Skip to main content
Top
Published in: Current Bladder Dysfunction Reports 4/2016

01-12-2016 | Neurogenic Bladder (C Powell, Section Editor)

Does the Technique or Pattern Matter When Injecting OnabotulinumtoxinA?

Authors: Michael A. Avallone, Michael L. Guralnick, R. Corey O’Connor

Published in: Current Bladder Dysfunction Reports | Issue 4/2016

Login to get access

Abstract

OnabotulinumtoxinA (BTX-A) is a treatment option for patients with neurogenic detrusor overactivity (NDO) or idiopathic overactive bladder (OAB) inadequately controlled with or intolerant to oral medications. The currently approved dosing is 100 U for OAB and 200 U for NDO which is commonly injected into the detrusor muscle via 20–30 trigone-sparing sites. Growing evidence suggests that the efficacy of BTX-A may be maintained with fewer injection sites, varying injection depth, and differing injection locations. This review focuses on the recent literature regarding various BTX-A injection techniques for the treatment of NDO and OAB.
Literature
1.
go back to reference Dykstra DD, Sidi AA. Treatment of detrusor-sphincter dyssynergia with botulinum A toxin: a double-blind study. Arch Phys Med Rehabil. 1990;71(1):24–6.PubMed Dykstra DD, Sidi AA. Treatment of detrusor-sphincter dyssynergia with botulinum A toxin: a double-blind study. Arch Phys Med Rehabil. 1990;71(1):24–6.PubMed
2.
go back to reference Schurch B, Stöhrer M, Kramer G, Schmid DM, Gaul G, Hauri D. Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol. 2000;164(3 Pt 1):692–7.CrossRefPubMed Schurch B, Stöhrer M, Kramer G, Schmid DM, Gaul G, Hauri D. Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results. J Urol. 2000;164(3 Pt 1):692–7.CrossRefPubMed
3.
go back to reference Cruz F, Herschorn S, Aliotta P, et al. Efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: a randomised, double-blind, placebo-controlled trial. Eur Urol. 2011;60(4):742–50.CrossRefPubMed Cruz F, Herschorn S, Aliotta P, et al. Efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: a randomised, double-blind, placebo-controlled trial. Eur Urol. 2011;60(4):742–50.CrossRefPubMed
4.
go back to reference Ginsberg D, Gousse A, Keppenne V, et al. Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. J Urol. 2012;187(6):2131–9.CrossRefPubMed Ginsberg D, Gousse A, Keppenne V, et al. Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. J Urol. 2012;187(6):2131–9.CrossRefPubMed
5.••
go back to reference Nitti VW, Dmochowski R, Herschorn S, et al. OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial. J Urol. 2013;189(6):2186–93. First large multicenter placebo controlled trial of BTX-A in anticholinergic refractory OAB patients with urge urinary incontinence and urinary frequency. 100u BTX-A cystoscopically injected into the detrusor at 20 sites in a grid-like pattern significantly decreased frequency of incontinent episodes over placebo, improved overactive bladder symptoms and improved quality of life. Nitti VW, Dmochowski R, Herschorn S, et al. OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial. J Urol. 2013;189(6):2186–93. First large multicenter placebo controlled trial of BTX-A in anticholinergic refractory OAB patients with urge urinary incontinence and urinary frequency. 100u BTX-A cystoscopically injected into the detrusor at 20 sites in a grid-like pattern significantly decreased frequency of incontinent episodes over placebo, improved overactive bladder symptoms and improved quality of life.
6.••
go back to reference Chapple C, Sievert KD, MacDiarmid S, et al. OnabotulinumtoxinA 100 U significantly improves all idiopathic overactive bladder symptoms and quality of life in patients with overactive bladder and urinary incontinence: a randomised, double-blind, placebo-controlled trial. Eur Urol. 2013;64(2):249–56. Pivotal multicenter placebo controlled trial of BTX-A in anticholinergic refractory OAB patients with urge urinary incontinence and urinary frequency. 100u BTX-A cystoscopically injected into the detrusor at 20 sites in a grid-like pattern significantly decreased frequency of incontinent episodes over placebo, improved overactive bladder symptoms and improved quality of life. Chapple C, Sievert KD, MacDiarmid S, et al. OnabotulinumtoxinA 100 U significantly improves all idiopathic overactive bladder symptoms and quality of life in patients with overactive bladder and urinary incontinence: a randomised, double-blind, placebo-controlled trial. Eur Urol. 2013;64(2):249–56. Pivotal multicenter placebo controlled trial of BTX-A in anticholinergic refractory OAB patients with urge urinary incontinence and urinary frequency. 100u BTX-A cystoscopically injected into the detrusor at 20 sites in a grid-like pattern significantly decreased frequency of incontinent episodes over placebo, improved overactive bladder symptoms and improved quality of life.
7.
go back to reference Cruz F. Targets for botulinum toxin in the lower urinary tract. Neurourol Urodyn. 2014;33(1):31–8.CrossRefPubMed Cruz F. Targets for botulinum toxin in the lower urinary tract. Neurourol Urodyn. 2014;33(1):31–8.CrossRefPubMed
8.
go back to reference Datta SN, Roosen A, Pullen A, et al. Immunohistochemical expression of muscarinic receptors in the urothelium and suburothelium of neurogenic and idiopathic overactive human bladders, and changes with botulinum neurotoxin administration. J Urol. 2010;184(6):2578–85.CrossRefPubMed Datta SN, Roosen A, Pullen A, et al. Immunohistochemical expression of muscarinic receptors in the urothelium and suburothelium of neurogenic and idiopathic overactive human bladders, and changes with botulinum neurotoxin administration. J Urol. 2010;184(6):2578–85.CrossRefPubMed
9.
go back to reference Apostolidis A, Dasgupta P, Fowler CJ. Proposed mechanism for the efficacy of injected botulinum toxin in the treatment of human detrusor overactivity. Eur Urol. 2006;49(4):644–50.CrossRefPubMed Apostolidis A, Dasgupta P, Fowler CJ. Proposed mechanism for the efficacy of injected botulinum toxin in the treatment of human detrusor overactivity. Eur Urol. 2006;49(4):644–50.CrossRefPubMed
10.
go back to reference Coelho A, Cruz F, Cruz CD, Avelino A. Effect of onabotulinumtoxinA on intramural parasympathetic ganglia: an experimental study in the guinea pig bladder. J Urol. 2012;187(3):1121–6.CrossRefPubMed Coelho A, Cruz F, Cruz CD, Avelino A. Effect of onabotulinumtoxinA on intramural parasympathetic ganglia: an experimental study in the guinea pig bladder. J Urol. 2012;187(3):1121–6.CrossRefPubMed
11.
go back to reference Rovner E, Kennelly M, Schulte-Baukloh H, Zhou J, Haag-Molkenteller C, Dasgupta P. Urodynamic results and clinical outcomes with intradetrusor injections of onabotulinumtoxinA in a randomized, placebo-controlled dose-finding study in idiopathic overactive bladder. Neurourol Urodyn. 2011;30(4):556–62.CrossRefPubMed Rovner E, Kennelly M, Schulte-Baukloh H, Zhou J, Haag-Molkenteller C, Dasgupta P. Urodynamic results and clinical outcomes with intradetrusor injections of onabotulinumtoxinA in a randomized, placebo-controlled dose-finding study in idiopathic overactive bladder. Neurourol Urodyn. 2011;30(4):556–62.CrossRefPubMed
12.
go back to reference Denys P, Le Normand L, Ghout I, et al. 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. 2012;61(3):520–9.CrossRefPubMed Denys P, Le Normand L, Ghout I, et al. 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. 2012;61(3):520–9.CrossRefPubMed
13.••
go back to reference Chen YC, Kuo HC. The therapeutic effects of repeated detrusor injections between 200 or 300 units of onabotulinumtoxinA in chronic spinal cord injured patients. Neurourol Urodyn. 2014;33(1):129–34. Anticholinergic refractory SCI patients with NDO were randomized to 200u or 300u every 6 months with the study endpoint being 6 months after the second treatment. 72 patients were enrolled and there were improvements within each group in frequency of incontinent episodes and quality of life but no differences between the two doses. Urodynamic parameters were also improved within each group but there was significantly greater improvement in DO in the 300u group. Chen YC, Kuo HC. The therapeutic effects of repeated detrusor injections between 200 or 300 units of onabotulinumtoxinA in chronic spinal cord injured patients. Neurourol Urodyn. 2014;33(1):129–34. Anticholinergic refractory SCI patients with NDO were randomized to 200u or 300u every 6 months with the study endpoint being 6 months after the second treatment. 72 patients were enrolled and there were improvements within each group in frequency of incontinent episodes and quality of life but no differences between the two doses. Urodynamic parameters were also improved within each group but there was significantly greater improvement in DO in the 300u group.
14.
go back to reference Dmochowski R, Chapple C, Nitti VW, et al. Efficacy and safety of onabotulinumtoxinA for idiopathic overactive bladder: a double-blind, placebo controlled, randomized, dose ranging trial. J Urol. 2010;184(6):2416–22.CrossRefPubMed Dmochowski R, Chapple C, Nitti VW, et al. Efficacy and safety of onabotulinumtoxinA for idiopathic overactive bladder: a double-blind, placebo controlled, randomized, dose ranging trial. J Urol. 2010;184(6):2416–22.CrossRefPubMed
15.
go back to reference Coelho A, Cruz F, Cruz CD, Avelino A. Spread of onabotulinumtoxinA after bladder injection. Experimental study using the distribution of cleaved SNAP-25 as the marker of the toxin action. Eur Urol. 2012;61(6):1178–84.CrossRefPubMed Coelho A, Cruz F, Cruz CD, Avelino A. Spread of onabotulinumtoxinA after bladder injection. Experimental study using the distribution of cleaved SNAP-25 as the marker of the toxin action. Eur Urol. 2012;61(6):1178–84.CrossRefPubMed
16.
go back to reference Kim HS, Hwang JH, Jeong ST, et al. Effect of muscle activity and botulinum toxin dilution volume on muscle paralysis. Dev Med Child Neurol. 2003;45(3):200–6.CrossRefPubMed Kim HS, Hwang JH, Jeong ST, et al. Effect of muscle activity and botulinum toxin dilution volume on muscle paralysis. Dev Med Child Neurol. 2003;45(3):200–6.CrossRefPubMed
17.
go back to reference Ramirez-Castaneda J, Jankovic J, Comella C, Dashtipour K, Fernandez HH, Mari Z. Diffusion, spread, and migration of botulinum toxin. Mov Disord. 2013;28(13):1775–83.CrossRefPubMed Ramirez-Castaneda J, Jankovic J, Comella C, Dashtipour K, Fernandez HH, Mari Z. Diffusion, spread, and migration of botulinum toxin. Mov Disord. 2013;28(13):1775–83.CrossRefPubMed
18.
go back to reference Mehnert U, Boy S, Schmid M, et al. A morphological evaluation of botulinum neurotoxin A injections into the detrusor muscle using magnetic resonance imaging. World J Urol. 2009;27(3):397–403.CrossRefPubMed Mehnert U, Boy S, Schmid M, et al. A morphological evaluation of botulinum neurotoxin A injections into the detrusor muscle using magnetic resonance imaging. World J Urol. 2009;27(3):397–403.CrossRefPubMed
19.
go back to reference Oliveira R, Coelho A, Charrua A, Avelino A, Cruz F. OnabotulinumtoxinA versus abobotulinumtoxinA: potency and diffusion capacity on the bladder wall. Abstract presented at the annual meeting of the American Urological Association, New Orleans, LA; 2015. Oliveira R, Coelho A, Charrua A, Avelino A, Cruz F. OnabotulinumtoxinA versus abobotulinumtoxinA: potency and diffusion capacity on the bladder wall. Abstract presented at the annual meeting of the American Urological Association, New Orleans, LA; 2015.
20.•
go back to reference Liao CH, Chen SF, Kuo HC. Different number of intravesical onabotulinumtoxinA injections for patients with refractory detrusor overactivity do not affect treatment outcome: a prospective randomized comparative study. Neurourol Urodyn; 2015. Anticholinergic refractory OAB patients with urgency or urgency incontinence were randomized to receive 100u BTX-A via 10, 20, or 40 suburothelial injection sites. 67 patients were randomized and there were no differences in clinical outcomes evaluated by validated questionnaires, subjective success, voiding diary, urodynamic parameters or adverse events between the three groups. Liao CH, Chen SF, Kuo HC. Different number of intravesical onabotulinumtoxinA injections for patients with refractory detrusor overactivity do not affect treatment outcome: a prospective randomized comparative study. Neurourol Urodyn; 2015. Anticholinergic refractory OAB patients with urgency or urgency incontinence were randomized to receive 100u BTX-A via 10, 20, or 40 suburothelial injection sites. 67 patients were randomized and there were no differences in clinical outcomes evaluated by validated questionnaires, subjective success, voiding diary, urodynamic parameters or adverse events between the three groups.
21.
go back to reference Karsenty G BS, Reitz A. Botulinum toxin-A (BTA) in the treatment of neurogenic detrusor overactivity incontinence (NDOI)—a prospective randomized study to compare 30 vs. 10 injection sites (Abstract). Neurourol Urodyn; 2005. 547–8. Karsenty G BS, Reitz A. Botulinum toxin-A (BTA) in the treatment of neurogenic detrusor overactivity incontinence (NDOI)—a prospective randomized study to compare 30 vs. 10 injection sites (Abstract). Neurourol Urodyn; 2005. 547–8.
22.•
go back to reference Avallone MA, Sack BS, El-Arabi A, Guralnick ML, O’Connor RC. Less is more—a pilot study evaluating one to three intradetrusor sites for injection of OnabotulinumtoxinA for neurogenic and idiopathic detrusor overactivity. Neurourol Urodyn; 2016. Pilot study that evaluated the efficacy, safety and durability of treating 45 anticholinergic refractory NDO and OAB patients with 100-300u BTX-A in one to three intradetrusor injection sites. Clinical success, determined by ICIQ-SF improvement was 73% for all patients and 91% for NDO patients. Durability of clinical improvement and rates of adverse events were comparable to the standard injection technique. Avallone MA, Sack BS, El-Arabi A, Guralnick ML, O’Connor RC. Less is more—a pilot study evaluating one to three intradetrusor sites for injection of OnabotulinumtoxinA for neurogenic and idiopathic detrusor overactivity. Neurourol Urodyn; 2016. Pilot study that evaluated the efficacy, safety and durability of treating 45 anticholinergic refractory NDO and OAB patients with 100-300u BTX-A in one to three intradetrusor injection sites. Clinical success, determined by ICIQ-SF improvement was 73% for all patients and 91% for NDO patients. Durability of clinical improvement and rates of adverse events were comparable to the standard injection technique.
23.
go back to reference Dmochowski R, Sand PK. Botulinum toxin A in the overactive bladder: current status and future directions. BJU Int. 2007;99(2):247–62.CrossRefPubMed Dmochowski R, Sand PK. Botulinum toxin A in the overactive bladder: current status and future directions. BJU Int. 2007;99(2):247–62.CrossRefPubMed
24.
go back to reference Krhut J, Samal V, Nemec D, Zvara P. Intradetrusor versus suburothelial onabotulinumtoxinA injections for neurogenic detrusor overactivity: a pilot study. Spinal Cord. 2012;50(12):904–7.CrossRefPubMed Krhut J, Samal V, Nemec D, Zvara P. Intradetrusor versus suburothelial onabotulinumtoxinA injections for neurogenic detrusor overactivity: a pilot study. Spinal Cord. 2012;50(12):904–7.CrossRefPubMed
25.
go back to reference Šámal V, Mečl J, Šrám J. Submucosal administration of onabotulinumtoxinA in the treatment of neurogenic detrusor overactivity: pilot single-centre experience and comparison with standard injection into the detrusor. Urol Int. 2013;91(4):423–8.CrossRefPubMed Šámal V, Mečl J, Šrám J. Submucosal administration of onabotulinumtoxinA in the treatment of neurogenic detrusor overactivity: pilot single-centre experience and comparison with standard injection into the detrusor. Urol Int. 2013;91(4):423–8.CrossRefPubMed
26.
go back to reference Kuo HC. Comparison of effectiveness of detrusor, suburothelial and bladder base injections of botulinum toxin a for idiopathic detrusor overactivity. J Urol. 2007;178(4 Pt 1):1359–63.CrossRefPubMed Kuo HC. Comparison of effectiveness of detrusor, suburothelial and bladder base injections of botulinum toxin a for idiopathic detrusor overactivity. J Urol. 2007;178(4 Pt 1):1359–63.CrossRefPubMed
27.
go back to reference Mascarenhas F, Cocuzza M, Gomes CM, Leão N. Trigonal injection of botulinum toxin-A does not cause vesicoureteral reflux in neurogenic patients. Neurourol Urodyn. 2008;27(4):311–4.CrossRefPubMed Mascarenhas F, Cocuzza M, Gomes CM, Leão N. Trigonal injection of botulinum toxin-A does not cause vesicoureteral reflux in neurogenic patients. Neurourol Urodyn. 2008;27(4):311–4.CrossRefPubMed
28.
go back to reference Andersson KE, McCloskey KD. Lamina propria: the functional center of the bladder? Neurourol Urodyn. 2014;33(1):9–16.CrossRefPubMed Andersson KE, McCloskey KD. Lamina propria: the functional center of the bladder? Neurourol Urodyn. 2014;33(1):9–16.CrossRefPubMed
29.
go back to reference Lucioni A, Rapp DE, Gong EM, Fedunok P, Bales GT. Intravesical botulinum type A toxin injection in patients with overactive bladder: trigone versus trigone-sparing injection. Can J Urol. 2006;13(5):3291–5.PubMed Lucioni A, Rapp DE, Gong EM, Fedunok P, Bales GT. Intravesical botulinum type A toxin injection in patients with overactive bladder: trigone versus trigone-sparing injection. Can J Urol. 2006;13(5):3291–5.PubMed
30.
go back to reference Kuo HC. Bladder base/trigone injection is safe and as effective as bladder body injection of onabotulinumtoxinA for idiopathic detrusor overactivity refractory to antimuscarinics. Neurourol Urodyn. 2011;30(7):1242–8.PubMed Kuo HC. Bladder base/trigone injection is safe and as effective as bladder body injection of onabotulinumtoxinA for idiopathic detrusor overactivity refractory to antimuscarinics. Neurourol Urodyn. 2011;30(7):1242–8.PubMed
31.••
go back to reference Hui C, Keji X, Chonghe J, et al. Combined detrusor-trigone BTX-A injections for urinary incontinence secondary to neurogenic detrusor overactivity. Spinal Cord. 2016;54(1):46–50. Multicenter trial of anticholinergic refractory SCI patients with NDO and urinary incontinence. 96 patients were randomized to receive 200u BTX-A with either trigone sparing or trigone inclusion injection templates. The trigone inclusion group had significantly better improvement in QOL, number of incontinent episodes, complete continence, and urodynamic parameters at 12 weeks post treatment. No patients developed de novo vesicoureteral reflux. Hui C, Keji X, Chonghe J, et al. Combined detrusor-trigone BTX-A injections for urinary incontinence secondary to neurogenic detrusor overactivity. Spinal Cord. 2016;54(1):46–50. Multicenter trial of anticholinergic refractory SCI patients with NDO and urinary incontinence. 96 patients were randomized to receive 200u BTX-A with either trigone sparing or trigone inclusion injection templates. The trigone inclusion group had significantly better improvement in QOL, number of incontinent episodes, complete continence, and urodynamic parameters at 12 weeks post treatment. No patients developed de novo vesicoureteral reflux.
32.
go back to reference Abdel-Meguid TA. Botulinum toxin-A injections into neurogenic overactive bladder—to include or exclude the trigone? A prospective, randomized, controlled trial. J Urol. 2010;184(6):2423–8.CrossRefPubMed Abdel-Meguid TA. Botulinum toxin-A injections into neurogenic overactive bladder—to include or exclude the trigone? A prospective, randomized, controlled trial. J Urol. 2010;184(6):2423–8.CrossRefPubMed
33.••
go back to reference Davis NF, Burke JP, Redmond EJ, Elamin S, Brady CM, Flood HD. Trigonal versus extratrigonal botulinum toxin-A: a systematic review and meta-analysis of efficacy and adverse events. Int Urogynecol J. 2015;26(3):313–9. A systematic review and meta-analysis that reviewed the literature regarding impact of trigone inclusion when injecting BTX-A. Six studies describing 258 NDO and OAB patients. Davis NF, Burke JP, Redmond EJ, Elamin S, Brady CM, Flood HD. Trigonal versus extratrigonal botulinum toxin-A: a systematic review and meta-analysis of efficacy and adverse events. Int Urogynecol J. 2015;26(3):313–9. A systematic review and meta-analysis that reviewed the literature regarding impact of trigone inclusion when injecting BTX-A. Six studies describing 258 NDO and OAB patients.
Metadata
Title
Does the Technique or Pattern Matter When Injecting OnabotulinumtoxinA?
Authors
Michael A. Avallone
Michael L. Guralnick
R. Corey O’Connor
Publication date
01-12-2016
Publisher
Springer US
Published in
Current Bladder Dysfunction Reports / Issue 4/2016
Print ISSN: 1931-7212
Electronic ISSN: 1931-7220
DOI
https://doi.org/10.1007/s11884-016-0384-1

Other articles of this Issue 4/2016

Current Bladder Dysfunction Reports 4/2016 Go to the issue

Reconstructed Bladder Function & Dysfunction (M Kaufman, Section Editor)

Surgical and Metabolic Management of Urolithiasis Following Bladder Reconstruction

Reconstructed Bladder Function & Dysfunction (M Kaufman, Section Editor)

Post Prostatectomy Bladder Dysfunction: Where Are We Now?

Reconstructed Bladder Function & Dysfunction (M Kaufman, Section Editor)

Minimally Invasive Approaches to Continent Urinary Diversion

Neurogenic Bladder (C Powell, Section Editor)

Bladder Re-Innervation—State of the Art

Reconstructed Bladder Function & Dysfunction (M Kaufman, Section Editor)

Neurogenic Bowel Dysfunction in Patients with Neurogenic Bladder