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The prognostic value of voiding chart data in therapy-resistant enuresis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Pediatrisk inflammations- och metabolismforskning samt barnhälsa)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.ORCID iD: 0000-0002-4590-4957
(English)Manuscript (preprint) (Other academic)
Abstract [en]

 

Introduction: The case history is the primary tool when investigating the enuretic child. To further determine whether nocturnal polyuria or detrusor overactivity is present, a full voiding chart, as defined by the ICCS, is the method of choice. However, there is no robust evidence that daytime voiding chart data actually do predict nocturnal detrusor function.

Aim: The aim of this study was to assess the predictive value of anamnestic data and the voiding chart in the treatment of children with therapy-resistant enuresis.

Patients and Methods: The patients all suffered from therapy-resistant nocturnal enuresis. In accordance with international recommendations, the children were first treated with anticholinergics. If the therapeutic effect was not satisfactory dosage was adjusted and desmopressin was added. If sufficient treatment effect was not achieved, antidepressant therapy was tried next, combined with desmopressin if needed. Since this was an evaluation of clinical practice, not a randomized trial, treatment success was graded according to family satisfaction, not the actual frequency of wet nights. Thus, only children who reported that they were completely dry were regarded as full responders and those who stated that there was a substantial and useful reduction of wet nights were labeled intermediate responders.

Results: Few and inconsistent differences were found between the groups responding or not responding to the various treatment regimens, and this was true both for anamnestic and voiding chart data. The only statistically significant findings were that responders to antidepressant therapy were older (p=0.013) than non-responders, and patients who benefited from addition of desmopressin had a higher micturition frequency than those who did not (p= 0.027). Surprisingly, the children who needed desmopressin as part of combination treatment to become dry did not have significantly higher nocturnal urine production than those who had no such benefit (p=0.619). Equally surprisingly, neither the presence of urgency nor a history of previous daytime incontinence was significantly  more common in children responding to anticholinergics (p = 0.375 and 0.072, respectively).

Discussion: No clear and consistent differences in either anamnestic factors or voiding chart data were found between the patients responding or not responding to the various treatment regimens. Not even urgency could predict anticholinergic efficacy. Somewhat surprisingly, no association between nocturnal polyuria and desmopressin benefit was found.

Conclusion: In this study no prognostic value was found in anamnestic or voiding chart data in children with therapy resistant enuresis.

Keywords [en]
Nocturnal enuresis, voiding chart, anticholinergics, antidepressants, desmopressin
National Category
Medical and Health Sciences
Research subject
Pediatrics; Pediatrics; Pediatrics
Identifiers
URN: urn:nbn:se:uu:diva-389835OAI: oai:DiVA.org:uu-389835DiVA, id: diva2:1339399
Available from: 2019-07-29 Created: 2019-07-29 Last updated: 2019-08-15Bibliographically approved
In thesis
1. Therapy-resistant enuresis: In search of new therapies and prognostic markers
Open this publication in new window or tab >>Therapy-resistant enuresis: In search of new therapies and prognostic markers
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A large minority of children with enuresis do not respond to treatment with either desmopressin or the enuresis alarm. Anticholinergics have not proven as successful as expected. The fourth evidence-based treatment of enuresis, the tricyclic antidepressant imipramine, is cardiotoxic when overdosed, which has led to diminished use. Since the long-term consequences of enuresis are potentially grave it is important that effective treatments of therapy-resistant enuresis are found.

When investigating the enuretic child a full voiding-chart - in addition to the case history - is the method of choice. However, there is no robust evidence that daytime voiding chart data actually do predict nocturnal detrusor function.

The aim of this thesis was to determine whether there is a role for the noradrenergic antidepressant reboxetine in the treatment of therapy-resistant enuresis, and whether anamnestic data and the voiding chart provides prognostic information regarding response to treatment with anticholinergics and antidepressants respectively in therapy-resistant patients.

In a retrospective evaluation of 61 children who for humanitarian purposes had been treated with reboxetine 32(52%) responded to this treatment, 21 of them after desmopressin had been added. We then proceeded with a randomized placebo-controlled study with 18 patients, in which the reduction of wet nights was much better with either reboxetine in monotherapy or in combination with desmopressin than during the placebo period (p=0.002). However, no patient achieved complete dryness. No prognostic markers for therapy-response were found in either of these studies.

In the randomized study we also sought to investigate whether reboxetine had any statistically significant effect on voiding-chart data. No such effect was found, but in respect to this secondary aim the sample size was too small. Nonetheless , this led to the speculation whether reboxetine exerts its antienuretic effect via modulation of arousal mechanisms.

Prognostic markers were sought in a retrospective evaluation of 154 patients treated with anticholinergics or antidepressants, but few and inconsistent differences were found between the groups responding or not responding to the various treatment regimens, and this was true both for anamnestic and voiding chart data.

In conclusion reboxetine seems to be an alternative in the treatment of enuretic children who have not responded to standard treatment, but further trials with higher doses and larger study populations are needed. The internationally recommended assessment of children with therapy-resistant enuresis does not seem to give the prognostic information intended.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 60
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1584
Keywords
Nocturnal enuresis, Reboxetine, Antidepressants, Desmopressin, Voiding chart
National Category
Medical and Health Sciences
Research subject
Pediatrics
Identifiers
urn:nbn:se:uu:diva-389838 (URN)978-91-513-0701-5 (ISBN)
Public defence
2019-10-04, Enghoff-salen, Akademiska Sjukhuset, Ing 50 bv, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2019-09-12 Created: 2019-07-29 Last updated: 2019-10-15

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