. 2000; Pannek et al. 2000; Ersoz et al. 2010) that the intravesical instillation of oxybutynin is an effective adjuvant therapy for individuals with SCI who manage their neurogenic bladder dysfunction with intermittent catheterization and oral oxybutynin.

There is level 4 evidence (from one pre-post study; Singh & Thomas 1995) that intravesical oxybutynin instillation is not effective in males with SCI following the surgical implantation of a Brindley anterior root stimulator.

  • Both propantheline and oxybutynin intravesical instillations improve cystometric parameters in individuals with SCI and neuropathic bladder, but propantheline provides superior improvement in more parameters.

  • Catheterization combined with intravesical instillation of oxybutynin alone or in addition to oral oxybutynin is effective in improving the symptoms of neuropathic bladder in individuals with SCI.

  • For individuals with SCI and neuropathic bladder, capsaicin can improve leak volume and frequency but can also worsen residual volume and cystometric capacity as well as induce hyperreflexia.

  • Intravesical instillation of oxybutynin is ineffective for male individuals with SCI who have an implanted Brindley anterior root stimulator.