Alkalinised lidocaine as an anaesthetic before onabotulinumtoxinA injections. a randomised trial.

The study received a grant from the Herlev and Gentofte University Hospital Research Fund.

We screened 60 women scheduled for BTX‐A treatment between September 2022 and May 2023. Of these, 50 signed informed consent, met eligibility criteria and completed the first treatment period. Two patients were treatment naïve. One patient withdrew due to adverse effects from the initial BTX‐A treatment but was later re‐enrolled. Another patient was excluded after receiving rimabotulinumtoxinB (Myobloc®, US WorldMeds, Louisville, KY, USA) after the first treatment period. Additionally, one patient was lost to follow‐up for the second treatment period, one postponed treatment due to other health issues, and one withdrew from the BTX‐A programme (Fig.  2 ). The CONSORT study flow chart. n =  number of patients. Created in BioRender. El Issaoui (2024) https://BioRender.com/l65c298 . A dosing error occurred during the second treatment period, when a patient received an incorrect dosing kit, that was intended for another patient. This protocol violation was identified when the intended patient came for the second treatment. The Hospital Pharmacy was consulted about the randomisation order, confirming that the patients had different treatment sequences. Consequently, the first patient was included in the ITT analysis, while the second patient was excluded due to not receiving the second treatment. The first three patients who received the first trial medication before protocol amendment were included in the ITT analyses. Demographics and baseline characteristics of the 45 ITT patients are listed in Table  1 . Baseline characteristics and demographics – ITT analysis ( N  = 45). POP‐Q, Pelvic Organ Prolapse Quantification. Sedation with intravenous propofol during monitored anaesthesia care. In total, 41 patients were evaluable for the primary endpoint and PPA, with 20 patients in alkalinised lidocaine–placebo sequence and 21 patients in the placebo–alkalinised lidocaine sequence (Table  2 ). Clinical characteristics reported by total and sequence for per‐protocol analysis. Wilcoxon rank‐sum test. t ‐test. Fisher's exact test. The mean VAS pain score was significantly lower following intravesical alkalinised lidocaine (mean 21.3 mm, 95% CI 14.7–27.8 mm) compared to placebo (41.6 mm, 95% CI 35.0–48.1 mm), with a mean difference of −20.3 mm (95% CI −29.2 to −11.5 mm; P  < 0.001). The period effect was insignificant ( P  = 0.723) as well as the sequence effect ( P  = 0.323) (Fig.  3 ). ( a ) Mean VAS pain scores (mm) with 95% CIs for placebo and alkalinised lidocaine. ( b ) Reported VAS pain scores (mm) for each patient in the sequence placebo–alkalinised lidocaine. ( c ) Reported VAS pain scores (mm) for each patient in the sequence alkalinised lidocaine–placebo. The ITT analysis aligned with the results of the PPA (alkalinised lidocaine: mean 20.9 mm, 95% CI 14.4–27.4 mm; placebo 41.6 mm, 95% CI 34.1–47.1 mm; mean difference −19.7 mm, 95% CI −27.9 to −11.5 mm; P  < 0.001). The median time between installation of the trial medication and the first BTX‐A injection did not vary significantly between the alkalinised lidocaine, at a median (interquartile range [IQR], Q1–Q3) of 18 (18–19) min and the placebo group at a median (IQR) of 19 (18–19) min ( P  = 0.139). We conducted a post hoc analysis, adjusting for the pre‐treatment use of analgesics, which consistently showed a statistically significant reduction in VAS pain scores for alkalinised lidocaine compared to placebo (adjusted P  < 0.001). The overall rate of adverse events did not differ significantly between the alkalinised lidocaine treatment and placebo ( P  = 0.825; Table  3 ). Secondary outcomes – adverse events, per‐protocol analyses ( n  = 41). UUI, urgency urinary incontinence. Wilcoxon signed‐rank test; McNemar's test. One patient presented with urinary retention necessitating CIC for 11 days and developed UTI following BTX‐A treatment with alkalinised lidocaine. Dysuria presented equally following both treatments (alkalinised lidocaine eight [16%] vs placebo eight [16%]; odds ratio [OR] 1.25, 95% CI 0.27–6.30). Perioperative Grade 1 haematuria occurred in six (12%) patients. After alkalinised lidocaine, four patients (8%) experienced haematuria, with two (4%) patients on rivaroxaban and clopidogrel. In the placebo group, haematuria was observed in two (4%) patients, including one on clopidogrel (OR 0.67, 95% CI 0.06–5.82). Procedure‐related UTIs were reported in seven (14%) patients, with five (10%) cases occurring after alkalinised lidocaine and two (4%) cases after placebo (OR 0, 95% CI 0.00–2.42). One patient required intravenous antibiotics for a multi‐drug resistant UTI caused by Morganella morganii . This infection was observed after both BTX‐A treatments, but hospital admission occurred following alkalinised lidocaine treatment in the second period, categorising it as a Grade 2 adverse event. The 5‐point satisfaction scores did not differ significantly between the alkalinised lidocaine and placebo treatments ( P  = 0.138). In both groups, the most frequent response was ‘very satisfied’ (Fig.  S1 ).

This single‐centre prospective, randomised, double‐blind, placebo‐controlled two period crossover trial (Fig.  1 ) was approved by the Danish Research Ethics Committees (number: H‐21072667), Danish Medicines Agency (European Union Drug Regulating Authorities Clinical Trials [EudraCT] number: 2021‐000559‐38), and the Capital Region's research registry Privacy (number: P‐2021‐881). The trial followed the Helsinki Declaration, European Union Directive on Good Clinical Practice, and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use‐Good Clinical Practice (ICH‐GCP) guidelines. The trial was registered at the United States National Institutes of Health ( ClinicalTrials.gov identifier: NCT05415865 ). Study design.. Created in BioRender. El Issaoui, (2024) https://BioRender.com/k22o977 . Eligible participants were recruited from the existing patient population enrolled in the BTX‐A programme at our tertiary urogynaecological clinic. Inclusion criteria were women aged ≥18 years referred for treatment with BTX‐A injections due to complaints of OAB symptoms. Patients should accept to receive BTX‐A injections in our outpatient clinic without the option of sedation. Standard BTX‐A treatment in our outpatient setting comprises Instillagel® (lidocaine hydrochloride, 20 mg/g; Farco‐Pharma GmbH, Cologne, Germany) instilled into the urethra as the sole anaesthetic. In the trial, the intervention was additional anaesthesia, whereas the placebo was standard care. Exclusion criteria were as follows: BTX‐A allergy, any neurological disorder that could impact the bladder function (e.g., multiple sclerosis or spinal cord injury), a neurological disorder with neuromuscular transmission failure (i.e., myasthenia gravis), ongoing UTI or symptoms of UTI before treatment assessed by the principal investigator, any other bladder pathology at the time of cystoscopy, pregnancy, or breastfeeding. The trial followed the Consolidated Standards of Reporting Trials (CONSORT) statement on crossover trials [ 11 ]. The primary outcome of the trial was the maximum pain score reported using the 100‐mm visual analogue scale (VAS) score immediately after BTX‐A injections. Secondary outcomes were adverse effects of BTX‐A treatment, including post‐void residual urine volume requiring clean intermittent catheterisation (CIC), procedure‐related UTI, and haematuria 1 week after the treatment. The Clavien–Dindo classification of postoperative complications was used to classify adverse events. Furthermore, we assessed patient satisfaction with the BTX‐A treatment using a 5‐point Likert scale: 1 = ‘very unsatisfied’, 2 = ‘unsatisfied’, 3 = ‘neither unsatisfied nor satisfied’, 4 = ‘satisfied’, and 5 = ‘very satisfied’. The hospital pharmacy produced the trial medication and the matching placebo, performed the randomisation, and packed the ‘blinded’ dosing kits with alkalinised lidocaine and placebo in a balanced design (alkalinised lidocaine: placebo sequence and placebo: alkalinised lidocaine sequence). After providing informed consent, patients were assigned consecutive randomisation numbers specifying the dosing kit they would receive. Patients, treating personnel, and study personnel were ‘blinded’ to the group assignments. Only the hospital pharmacy had knowledge of treatment assignments. All personnel involved in enrolment, randomisation, medication administration, and outcome assessment remained ‘blinded’ until the outcomes were analysed. Active treatment was a buffer of lidocaine hydrochloride 20 mg/mL, 20 mL; sodium hydrogen carbonate 1 mmoL/mL, 10 mL; and sodium chloride 9 g/L, 10 mL. Lidocaine hydrochloride and sodium hydrogen carbonate were packed in separate glass vials in the ‘blinded’ dosing kits, and sodium chloride was delivered as ampoules. Matched placebo solution comprised sodium chloride 9 g/L, 20 mL; sodium chloride 9 g/L, 10 mL; and sodium chloride 9 g/L, 10 mL. Women in the fertile stage had pregnancy tests taken on the study site. Medical history and medication were updated. Any pre‐treatment pain relief medication, including daily pain relief medication for other indications were documented. For the trial, patients were instructed to use paracetamol and ibuprofen as pre‐medication and to adhere to the same protocol for the subsequent treatment within the trial. Antibiotic use was documented if patients were on current treatment or long‐term prophylaxis for recurrent UTIs. Perioperative prophylactic antibiotics are not routinely administered but are prescribed if the clinician identifies an increased risk of post‐treatment UTI or observes perioperative signs or symptoms of a UTI. Following randomisation, the trial medication was prepared on‐site by a study nurse. Certified nurses performed the BTX‐A treatments in our outpatient clinic. Instillagel was instilled into the urethra as part of the standard BTX‐A treatment. The bladder was drained before instilling the trial medication using a Luer lock catheter. Subsequently, the bladder was emptied after 15 min (using a timer) and distended with tempered physiological saline 0.9% with a minimum of 100 mL. Patients were treated with BTX‐A (Botox®, Allergan, Irvine, CA, USA). BTX‐A was dissolved in 10 mL sodium chloride 9 g/L and injected into the detrusor at 10–20 sites, sparing the trigone, using a rigid Karl Storz 30° endoscope system (Karl Storz SE & Co. KG, Tuttlingen, Germany). Patients were given a paper‐based VAS score and asked to rate their procedure‐related pain intensity immediately after the BTX‐A injections and once dressed. Patients received standardised postoperative instructions. A telephone consultation was scheduled and conducted 1 week after treatment by the principal investigator. Patients were asked to rate their experience with the BTX‐A procedure and to report any adverse effects, including symptoms such as dysuria, cloudy urine, polyuria, nocturia, haematuria, and bladder emptying problems. Follow‐up assessments were arranged if the investigator identified a potential risk for adverse effects. The trial's washout period followed the 3‐month washout period for BTX‐A injections. Patients were instructed to contact the clinic for the subsequent BTX‐A treatment upon sensing a relapse of OAB symptoms. Treatment intervals varied among patients based on individual responses. If a patient did not contact the clinic within 12 months after the first treatment, the principal investigator followed up with a telephone call. In the second treatment period, patients received the alternate treatment, with a maintained double‐blind protocol and all procedures consistent with those in the first treatment period. We requested a protocol amendment after enrolling the first three patients in the trial because the treating nurse observed a milky white appearance in the trial medication after mixing. Our initial protocol followed the same solution administered in the RCT by Pereira E Silva et al. [ 9 ], which comprised 20 mL of 2% lidocaine hydrochloride with 10 mL of 8.4% sodium bicarbonate. As a result, the trial was halted due to the compromised double‐blind conditions. We consulted the Capital Region of Denmark's unit for pharmaceutical advice. The unit stated that the mixture of lidocaine hydrochloride 20 mg/mL and sodium hydrogen carbonate 1 mmoL/mL was unstable and could precipitate. This could lead to reduced anaesthetic effect compared to anticipated results. Additionally, the solution could potentially irritate the bladder mucosa. The hospital pharmacy conducted new analyses and recommended dissolving the mixture in 10 mL sodium chloride (9 g/L). This prevented the milky white appearance or precipitation of the trial medication. Amendment approval for 10 mL sodium chloride was obtained from the Danish Research Ethics Committees and the Danish Medicines Agency. The trial was resumed in January 2023. In this crossover trial, a difference of 10 mm [ 12 , 13 ] on the 100‐mm VAS pain score was considered a minimal clinically important difference (MCID). To detect a difference of 10 mm (SD 20 mm) with a power of 0.80 and an α of 0.05, a total of 34 patients were required [ 14 ]. Accounting for a dropout rate of up to 32%, 50 patients were included in the trial. Comparisons of baseline parameters between the allocated treatment protocols were performed using the Wilcoxon rank sum test and Fisher's exact test for non‐parametric data, and Student's t ‐test for parametric data. The difference in VAS pain scores between alkalinised lidocaine and placebo treatments was calculated using repeated measures analysis of covariance ( ancova ), including the treatment order as a covariate. Least squares mean differences between treatment groups were calculated with 95% CIs. Exact McNemar's test and Wilcoxon signed‐rank test were used for the secondary outcome analyses. A P  < 0.05 was considered statistically significant. Additionally, a post hoc ancova analysis adjusting for the pre‐treatment use of analgesics was performed. We performed intention‐to‐treat (ITT) analyses, which included all patients who received both treatments. Per‐protocol analyses (PPA) included patients who completed the trial according to the amendment protocol. No imputation for missing data was performed, as the dropout rate was <32%. Statistical analyses were performed using R Studio (R Foundation for Statistical Computing, Vienna, Austria). All collected data were stored in the on‐line database Research Electronic Data Capture (REDCap).

Authors declare that they have no conflicts of interest.

This study presents the first randomised, double‐blind, placebo‐controlled crossover trial to evaluate the effect of intravesical alkalinised lidocaine. We observed a significant reduction in pain, with VAS pain scores nearly halving, in women who received a 15‐min intravesical anaesthetic treatment with alkalinised lidocaine compared to placebo. Our findings align with the previous RCT by Pereira E Silva et al. [ 9 ], which demonstrated a significant reduction in the numeric rating scale (NRS) for pain during BTX‐A injections in the group receiving alkalinised lidocaine, at a mean (standard error [SE]) NRS score of 2.37 (0.31) ( n  = 57) compared to lidocaine at a mean (SE) of 4.44 (0.36) ( n  = 59). The mean difference in the pain score was 2.1 (95% CI 1.1–3.0, P  < 0.001). The authors found no differences in pain scores between the two groups 1 h after treatment ( P  = 0.487) [ 9 ]. As BTX‐A treatment is a minimally invasive procedure, we did not collect a 1‐h post‐treatment pain score. Furthermore, we used the VAS pain score due to its continuous scale, which is sensitive to small changes in pain intensity. In a double‐blind RCT by Nambiar et al. [ 10 ], 54 patients were treated with alkalinised lidocaine gel (10 mL 8.4% sodium bicarbonate, 20 mL 2% lidocaine, 22 mL Aquagel) or standard lidocaine gel (22 mL Instillagel, 30 mL 0.9% saline). There was no significant difference in the VAS pain scores at the end of the procedure ( P  = 0.656). Limitations of that RCT included a small population and the use of gel solution, which could cause impaired distribution of the alkalinised lidocaine in the bladder. In our power analysis, we determined a 10 mm change as MCID. A previous observational study by Myles et al. [ 12 ] evaluated adult patients recovering from surgery including gynaecological and urological procedures and suggested that a 10‐point change in the pain score on the 100‐mm VAS indicated a MCID. The same MCID has been applied to endometriosis‐associated pelvic pain [ 13 ]. However, the MCID can vary depending on the pain condition [ 15 ]. In the study by Myles et al. [ 12 ], a VAS pain score of ≤33 mm indicated satisfactory pain control following surgery. After receiving alkalinised lidocaine, 80.5% ( n  = 30) reported a VAS pain score of ≤33 mm, whereas only 46.3% ( n  = 19) reported the same after placebo in our trial. The 15‐min bladder anaesthetic instillation effectively reduced the VAS pain score, consistent with the findings of the RCT by Pereira E Silva et al. [ 9 ]. In our trial, seven patients received an increased BTX‐A dose during the second treatment period, leading to more injections compared to the first period. Of these, two of three patients in the alkalinised lidocaine–placebo sequence group reported higher VAS pain scores. All four patients in the placebo–alkalinised lidocaine sequence group reported lower VAS pain scores despite the increased BTX‐A dose. A recent RCT evaluated procedure‐related pain by comparing 10 injection sites with 20 injection sites in 50 women treated with 100 units of BTX‐A. On an 11‐point pain NRS, no statistically significant difference was found (median [IQR]: 4 [1.5–5] for 10 injections vs 3 [1–4] for 20 injections, P  = 0.823). All participants received bladder anaesthetics with urethral lidocaine gel and intravesical instillation of 30 mL bupivacaine and 5 mL sodium hydrogen carbonate solution for 15 min [ 16 ]. Our initial protocol followed the same solution of alkalinised lidocaine administered by Pereira E Silva et al. [ 9 ]. We contacted the authors, who reported no occurrence of milky white solution precipitation in lidocaine buffered with sodium hydrogen carbonate. A previous study by Henry et al. [ 7 ] assessed the pharmacokinetics of alkalised intravesical lidocaine in healthy volunteers and patients with interstitial cystitis. The study aimed to determine a safe dose of buffered lidocaine, evaluate its absorption in patients with interstitial cystitis, and assess its efficacy in reducing bladder pain. Lidocaine hydrochloride as xylocaine (5 mg/kg 5% in 5% dextrose water and 10 mL 8.4% sodium bicarbonate) was reported to be administered sequentially to prevent precipitation of the lidocaine [ 7 ]. The pharmacist from the Capital Region of Denmark's Unit for Pharmaceutical Advice also noted that, unlike xylocaine, which is pH adjusted, lidocaine hydrochloride 20 mg/mL becomes less soluble at pH levels >6.4. Consequently, when mixing it with alkaline solutions, such as carbonates, precautions must be taken to prevent lidocaine from precipitating [ 17 ]. After unblinding, it was revealed that only one patient received the initial alkalinised lidocaine, which became milky white. The patient reported dysuria. After receiving alkalinised lidocaine, this patient reported a VAS score of 0 compared to a VAS score of 3 after receiving placebo. The clinical implementation of alkalinised lidocaine could be optimised by administrating xylocaine. Grade 1 haematuria occurred in seven cases overall (Table  3 ), with five (10.4%) of these cases after treatment with alkalinised lidocaine. However, no significant evidence of a difference in the odds of haematuria between alkalinised lidocaine and placebo was observed in the PPA analysis (OR 0.67, 95% CI 0.06–5.82). Pereira E Silva et al. [ 9 ] reported comparable rates of haematuria in their study. Bleeding cases originated from the injection sites and are likely unrelated to the anaesthesia protocol. However, potential irritation of the bladder wall due to the hypertonic solution of alkalinised lidocaine cannot be excluded. Furthermore, two patients with reported haematuria had post‐treatment UTI. Among patients included in the trial, eight (16%) administered perioperative antithrombotic therapy. Of those who experienced haematuria, three (37.5%) were undergoing antithrombotic treatment. We previously evaluated 1059 BTX‐A injections in 400 patients from our clinic and found no symptomatic haematuria necessitating treatment [ 18 ]. Dysuria was observed with equal frequency following alkalinised lidocaine and placebo. While dysuria and urethral discomfort are reported adverse effects after voiding lidocaine [ 7 ], it is also a known adverse event following BTX‐A injections [ 4 ]. Urinary retention necessitating CIC was observed in only one (2.4%) patient following alkalinised lidocaine treatment. This low CIC rate is likely because only two patients were BTX‐A treatment naïve, while the majority had prior exposure to BTX‐A treatments. Following treatment with alkalinised lidocaine, five (12.2%) patients developed post‐procedural UTIs, compared to two (4.9%) patients after placebo. However, this observed difference did not reach statistical significance ( P  = 0.250). One patient in the placebo sequence received prophylactic antibiotics for recurrent UTIs. Pereira E Silva et al. [ 9 ] reported no UTIs in their trial, where all patients received a single dose of fosfomycin 3000 mg administered after the BTX‐A procedure. Intravesical lidocaine has previously been suggested to have anti‐inflammatory and possible bactericidal effects [ 19 , 20 ]. The overall rate of adverse events did not differ significantly between the alkalinised lidocaine treatment and placebo ( P  = 0.825), suggesting that alkalinised lidocaine does not pose a higher risk of complications. Our findings align with the Faure Walker et al. [ 2 ] review, which assessed the tolerability of local anaesthetic BTX‐A injections. This is further supported by comparable 5‐point satisfaction scores between the alkalinised lidocaine and placebo 1 week post‐treatment. These results indicate that BTX‐A injections are generally well‐tolerated in terms of both complications and patient experience. Notably, the mean VAS pain score with placebo was 41.6 mm, reflecting the tolerability of the standard treatment. However, alkalinised lidocaine administration resulted in nearly a 50% reduction in VAS pain scores, demonstrating its superior efficacy. Henry et al. [ 7 ] found serum concentrations of alkalinised lidocaine to be low following intravesical administration and within therapeutic ranges. Systemic symptoms are rare, underscoring the safety and convenience of using the buffer for intravesical administration. The trial's strengths include its double‐blind randomisation and crossover design, which allows patients to serve as their own controls, minimising confounding. This approach also enhances statistical power and reduces the sample size needed [ 21 ]. However, some limitations must be noted. Prior experience with BTX‐A injections may have an influence on reported pain levels. In this trial, only two patients were treatment naïve at inclusion. Despite a small sample size, Nambiar et al. [ 10 ] found no significant differences in VAS scores between treatment‐naïve patients and those previously treated with BTX‐A injections. Reliance on self‐reported symptoms to diagnose our secondary outcomes and adverse events 1 week post‐procedure may have caused an underestimation of the true incidence of adverse events. Previous treatment may have influenced patients’ pain perception, introducing a potential bias. Most patients previously received BTX‐A treatment in our outpatient setting. Given their previous exposure to placebo and demonstrated tolerance to BTX‐A standard care, there is a potential for expectation bias. Based on the results of this placebo‐controlled RCT, we recommend considering alkalinised lidocaine as a first‐line anaesthetic for BTX‐A injections alongside urethral lidocaine gel. This protocol may also apply to other minimally invasive cystoscopy procedures. Consequently, our clinical practice will now include the option of administering intravesical alkalinised lidocaine 15 min before BTX‐A injections as part of our standard anaesthetic regimen.

Intravesical instillation of alkalinised lidocaine before BTX‐A injections in women with OAB symptoms resulted in a significant and clinically relevant reduction in VAS pain scores compared to placebo, thereby decreasing procedural discomfort. Adverse events were not significantly more frequent in patients receiving alkalinised lidocaine, confirming the anaesthetic's safety. To the best of our knowledge, this is the first placebo‐controlled crossover RCT to confirm that alkalinised lidocaine is an effective anaesthetic treatment option. We recommend the use of alkalinised lidocaine for patients undergoing BTX‐A injections.

Intradetrusor onabotulinumtoxinA (BTX‐A) injections are a third‐line treatment for overactive bladder (OAB) syndrome with proven efficacy, as demonstrated by randomised controlled studies (RCTs) and systematic reviews and meta‐analyses [ 1 ]. Treatments with BTX‐A are well‐established, providing effects lasting from 3 to 12 months. More than 800 treatments are administered in our department yearly, and the numbers are increasing. BTX‐A is directly injected into the bladder wall with a needle under cystoscope guidance. Depending on anaesthesia requirements, BTX‐A injections are performed in an outpatient setting or an operating theatre. Some patients tolerate the procedure with only local anaesthetic gel applied to the urethra, while others require additional sedation or general anaesthesia to achieve adequate pain management and comfort. Currently, no standardised anaesthetic protocol for BTX‐A injections is available, resulting in varied department practices [ 2 ]. In our department, most patients receive treatment in the outpatient clinic with local anaesthetic gel. Performing the procedure under local anaesthesia is preferable as it minimises the risks associated with general anaesthesia and is more cost‐effective. This approach is particularly advantageous as most patients typically require one to four BTX‐A treatments per year to maintain a therapeutic effect [ 3 , 4 ]. However, there remains a need to optimise the local anaesthetic protocol to enhance patient comfort. Intravesical use of lidocaine as an anaesthetic therapy before BTX‐A injections was previously evaluated, with findings indicating no significant anaesthetic effect [ 2 , 5 ]. Lidocaine is a weak base and is commonly produced as an acidic, ionised, water‐soluble solution. Lidocaine blocks sodium channels, inhibiting depolarisation and disrupting electrical signal transmission in afferent sensory nerves, producing its anaesthetic effect. However, in acidic environments, such as urine, lidocaine remains predominantly ionised, which hinders its ability to diffuse through lipid membranes. Alkalinising lidocaine with sodium bicarbonate reduces its ionisation, enhancing drug diffusion and intravesical uptake. This could facilitate a more rapid onset of nerve blockade and potentially improve the anaesthetic's absorption into the bladder wall Additionally, lidocaine may provide anti‐inflammatory benefits by stabilising mast cells and inhibiting histamine release [ 6 , 7 ]. Currently, alkalinised lidocaine is administered in patients with interstitial cystitis and painful bladder syndrome [ 8 ]. Few studies have evaluated alkalinised lidocaine with bicarbonate as an intravesical anaesthetic for BTX‐A treatment. A previous double‐blind RCT comparing intravesical alkalinised lidocaine with a standard lidocaine solution found significantly lower pain scores during injections in the group receiving alkalinised lidocaine [ 9 ]. Another RCT compared intravesical alkalinised lidocaine to standard lidocaine gel and found no significant difference in pain reduction between the two treatments [ 10 ]. However, the efficacy of alkalinised lidocaine in reducing pain during BTX‐A injections remains inconclusive, as it has not been compared to a placebo control. This study aimed to assess the effect of intravesical alkalinised lidocaine solution on pain experienced during BTX‐A injections, compared to placebo. We hypothesised that intravesical alkalinised lidocaine would reduce procedural pain during BTX‐A injections.

Fig. S1. Graph illustrates the distribution of 5‐point satisfaction scores for treatment with placebo and alkalinised lidocaine 1 week after BTX‐A injection.