Dr. Amita Jain Consultant UrogynaecologistMedanta Institute of Kidney & Urology Medanta -The MedicityGurgaon, Haryana -122001, INDIA

Irreversible binding to the presynaptic membrane, producing a long-lasting paralytic effect.

Action dose- and site-specific, may take 24–48 hrs to exert its effects.

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Neuropathic bladder conditions◦ Detrusor overactivity

◦ Detrusor sphincter dysenergia

Bladder overactivity Painful bladder syndrome Pelvic pain Outflow obstruction symptoms Urinary retention

Intradetrusor injection of BTx was approved in 2011 by FDA for neurogenic detrusor overactivity only, but the off-label use is increasingly common.

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9 ½ Years girlK/C of Langerhan’s Histocytosis ( on & off steroids)PRESENTING COMPLAINTS (March 2009) Recurrent UTI Nocturnal Enuresis Daytime incontinence Difficulty in passing urinePAST H/O Gross haematuria in 2009 (USG KUB / CECT - mild diffuse thickening of

bladder wall ?Cystitis) CPE +urethral dilatation in 2010 (DMSA/ DRCG/KFT – WNL) Protenuria suggestive of ? Ig A Nephropathy/ Nephrotic SyndromePHYSICAL EXAMINATION Normal

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Micturating cystourethrogram (2010)- no reflux, no urethral obstruction

MRI Spine - normal

USG KUB - B/L mild HUN, persisting post void Thickened & irregular bladder wall PVR 126 cc

Failed trial of antimuscarinics & alpha blockers, biofeedback and other conservative management.

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Sensation Bladder filling

Pdet

First sensation

21 cc -2 cmH2O

First desire 48 cc 29 cmH2O

Normal desire

70 cc 43 cmH2O

Strong desire 91 cc 159 cmH2O

Max cyst capacity

91 cc 158 cmH2O

Total bladder capacity 180 cc

Voided volume 71 cc

Peak flow rate 3 ml/s

Pdet at peak flow 8 cmH2O

Average flow rate 3 ml/s

Residual Urine 109 ml

Opening Pdet 12 cmH2O

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Refractory idiopathic detrusor overactivity with superimposed dysfunctional voiding (non-neuropathic bladder-sphincter dysfunction )

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Sensation Bladder filling

Pdet

First sensation

42 cc 7 cmH2O

First desire 84 cc 14 cmH2O

Normal desire 88 cc 16 cmH2O

Strong desire 110 cc 32 cmH2O

Max cyst capacity

110 cc 33 cmH2O

Total bladder capacity 110 cc

Voided volume 73 cc

Peak flow rate 6 ml/s

Pdet at peak flow 33 cmH2O

Average flow rate 3 ml/s

Residual Urine 37 ml

Opening Pdet 24 cmH2O

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48 years librarianK/C of Interstitial Cystitis Dx on Cystoscopy + bladder biopsy (2/8/10) PRESENTING COMPLAINTS (May 2011) Severe dysuria Frequent urination Feeling of incomplete emptying of bladder Poor flowsPAST H/O Urethral dilatation in 2000 Failed conservative ( lifestyle & diet modification), medical

management (Amitryptalline/PMSO) and Intravesical instillation therapies

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Sensation Bladder filling

Pdet

First sensation 59 cc 2 cmH2O

First desire 65 cc 2 cmH2O

Normal desire 79 cc 2 cmH2O

Strong desire 88 cc 3 cmH2O

Max cyst capacity

104 cc 5 cmH2O

Total bladder capacity 106 cc

Voided volume 55 cc

Peak flow rate 3 ml/s

Pdet at peak flow 19 cmH2O

Average flow rate 2 ml/s

Residual Urine 51 ml

Opening Pdet 15 cmH2O

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Painful bladder Syndrome/IC(hypersensitive low capacity bladder)

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200 units diluted with 20mls of normal saline

Given as 1 ml injections at 20 different sites including trigone*

Fig. 1. Injection technique for BoNT into the overactive bladderDae Kyung Kim et al Urol Clin N Am 33 (2006) 503-510

*Kuo HC (2011) Bladder base/trigone injection is safe and as effective as bladder body injection of onabotulinumtoxinA for idiopathic detrusor overactivity refractory to antimuscarinics. Neurourol Urodyn 30:1242–1248*Pinto R et al (2010) Trigonal injection of botulinum toxin A in patients with refractory bladder pain syndrome/interstitial cystitis. Eur Urol. Sep;58(3):360-5

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Minor effects (Karsenty et al, 2008)◦ most frequent◦ injection site pain◦ procedure-related urinary tract infection◦ mild hematuria◦ Increase in PVR Severe effects (Systemic)◦ Very rare◦ Drug reaction - rash of a flu- like illness◦ Nausea, vomitting◦ dysphagia, diplopia, blurred vision◦ Mouth & respiratory weakness◦ periheral muscle weakness Contraindications◦ pre-existing neuromuscular conditions

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Linda Brubaker et al (2012) Treatment satisfaction and goal attainment with onabotulinumtoxinA in patients with incontinence due to idiopathic OAB Int Urogynecol J 23:1017–1025

Denys P et al (2012) Efficacy and Safety of Low Doses of OnabotulinumtoxinA for the Treatment of Refractory Idiopathic Overactive Bladder: A Multicentre, Double-Blind, Randomised, Placebo-Controlled Dose-Ranging Study. Eur Urol 61:520–529

Rovner E et al (2011) Urodynamic results and clinical outcomes with intradetrusor injections of onabotulinumtoxin A in a randomized, placebo-controlled dose-finding study in idiopathic overactive bladder. Neurourol Urodyn 30:556–562

Duthie JB et al (2011) Botulinum toxin injections for adults with overactive bladder syndrome. Cochrane Database Syst Rev (12):CD005493

Dmochowski R et al (2010) Efficacy and safety of onabotulinumtoxinA for idiopathic overactive bladder: a double-blind, placebo controlled, randomized, dose ranging trial. J Urol 184:2416–2422

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Shiu-Dong Chung et al (2012) Intravesical OnabotulinumtoxinA Injections for Refractory Painful Bladder Syndrome. Pain Physician; 15:197-202 • ISSN 1533-3159

Giannantoni A et al (2008) Botulinum A toxin intravesical injection in patients with painful bladder syndrome: 1-year followup. J Urol ; 179:1031- 1034.

Giannantoni A et al(2006) Botulinum A toxin intravesical injections in the treatment of painful bladder syndrome: A pilot study. Eur Urol ; 49:704-709.

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No universally accepted dose and technique.

Exact targeted depth of injection remains controversial.

Promising alternative option for varied indications in future.

Thanks

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Dr. Amita JainUrogynaecology Clinic

12th Floor, OPD Wing,Medanta -The Medicity

Gurgaon, Haryana -122001, INDIATel: +91 124 4141 414 info@medanta.org www.medanta.org

MOB. +91-9871136110 http://www.urogynecologistindia.in/

http://amitajainurogynaecolgist.blogspot.in/http://www.linkedin.com/mbox?displayMBoxItem=&itemID=I225857003_75

Medanta Institute of Kidney & Urology