Pediatric Nephrology

, Volume 20, Issue 9, pp 1343–1345

Management of nocturnal enuresis in Greek children

Authors

    • Department of Urology, School of MedicineDemocritus University of Thrace, University Hospital of Alexandroupolis
  • S. Charalambous
    • Department of UrologyHippokrateion General Hospital
  • A. G. Papatsoris
    • Department of Urology, School of MedicineUniversity of Athens, Sismanogleio General Hospital
  • A. Papathanasiou
    • Department of UrologyHippokrateion General Hospital
  • C. Kalaitzis
    • Department of Urology, School of MedicineDemocritus University of Thrace, University Hospital of Alexandroupolis
  • V. Rombis
    • Department of UrologyHippokrateion General Hospital
  • S. Touloupidis
    • Department of Urology, School of MedicineDemocritus University of Thrace, University Hospital of Alexandroupolis
Brief Report

DOI: 10.1007/s00467-005-1921-x

Cite this article as:
Triantafyllidis, A., Charalambous, S., Papatsoris, A.G. et al. Pediatr Nephrol (2005) 20: 1343. doi:10.1007/s00467-005-1921-x
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Abstract

Our experiences of managing nocturnal enuresis in Greek children at our Outpatient Clinics of Pediatric Urology are described. Between March 2001 and October 2003, 142 children with primary nocturnal enuresis (93 boys and 49 girls), aged 7–18 years old (mean: 9.0±0.5) were included in this prospective study. Initially, behavioral conditioning therapy, using a body-worn urinary alarm, was instructed in all cases. If no improvement was recorded, 40 μg of intranasal desmopressin was administered, initially for three months. If urodynamic studies demonstrated pure detrusor instability, anticholinergics (5 mg oxybutinine or 2 mg tolterodine) were given instead. Combination medication (desmopressin and anticholinergics) was administered for coexisting diurnal enuresis, which was present in 8 children. Among the 142 children the overall response rate was 51.41%. Successful response was recorded in 16 children practicing conditioning behavioral therapy, in 47 receiving desmopressin (with or without anticholinergics), and in 10 children receiving only anticholinergics. During the follow-up period (mean: 6.2 months), no serious side effect was recorded. The use of desmopressin, and anticholinergics in specific subgroups, was found to be effective and safe for the management of nocturnal enuresis in children.

Keywords

Nocturnal enuresisBedwettingUrinary alarmDesmopressinAnticholinergics

Introduction

Enuresis is a common disorder causing considerable distress and discomfort to millions of children worldwide. It is defined as repeated involuntary or unintentional voiding. When this happens during the night, is called nocturnal enuresis. Diurnal enuresis happens during the day, and when it occurs during both the day and the night, it is known as mixed enuresis. The term primary enuresis is used if the disorder has remained from the infantile period, while enuresis is characterized as secondary if a period of at least six months of continence occurred. The frequency of bed-wetting varies between once a week to once a semester. In our study, we use the term where at least two episodes a week occur after the fifth year of life.

Nocturnal enuresis, or bedwetting, affects around 15–20% of 5-year-olds, and up to 2% of young adults [1]. It is an old but still prevalent and socially disruptive clinical problem causing considerable distress in both children and parents. Recent research has helped to correct some traditional misconceptions and unveil the underlying pathophysiological mechanisms. It has been demonstrated that nocturnal enuresis is a heterogeneous disorder with various pathophysiological causes, resulting in a mismatch between the nocturnal bladder capacity and the amount or urine produced during sleep at night, in association with a simultaneous failure of conscious arousal in response to the sensation of bladder fullness [2]. Nowadays, nocturnal enuresis is not considered a self-limited condition, but a disease that necessitates appropriate diagnostic and therapeutic work-up. Herein, we present our experiences of managing nocturnal enuresis in Greek children at our Outpatient Clinics of Pediatric Urology.

Materials and methods

142 children that consulted our Outpatient Clinics of Pediatric Urology between March 2001 and October 2003 complaining of primary nocturnal enuresis were included in this prospective study. Ninety-three of the children were boys (65.5%) and 49 were girls (34.5%), aged 7–18 years old (mean age: 9.0±0.5 years). One hundred and thirty four (94.3%) children reported monosymptomatic nocturnal enuresis, while 8 (5.6%) reported mixed nocturnal and diurnal enuresis. None of the patients have ever received any treatment for his/her enuresis.

All enuretic episodes were recorded under the supervision of the parents in a special calendar. In the cases of coexisting diurnal enuresis, an ultrasonogram was performed in order to check for signs of urinary tract obstruction. Also, when bladder instability symptoms (such as urgency, frequency, urge incontinence) were reported, when enuresis was diurnal or secondary, and when encopresis also occurred, urodynamic investigations (pressure-flow test) were performed.

Initially, behavioral conditioning therapy, achieved using a body-worn urinary alarm, was instructed in all cases. Also, bladder behavioral therapy was instructed to every child and his/her parents; in other words, to eat, drink and void regularly during the day, reduce fluid uptake in the evening and completely abstain at least two hours before going to bed, to void before sleep and to avoid intense and tiring activities in the evening as much as possible to avoid a deep sleep.

If after one month of behavioral therapy no improvement was recorded, 40 μg of intranasal desmopressin was administered before sleep. In cases of response to desmopressin, medication continued for three months, and if children experienced recurrence two weeks thereafter, desmopressin administration continued for another trimester. In cases of bladder instability symptoms with no urodynamic findings, after behavioral treatment, desmopressin was combined with anticholinergics (5 mg oxybutinine or 2 mg tolterodine). If urodynamic studies demonstrated pure detrusor instability, anticholinergics were administrated after behavioral treatment. Combination medication (desmopressin and anticholinergics) was also administered in the cases of coexisting diurnal enuresis, provided that imaging tests revealed no sign of urinary tract obstruction. It should be mentioned that on the nights that desmopressin was administered, children were recommended to limit fluids to no more than 240 ml, in order to minimize the risk of water intoxication. Chi-square test was used to assess any potential association between categorical variables, and a p value <0.05 was considered to be statistically significant.

Results

We consider a “successful response” to be one where the child experiences no more than one wet episode weekly, or no more than three episodes monthly, after three months of therapy.

Behavioral conditioning therapy was practiced in all 142 children, resulting in successful responses in 16 children (11.2%). One hundred and one children received desmopressin; as monotherapy in 91 cases (64.1%), or in combination with anticholinergics: oxybutinine in 11 children (7.7%), and tolterodine in 9 children (6.3%). In the cases of coexisting diurnal enuresis, imaging of the urinary tract did not reveal any sign of obstruction. Also, in 15 children (10.5%) with urodynamic diagnosis of detrusor instability, anticholinergics were administered [oxybutinine in 11 (7.7%) children and tolterodine in 4 (2.8%)]. From the 111 children who received desmopressin (whether combined with anticholinergics or not), 66 (59.4%) initially responded to treatment, but after discontinuation 28 children (42.4%) relapsed. These 28 children continued desmopressin for another trimester and 9 of them (32.1%) responded. Hence, from the 111 children that received desmopressin (as monotherapy, or in combination with anticholinergics), 47 eventually responded (42.3%). Moreover, from the 15 children with detrusor instability, oxybutinine or tolterodine resulted in both clinical and urodynamic improvement in 10 cases (66.7%), which was not statistically significant in comparison with the desmopressin group (p=0.94). Collectively, successful responses were recorded in 16 children practicing behavioral conditioning therapy, in 47 receiving desmopressin (with or without anticholinergics), and in 10 children receiving only anticholinergics (Fig. 1). Thus, among the 142 children, the overall response rate was 51.4%. During the follow-up period (mean: 6.2 months), no serious side effects were recorded. In particular, 3 children on desmopressin (2.7%) manifested nasal irritation and headache, while 2 children on oxybutinine (18.1%) complained of mouth dryness.
Fig. 1

Therapy results

Discussion

A number of theories have been proposed to explain why children with nocturnal enuresis fail to recognize or respond to their full or contracting bladder during sleep. Although these theories, which include behavioral, developmental, psychological, genetic, neurological, urodynamic, and organic causes, are diverse and may be able to explain selected cases, there is no single explanation for nocturnal enuresis [2, 3]. Clearly, the vast majority of children with nocturnal enuresis do not suffer from psychiatric, neurological, or urologic disturbances, and investigation along these lines was worthless. Generally, treatment of nocturnal enuresis is discouraged before 7 years of age as this is the age when children, peers, and parents generally begin to expect dryness and when bedwetting starts to interfere with social activities such as sleepovers [3]. The epidemiological data from our patients were comparable with other relevant clinical studies.

Modification of behavior to control enuresis has met with varied success and should be considered the first-line approach to the management of nocturnal enuresis. Randomized controlled trials and clinical studies have shown that conditional therapy using the urinary alarm is the most effective means of eliminating bedwetting [3]. Nevertheless, in our study, the success rate of behavior therapy was relatively low. A possible explanation of the failure of behavior conditioning therapy could be the lack of child and parental understanding and commitment, without excluding our relevant responsibility. This problem might be minimized by proper instruction and supervision as well as recognition that the period of therapy could be lengthy. Possibly, not all parents really wanted and not all children were ready for a treatment program. Therefore, it would be useful if we had determined whether the child was sufficiently old, mature, and motivated, and whether the family was supportive enough to begin a treatment program that might be lengthy and initially unsuccessful.

Normal individuals have a marked circadian variation in urine output leading to a significant decrease in urine excretion and a corresponding increase in urine osmolarity occurring at night. This occurs in a similar pulsate fashion to the secretion of arginine vasopressin (AVP) antidiuretic hormone. This hormone is normally excreted from the pituitary gland and its function is to enhance water reabsorption, thereby allowing the body to produce smaller volumes of more concentrated urine at night [4]. In many children with nocturnal enuresis, there is an absence of an arginine-vasopressin circadian rhythm during both the day and the night, resulting in the production of larger amounts of dilute urine at night [5]. Desmopressin is an analogue of vasopressin that is free from its dangerous and unpleasant side effects. In Moffatt’s review of randomized clinical studies using desmopressin therapy, nearly all studies demonstrated a statistically significant reduction in wet nights [6]. Moreover, studies have demonstrated that desmopressin was effective at rapidly reducing bedwetting in a variety of doses and forms [7, 8, 9]. In our study, intranasal desmopressin provided an effective and well-tolerated means of providing control in children with nocturnal enuresis. We did not record any case of water intoxication due to desmopressin intake, and the most common non-serious side effect was nasal irritation associated with the nasal spray. Of course, it must be mentioned that a serious drawback of desmopressin therapy is that it is relatively expensive, in comparison with the other treatment modalities.

Children with various types of occult bladder dysfunction, which result in a small nocturnal bladder functional capacity, generally have a poor response to desmopressin monotherapy, and might benefit more from the addition of anticholinergic agents [3, 10]. Cigna et al performed urodynamic studies in 130 children with polysymptomatic nocturnal enuresis in association with urinary symptoms (such as urgency, urge incontinence), and concluded that bladder instability was the most common disorder [10]. Studies suggest that anticholinergic agents are extremely effective for certain subgroups of enuretics; they are very effective in treating children with proven bladder instability and those with combined day and night-time enuresis [3]. In our study, the administration of anticholinergics to these subgroups of children resulted in high success rates. We did not record any statistically significant difference between the effectiveness of oxybutinine and tolterodine.

In conclusion, the use of desmopressin, and anticholinergics in specific subgroups, was effective and safe for the management of nocturnal enuresis in children. Further research is needed into comparisons between behavioral treatments and anti-enuretic medications, and these should include relapse rates after treatment is finished.

Acknowledgements

We would like to thank Dr. Grigorios Tripsianis, Associate Professor of Medical Statistics, for his valuable help in analyzing the data.

Copyright information

© IPNA 2005