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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 under toxins, but in fact may also be administered as an intravesical instillation. Other medications used in this manner are anticholinergics such as OXY 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.

Table: Intravesical Instillations for SCI-Related Detrusor Overactivity

Discussion

George et al. (2007) described results with a double-blind crossover (6 day washout) trial comparing propantheline (15mg) and OXY (5mg) solutions (10ml) for thrice daily intravesical instillation in 18 patients with SCI that managed their neuropathic bladder 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. OXY) 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 OXY. 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 patients with the OXY instillations developed systemic side effects (e.g., dry mouth) typical of those on oral OXY. Two patients 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 OXY was added in five patients to overcome mild to moderate urine leaks between intermittan catheterizations. As a result of unacceptable side effects, oral OXY 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 these five patients reported continued nocturnal leaking 1-2 times per week when IC was accompanied by intravesical instillation. In all seven patients, QoL scores were mixed with IC alone but showed a definite improvement when OXY was added.

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

Haferkamp et al. (2000) studied addition of intravesical OXY instillation in patients 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 patients were included who had difficulty swallowing OXY tablets. Of the 32 patients with SCI and neurogenic bladder function, 21 patients became continent with a standard dosage (0.3-0.7mg/kg/day) and 11 patients required a higher dosage (0.9mg/kg/day). Only two patients treated with the higher dose complained of constipation and dryness of the mouth; none of the patients withdrew from treatment.

Intravesical OXY (15mg TID) treatment was combined with oral treatment (5 mg four times daily) in a group of 25 patients with SCI that had detrusor storage pressure greater than 40cm H2O (n=21) or persistent autonomic dysregulation (n=5) for at least 3 months (Pannek et al. 2000). All patients used clean IC and 8 of 25 patients also received desipramine treatment. Although detrusor storage pressure responded well and no patients discontinued 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 patients as a result of the intravesical and oral OXY combination treatment. When combined therapy proved successful, a structured reduction of oral OXY was undertaken in 11 of 25 patients and this likely contributed to the lack of side effects reported in this study.

Intravesical instillation of OXY (5 mg suspended in 10 ml water) combined with clean IC was reported to increase bladder capacity in a group of 12 patients (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), for up to 240 minutes after removal of the drug. 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 patients (including an initial non-responder) with SCI treated with intravesical OXY (5 mg Ditropan diluted in 30 ml saline, tid for 3 months). Patients were selected if they practiced clean IC but were intolerant to 5 mg TID oral OXY. 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 OXY instillation post-operatively.

In contrast, Singh and Thomas (1995) presented a pre-post study with OXY instillations (10 mg) in 6 male patients who had the Brindley anterior root stimulator implanted, and were unable to show any significant improvements in peak detrusor pressure during voiding and peak flow rate. Considering OXY effectiveness in patients managing their bladder with catheterization, the question of the requirement of an intact sacral arc may be relevant to the mechanism of action for OXY.

Conclusion

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

There is level 4 evidence (from a pre-post study; George et al. 2007) that supports the use of capsaicin intravesical instillation to improve leak volume and frequency. However, this study also revealed that capsaicin intravesical instillation worsened residual volume and cystometric capacity, and can induce hyperreflexia in patients with SCI and neuropathic bladder.

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 in the treatment of neuropathic bladder in patients with SCI.

There is level 4 evidence (from three pre-post studies; Haferkamp et al. 2000; Pannek et al. 2000; Ersoz et al. 2010) that suggest instravesical instillation of oxybutynin is an effective adjuvant therapy for patients with SCI managing their neuropathic bladder with 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 male, SCI patients with an implanted Brindley anterior root stimulator.

  • Both propantheline and oxybutynin intravesical instillations improve cystometric parameters in patients 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 patients with SCI who have an implanted Brindley anterior root stimulator.