Effect of Long Acting Anticholinergic on Nocturnal Incontinence After Radical Cystectomy and Orthotopic Neobladder. A Randomized Placebo-controlled Crossover Study

Introduction:

Radical cystectomy (RC) and urinary diversion remain the gold standard for treatment of muscle invasive bladder cancer.1 The optimal goal is to control the malignancy, preserve renal function and optimize health related quality of life. Decision of urinary diversion selection has been changed in the last three decades from non-continent diversion to orthotopic neobladder (ONB), to maintain voiding pattern closely similar to normal pattern and to improve the overall health related quality of life (HRQOL).2 However, the continence status after ONB is affected by many factors, such as patient's age, mental status, intact and innervated external urethral sphincter, the reservoir capacity and pressure, presence of infection and the completeness of voiding.3 The recovery of continence status takes from six to 12 months after the operation to achieve day time continence which is regained earlier than nocturnal continence which takes 12 to 24 months.3 The reported day time continence ranges from 85 to 90% and NI in most series ranges from 20 to 40%.4- 7 in women, the reported incidence of day time and NI ranged from 68 to 100% and 26 to 89%, respectively.8- 11 Nocturnal incontinence is a major problem that affect HRQOL . In a multicenter study, individuals with ONB and NI have lower HRQOL, 12 this is similar to our data on female patients with ONB.2 Nocturnal incontinence may be due to patient and pouch causes. Loss of afferent input from the Detrusor muscle to the central nervous system is thought to account for the worsening of nocturnal continence.13 In a study, done by El Bahnasawy et al, to evaluate the factors affecting the NI after RC and ONB; higher pressure, positive urine culture, large post voiding residual volume, decreased maximal urethral pressure, decreased flow rate and patient compliance are associated with higher incidence of NI. However, on multivariate analysis, only post voiding residual volumes, frequency, and maximal amplitude of uninhibited contractions remained significantly associated with NI.14 Fifty percent of women with NI after RC and ONB have had pouch hyperactivity on urodynamic evaluation.15 To optimize nocturnal continence, patients are recommended to avoid sleeping pills and alcohol in the evening, to void before going to sleep, and to set up an alarm to void at least once during the night. Also proper treatment of infection is recommended.3 Up to 25% of patients reported an improved nocturnal continence with the use of imipramine hydrochloride 25 mg at bedtime. 14,16In a prospective randomized crossover study comparing 20 male enuretic patients with ileal ONB receiving oxybutynin versus verapamil, both groups showed improved urodynamic parameters and nocturnal continence status in 70% and 55% of patients, respectively.17 Ali-El-Dein et al, reported that treatment of female patients, who have NI after RC and ONB, with anticholinergic drugs (tolterodine or oxybutynin chloride) has associated with improvement and cure of NI in 36% and 23%, respectively.15 These data confirmed the efficacy of the anticholinergic use in treatment of NI after RC and ONB.

In the current study, we will study the role of long acting anticholinergic (tolterodine 4 mg) at bedtime in management of NI after RC and ONB through a prospective randomized placebo-controlled crossover study.

Material and methods:

Patients: