BJUI. Surgery Illustrated Surgical Atlas Botulinum toxin injections into the detrusor

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1 c c WÖLLNER nd KESSLER BJUI Surgery Illustrted Surgicl Atls Botulinum toxin injections into the detrusor Jens W ö llner * nd Thoms M. Kessler * *Neuro-Urology, Spinl Cord Injury Center nd Reserch, University of Zürich, Blgrist University Hospitl, Switzerlnd nd Deprtment of Urology, University Medicl Center, University of Minz, Germny ILLUSTRATIONS y STEPHAN SPITZER, INTRODUCTION Overctive ldder syndrome (OAB), chrcterized y urgency, with or without urgency incontinence, usully with frequency nd nocturi [1 ], is highly prevlent, ffects the life of millions of people worldwide, nd lso imposes sustntil economic urden for every helthcre system, s direct nnul costs re comprle to those of other chronic diseses such s dementi nd dietes mellitus [2 ]. Antimuscrinics re the phrmcologicl tretment of choice for OAB. However, the effectiveness is limited nd mny ptients discontinue tretment due to dverse events. In 2000, Schurch et l. [3, 4 ] first pulished on the use of otulinum toxin injections into the detrusor for treting neurogenic detrusor overctivity in ptients with spinl cord injury. Since then, intrdetrusor otulinum toxin injections hve ecome well-estlished nd widely ccepted therpy for refrctory neurogenic nd non-neurogenic OAB, with or without urodynmiclly confirmed detrusor overctivity [5, 6 ]. Although otulinum toxin injections into the detrusor is highly effective, minimlly invsive, nd generlly well-tolerted tretment tht improves helth-relted qulity of life (HRQL), the use of otulinum toxin in the lower urinry trct remins unlicensed in most countries. There re seven serotypes of otulinum toxin, i.e. types A to G. Botulinum toxin A is the most commonly used nd it is ville under severl trde nmes, i.e. Botox [onotulinumtoxina ] (Allergn Phrmceuticls, Irvine, CA, USA), Dysport [ootulinumtoxina ] (Ipsen Biophrm Ltd, Slough, UK), Xeomin [ incootulinumtoxina ] , doi: /j x x

2 SURGERY ILLUSTRATED (Merz Phrmceuticls UK Ltd, Herts, UK), Prosigne (Lnzhou Biologicl Products, Lnzhou, Chin), nd PurTox (Mentor Corportion, Mdison, WI, USA) [6 ]. Importntly, the different otulinum toxin A products cnnot e considered generic equivlents nd there re no rndomised trils directly compring the different rnds. Nevertheless, 1 U Botox seems to hve similr efficcy to 3 5 U Dysport, to 1 U Xeomin, nd to 1 U Prosigne [6 ]. For urologicl pplictions, usully U Botox nd U Dysport re used. Despite the populrity of intrdetrusor otulinum toxin injections, the exct mechnism of ction remins to e elucidted. Nevertheless, it seems highly prole tht, in ddition to direct efferent effect locking the presynptic relese of cetylcholine from the prsympthetic innervtion resulting in temporry chemodenervtion of the detrusor, otulinum toxin lso modultes fferent pthwys [7 ]. The ppliction technology nd technique hve undergone mjor developments in the pst decde. Trditionlly, otulinum toxin ws injected into the detrusor t sites, spring the trigone through rigid cystoscope nd pplying re-usele needle. The Dsgupt technique [8 ] introduced the use of n ultrfine, singleuse injection needle vi flexile cystoscope under locl nesthesi in n outptient setting. Bsed on mounting evidence tht otulinum toxin my lso ffect sensory pthwys, injecting the trigone nd/or the suurothelil spce hs een reported without evidence of new or worsening of pre-existing vesico-uretero-renl reflux [5 ]. In ddition, different numers of injection sites nd vrious dilutions nd doses hve een descried. In the present rticle, we summrise the most importnt steps of otulinum toxin injections into the detrusor, showing the different techniques. PLANNING AND PREPARATION Before considering otulinum toxin injections into the detrusor, UTI nd other ovious pthology needing different types of tretment hve to e excluded. Thus, we recommend complete urologicl evlution including medicl history, physicl exmintion, ldder diry, urine nlysis, urine culture, urinry trct ultrsonogrphy, urethro-cystoscopy, ldder wshing cytology, nd urodynmic investigtion. PATIENT SELECTION Ptients with refrctory OAB, i.e. filure to respond to ehviourl tretment (lifestyle modifictions nd ldder trining) nd phrmcotherpy with more thn one ntimuscrinic for t lest 4 weeks, re cndidtes for otulinum toxin injections into the detrusor. Among the dverse events of otulinum toxin injections, incresed postvoid residul urine volume (PVR) with the potentil need for ctheteristion is the most significnt prolem. Thus, ll our ptients re informed of the potentil need for intermittent or indwelling ctheteristion nd willingness to do so is prerequisite for this tretment. Ptients with pre-existing voiding dysfunction nd those t high risk for otulinum toxin induced high PVR (neurologicl ptients, ldder outlet ostruction in pressure-flow study) re instructed to perform clen intermittent self-ctheteristion (CISC) efore tretment. In ddition, cost-covering issues of this in most countries still unlicensed off-lel tretment should e clrified for ech individul ptient nd informed consent provided efore tretment. SPECIFIC EQUIPMENT AND MATERIALS Rigid cystoscope with working chnnel injection needle (e.g. Bonee, Porgès / Coloplst, needle dimeter 22 G, needle length 4 mm, working length 350/700 mm, 5/6 F) Flexile cystoscope with working chnnel injection needle (e.g. MAJ-656 needle nd NM-101C-427 injector, Olympus, needle dimeter 27 G, needle length 4 mm, working length 1050 mm, 6 F) Botulinum toxin A U Botox or U Dysport SPECIFIC PATIENT PREPARATION UTI is to e excluded nd dequtely treted ccording to the ntiiotic sensitivity pttern efore otulinum toxin injections into the detrusor voiding minoglycosides, s they my potentite the neuromusculr locking effects of otulinum toxin. For locl nesthesi, lidocine gel (Instillgel 2 10 ml, Frco-Phrm GmH, Germny) is instilled into the urethr nd exposed for 10 min. In the rre cse tht otulinum toxin injections re performed under generl or spinl nesthesi, preopertive lortory my e necessry depending on the nesthetist. SPECIFIC PATIENT POSITIONING The ptient is plced in lithotomy or supine position, generlly depending on the cystoscope used, i.e. rigid or flexile instrument, respectively

3 WÖLLNER nd KESSLER SURGICAL STEPS Figure 1 Botulinum toxin injections re performed through rigid () or flexile cystoscope (). The injection needle is inserted into the working chnnel (c) usully fter overview urethro-cystoscopy. This voids potentil urethrl lesions during pushing of the cystoscope through the urethr into the ldder y n injection needle ccidentlly protruding out of the working chnnel. c

4 SURGERY ILLUSTRATED Figure 2 Urethro-cystoscopy is used to exclude pthologicl findings such s urethrl stricture, ldder neck sclerosis, urethrl/ ldder stones, nd ldder tumours requiring tretment other thn intrdetrusor otulinum toxin injections. In ddition, we routinely perform ldder wshing cytology to exclude crcinom in situ potentilly cusing OAB

5 WÖLLNER nd KESSLER Figure 3 We generlly use the rigid cystoscope in women () nd the flexile cystoscope in men () ut this is t the preference of the treting physicin. After overview urethrocystoscopy, the injection needle is inserted into the working chnnel nd pushed forwrd upon ppernce in the visul field (c). Before strting otulinum toxin injections, the 1 ml ded spce of the injection needle is flushed with 0.9% sline. c

6 SURGERY ILLUSTRATED Figure 4 Chrcteristic ldder chnges such s trecule, pseudo-diverticul, nd diverticul re often found in ptients with refrctory OAB, especilly in those with n underlying neurologicl disese (). Botulinum toxin is injected directly into the trecule (). Pseudo-diverticul nd diverticul must e inspected crefully to void missing ldder tumour

7 WÖLLNER nd KESSLER Figure 5 Considering tht otulinum toxin lso ffects sensory pthwys with n importnt role of the suurothelil lyer, suurothelil injections hve een introduced showing similr efficcy to intrdetrusor injections. When injecting the suurothelil lyer, typicl ule occurs. Although specil injection needle with the possiility of djusting the needle s penetrtion depth is commercilly ville (injetak, Lorie, needle dimeter 25 G, djustle needle length 0, 2, 3, nd 5 mm, working length 350/500 mm, 6 F), suurothelil injections re esily performed with non-djustle injection needle

8 SURGERY ILLUSTRATED Figure 6 Botulinum toxin is usully injected t different sites depending on the dilution nd dose used, nd the trigone is trditionlly spred (). There is no evidence of new or worsening of pre-existing vesico-ureterorenl reflux fter trigonl injections (), so tht this technique hs lso ecome well ccepted, especilly tking into ccount the effect of otulinum toxin on fferent pthwys

9 WÖLLNER nd KESSLER Figure 7 After the procedure, relevnt leeding is excluded y finl cystoscopy. The ldder is emptied nd the ptient is dischrged home without n indwelling ctheter. Bldder irrigtion or fulgurtion is very rrely needed ecuse of refrctory hemturi

10 SURGERY ILLUSTRATED POSTOPERATIVE CARE Most ptients cn e mnged in n outptient setting nd re dischrged home fter tretment. The vlue of peri-/ postopertive ntiiotic prophylxis is uncler nd we do not use it routinely. The effect of otulinum toxin ecomes ovious 5 10 dys (not just immeditely) fter tretment. In ptients voiding spontneously, we ssess PVR 2 weeks fter injections. Although there re no generlly ccepted criteri for inititing CISC, we usully tke PVR of > 150 ml with lower urinry trct symptoms s n indiction for CISC. Follow-up fter intrdetrusor otulinum toxin injections is not yet stndrdised. Time points nd types of ssessment (including ldder diry, HRQL questionnires, urine nlysis, urine culture, PVR, (video-) urodynmic investigtion, no follow-up t ll) vry widely nd lrgely depend on the treting physicin. In ptients with high intrvesicl pressure nd/or vesico-ureterorenl reflux, ssessment of the tretment effect y (video-)urodynmic investigtion 1 3 months fter injections seems wrrnted. Although it is controversil whether ptients with recurrent OAB symptoms need follow-up urodynmics efore repet otulinum toxin injections, doing so should e considered, especilly considering tht the tretment is still unlicensed in most countries. FROM SURGEON TO SURGEON Botulinum toxin injections into the detrusor is truly minimlly invsive, highly effective procedure for treting refrctory OAB; usully performed in n outptient setting. The most relevnt dverse event is incresed PVR with the potentil need for ctheteristion. Importntly, CISC fter otulinum toxin tretment does not impir HRQL in ppropritely informed nd selected ptients [9 ], emphsizing the significnce of n pproprite informed consent procedure [10 ]. Ptients with spinl cord injury ove T6 re prone to utonomic dysreflexi, potentilly life-thretening compliction; so tht pproprite nesthesi of the ldder mucos hs to e ensured nd continuous crdiovsculr monitoring s well s nesthesiologicl stnd-y hs een recommended. Using the previously mentioned ultrfine single-use injection needles, intrdetrusor otulinum toxin injections cn e sfely performed under orl nticogultion nd/or ntipltelet tretment. The effect of otulinum toxin my e potentited y neuromusculr lockers nd minoglycoside ntiiotics so tht cution is dvised if such sustnces re used in comintion. REFERENCES 1 Arms P, Crdozo L, Fll M et l. The stndrdistion of terminology of lower urinry trct function: report from the Stndrdistion Su-committee of the Interntionl Continence Society. Neurourol Urodyn 2002 ; 21 : Klotz T, Bruggenjurgen B, Burkrt M, Resch A. The economic costs of overctive ldder in Germny. Eur Urol 2007 ; 51 : Schurch B, Stohrer M, Krmer G, Schmid DM, Gul G, Huri D. Botulinum-A toxin for treting detrusor hyperreflexi in spinl cord injured ptients: new lterntive to nticholinergic drugs? Preliminry results. J Urol 2000 ; 164 : Schurch B, Schmid DM, Stohrer M. Tretment of neurogenic incontinence with otulinum toxin A. N Engl J Med 2000 ; 342 : Apostolidis A, Dsgupt P, Denys P et l. Recommendtions on the use of otulinum toxin in the tretment of lower urinry trct disorders nd pelvic floor dysfunctions: Europen consensus report. Eur Urol 2009 ; 55 : Mnger A, Andersson KE, Apostolidis A et l. Contemporry mngement of lower urinry trct disese with otulinum toxin A: systemtic review of Botox (OnotulinumtoxinA) nd Dysport (AootulinumtoxinA). Eur Urol 2 011, 60 : Apostolidis A, Dsgupt P, Fowler CJ. Proposed mechnism for the efficcy of injected otulinum toxin in the tretment of humn detrusor overctivity. Eur Urol 2006 ; 49 : Hrper M, Popt RB, Dsgupt R, Fowler CJ, Dsgupt P. A minimlly invsive technique for outptient locl nesthetic dministrtion of intrdetrusor otulinum toxin in intrctle detrusor overctivity. BJU Int 2003 ; 92 : Kessler TM, Khn S, Pnicker J, Roosen A, Elneil S, Fowler CJ. Clen intermittent self-ctheteriztion fter otulinum neurotoxin type A injections: short-term effect on qulity of life. Ostet Gynecol 2009 ; 113 : Ghulm AT, Kessler M, Bchmnn LM, Hller U, Kessler TM. Ptients stisfction with the preopertive informed consent procedure: multicenter questionnire survey in Switzerlnd. Myo Clin Proc 2006 ; 81 : Correspondence: Jens Wöllner, Neuro- Urology, Spinl Cord Injury Center nd Reserch, University of Z ü rich, Blgrist University Hospitl, Forchstrsse 340, 8008 Zürich, Switzerlnd. e-mil: jwoellner@prl.lgrist.ch Arevitions : OAB, overctive ldder syndrome ; HRQL, helth-relted qulity of life ; PVR, postvoid residul urine volume ; CISC, clen intermittent self-ctheteristion