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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 26  |  Issue : 2  |  Page : 180-183

Intravesical oxybutynin – A better option to treat catheter-related bladder discomfort?


Division of Urology, Lourdes Institute of Nephro-Urology, Lourdes Hospital, Kochi, Kerala, India

Date of Submission03-Aug-2020
Date of Decision11-Aug-2020
Date of Acceptance14-Oct-2020
Date of Web Publication07-Nov-2020

Correspondence Address:
Dr. H Krishna Moorthy
Division of Urology, Lourdes Institute of Nephro.Urology, Lourdes Hospital, Kochi - 682 012, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ksj.ksj_19_20

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  Abstract 


Introduction: Catheter-related bladder discomfort (CRBD) is a distressing symptom due to bladder spasm occurring in patients who are on catheter. This study was conducted to evaluate the efficacy of intravesical Oxybutynin as an alternate to the existing treatment for the management of CRBD. Materials and Methods: Two hundred and thirty four patients requiring bladder catheterization for >48 h following various surgeries were randomized into three groups of 78 each, once they developed CRBD. Group OO (Oxybutynin) received oral oxybutynin 5 thrice a day, Group OS (Solifenacin) received oral Solifenacin 10 mg once a day and Group OI (intravesical Oxybutynin) received Oxybutynin 5 mg dissolved in 30 ml normal saline instilled intravesically. The bladder discomfort was assessed according to visual analogue scale at 1, 6 and 24 h after drugs administration. The relief in CRBD and the side effects of the drugs were compared. Results: Out of 234 patients, relief of CRBD observed with intravesical oxybutynin was higher (87%) as compared to oral Oxybutynin and oral Solifenacin (66.3% and 74.3%, respectively; P < 0.05). OO group had maximum side effects and intravesical group had least side effects. Conclusions: Intravesical Oxybutynin therapy is a better option for the management of CRBD with minimal side effects.

Keywords: Catheter related bladder discomfort, intravesical oxybutynin, solifenacin


How to cite this article:
Bansal D, Pillai BS, Sam MP, Moorthy H K. Intravesical oxybutynin – A better option to treat catheter-related bladder discomfort?. Kerala Surg J 2020;26:180-3

How to cite this URL:
Bansal D, Pillai BS, Sam MP, Moorthy H K. Intravesical oxybutynin – A better option to treat catheter-related bladder discomfort?. Kerala Surg J [serial online] 2020 [cited 2020 Nov 26];26:180-3. Available from: http://www.keralasurgj.com/text.asp?2020/26/2/180/300227




  Introduction Top


After surgical procedures, many patients require urinary bladder catheterisation for bladder drainage. However, most of these patients on indwelling catheter for >48 h complain of catheter-related bladder discomfort (CRBD - an urge to void or discomfort in the suprapubic region with peri-catheter leakage of urine) due to the irritation of the catheter causing bladder spasms.[1] These symptoms are similar to symptoms of overactive bladder (OAB).[2] Certain Muscarinic-receptor antagonists that have been used successfully in the management of OAB were also reported to reduce CRBD.[3] However, the adverse events of muscarinic receptor antagonists (dry mouth, constipation, dysuria and dyspepsia) are often troublesome.[4] Although oral Oxybutynin and Solifenacin are commonly used agents having variable efficacy in the treatment of OAB, only very limited data are available on their relative efficacy in CRBD.[5],[6],[7] There have been no studies on the effect of intravesical Oxybutynin in the treatment of CRBD. This study was therefore conducted to evaluate and compare the efficacy of oral Oxybutynin, oral Solifenacin and intravesically administered Oxybutynin in the treatment of CRBD.


  Materials and Methods Top


The prospective study was conducted after approval from the Institute's Ethics Committee and obtaining written informed consent from the patients undergoing the study.

Two hundred and thirty four patients (37–86 year), of either sex, undergoing elective urological surgery for various indications, requiring catheter drainage of the urinary bladder for >48 h and who experienced CRBD were included in the study. Patients with a history of neurogenic bladder, patients with existing confirmed urinary tract infection (UTI) and patients with a history of surgeries performed on urinary bladder were excluded from the study. Patients with the ureteral stent in situ were also excluded from the study.

The incidence of urinary CRBD has been reported to be 55%.[8] Assuming that this incidence would reduce to 30% after therapy and with power 80% (b = 0.80) and the level of significance 5% (a = 0.05), we calculated 78 patients in each group required for results to be statistically significant.

All the patients in the study had Foley's urethral catheter of size 18–20 Fr (Rusch) with the balloon inflated with 20–30 ml distilled water. In all cases, Lignocaine 2% jelly (a water-based lubricating gel) was used for the lubrication of the catheter before insertion. There was no traction given on the catheter, and it was always left for continuous drainage into an external uro-bag.

Patients who complained of CRBD were randomly assigned into three groups by computer-generated random numbers. Patients belonging to Group OO received oral oxybutynin 5 mg three times a day, Group OS received oral Solifenacin 10 mg once daily and Group OI received intravesical Oxybutynin 5 mg dissolved in 30 ml normal saline instilled into the urinary bladder three times a day and catheter clamped for 30 min after instillation of drug.

Assessment of bladder discomfort (urge to pass urine or discomfort in the suprapubic region) according to visual analogue scale was carried out by another observer in all cases at 1, 6 and 24 h after administration of drugs, and graded as mild (1–4), moderate (5–7) and severe (8–10). Post-drug administration adverse effects such as nausea and vomiting (dyspepsia), dry mouth, constipation, drowsiness and UTI were noted in these patients till the day of catheter removal.

Differences in the age and weight among the groups were compared by one-way ANOVA test whereas, the incidence of bladder discomfort, the severity of bladder discomfort (mild, moderate and severe) and side-effects among the groups were analysed using Chi-square test and ANOVA test. MedCalc statistical software version 14.8.1 (MedCalc software bvba, Ostend, Belgium) was used for the statistical analysis of data.


  Results Top


There were no significant differences in the patient characteristics, including age, gender and body weight, between all three groups [Table 1].
Table 1: Patients characteristics

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It was observed that out of 234 patients, relief of CRBD was seen in intravesical Oxybutynin in 68/78 patients (87.1%) as compared to OO and OS groups; 51/78 (66.3%) and 58/78 (74.3%), respectively (P < 0.05).

The incidences of severe bladder discomfort at 1 h, 6 h and 24 h were higher in the oral Oxybutynin group (8.9%, 7.6% and 3.8%, respectively) and least in the intravesical Oxybutynin group (3.8%, 2.5% and 0%, respectively) (P < 0.05). The reduction in the severity of CRBD was higher in the IO group as compared to the other two groups [Table 2].
Table 2: Relief of catheter-related bladder discomfort in different study groups (n=78 in all groups)

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[Table 3] shows the incidence of various side effects of drugs in the three groups observed till the day of catheter removal. IO group had the least overall side effects compared to the other 2 groups studied, while OO group had the maximum incidence of side effects (P < 0.05). Urinary tract infection was noted in the IO group in a small number of patients (3.8%).
Table 3: Incidence of side-effects

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  Discussion Top


CRBD is a common clinical entity in patients requiring prolonged bladder catheter drainage, probably due to muscarinic receptor stimulation. Antimuscarinic agents used to prevent/treat CRBD are normally administered orally and associated with significant side effects.

The succinate salt of Solifenacin, a tertiary amine with anticholinergic properties, is used for symptomatic treatment of the bladder spasm. Solifenacin peak plasma concentrations of 24 ng/ml are reached 3–4 h after long-term oral administration of a 5 mg Solifenacin. Solifenacin is 93%–96% plasma protein-bound, and probably crosses the blood–brain barrier.[9]

Oxybutynin is a tertiary amine and its efficacy is attributed to a combination of anticholinergic, antispasmodic, local anaesthetic effect. It is readily absorbed from the gastrointestinal tract, with the highest concentration at 1–2 h after oral administration, followed by a rapid decrease. Oral Oxybutynin passes into the liver through the portal circulation immediately after being absorbed, with rapid hepatic metabolism by liver microsomes to oxidation products, mainly N-desethyl-Oxybutynin (NSDO).[10]

While it is true that oral Oxybutynin chloride is commonly used for the treatment of bladder related symptoms, the high incidence of systemic side effects is likely to compromise its compliance, resulting in dose reductions or even discontinuation of treatment. The intravesical administration of Oxybutynin was introduced as an alternative in managing the dysfunctional bladder with better tolerance and efficacy.[11]

In 1989, Brendler et al. first reported the treatment of intravesical Oxybutynin chloride for OAB.[12] By dissolving 5 mg Oxybutynin in 30 ml saline for administration twice daily, Brendler was able to produce a subjective improvement in 91% of the patients in his study. The mechanism of action of intravesical Oxybutynin may involve a direct effect on the M3 receptors in the detrusor, a topical anesthetic effect, or an indirect effect of absorbed Oxybutynin and its metabolites.[13]

After intravesical administration, Oxybutynin gets readily absorbed from the bladder, but due to a reduced first-pass metabolism, the parent drug/metabolite (NDO) ratio is much higher. The reduced formation of metabolite NDO, may explain the clinically relevant reduced side effects with intravesical compared with oral Oxybutynin therapy.[14]

Herschorn et al. in their study of comparison of Solifenacin versus Oxybutynin reported the overall incidence of adverse events as 70% in the Oxybutynin group and 59% in the Solifenacin group.[15] Significantly fewer patients on Solifenacin reported dry mouth as compared to the Oxybutynin. We observed similar result of less overall side effect including dry mouth with oral Solifenacin as compared to oral Oxybutynin. Bonney et al. investigated topical effects of intravesical Oxybutynin and found no evidence of drug-related mucosal or bladder wall change.[16]

We also observed that intravesical Oxybutynin was more effective in relieving CRBD in our study with reduced side effects. Only 10% of patients developed anticholinergic side effects after intravesical Oxybutynin and these results are supported by studies done by Connor et al.[17] and Painter et al.,[18] which also showed 15.4% and 7.2% evidence of anticholinergic side effect after intravesical Oxybutynin, respectively.

3.8% of patients developed UTI after intravesical instillation of Oxybutynin, which was similar to the study of Kasabian et al.,[19] which showed 9.1% incidence of UTI in his study.


  Conclusions Top


Intravesical Oxybutynin instillation therapy is a better option for the management of CRBD with better efficacy then oral administration and with minimal systemic side effects. The intravesical route may also be preferred in patients who do not respond to oral medication or have unacceptable side effects, which may result in withdrawal of treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Yates V, Tanner J, Crossley A. Bladder spasm following transurethral surgery. Br J Perioper Nurs 2004;14:259-60, 262-4.  Back to cited text no. 1
    
2.
Freeman R, Hill S, Millard R, Slack M, Sutherst J, Tolterodine Study Group. Reduced perception of urgency in treatment of overactive bladder with extended-release tolterodine. Obstet Gynecol 2003;102:605-11.  Back to cited text no. 2
    
3.
Chapple CR, Van Kerrebroeck PE, Jünemann KP, Wang JT, Brodsky M. Comparison of fesoterodine and tolterodine in patients with overactive bladder. BJU Int 2008;102:1128-32.  Back to cited text no. 3
    
4.
Andersson KE, Chapple CR. Oxybutynin and the overactive bladder. World J Urol 2001;19:319-23.  Back to cited text no. 4
    
5.
Agarwal A, Dhiraaj S, Singhal V, Kapoor R, Tandon M. Comparison of efficacy of oxybutynin and tolterodine for prevention of catheter related bladder discomfort: A prospective, randomized, placebo-controlled, double-blind study. Br J Anaesth 2006;96:377-80.  Back to cited text no. 5
    
6.
Moodie P. PHARMAC responds on tolterodine for overactive bladder. N Z Med J 2005;119:U1871.  Back to cited text no. 6
    
7.
Zhang N, Zhang P, Zhang X, Yang Y. The efficacy of resiniferatoxin in prevention of catheter related bladder discomfort in patients after TURP-A pilot, randomized, open study. Transl Androl Urol 2012;1:14-8.  Back to cited text no. 7
    
8.
Agarwal A, Raza M, Singhal V, Dhiraaj S, Kapoor R, Srivastava A, et al. The efficacy of tolterodine for prevention of catheter-related bladder discomfort: A prospective, randomized, placebo-controlled, double-blind study. Anesth Analg 2005;101:1065-7, table of contents.  Back to cited text no. 8
    
9.
Doroshyenko O, Fuhr U. Clinical pharmacokinetics and pharmacodynamics of solifenacin. Clin Pharmacokinet 2009;48:281-302.  Back to cited text no. 9
    
10.
Massad CA, Kogan BA, Trigo-Rocha FE. The pharmacokinetics of intravesical and oral oxybutynin chloride. J Urol 1992;148:595-7.  Back to cited text no. 10
    
11.
Kaefer M, Pabby A, Kelly M, Darbey M, Bauer SB. Improved bladder function after prophylactic treatment of the high risk neurogenic bladder in newborns with myelomentingocele. J Urol 1999;162:1068-71.  Back to cited text no. 11
    
12.
Brendler CB, Radebaugh LC, Mohler JL. Topical oxybutynin chloride for relaxation of dysfunctional bladders. J Urol 1989;141:1350-2.  Back to cited text no. 12
    
13.
Di Stasi SM, Giannantoni A, Navarra P, Capelli G, Storti L, Porena M, et al. Intravesical oxybutynin: Mode of action assessed by passive diffusion and electromotive administration with pharmacokinetics of oxybutynin and N-desethyl oxybutynin. J Urol 2001;166:2232-6.  Back to cited text no. 13
    
14.
Lehtoranta K, Tainio H, Lukkari-Lax E, Hakonen T, Tammela TL. Pharmacokinetics, efficacy, and safety of intravesical formulation of oxybutynin in patients with detrusor overactivity. Scand J Urol Nephrol 2002;36:18-24.  Back to cited text no. 14
    
15.
Herschorn S, Stothers L, Carlson K, Egerdie B, Gajewski JB, Pommerville P, et al. Tolerability of 5 mg solifenacin once daily versus 5 mg oxybutynin immediate release 3 times daily: Results of the VECTOR trial. J Urol 2010;183:1892-8.  Back to cited text no. 15
    
16.
Bonney WW, Robinson RA, Theobald RJ Jr. Topical effect of intravesical oxybutynin. J Urol 1993;150:1522-5.  Back to cited text no. 16
    
17.
Connor JP, Betrus G, Fleming P, Perlmutter AD, Reitelman C. Early cystometrograms can predict the response to intravesical instillation of oxybutynin chloride in myelomeningocele patients. J Urol 1994;151:1045-7.  Back to cited text no. 17
    
18.
Painter KA, Vates TS, Bukowski TP, Fleming P, Freedman AL, Smith CA, et al. Long-term intravesical oxybutynin chloride therapy in children with myelodysplasia. J Urol 1996;156:1459-62.  Back to cited text no. 18
    
19.
Kasabian NG, Vlachiotis JD, Lais A, Klumpp B, Kelly MD, Siroky MB, et al. The use of intravesical oxybutynin chloride in patients with detrusor hypertonicity and detrusor hyperreflexia. J Urol 1994;151:944-5.  Back to cited text no. 19
    



 
 
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