Introduction

Figure 1. Age and sex distribution for each patient stratified by awake injection vs under general anesthesia. Within the awake injection group, only 3 of the 18 patients (17%) did not proceed with or plan for subsequent awake botulinum neurotoxin (BoNT) injection procedures. Of these, one 10-year-old female patient proceeded directly to bladder augment (1), 1 insensate 7-year-old male patient with anxiety, attention-deficit/hyperactivity disorder and a conduct disorder tolerated the initial awake attempt, but family requested subsequent injections be performed under general anesthesia due to progression of his conduct disorder (2), and a sensate 20-year-old female patient with severe anxiety required conversion to general anesthesia during the initial attempt but also did not have a sufficient response to BoNT injection to merit repeat injection (3). A fourth patient, an insensate 10-year-old male with hearing loss who had difficulty communicating with the operating room team, opted to convert to a general anesthetic prior to scope placement, but has since decided to proceed with awake BoNT injection in clinic with an American Sign Language interpreter present (4). Adapted with permission from Overland, J Urol. 2022;208(3):702-710.9

Figure 2. Operating room (OR) charge distribution per encounter stratified by awake injection vs under general anesthesia. Average charges for awake botulinum neurotoxin (BoNT) injection episodes in the OR were lower than for BoNT injection under general anesthesia ($26,000±$3,260 vs $30,700±$6,850, P < .01). Adapted with permission from Overland, J Urol. 2022;208(3):702-710.9

Intravesical botulinum neurotoxin (BoNT) injection is used to treat bladder dysfunction in both pediatric and adult patients.¹ The Food and Drug Administration approved intravesical BoNT injection in 2021 for patients ≥5 years old with inadequate response to or intolerance of anticholinergic medication. BoNT is also approved for treatment of muscular spasticity in patients as young as age 2.² While the demonstrated efficacy of BoNT injection for overactive bladder in spina bifida has been mixed,^3,4 it has been shown to improve both clinical symptoms and maximum cystometric capacity in the pediatric spina bifida population with neurogenic bladder and to reduce maximum detrusor pressures.^5,6

BoNT injection must be repeated every 3-6 months to maintain its effects. In adults, injection is routinely performed with local analgesics in the office,⁷ but awake invasive procedures in children are anathema to many urologists. Thus, pediatric BoNT injection is traditionally performed under general anesthetic, accumulating repeated anesthetic exposures and high costs. Most patients with neurogenic bladder who are candidates for BoNT injection already tolerate clean intermittent catheterization (CIC) with variable sensation. To incorporate BoNT into our standard arsenal without accumulating anesthetic exposures, we offer an awake injection trial. We present a retrospective review of our initial single-surgeon experience in a pediatric population with neurogenic bladder at the University of California, San Francisco.

Methods

Procedural details. Injections were performed in the operating room (OR) with an anesthesia provider available. A parent or guardian accompanied the patient, as is our standard practice, and the patient was offered a movie to watch or video game to play. A 9.5F offset rigid cystoscope or 17F flexible cystoscope was used based upon urethral size and anatomy in supine, frogleg, or low lithotomy position, as appropriate for age and habitus. We injected weight-dosed onabutulinumtoxinA in 10 U/L mL saline increments into the detrusor muscle and submucosal layer of the bladder in trigone-sparing fashion. If the patient expressed discomfort or distress, we offered to convert to general anesthesia. A 2% preprocedural bladder lidocaine soak was added partway through the study period, and intraurethral lidocaine was administered on a case-by-case basis.

Chart review. Surgical records from 2018-2020 were searched to identify all pediatric patients under age 21 with neurogenic bladder who underwent isolated intravesical BoNT injection in the OR with H.L.C. as the primary provider. Procedure details were extracted from the operative report. Intraoperative procedure duration and use of general anesthesia were determined from anesthesia reports. Postoperative notes were reviewed to assess for subsequent planned or completed awake BoNT injection.

Results

Table 1. Summary Statistics of All Included Patients Undergoing Bladder Botulinum Neurotoxin Injection in the Operating Room Stratified by Anesthesia Utilization: No General Anesthesia (Awake) vs Under General Anesthesia

A total of 43 BoNT injection encounters in the OR were identified for 22 pediatric patients meeting inclusion criteria, and awake injection was offered to all of them within the study period. All patients catheterized at baseline. Eighteen families (82%) accepted a trial while 4 declined and proceeded under general anesthesia (Table 1). Sixteen of the 18 patients (89%) tolerated awake injection (Figure 1) and no intraoperative complications occurred. Of the 18 patients who underwent a trial of awake injection, 8 were female and 10 were male, aged 4-20 years old. Sixteen patients (89%) had a diagnosis of spina bifida. Fourteen patients (78%) had documented behavioral or mental health issues, 10 (56%) had a cognitive delay, and 7 (39%) had a sensory level below S2 on exam. Flexible cystoscopes were used for 3 male patients over the age of 14. Median follow-up was 2.0 years (Table 2).

Fifteen of 18 patients opted to proceed with subsequent awake injections, with a median of 1.5 awake procedures in the OR and 1.0 awake procedure in clinic per patient within the follow-up period. Procedure duration of the 43 BoNT injection events in the OR during the study period (24 awake, 17 under general anesthetic, and 2 awake attempts that required conversion) was not statistically different between the awake and general anesthesia groups (median duration 23 minutes vs 18 minutes, P = .1), though increased variability was seen in the awake group with a maximum procedure duration of 47 minutes. Average charges for awake BoNT injection episodes in the OR were lower than for BoNT injection under general anesthesia ($26,000±$3,260 vs $30,100±$4,960, P < .01; Figure 2).

Table 2. Summary Statistics and Procedural Details for All Patients Undergoing Trial of Awake Bladder Botulinum Neurotoxin Injection in the Operating Room Stratified by Patient Sex

Discussion

Our experience supports awake BoNT injection as a feasible option for patients with neurogenic bladder managed with CIC as young as age 4, even in the setting of intact sensation, well-managed mental health issues, or cognitive delay. Thorough discussion of the risks, benefits, and procedure details (including possible conversion to general anesthesia if needed) with the family and patient was key in the shared decision-making to proceed with a trial of awake injection.

Although we predicted that sensation with catheterization and scope placement might influence the success of the procedure, 6 of our 7 patients with a sensory level below S2 (86%) tolerated awake injection.⁸ We also were concerned that rigid cystoscopy might be poorly tolerated in awake male patients, but this was not the case. Young age did not preclude successful awake injection, and we have since successfully performed awake injections in patients as young as 2 years old. We now regularly perform awake BoNT injections in our pediatric clinic, allowing families to avoid the hassles of the perioperative experience. In our current preliminary experience, charges for clinic encounters are approximately 70% lower than for injection under anesthesia, providing further opportunity for significant cost and resource saving.

We have begun to prospectively study the experience of in-clinic injections for our patients and their families to further elucidate the intrinsic and modifiable factors that define a good pediatric candidate for awake BoNT injection, as well as to quantify the risk-benefit balance of interventions such as lidocaine soaks through controlled trials.

Conclusion

Awake BoNT injection in patients with neurogenic bladder managed with CIC is feasible in very young children, even in the setting of intact sensation, well-managed mental health issues, or cognitive delay. The ability to routinely offer this procedure without anesthesia for well-selected patients increases the viability of BoNT as an early tool in the armamentarium of the pediatric urologist managing a recalcitrant neurogenic bladder.

Support: UCSF Department of Urology intramural funds.