Enürezis Nokturna klinik araştırmalar

Enürezis nokturna (uykuda işeme) günümüzde sağlıklı okul çocuklarının %15-30’unu etkileyebilen ve çoğunlukla monosemptomatik tipte (sadece gece işemeleri şeklinde) seyreden bir rahatsızlıktır 1,2. Gece işemesi bilimsel olarak, 5 yaşından sonra –haftada 2 defadan fazla olmak üzere- mesanenin yalnış yer ve zamanda tam olarak boşalması olarak ifade edilmektedir 3. Bu problem 5 yaş civarındakilerin yaklaşık %10’ unu, 10 yaş civarındakilerin yaklaşık %5’ ini ve daha üst yaştakilerin yaklaşık olarak %2’ sini etkileyebilmektedir. Bunun yanısıra bu sorun %1 oranında 18 yaş ve üzerinde devam etmektedir. Amerika’da gece işemesi sorunu olan 7 milyon çocuk vardır. Gece işemesi  (Enürezis nokturna) çok yaygın fakat aynı zamanda bir o kadar gizli bir problemdir.  

Primer nokturnal enürezisin (uykuda işeme) etiyolojisinde çelişkiler olmasına karşın genetik faktörler (örneğin ebeveynlerden birisi çocukken bu rahatsızlığı yaşamışsa çocuğunun aynı sorunla karşılaşma olasılığı %40’tır. Eğer hem anne hem baba aynı sorunla karşı karşıya kalmışlarsa çocukta bu oran %75’e yükselmektedir), fonksiyonel mesane kapasitenin azlığı, geceleri artan diürez, uyku rahatsızlıkları, antidiüretik hormon salınımında anormallikler, ruhsal rahatsızlıklar, diet ve bakteriürinin rol oynayabileceği düşünülmektedir. Buna karşılık gece işemesi, bir tembellik sorunu, aile terbiyesinin eksikliğinden kaynaklanan bir problem, anti-diüretik hormonların azlığından kaynaklanan bir sorun veya özel diet eksikliği sorunu değildir. Ayrıca pahalı bir tedavi gerektiren bir sorun da değildir 4,5

Gece işemesi bir uyku hastalığıdır (parasomniadır). Hasta, derin uykuda olduğundan normal olarak oluşan mesane kasılmalarını algılayamaz ve mesane basıncındaki artışını hissedemez sonuç olarak yatağı ıslatır. Grafikte görülebileceği gibi normal bir insanın (kesikli çizgi) başını yastığa koymasını takiben uykuya dalması 1. Basamağı oluşturur. Uyku devresi buradan 2.  3. ve son olarak 4. Basamağa kadar ilerler. 4. Basamak en derin uyku devresidir. Yaklaşık 20 dakika sürer. Süre bitiminde tekrar 3. , 2. Ve 1. basamaklara geri dönülür. 2. Basamaktan 1. Basamağa geçiş R.E.M. (rapid eye movement (hızlı göz hareketleri)) uykusu olarak adlandırılır. Bu devre uykunun rüya görülen devresidir. Bu devre insanın gün içinde çevreden aldığı, depoladığı veya attığı tüm bilgilerin nerede tutulacağı bakımından önemlidir. Bu dönem ayrıca mesaneden beyine giden sinyallerin değerlendirildiği ve bu sinyallere cevap olarak, tuvalete mi gidileceğinin yoksa uykuya mı devam  edileceğinin kararının verildiği dönemdir. R.E.M. uykusu yaklaşık 20 dakika sürmektedir. Bu devrenin bitiminde uyku siklusu devam eder. Bir gecelik uykuda normal insan bu siklusu ortalama 4-6 defa yaşar.
Yine grafikte görüleceği üzere gece işemesi sorunu olan kişiler derin uykuya çok çabuk dalarak direkt olarak uykunun 4. devresine girerler ve burada kalırlar (düz çizgi ile gösterilmiştir). Bir süre sonra (zamanı tam olarak bilinmemektedir, yarım saat veya saatler sonra olabilir) mesane, beyine tuvalete gitmesi için mesaj gönderir. Bundan sonra uykuda R.E.M. dönemi yükselir. Bu sadece 20-90 saniye sürer. Buna karşılık hasta derin uykuda olduğundan bu sinyale cevap veremez. Tüm bu sebeplerden hastaların geceden içecek almalarını önlemek, gece vakti onları tuvalete kaldırmak faydasızdır. Zira bu sebepler gece işemesinde  rol oynamazlar. Gece işemesi basitçe uykuda kontrolün yitirilmesidir. Bu sorun 4 yaşındakilerde de, 30 yaşındakilerde de aynıdır.  

5 - 6 yaşından sonra çocukların yataklarını ıslatmaları normal değildir. Bu nedenle oluşabilecek sosyal ve psikolojik bozukluklar sebebiyle tedavisi zorunlu bir sorundur.  

Enürezis alarmı, gece işemesi sorununun ekonomik yönden pahalı ve yan etkileri olan ilaçlarla tedavisi yerine ekonomik olarak ucuz, kalıcı, güvenli ve maximum başarı oranıyla çözümünü  sağlamak amacıyla üretilmiştir. Enürezis alarm ilk olarak 1904 yılında bildirilmiş olmasına karşın, rutin kullanıma ancak 1930’ larda geçilmiştir 6.  

Enürezis alarm gece elbisesinin yakasına rahatlıkla tutturulabilecek şekilde yapılmış olan hafif plastik kutu içerisindeki güvenli elektronik devreden ibarettir. Alarm, ince, sökülüp-takılabilir, sterilize edilebilir, paslanmaz, neme duyarlı bir sensöre (duyarga) bağlıdır. Bu sensör, iç çamaşırın dışına yerleştirilir. İdrar geldiğinde duyarga nemlenir ve alarm çalışır ve uyarı aktive olur. Uyaran çocuğu uyandırır ve daha önemlisi external sfinkter kasının aniden kasılmasına neden olarak idrarın mesaneden akmasını önler. Uyarı ses şeklindedir. İdrar gelmesini takiben alarmın çalışmasıyla tekrar tekrar uyandırılma beyni, mesane üzerindeki otomatik kontrolü sağlaması konusunda eğitir. Nihayetinde, hasta ya idrar gelmeden uyanacaktır veya mesaneyi boşaltmaya ihtiyaç duymadan bütün gece uyuyacaktır. Enürezis nokturnanın (uykuda işeme) tedavisi geceleri hastanın kendi kendine uyanarak tuvalete gitmesidir. Enürezis alarm hastaya bu yeteneği kazandırdığı için daha kalıcı ve nüksetme olasılığı çok daha az bir tedavi olanağı sağlar. Ayrıca enürezis alarmın fonksiyonel mesane kapasitesini artırdığı yapılan çalışmalarda gösterilmiştir7. Enürezis alarmın bu etkisinin de sağladığı tedavide rolü olduğu düşünülmektedir. Bunun yanısıra alarmın fiyatı,  sadece 2 haftalık desmopressin uygulamasının hastaya maliyetine eşittir 8.

 

Bu tedavi şekli; güvenli ve ekonomik bir şekilde (1), yan etkisiz (2) birkaç hafta içinde %80’nin üzerinde başarıyla gece işemesi sorununu gidermektedir. Ürolog Dr. Bruce L. Dunn, M.D., 1978-79 yıllarında yaptığı çalışmada, gece işeme problemi olan 125 çocukta alarm kullanarak yaptığı tedavide %76 başarı sağladığını bildirmiştir.  

Faraj ve arkadaşları tarafından 1999’da yapılan çalışmada, enürezis nokturna tedavisinde sıkça kullanılan 40 mikrogram intranazal desmopressin uygulamasının (n=33) kısa dönemde etkili olduğu ancak 3 aydan sonra etkisinin azalmaya başladığı (kuru geçen gece oranı, ilaç tedavisinden 15 gün sonra %80, 3 ay sonra %85, 6 ay sonra %78) buna karşılık enürezis alarm  ile tedavide (n=43) zamanla tedavi oranında artış olduğu (kuru geçen gece oranı, tedavi başlangıcından 15 gün sonra %50, 3 ay sonra %90, 6 ay sonra %94) gösterilmiştir 9.  
1991’de yayınlanan bir makalede, 6 ile 19 yaş arasındaki 326 hastanın 76’sının (%23) kendi kendilerine tedavi oldukları, geri kalan 250 hastanın (161 erkek, 89 bayan) 211’inin (%84) alarm ile tedavi oldukları, geri kalan 39 hastanın (%16) tedavi olamadıkları bildirilmiştir 10.  
Yachiku ve ark. tarafından 1989’ da yapılan çalışmada; alarm tedavisiyle 3 ay içerisinde 50 hastanın 28 ‘inde (%56) tam, 12’sinde (%24) tatminkar, 9’ unda (%18) hafif tedavi cevabı alındığını buna karşılık 1 hastada (%2) hiç cevap alınmadığını bildirmişler böylece alarm ile tedavinin %80 başarı sağladığını, bu nedenle alarm ile tedavinin trisiklik antidepresanlar ile tedaviden çok daha etkili olduğunu  göstermişlerdir 11.   
Bartolozzi ve ark. yaptıkları çalışmada 6-15 yaş arasındaki 130 hastada (primer ve sekonder enürezisli) enürezis alarmı denemişler ve çoğu hastanın (%77) 12 hafta içerisinde tedavi olduğunu göstermişlerdir 12.  

Monda ve arkadaşları tarafından 1995 yılında yapılan çalışmada hastalar, kontrol (n=50), İmipramin (n=44), desmopressin (n=88) ve alarm (n=79) grubu olmak üzere 4 gruba ayrılmış ve tedavilerine başlanmıştır. Gözlemler tedavinin 6. ve 12. Ayında yapılmış ve tedavi olanların yüzdesi hesaplanmıştır. Kontrol grubunda sırası ile %6, % 16; İmipramin grubunda %36, %16; Desmopressin grubunda %68, %10; alarm grubunda ise %63, %56 tedavi sağlanmıştır. Bu sonuçlar ile alarm ile tedavinin en kalıcı ve en etkili yöntem olduğu gösterilmiştir 13.  

Bu çalışmaların yanısıra Enürezis alarm tedavisinin  40 mikrogram intranazal Desmopressin tedavisi ile desteklenmesinin sorunu daha kısa sürede ve kalıcı olarak ortadan kaldırdığını gösteren çalışmalar da vardır.  

Bradbury 1995 ve 1997 ‘ de yaptığı ayrı çalışmalarda da Alarm ile tedavinin 40 mikrogram intarnazal desmopressin ile desteklenmesinin (n=35), alarm ile tek başına tedaviden daha etkili olduğunu göstermiştir (alarm ve desmopressinin birlikte uygulandığı grupta 1 haftada kuru geçen gece ortalaması 6.1 iken, sadece alarm tedavisi gören grupta bu oran 4.8’dir).Ayrıca 4 hafta süren kuru döneme ulaşabilen çocukların sayısı, kombine tedavi gören grupta 27 (%75) iken diğer grupta 16 (%46)’ dır 14,15.

Bunun yanısıra Hjalmas ve ark. Tarafından İsveç’te yapılan çalışmada da kombine tedavinin daha etkili olduğu sonucuna varılmıştır 16.  
Sukhai ve ark. Yaptıkları çalışmada, 2 hafta içerisinde, Alarm tedavisi ile birlikte 20 mikrogram intranazal desmopressin uygulanması sonucunda bir haftadaki kuru gece sayısı ortalamasının 5.1’e  (kuru gece/hafta) yükseldiğini buna karşılık sadece alarm tedavisi gören hastalarda ortalamanın 4.1 olduğunu göstermişlerdir17.  

(1)1994’ te Danimarka’ da yapılan araştırmada, ülke genelinde Desmopressin tedavisinin 1 yıllık giderinin 44.8 milyon DKK olduğu, buna karşılık alarm ile tedavi giderinin 19.2 milyon DKK olduğu gösterilmiştir 18.  

(2) Daha önce alarm tedavisi görmüş 7-14 yaşındaki çocuklarda yapılan araştırmada, psikosomatik semptomlarda dahil olmak üzere hiçbir mental yan etkiye rastlanmadığı, herhangi bir artık etkininde görülmediği bunun yanısıra tedavi gören hastalarının çoğunun gördükleri tedaviyi olumlu ve etkili bulduklarını bildirilmiştir 19.  

KAYNAKLAR
1.An update on clinical and therapeutic aspects of nocturnal enuresis.
[Article in Italian]
Chiozza ML
Dipartimento di Pediatria, Universita degli Studi di Padova, Italia.
Pediatr Med Chir 1997 Sep-Oct;19(5):385-90  
Justification of early treatment of nocturnal enuresis is founded in the negative psychological impact on the child. In fact nocturnal enuresis delays early autonomy and socialisation by decreasing in self-esteem and self-confidence. Nocturnal enuresis classification is the preliminary step to correct therapy. Enuresis must be classified as primary (never acquired nocturnal control) or secondary (at least 6 months of dry nights). A child is also classified as having monosymptomatic enuresis if she/he experienced only night wetting and symptomatic enuresis if she/he experienced night wetting associated with diurnal voiding symptoms (urinated > or = 7 times a day, urgency, damp pants, squatting, holding the perineum, sitting on one heel). Monosymptomatic patients must be treated with desmopressin nasal spray at the daily dose of 20 micrograms at bed time. If the reduction of at least the 50% of the basal number of the wet nights is not achieved, the dosage must be increased until 40 micrograms. For patients affected by rhinitis or asthma, desmopressin is now available in tablets. In symptomatic patients desmopressin therapy must be associated to oxybutinin (5 mg x 2). Therapy interruption must be gradual with desmopressin reduction of 10 micrograms every 30 days. In symptomatic patients oxybutinin must be introduced only at bed time. The efficacy of the drugs depends on the therapy length. The highest percentage of success is obtained if the treatment is protracted for at least six months. Antidepressants are also used for nocturnal enuresis especially imipramine. The dosage varies between 0.5-1.5 mg/ kg/daily. As plasmatic levels are achieved only in 30% of treated patients, a 3-5 fold increase in suggested. Nevertheless these levels result in near toxic threshold concentration. Sporadic treatment purposes include amytriptiline, diclofenac sodicum, viloxsazine and methilphenidate if giggle incontinence is present. Non responders may be treated with alarm. If after 16 weeks of treatment no success is obtained alarm use must be interrupted.  

2. Primary enuresis in children. Which treatment today?

[Article in Italian]
Caione P, Nappo S, Capozza N, Minni B, Ferro F
Dipartimento di Chirurgia, Ospedale Pediatrico Bambino Gesu-Roma.
Minerva Pediatr 1994 Oct;46(10):437-43  
Nowadays enuresis is a problem that pediatric urologists are often called to treat, since it affects 15 to 30% of school-age children. In 85% of affected children bedwetting is monosymptomatic, not accompanied by other voiding disorders or daytime incontinence. Treatment of choice is still highly controversial, as the physiopathology is not yet fully understood and the pathogenesis is multifactorial: genetic and psychological factors, sleep disorders, urinary reservoir abnormalities, urine production disorders can all play a part. Behavioural treatments (psychotherapy, bladder training and biofeedback, electric alarm) and pharmacological therapy (tricyclic antidepressants, anticholinergics, DDAVP) have been used with variable results. In our 1 year experience (54 enuretic children) DDAVP proved to be effective in reducing the number of wet nights per week in 79% of cases. Acupuncture, which we have been using for many years, also gave good results in 55% of treated patients. Long term success of DDAVP and acupuncture was respectively 50 and 40%. We discuss the probable pathophysiology and present our own results and those reported in the literature. It has to be stressed that an accurate diagnostic selection of patients and a better understanding of physiopathology are the basis of effective treatment of enuresis.  

3. Enuresis and pediatric urinary incontinence-epidemiology, diagnosis and therapy today.

[Article in German]
Stehr M, Schuster T, Dietz HG
Kinderchirurgischen Klinik, Dr.-von-Haunerschen Kinderspitals der Ludwig-Maximilians-Universitat Munchen, Deutschland. mstehr@kk-i.med.uni-muenchen.de
Wien Med Wochenschr 1998;148(22):521-4  
To describe epidemiology, diagnosis and therapy of enuresis and urinary incontinence in children we have to work with exact definitions. Enuresis is defined as a normal nearly complete emptying of the bladder at a wrong locality at a wrong time at least twice a month after the 5th year of life. Enuresis is regarded as delayed development of bladder function. From enuresis we have to differentiate urinary incontinence in children, which is any kind of loss of urine without normal emptying the bladder. Wetting in those cases is a symptom of a disease (structural, neurogenic, psychogenic or functional). A detailed anamnesis is the most important diagnostic tool in enuresis whereas in the case of urinary incontinence a lot of diagnostics from non-invasive to invasive have to be performed. Enuresis can be treated with alarm or you can apply Desmopressin (DDAVP). Therapy of urinary incontinence in children depends on the disease causing the symptom of wetting.  
4. Diagnosis and management of nocturnal enuresis.
Ullom-Minnich MR
University of Kansas School of Medicine-Wichita, USA.
Am Fam Physician 1996 Nov 15;54(7):2259-66, 2271  
The etiology of primary nocturnal enuresis remains somewhat controversial but may include genetic factors, decreased functional bladder capacity, increased diuresis at night, and constipation. Deep sleep and emotional illness usually play only a minimal role. A detailed description of the enuretic episodes should be obtained, and a neurologic examination should be performed as part of the physical evaluation of a child with nocturnal enuresis. In uncomplicated cases, urinalysis and a urine culture are the only required laboratory tests. The specific cause of the nocturnal enuresis usually is not determined. Treatment options include the urine alarm system, pharmacotherapy and complex regimens such as dry-bed training. Treatments are often combined. Nocturnal enuresis eventually resolves in the majority of cases.  
5. Nocturnal enuresis: a guide to evaluation and treatment.
Tietjen DN, Husmann DA
Department of Urology, Mayo Clinic Rochester, Minnesota 55905, USA.
Mayo Clin Proc 1996 Sep;71(9):857-62  
Nocturnal enuresis has several possible causes, including genetic inheritance, reduced bladder capacity, sleep disorders, abnormal secretion of antidiuretic hormone, psychologic abnormalities, neurologic dysfunction, bacteriuria, and diet. A through assessment of the patient's voiding history is of major importance in the management of nocturnal enuresis. Whether the patient has monosymptomatic or polysymptomatic nocturnal enuresis must be determined. Treatment options include pharmacotherapy, behavioral modification with an alarm system, or a combination of these modalities. In order for treatment to be successful, the physician, patient, and patient's parents must be involved in the decision-making process.  
6. Prognostic factors for alarm treatment.
Rappaport L
Division of General Pediatrics, Children's Hospital, Boston, MA 02115, USA.
Scand J Urol Nephrol Suppl 1997;183:55-7; discussion 57-8  
A review of the literature concerning the use of enuresis alarms highlighted the lack of standardised definitions used to define enuresis and the insufficient understanding of the working mechanisms of alarms. Although first reported in 1904, enuresis alarms were not in routine use until the 1930's. Sensors in the bed or underwear, in conjunction with audible warning devices are the most common types of alarms. The alarm success rate of approximately 75% is independent of the type of alarm and there is a low relapse rate. In predicting alarm response, studies utilizing multivariate analysis techniques are superior to univariate techniques, but no one or combination of predictor variables is currently known to predict outcome accurately enough to alter standard clinical decision making. It is imperative that definitions are standardized and that study protocols are applied uniformly to well-defined populations that have a better potential response to enuresis alarms-the best intervention currently available.  
7. Alarm treatment: influence on functional bladder capacity.
Hansen AF, Jorgensen TM
International Enuresis Research Centre, Skejby Hospital, University Hospital of Aarhus, Denmark.
Scand J Urol Nephrol Suppl 1997;183:59-60  
Home recordings were used to study the effect of alarm treatment, over a period of 6 weeks, in children with monosymptomatic nocturnal enuresis. Vasopressin day/night ratios were shown to be a good indicator of alarm treatment success. Serial measurement of plasma vasopressin levels is, however, unsuitable for use in the clinic, as extensive analyses would have to be performed to obtain the necessary results. Use of an alarm increased nocturnal bladder capacity, but had no effect on daytime bladder capacity, sleep patterns, vasopressin secretion, nocturnal urine output or pelvic floor activity. In addition, the results of the study suggest that an alarm treatment period of 2 months would lead to more successful results than the 6 weeks used in the study.  

8. Nocturnal enuresis.

Schmitt BD
University of Colorado School of Medicine, Denver, USA.
Pediatr Rev 1997 Jun;18(6):183-90; quiz 91  
The answer to nocturnal enuresis is nocturnal self-awakening. Enuresis alarms teach this skill and, therefore, have the highest cure rate and the lowest relapse rate of any intervention. An alarm costs the same as a 2-week supply of desmopressin. Alarms can be used anytime from age 5 onward if the child elects to use one. If an alarm alone is not successful, combining it with medication increases the cure rate. The ability to teach a family how to use an enuresis alarm is an important part of pediatric office practice.  

9. Treatment of isolated nocturnal enuresis: alarm or desmopressin?

[Article in French]
Faraj G, Cochat P, Cavailles ML, Chevallier C
Unite de nephrologie pediatrique, hopital Edouard-Herriot, Lyon, France.
Arch Pediatr 1999 Mar;6(3):271-4  
BACKGROUND: Monosymptomatic nocturnal enuresis is common in healthy school children. Treatment is often required because of social and psychological convenience. We therefore conducted a randomized prospective trial using either desmopressin (D) or alarm (A). PATIENTS AND METHODS: Patients (n = 135) aged 6 to 16 years were enrolled between January 1992 and December 1994. Desmopressin (Minirin spray, Ferring SA) was given intranasally at a dose of 20 micrograms at bedtime and increased to 40 micrograms after 2 weeks if partial result was obtained. The alarm was a pad-bell device and the sound source was attached to the upper part of the pajamas. Inclusion criteria were: primary monosymptomatic nocturnal enuresis in healthy children, age > or = 6 years, absence of previous treatment using either desmopressin or alarm. The aim of the treatment was to achieve 100% dry nights. Patients were evaluated after 15 days on therapy by phone call and thereafter by attending the outpatient clinic at 2-3 and 4-6 months. At the time of the second evaluation, a switch from alarm to desmopressin (or vice-versa) was proposed to those who did not respond to the initial treatment. RESULTS: In group D (n = 62), only 27 children were included since 12 (19%) were switched to alarm and 23 (37%) were excluded because they were either non-compliant or lost to follow-up. In group A (n = 73), only 31 were included since six (8%) were switched to desmopressin and 36 (49%) were excluded for the same reasons as in group D. Prior to inclusion, the percentage of dry nights was 21% in group D and 14% in group A. After 15 days on therapy, patients from group D achieved 80% dry nights compared to 50% in group A (P = 0.001). After 3 months, patients from group D attained 85% dry nights vs 90% in group A. After 6 months, children from group A achieved 94% dry nights vs 78% in group D (P = 0.01). CONCLUSION: Desmopressin offers better short-term results than enuresis alarm but the latter is significantly more efficient in the long term. In France, the alarm device is not reimbursed by the national health service and therefore is poorly accepted, as suggested from the high rate of patients lost to follow-up.

10. Evaluation and treatment of the enuretic child: eight years' experience.

[Article in Italian]
Bartolozzi G, Boldrini A, Salmeri A, Vitali E
Clinica Pediatrica I, Universita di Firenze, Ospedale Meyer, Italia.
Pediatr Med Chir 1991 Jul-Aug;13(4):389-93  
Enuresis is a common functional problem among children which is defined as a complete involuntary voiding of urine at an age which control should be present. Bed wetting generally resolves with increasing age, but the restriction in social life and the psychological secondary problems, so frequent in older patients, justify an appropriate treatment of the problem in the child over seven. At children's Hospital of Florence University an enuresis service exists since 1983, and during these years 541 children applied to the structure. 326 children completed the treatment, among these there were 202 boy and 124 girls with age between 6 and 19. All the patients have been initially helped only with conversation (motivational counseling) and 76 among them (23% of the whole) obtained permanent cure. The remaining 250 children were treated with the conditioning alarm system, always associated to periodic conversation, urine stop exercises and other psychological support (token economy, etc). There were 161 boys and 89 girls: 220 children had nocturnal primary enuresis and 30 secondary. The family history was positive in 77%. The results obtained of this kind of treatment after a follow-up of 6 months, were permanent recovery in 211 children (84%) and failure in 39 patients (16% of the cases). There have been 35 relaxes. Regarding the sex, no significant difference was noted. These positive results with the conditioning devices favor the view that the etiology of primary enuresis is mainly biologic. The bell alarm represents the most effective treatment for nocturnal enuresis included more than seven.  
11. A study of conditioning treatment of nocturnal enuresis by buzzer alarms.
[Article in Japanese]
Yachiku S, Kaneko S, Kurita T, Yachiku S
Department of Urology, School of Medicine, Kinki University.
Hinyokika Kiyo 1989 Apr;35(4):597-601  
A study of conditioning treatment with a buzzer alarm was made on 50 children with functional enuresis. The treatment was completely effective in 28 patients (56%), satisfactorily effective in 12 patients (24%), fairly effective in 9 patients (18%) and ineffective in 1 patient (2%). COmbining the numbers of the completely effective and satisfactorily effective groups, the cured rate was 80%. Within 3 months, 26% of the subjects were completely cured and 2% satisfactorily cured, and within 6 months, 44% were completely cured and 16% satisfactorily cured. This means that 60% were satisfactorily cured or better within 6 months. Though symptom of enuresis relapsed in 5 patients, all of them were finally cured. The treatment of enuresis with the alarm system was significantly more effective than medical treatment using tricyclic antidepressants and so on, and was assessed as the most successful treatment available at the present time.  
12. Treatment of nocturnal enuresis with a sound alarm. Study of 130 cases.
[Article in Italian]
Bartolozzi G, Savino B, Calzolari C, Danti DA, Ricciardi R, Ceretelli P
Pediatr Med Chir 1985 Jan-Feb;7(1):115-20  
Nocturnal enuresis is a very common problem in childhood, various treatment have been suggested to cure bed-wetting, but the two most commonly used methods are the buzzer alarm and drugs. At Children's Hospital of Florence University, we dealt a trial to evaluate the effectiveness of conditioning treatment for nocturnal enuresis. We used a model alarm called "bell and pad". The child sleeps on a detector mechanism such as two separate metal mats that are connected with a buzzer alarm. When the voided urine wets the sheet, completing the electrical circuit, triggers the alarm and the child awakes. With repetition and unconscious inhibitory reflex is developed. 130 children were treated, 84 males and 46 females. Subjects were at least 6 years of age and not older than 15. 112 children had nocturnal primary enuresis and 18 secondary. The family history was positive in 70%. We had an initial interview with child and his parents. During this initial approach we explained the conditioning treatment. The child was given a diary card to record the bedwetting nights. We liked to see the child at three weekly intervals. After the child was dry for three consecutive weeks the metal mats was removed the bed. After a further three weeks of dryness the alarm was returned. Out of 130 cases there have been 109 cures (83%), whereas 21 (17%) haven't achieved dryness. There have been 14 relapses. Most children (77%) became dry within 12 weeks. The children with nocturnal secondary enuresis achieved later dryness. We believe that the use of enuresis alarm gives a high cure rate.  
13. Primary nocturnal enuresis: a comparison among observation, imipramine, desmopressin acetate and bed-wetting alarm systems.
Monda JM, Husmann DA
Department of Urology, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Urol 1995 Aug;154(2 Pt 2):745-8  
Patients with primary nocturnal enuresis were entered into 4 treatment groups: observation, imipramine, desmopressin acetate or alarm therapy. Patients were weaned from therapy 6 months after inclusion in the study and were evaluated for continence at 3, 6, 9 and 12 months after beginning the study protocol. Of the 50 patients under observation 6% were continent at 6 months and 16% were continent within 12 months. Of 44 patients treated with imipramine 36% were continent at 6 months on medication; however, only 16% were continent at 12 months, off medication. Similarly, of the 88 patients treated with desmopressin acetate 68% were continent at 6 months but only 10% were continent at 12 months. Of the 79 patients treated with alarm therapy 63% were continent at 6 months and 56% were dry at 12 months. Although each form of therapy improved continence over observation alone (p < 0.01), only the bed-wetting alarm system demonstrated persistent effectiveness (p < 0.001).  
14. Combined treatment with enuresis alarm and desmopressin for nocturnal enuresis.
Bradbury MG, Meadow SR
Department of Paediatrics and Child Health, St James's University Hospital, Leeds, UK.
Acta Paediatr 1995 Sep;84(9):1014-8  
Seventy-one children with nocturnal enuresis were enrolled in a controlled trial. The children were allocated to two matched groups. Children in both groups used an enuresis alarm until the end of treatment. Children in the first group were treated with 40 micrograms of intranasal desmopressin (Desmospray) for up to 6 weeks at the start of treatment with the alarm. During the observation period treatment there were 2.3 dry nights per week in both groups. At the end of treatment there was a significant difference in the mean number of dry nights per week between the two groups (6.3 in the alarm and desmopressin group and 4.8 in the alarm group) and also in the number of children becoming reliably dry. The combination of desmopressin and alarm was particularly helpful for children with severe wetting and those with family and behavioural problems.  
15. Combination therapy for nocturnal enuresis with desmopressin and an alarm device.
Bradbury M
School of Medicine, Division of Paediatrics and Child Health, St. James's Hospital, Leeds, UK.
Scand J Urol Nephrol Suppl 1997;183:61-3  
The efficacy of alarm monotherapy (35 children) was compared with the efficacy of alarm treatment in combination with 40 micrograms desmopressin (Minirin, DDAVP) nasal spray (36 children). At the end of the treatment period, children receiving combination therapy had more dry nights per week (mean: 6.1) than children using an alarm alone (mean: 4.8). In addition, more children achieved an initial success (4 weeks of dryness) following combination treatment (27 children [75%]) compared with alarm monotherapy (16 children [46%], P < 0.005). This improvement with alarm plus desmopressin was particularly pronounced in children with severe wetting (> or = 6 nights per week), family problems or behavioural problems. It may, therefore, be appropriate to manage children in these categories with an enuresis alarm supplemented with desmopressin to improve treatment outcome.  
16. Efficacy, safety, and dosing of desmopressin for nocturnal enuresis in Europe.
Hjalmas K, Bengtsson B
Ostra Hospital, Gothenburg, Sweden.
Clin Pediatr (Phila) 1993 Jul;Spec No:19-24  
Desmopressin is a potent antidiuretic for nocturnal enuresis with few and mostly insignificant adverse reactions. Almost 80 years ago, the antidiuretic effects of extracts of the posterior pituitary were first reported. The molecular structure of the peptide vasopressin arginine vasopressin (AVP) became known in 1956, and by 1967, a synthesized modification of AVP, known as DDAVP, or desmopressin, was introduced. Toxicity studies performed on experimental animals support the conclusion that desmopressin is considerably more potent as an antidiuretic than AVP and has an exceptional safety margin. Further, clinical experience reveals that from 1974 to June 1992 only 21 patients using desmopressin had serious adverse reactions (water intoxication), and no fatalities occurred. Seven of 10 children with nocturnal enuresis who receive desmopressin stop their bedwetting completely or reduce it significantly, with best results noted in children over 10 years of age. Given these results, the preferred treatment in Europe for children with nocturnal enuresis is the sequential combination of desmopressin and the enuresis alarm.  
17. Combined therapy of enuresis alarm and desmopressin in the treatment of nocturnal enuresis.
Sukhai RN, Mol J, Harris AS
Zuiderziekenhuis Rotterdam, Afdeling Kindergeneeskunde, The Netherlands.
Eur J Pediatr 1989 Feb;148(5):465-7  
Twenty-eight children with primary nocturnal enuresis were blindly allocated at random to a combination of enuresis alarm and 20 micrograms intranasal desmopressin or alarm and placebo for 2 weeks. Patients received the other therapy after a 2-week treatment-free period. The combined treatment of desmopressin and alarm showed 5.1 +/- 0.4 (mean +/- SEM) dry nights per week and resulted in significantly more dry nights per week during the 2 weeks of observation than placebo and alarm (4.1 +/- 0.4, P less than 0.05).  
18. Costs of the treatment of enuresis nocturna. Health economic consequences of alternative methods in the treatment of enuresis nocturna.
[Article in Danish]
Ankjaer-Jensen A, Sejr TE
Dansk Sygehus Institut, Kobenhavn.
Ugeskr Laeger 1994 Jul 25;156(30):4355-60  
The health economic consequences of treating nocturnal enuresis with a buzzer alarm is compared to treatment with Desmopressin. Based on age specific prevalence estimates and reported effects of the two treatments a cost-effectiveness analysis (CEA) was performed. The analysis showed a considerable difference between the costs of the two alternative treatments. A treatment based upon the buzzer alarm could result in a net saving to society of 19.2 million DKK, while a treatment based upon Desmopressin could result in expenses for society of 44.8 million DKK. A treatment based on a combination of the two will be economically neutral to the society. Treatment with a buzzer alarm or a combined treatment is therefore from a health economic point of view preferable. The health economic consequences of the introduction of new treatments are discussed, and it is recommended that health economic analyses are performed before the introduction of new treatments.  
19. Dry bed--but how? A follow-up study of children with enuresis treated with a bed alarm.
[Article in Danish]
Thomsen PH, Stromgren AS
Institut for psykiatrisk demografi, Psykiatrisk Hospital, Risskov.
Ugeskr Laeger 1991 Apr 8;153(15):1063-5  
At follow-up, 29 young adults treated previously (ages 7-14 years) for nocturnal enuresis by means of conditioning, mostly with a bed alarm, showed no excess of mental abnormalities, including psychosomatic symptoms. Most of the probands recollected the treatment as positive and effective. It is concluded that conditioning is effective in the treatment of nocturnal enuresis and that it does not seem to leave any undesirable after-effects. Nothing seems to indicate that omission of more intensive, conflict-solving psychotherapy has implied any disadvantage for the patient. Thus, the bed alarm method can still be recommended as the treatment of first choice.

ANA SAYFA