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Low-dose oral desmopressin for treatment of nocturia and nocturnal enuresis in patients after radical cystectomy and orthotopic urinary diversion

By H. Goldberg, J. Baniel, R. Mano, G. Gillon, D. Kedar and O. Yossepowitch.

BJU International, Volume 114, Issue 5, 1 November 2014, Pages 727-732

Editor’s comments:
In the following article, the Authors reported the results on the use of low-dose oral desmopressin in the treatment of nocturia and nocturnal enuresis in 34 patients (32 males and 2 females) who underwent radical cystectomy and orthotopic ileal neobladder for urothelial cancer. This represents a pivotal proof of concept, not a placebo controlled study. The topic is very interesting as, despite the attainment of low-pressure-large capacity and highly compliant reservoirs, nocturia and nocturnal enuresis remain prevalent in about 60% of patients irrespective of the type of the reconstructed reservoir. Obviously, nocturia and nocturnal enuresis deeply affect the quality of life of these patients.

Several mechanisms have been considered as possible causes of nocturnal enuresis in patients with neobladder, as loss of the guarding reflex which increases uretra sphincter tone during bladder filling, decreased sensitivity of the membranous urethra after radical cystectomy, and/or presence of high pressure contractions of the neobladder. Another supposed mechanism could be the shifting of free water from the reservoir wall into the hyperosmolar urine resulting in global and nocturnal polyuria.

Patients included in the study had to show GFR >50 mL/min/1.73 m2, normal baseline sodium serum level, diurnal urinary continence, any degree of nocturia or nocturnal enuresis, and no known allergy to desmopressin. They received once daily oral desmopressin 0.1 mg at bedtime for a consecutive period of 30 days. Importantly, patients completed the validated Nocturia, Nocturnal Enuresis and Sleep-Interruption Questionnaire (NNES-Q). It was found that nightly treatment with low-dose (0.1 mg) oral desmopressin was associated with fewer nocturnal voids and more consecutive sleeping hours in ∼50% of the patients.

Particularly, at the end of the trial, 42% of patients reported longer consecutive sleeping time, with a minimum of 1–2 h of additional sleep until the first episode of nocturnal enuresis. No hyponatraemia was noted in any patient, with sodium levels remaining the same throughout the trial period.

This is the first study which shows that oral desmopressin is safe and effective in reducing nocturia and nocturnal enuresis in patients with orthotopic neobladder. Of course, randomized, placebo-controlled studies are needed to confirm these results and to assess the optimum dosage of desmopressin also in a long term follow up.

ABSTRACT

Objectives

To assess the effect of oral desmopressin on nocturia and nocturnal enuresis in patients after orthotopic neobladder reconstruction.

Patients and Methods
Of 55 patients who underwent radical cystectomy and orthotopic neobladder reconstruction at our medical centre in the period 2004–2011, 34 patients were deemed eligible for the present study. Inclusion criteria were estimated glomerular filtration rate >50 mL/min/1.73 m2, normal baseline sodium serum level, intact daytime urinary continence, and any degree of nocturia or nocturnal enuresis. Patients were treated daily with oral desmopressin 0.1 mg at bedtime for 30 days and completed the Nocturia, Nocturnal Enuresis and Sleep Interruption Questionnaire at trial enrolment and closure. Sodium serum levels were monitored throughout.

Results
Three patients withdrew from the trial because of headaches or anxiety. The mean (sd) number of nocturnal voids decreased from 2.5 (1.4)/night at baseline to 1.5 (1.3)/night at trial closure (P = 0.015). The number of patients with one or no episodes of nocturnal enuresis per week increased from six to 12 (19 to 39%; P = 0.065). Thirteen patients (42%) reported an increase of a minimum 1–2 h of sleep until the first nocturnal void; all of them asked to continue the drug. No significant adverse events or changes in sodium level were observed.

Conclusions
Bedtime treatment with low-dose oral desmopressin appears to decrease episodes of nocturia and nocturnal enuresis effectively and safely in ∼50% of the patients with neobladder, allowing longer undisrupted sleep time and improved quality of life. Further investigation is warranted to determine if higher doses would result in a more meaningful clinical response.