**7. Adverse Events after BoNT-A Injection for Sensory Bladder Disorders**

Intravesical injection of BoNT-A has been demonstrated to be effective in treatment of NDO, IDO, OAB and IC, however, the high rates of treatment-related adverse events (AEs) still need attention. The most common AEs are large PVR, difficulty in urination, UTI and acute urinary retention [80]. For the male gender with IDO, a baseline PVR more than 100 mL with medical comorbidity and BoNT-A dose greater than 100 U are risk factors for AEs to increase after treatment [80]. The odds of increased PVR after BoNT-A injection were a nine-fold increase in comparison with placebo [92]. At the first treatment, the incidence of needing clean intermittent catheterization (CIC) was 35% and bacteriuria was 21% [113]. Poor efficiency, UTI and CIC-related issues are the most common causes of discontinuation of BoNT-A injections for DO over a seven-year span [114]. Large PVR after BoNT-A injection was significantly more in the frail elderly than elderly without frailty and younger patients; in frail elderly patients (60.7% v 39.7% v 35.7%, *p* = 0.018), the long-term success rate was significantly lower [82]. The incidence of AEs is closely related with the injected BoNT-A dose [77].

Regarding the AEs after BoNT-A injection for treatment of bladder and frequency in patients with IC, difficulty in urination and large PVR are the most common AEs [115]. The incidence of AEs in IC or OAB patients after BoNT-A injection is also related to the dose of BoNT-A. Injecting 100 U of onabotulinumtoxinA has less AEs than 200 U, while injecting 100 U of BoNT-A into the trigone showed no acute urinary retention and minimal AEs in both IC and OAB patients [102,104,112]. Interestingly, compared with IC, OAB patients suffered more frequently from AEs of hematuria, UTI, and large PVR (>200 mL) after BoNT-A injection, but less frequently from events of straining to void. OAB women had higher PVR volume and lower voiding efficiency than those in IC after BoNT-A injections, implying the bladder contractility of OAB patients are more susceptible to BoNT-A than IC patients [115]. However, in a randomized, double blind, placebo-controlled trial examining the effects of BoNT-A in patients with bladder oversensitivity, the significant increase in maximal cystometric capacity did not translate to clinical benefit in the majority of patients. Patients with bladder oversensitivity without DO had storage symptoms remain unchanged following BoNT-A injection and CIC was needed in three patients without clinical improvement [116].
