- Email: [email protected]
Combination of the Enuresis Alarm and Desmopressin: Second Line Treatment for Nocturnal Enuresis
Combination of the Enuresis Alarm and Desmopressin: Second Line Treatment for Nocturnal Enuresis Konstantinos Kamperis,* Soren Hagstroem, Soren Rittig and Jens C. Djurhuus From the Clinical Institute, University of Aarhus and Department of Pediatrics, Aarhus University Hospital, Skejby Sygehus (SR), Aarhus, Denmark
Purpose: We sought to evaluate the combination of the enuresis alarm and desmopressin in treating children with enuresis. Materials and Methods: A retrospective analysis was performed on data from 423 children treated at our clinics with the enuresis alarm during the years 2000 to 2004. Frequency volume charts and desmopressin titration facilitated characterization of the participants using the current International Children’s Continence Society standardization. Children were treated with the enuresis alarm as monotherapy before the addition of desmopressin, which commenced after 6 weeks in patients exhibiting inadequate response to alarm or after 2 weeks in patients experiencing multiple enuretic episodes per night or showing no indication of improvement. Results: Of the initial population 315 children (74%) were treated only with alarm, of whom 290 became dry. A total of 108 children (26%) were treated with a combination of alarm and desmopressin, with 80 being cured. Children dry on alarm therapy were not different from those needing the addition of desmopressin in terms of demographics. Children dry on desmopressin plus alarm had higher average nocturnal urine production on wet nights (303 ⫾ 12 ml compared to 269 ⫾ 5 ml, p ⬍0.001). Maximum voided volume before treatment corrected for age was not different between children dry on alarm and those dry on combination therapy (0.84 ⫾ 0.02 compared to 0.86 ⫾ 0.05, not significant). Conclusions: Children needing the addition of desmopressin have a higher nocturnal urine production on wet nights but do not seem to differ in terms of bladder reservoir function characteristics. Key Words: acoustic stimulation, deamino arginine vasopressin, urinary bladder, polyuria, nocturnal enuresis
onditioning with the enuresis alarm is a common remedy in the treatment of nocturnal enuresis. Although the principles of alarm device treatment of nocturnal enuresis were first described in 1904,1 the clinical effect was demonstrated several decades later.2 Today the ease of use, proved efficacy and lack of adverse events make the enuresis alarm first line treatment,3,4 and recent research has revealed factors influencing the efficacy. There is sharp contrast among the number of theories that have been suggested regarding the mechanism of action of nocturnal enuresis, the characteristics of patients responding to treatment and the number of scientific studies addressing the issue. Modern enuresis treatment is dictated by pathophysiology, and the enuresis alarm is first line treatment in children with bladder reservoir function problems. However, there is a significant overlap between the populations of children with bladder function abnormalities and nocturnal polyuria, and physicians treating enuresis are often confronted with the difficult task of treating children with both conditions. During recent years treatment modalities consisting of a combination of different remedies have
C
Submitted for publication July 4, 2007. Study received approval of Danish Data Protection Agency. Presented at the biennial meeting of the International Children’s Continence Society, Antalya, Turkey, September 14-17, 2006. * Correspondence: Department of Pediatrics, Aarhus University Hospital Skejby, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark (telephone: 45-89496773; e-mail: [email protected]).
See Editorial on page 817.
0022-5347/08/1793-1128/0 THE JOURNAL OF UROLOGY® Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION
emerged but unfortunately they are seldom based on experimental data. This retrospective analysis concerns a population of children with enuresis treated at our outpatient clinics with the enuresis alarm as monotherapy or in combination with desmopressin during a period of 5 years. We evaluated the characteristics of the responders and nonresponders, and tried to define parameters that could predict the necessity of the addition of dDAVP to the enuresis alarm.
MATERIALS AND METHODS Study Subjects and Diagnostic Protocol A total of 908 patients were referred to our institution during the period 2000 to 2004. In this study we analyzed data from all children treated with the enuresis alarm during this period. The diagnostic protocol of our clinics consists of uroflowmetry and urinalysis, which was performed in all children, as well as home recordings. Standard frequency volume charts and 2-week titration with dDAVP allowed characterization of the patients according to the latest International Children’s Continence Society standardization in terms of diagnosis (nocturnal enuresis with or without daytime symptoms) and dDAVP response.5 Expected bladder capacity for age was calculated for all children using the formula, bladder capacity (ml) ⫽ age(years) ⫻ 30 ⫹ 30.6 Maximum voided volumes and average voided volumes were expressed as ratio to the expected maximum voided volume for age, and were used to evaluate bladder reservoir func-
1128
Vol. 179, 1128-1131, March 2008 Printed in U.S.A. DOI:10.1016/j.juro.2007.10.088
COMBINATION OF ALARM AND DESMOPRESSIN FOR NOCTURNAL ENURESIS
1129
RESULTS
FIG. 1. Flow of patients across alarm treatment protocol
tion. Based on home recordings, several parameters were calculated and used for comparisons, including corrected MVV, aVV, VF, and wNV and dNV.
Figure 1 demonstrates the flow of patients treated with an enuresis alarm. The table summarizes demographic data, bladder characteristics and nocturnal urine production of responders and nonresponders treated with alarm and alarm plus desmopressin. In terms of age and gender no differences were seen between responders and nonresponders to alarm, and children treated with alarm plus desmopressin. The overall male-to-female ratio was 2.7:1. Of the initial population of children treated with alarm 216 (51%) were characterized as having monosymptomatic nocturnal enuresis, 207 (49%) presented with daytime symptoms and 13 (3%) were previously or are currently being treated for fecal incontinence. In 232 children (55%) family disposition for incontinence was seen. In 108 cases desmopressin was added to the enuresis alarm. Of 315 cases where alarm was used as monotherapy dryness was achieved in 290 and 25 did not receive combination treatment due to family decision or because another treatment modality was initiated. Based on this patient distribution, the groups used for comparisons were children dry on alarm, children dry on alarm plus desmopressin and nonresponders to combination treatment.
Enuresis Alarm Treatment Protocol At our clinics children with nocturnal enuresis were considered for treatment with the enuresis alarm after fecal incontinence and daytime incontinence were successfully treated. Generally, children treated with an alarm were dDAVP nonresponders. The enuresis alarms used were the Wet-Stop® and Petit Advance (Astrid Leisner and Son, Assens, Denmark), both of which use buzzers. During treatment with the alarm children were followed by our urotherapists every 2 weeks until dryness was achieved or treatment was discontinued. Desmopressin was added if no improvement with the alarm was seen during an initial period of at least 2 weeks, or if children were consistently experiencing more than 1 enuresis episode nightly. In those children showing improvement on alarm as monotherapy, even if inadequate, treatment was continued until cure or for at least 6 weeks. If at that point the response was less than 50%, desmopressin was added. Dose was titrated up to 0.4 mg tablets, 40 mcg spray or 240 mcg smelt tablets. Dryness was defined as no enuresis occurring during 3 consecutive weeks. Children registered the dry and wet nights at home.
Bladder Characteristics Bladder reservoir function was evaluated by age corrected maximum voided volumes, average voided volumes and voided frequency in the daytime. Overall, the population of children had maximum voided volumes significantly lower than expected for age (0.84 ⫾ 0.02, p ⬎0.001). We did not find differences in pretreatment values of MVV, aVV or VF between children dry with alarm monotherapy and those dry with alarm plus dDAVP (MVV 0.84 ⫾ 0.02 vs 0.86 ⫾ 0.05; aVV 0.70 ⫾ 0.03 ml vs 0.73 ⫾ 0.04 ml; VF 6.0 ⫾ 0.7 vs 5.8 ⫾ 0.2). Enuresis frequency was also similar between the 2 groups. When we analyzed data from the cases where alarm or combination treatment was unsuccessful we did not find any differences in terms of bladder reservoir function compared to cases that achieved dryness.
Statistical Analysis All parameters are expressed as mean ⫾ SE. Comparisons between groups were performed on pretreatment demographic, bladder and urine production characteristics using 1-way ANOVA with the least square difference as post hoc test, and Student’s t test.
Nocturnal Urine Production We then evaluated the home recordings of patients with regard to nocturnal urine production. We found that children achieving dryness with alarm monotherapy had significantly lower average wNV before treatment compared to children dry with alarm plus dDAVP (269 ⫾ 5 ml compared
Demographic data, bladder reservoir function and nocturnal urine production for participant groups Dry With Alarm No. pts Pt demographics: Mean yrs age ⫾ SD Gender Mean enuresis episodes/wk ⫾ SD Bladder characteristics: Mean ml MVV ⫾ SD Mean ml aVV ⫾ SD Mean daily VF ⫾ SD Nocturnal urine production: Mean ml wNV ⫾ SD* Mean ml dNV ⫾ SD
290
80
7.9 ⫾ 0.1 204 M, 86 F 6.4 ⫾ 0.1 0.84 ⫾ 0.02 0.70 ⫾ 0.02 6.0 ⫾ 0.7 268 191
Dry With Combination Therapy
⫾5 ⫾6
* p ⬍0.05. For all other parameters differences were not statistically significant.
Nonresponders 53
8.2 ⫾ 0.2 63 M, 17 F 6.4 ⫾ 0.1
8.5 ⫾ 0.2 41 M, 12 F 5.8 ⫾ 0.3
0.86 ⫾ 0.05 0.73 ⫾ 0.04 5.8 ⫾ 0.2
0.82 ⫾ 0.04 0.75 ⫾ 0.05 5.2 ⫾ 0.3
302 201
⫾ 12 ⫾ 13
285 213
⫾ 16 ⫾ 21
1130
COMBINATION OF ALARM AND DESMOPRESSIN FOR NOCTURNAL ENURESIS
FIG. 2. Box and whisker plots represent average nocturnal urine output on wet nights in children dry on alarm, children dry on alarm plus dDAVP therapy and nonresponders. Children dry on alarm plus dDAVP excreted larger volumes of urine during nights with enuresis.
to 302 ⫾ 12 ml, p ⬍0.01, fig. 2). Cases refractory to alarm treatment presented with nocturnal urine production that was not significantly different compared to responders (285 ⫾ 16 ml). Comparison of spontaneous dNV did not reveal differences between the groups. DISCUSSION Conditional treatment for nocturnal enuresis has been established as an efficient, safe and inexpensive treatment modality.3 Different theories exist as to the mechanisms of action and several predictive factors have been identified, with bladder capacity and high frequency of enuresis predicting positive outcome,7 while failure of the alarm to awaken the child, low parent concern, low maternal education and multiple enuretic episodes nightly predict a poor response to treatment.8,9 The net effect of alarm treatment seems to be improvement of bladder reservoir function.10 Thus, treatment with the enuresis alarm is considered first line therapy for enuretic cases with bladder capacity related problems. The enuresis alarm can be combined with dDAVP, and in the few studies found in the literature there seems to be evidence that the combination may be more effective than alarm as monotherapy,11–14 although data refuting this hypothesis are also available.15 The purpose of this retrospective study was to characterize the population of children who could benefit from a combination of alarm and dDAVP. During the years 2000 to 2004 a total of 908 children were referred to our clinics, and approximately 50% received treatment with an enuresis alarm. We were able to show that children responding to alarm as monotherapy shared the same demographic characteristics as those responding to alarm plus dDAVP therapy and those refractory to alarm treatment. Bladder function characteristics were not significantly different between the subgroups of children, although it was previously established that a large bladder capacity has a positive predictive value for alarm treatment. The data from our population do not seem to confirm this
hypothesis, but differences in population characteristics may account for these discrepancies. The children participating in this analysis had bladder capacities that were lower than predicted for age, which may be reflective of the fact that these children are a selected population of nonresponders to dDAVP. Nocturnal urine production was the main parameter that could predict the necessity of the addition of dDAVP in our population. Children dry on alarm plus dDAVP produced significantly more urine at night. This finding probably explains the need for antidiuresis at night to achieve dryness, and dDAVP represents a rational option. Considering the 2 main pathophysiological factors of enuresis— bladder reservoir function abnormalities and excess nocturnal urine production—it seems possible that these children requiring alarm plus dDAVP therapy to achieve dryness share elements of both enuresis prototypes, namely small bladder and nocturnal polyuria. The addition of dDAVP to alarm seems to improve its efficacy, and this combination may even be the treatment of choice in cases where dDAVP and the alarm are inadequate as monotherapy. Further optimization of treatment of the enuresis alarm as well as the characterization of the patient subgroups that could benefit from such treatment strategy are goals of future enuresis research. CONCLUSIONS Children needing a combination of alarm and dDAVP therapy to achieve dryness present with larger urine output at night compared to those dry with an alarm as monotherapy. The addition of dDAVP may further optimize the conditional treatment of enuresis.
Abbreviations and Acronyms aVV dDAVP dNV MVV NS VF wNV
⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽
average voided volume desmopressin nocturnal urine output on dry nights maximum voided volume not significant voiding frequency nocturnal urine output on wet nights
REFERENCES 1.
Pfaundler M: Demonstration eines apparates zur selbsttatigen signalisierung stattgehabter bettnassung. Verh Ges Kinderheilkd 1904; 21: 219. 2. Mowrer OH: Apparatus for the study and treatment of enuresis. Am J Psychol 1938; 51: 163. 3. Glazener CM, Evans JH and Peto RE: Alarm interventions for nocturnal enuresis in children. Cochrane Database Syst Rev 2005; 2: CD002911. 4. Forsythe WI and Butler RJ: Fifty years of enuretic alarms. Arch Dis Child 1989; 64: 879. 5. Neveus T, von Gontard A, Hoebeke P, Hjalmas K, Bauer S, Bower W et al: The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children’s Continence Society. J Urol 2006; 176: 314. 6. Koff SA: Estimating bladder capacity in children. Urology 1983; 21: 248. 7. Berg I, Forsythe I and McGuire R: Response of bedwetting to the enuresis alarm. Influence of psychiatric disturbance
COMBINATION OF ALARM AND DESMOPRESSIN FOR NOCTURNAL ENURESIS and maximum functional bladder capacity. Arch Dis Child 1982; 57: 394. 8. Jensen IN and Kristensen G: Frequency of nightly wetting and the efficiency of alarm treatment of nocturnal enuresis. Scand J Urol Nephrol 2001; 35: 357. 9. Moffatt ME and Cheang M: Predicting treatment outcome with conditioning alarms. Scand J Urol Nephrol, suppl., 1995; 173: 119. 10. Hvistendahl GM, Kamperis K, Rawashdeh YF, Rittig S and Djurhuus JC: The effect of alarm treatment on the functional bladder capacity in children with monosymptomatic nocturnal enuresis. J Urol 2004; 171: 2611. 11. Bradbury MG and Meadow SR: Combined treatment with enuresis alarm and desmopressin for nocturnal enuresis. Acta Paediatr 1995; 84: 1014.
12.
1131
Gibb S, Nolan T, South M, Noad L, Bates G and Vidmar S: Evidence against a synergistic effect of desmopressin with conditioning in the treatment of nocturnal enuresis. J Pediatr 2004; 144: 351. 13. Leebeek-Groenewegen A, Blom J, Sukhai R and Van Der Heijden B: Efficacy of desmopressin combined with alarm therapy for monosymptomatic nocturnal enuresis. J Urol 2001; 166: 2456. 14. Sukhai RN, Mol J and Harris AS: Combined therapy of enuresis alarm and desmopressin in the treatment of nocturnal enuresis. Eur J Pediatr 1989; 148: 465. 15. Naitoh Y, Kawauchi A, Yamao Y, Seki H, Soh J, Yoneda K et al: Combination therapy with alarm and drugs for monosymptomatic nocturnal enuresis not superior to alarm monotherapy. Urology 2005; 66: 632.
Purpose: We sought to evaluate the combination of the enuresis alarm and desmopressin in treating children with enuresis. Materials and Methods: A retrospective analysis was performed on data from 423 children treated at our clinics with the enuresis alarm during the years 2000 to 2004. Frequency volume charts and desmopressin titration facilitated characterization of the participants using the current International Children’s Continence Society standardization. Children were treated with the enuresis alarm as monotherapy before the addition of desmopressin, which commenced after 6 weeks in patients exhibiting inadequate response to alarm or after 2 weeks in patients experiencing multiple enuretic episodes per night or showing no indication of improvement. Results: Of the initial population 315 children (74%) were treated only with alarm, of whom 290 became dry. A total of 108 children (26%) were treated with a combination of alarm and desmopressin, with 80 being cured. Children dry on alarm therapy were not different from those needing the addition of desmopressin in terms of demographics. Children dry on desmopressin plus alarm had higher average nocturnal urine production on wet nights (303 ⫾ 12 ml compared to 269 ⫾ 5 ml, p ⬍0.001). Maximum voided volume before treatment corrected for age was not different between children dry on alarm and those dry on combination therapy (0.84 ⫾ 0.02 compared to 0.86 ⫾ 0.05, not significant). Conclusions: Children needing the addition of desmopressin have a higher nocturnal urine production on wet nights but do not seem to differ in terms of bladder reservoir function characteristics. Key Words: acoustic stimulation, deamino arginine vasopressin, urinary bladder, polyuria, nocturnal enuresis
onditioning with the enuresis alarm is a common remedy in the treatment of nocturnal enuresis. Although the principles of alarm device treatment of nocturnal enuresis were first described in 1904,1 the clinical effect was demonstrated several decades later.2 Today the ease of use, proved efficacy and lack of adverse events make the enuresis alarm first line treatment,3,4 and recent research has revealed factors influencing the efficacy. There is sharp contrast among the number of theories that have been suggested regarding the mechanism of action of nocturnal enuresis, the characteristics of patients responding to treatment and the number of scientific studies addressing the issue. Modern enuresis treatment is dictated by pathophysiology, and the enuresis alarm is first line treatment in children with bladder reservoir function problems. However, there is a significant overlap between the populations of children with bladder function abnormalities and nocturnal polyuria, and physicians treating enuresis are often confronted with the difficult task of treating children with both conditions. During recent years treatment modalities consisting of a combination of different remedies have
C
Submitted for publication July 4, 2007. Study received approval of Danish Data Protection Agency. Presented at the biennial meeting of the International Children’s Continence Society, Antalya, Turkey, September 14-17, 2006. * Correspondence: Department of Pediatrics, Aarhus University Hospital Skejby, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark (telephone: 45-89496773; e-mail: [email protected]).
See Editorial on page 817.
0022-5347/08/1793-1128/0 THE JOURNAL OF UROLOGY® Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION
emerged but unfortunately they are seldom based on experimental data. This retrospective analysis concerns a population of children with enuresis treated at our outpatient clinics with the enuresis alarm as monotherapy or in combination with desmopressin during a period of 5 years. We evaluated the characteristics of the responders and nonresponders, and tried to define parameters that could predict the necessity of the addition of dDAVP to the enuresis alarm.
MATERIALS AND METHODS Study Subjects and Diagnostic Protocol A total of 908 patients were referred to our institution during the period 2000 to 2004. In this study we analyzed data from all children treated with the enuresis alarm during this period. The diagnostic protocol of our clinics consists of uroflowmetry and urinalysis, which was performed in all children, as well as home recordings. Standard frequency volume charts and 2-week titration with dDAVP allowed characterization of the patients according to the latest International Children’s Continence Society standardization in terms of diagnosis (nocturnal enuresis with or without daytime symptoms) and dDAVP response.5 Expected bladder capacity for age was calculated for all children using the formula, bladder capacity (ml) ⫽ age(years) ⫻ 30 ⫹ 30.6 Maximum voided volumes and average voided volumes were expressed as ratio to the expected maximum voided volume for age, and were used to evaluate bladder reservoir func-
1128
Vol. 179, 1128-1131, March 2008 Printed in U.S.A. DOI:10.1016/j.juro.2007.10.088
COMBINATION OF ALARM AND DESMOPRESSIN FOR NOCTURNAL ENURESIS
1129
RESULTS
FIG. 1. Flow of patients across alarm treatment protocol
tion. Based on home recordings, several parameters were calculated and used for comparisons, including corrected MVV, aVV, VF, and wNV and dNV.
Figure 1 demonstrates the flow of patients treated with an enuresis alarm. The table summarizes demographic data, bladder characteristics and nocturnal urine production of responders and nonresponders treated with alarm and alarm plus desmopressin. In terms of age and gender no differences were seen between responders and nonresponders to alarm, and children treated with alarm plus desmopressin. The overall male-to-female ratio was 2.7:1. Of the initial population of children treated with alarm 216 (51%) were characterized as having monosymptomatic nocturnal enuresis, 207 (49%) presented with daytime symptoms and 13 (3%) were previously or are currently being treated for fecal incontinence. In 232 children (55%) family disposition for incontinence was seen. In 108 cases desmopressin was added to the enuresis alarm. Of 315 cases where alarm was used as monotherapy dryness was achieved in 290 and 25 did not receive combination treatment due to family decision or because another treatment modality was initiated. Based on this patient distribution, the groups used for comparisons were children dry on alarm, children dry on alarm plus desmopressin and nonresponders to combination treatment.
Enuresis Alarm Treatment Protocol At our clinics children with nocturnal enuresis were considered for treatment with the enuresis alarm after fecal incontinence and daytime incontinence were successfully treated. Generally, children treated with an alarm were dDAVP nonresponders. The enuresis alarms used were the Wet-Stop® and Petit Advance (Astrid Leisner and Son, Assens, Denmark), both of which use buzzers. During treatment with the alarm children were followed by our urotherapists every 2 weeks until dryness was achieved or treatment was discontinued. Desmopressin was added if no improvement with the alarm was seen during an initial period of at least 2 weeks, or if children were consistently experiencing more than 1 enuresis episode nightly. In those children showing improvement on alarm as monotherapy, even if inadequate, treatment was continued until cure or for at least 6 weeks. If at that point the response was less than 50%, desmopressin was added. Dose was titrated up to 0.4 mg tablets, 40 mcg spray or 240 mcg smelt tablets. Dryness was defined as no enuresis occurring during 3 consecutive weeks. Children registered the dry and wet nights at home.
Bladder Characteristics Bladder reservoir function was evaluated by age corrected maximum voided volumes, average voided volumes and voided frequency in the daytime. Overall, the population of children had maximum voided volumes significantly lower than expected for age (0.84 ⫾ 0.02, p ⬎0.001). We did not find differences in pretreatment values of MVV, aVV or VF between children dry with alarm monotherapy and those dry with alarm plus dDAVP (MVV 0.84 ⫾ 0.02 vs 0.86 ⫾ 0.05; aVV 0.70 ⫾ 0.03 ml vs 0.73 ⫾ 0.04 ml; VF 6.0 ⫾ 0.7 vs 5.8 ⫾ 0.2). Enuresis frequency was also similar between the 2 groups. When we analyzed data from the cases where alarm or combination treatment was unsuccessful we did not find any differences in terms of bladder reservoir function compared to cases that achieved dryness.
Statistical Analysis All parameters are expressed as mean ⫾ SE. Comparisons between groups were performed on pretreatment demographic, bladder and urine production characteristics using 1-way ANOVA with the least square difference as post hoc test, and Student’s t test.
Nocturnal Urine Production We then evaluated the home recordings of patients with regard to nocturnal urine production. We found that children achieving dryness with alarm monotherapy had significantly lower average wNV before treatment compared to children dry with alarm plus dDAVP (269 ⫾ 5 ml compared
Demographic data, bladder reservoir function and nocturnal urine production for participant groups Dry With Alarm No. pts Pt demographics: Mean yrs age ⫾ SD Gender Mean enuresis episodes/wk ⫾ SD Bladder characteristics: Mean ml MVV ⫾ SD Mean ml aVV ⫾ SD Mean daily VF ⫾ SD Nocturnal urine production: Mean ml wNV ⫾ SD* Mean ml dNV ⫾ SD
290
80
7.9 ⫾ 0.1 204 M, 86 F 6.4 ⫾ 0.1 0.84 ⫾ 0.02 0.70 ⫾ 0.02 6.0 ⫾ 0.7 268 191
Dry With Combination Therapy
⫾5 ⫾6
* p ⬍0.05. For all other parameters differences were not statistically significant.
Nonresponders 53
8.2 ⫾ 0.2 63 M, 17 F 6.4 ⫾ 0.1
8.5 ⫾ 0.2 41 M, 12 F 5.8 ⫾ 0.3
0.86 ⫾ 0.05 0.73 ⫾ 0.04 5.8 ⫾ 0.2
0.82 ⫾ 0.04 0.75 ⫾ 0.05 5.2 ⫾ 0.3
302 201
⫾ 12 ⫾ 13
285 213
⫾ 16 ⫾ 21
1130
COMBINATION OF ALARM AND DESMOPRESSIN FOR NOCTURNAL ENURESIS
FIG. 2. Box and whisker plots represent average nocturnal urine output on wet nights in children dry on alarm, children dry on alarm plus dDAVP therapy and nonresponders. Children dry on alarm plus dDAVP excreted larger volumes of urine during nights with enuresis.
to 302 ⫾ 12 ml, p ⬍0.01, fig. 2). Cases refractory to alarm treatment presented with nocturnal urine production that was not significantly different compared to responders (285 ⫾ 16 ml). Comparison of spontaneous dNV did not reveal differences between the groups. DISCUSSION Conditional treatment for nocturnal enuresis has been established as an efficient, safe and inexpensive treatment modality.3 Different theories exist as to the mechanisms of action and several predictive factors have been identified, with bladder capacity and high frequency of enuresis predicting positive outcome,7 while failure of the alarm to awaken the child, low parent concern, low maternal education and multiple enuretic episodes nightly predict a poor response to treatment.8,9 The net effect of alarm treatment seems to be improvement of bladder reservoir function.10 Thus, treatment with the enuresis alarm is considered first line therapy for enuretic cases with bladder capacity related problems. The enuresis alarm can be combined with dDAVP, and in the few studies found in the literature there seems to be evidence that the combination may be more effective than alarm as monotherapy,11–14 although data refuting this hypothesis are also available.15 The purpose of this retrospective study was to characterize the population of children who could benefit from a combination of alarm and dDAVP. During the years 2000 to 2004 a total of 908 children were referred to our clinics, and approximately 50% received treatment with an enuresis alarm. We were able to show that children responding to alarm as monotherapy shared the same demographic characteristics as those responding to alarm plus dDAVP therapy and those refractory to alarm treatment. Bladder function characteristics were not significantly different between the subgroups of children, although it was previously established that a large bladder capacity has a positive predictive value for alarm treatment. The data from our population do not seem to confirm this
hypothesis, but differences in population characteristics may account for these discrepancies. The children participating in this analysis had bladder capacities that were lower than predicted for age, which may be reflective of the fact that these children are a selected population of nonresponders to dDAVP. Nocturnal urine production was the main parameter that could predict the necessity of the addition of dDAVP in our population. Children dry on alarm plus dDAVP produced significantly more urine at night. This finding probably explains the need for antidiuresis at night to achieve dryness, and dDAVP represents a rational option. Considering the 2 main pathophysiological factors of enuresis— bladder reservoir function abnormalities and excess nocturnal urine production—it seems possible that these children requiring alarm plus dDAVP therapy to achieve dryness share elements of both enuresis prototypes, namely small bladder and nocturnal polyuria. The addition of dDAVP to alarm seems to improve its efficacy, and this combination may even be the treatment of choice in cases where dDAVP and the alarm are inadequate as monotherapy. Further optimization of treatment of the enuresis alarm as well as the characterization of the patient subgroups that could benefit from such treatment strategy are goals of future enuresis research. CONCLUSIONS Children needing a combination of alarm and dDAVP therapy to achieve dryness present with larger urine output at night compared to those dry with an alarm as monotherapy. The addition of dDAVP may further optimize the conditional treatment of enuresis.
Abbreviations and Acronyms aVV dDAVP dNV MVV NS VF wNV
⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽
average voided volume desmopressin nocturnal urine output on dry nights maximum voided volume not significant voiding frequency nocturnal urine output on wet nights
REFERENCES 1.
Pfaundler M: Demonstration eines apparates zur selbsttatigen signalisierung stattgehabter bettnassung. Verh Ges Kinderheilkd 1904; 21: 219. 2. Mowrer OH: Apparatus for the study and treatment of enuresis. Am J Psychol 1938; 51: 163. 3. Glazener CM, Evans JH and Peto RE: Alarm interventions for nocturnal enuresis in children. Cochrane Database Syst Rev 2005; 2: CD002911. 4. Forsythe WI and Butler RJ: Fifty years of enuretic alarms. Arch Dis Child 1989; 64: 879. 5. Neveus T, von Gontard A, Hoebeke P, Hjalmas K, Bauer S, Bower W et al: The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children’s Continence Society. J Urol 2006; 176: 314. 6. Koff SA: Estimating bladder capacity in children. Urology 1983; 21: 248. 7. Berg I, Forsythe I and McGuire R: Response of bedwetting to the enuresis alarm. Influence of psychiatric disturbance
COMBINATION OF ALARM AND DESMOPRESSIN FOR NOCTURNAL ENURESIS and maximum functional bladder capacity. Arch Dis Child 1982; 57: 394. 8. Jensen IN and Kristensen G: Frequency of nightly wetting and the efficiency of alarm treatment of nocturnal enuresis. Scand J Urol Nephrol 2001; 35: 357. 9. Moffatt ME and Cheang M: Predicting treatment outcome with conditioning alarms. Scand J Urol Nephrol, suppl., 1995; 173: 119. 10. Hvistendahl GM, Kamperis K, Rawashdeh YF, Rittig S and Djurhuus JC: The effect of alarm treatment on the functional bladder capacity in children with monosymptomatic nocturnal enuresis. J Urol 2004; 171: 2611. 11. Bradbury MG and Meadow SR: Combined treatment with enuresis alarm and desmopressin for nocturnal enuresis. Acta Paediatr 1995; 84: 1014.
12.
1131
Gibb S, Nolan T, South M, Noad L, Bates G and Vidmar S: Evidence against a synergistic effect of desmopressin with conditioning in the treatment of nocturnal enuresis. J Pediatr 2004; 144: 351. 13. Leebeek-Groenewegen A, Blom J, Sukhai R and Van Der Heijden B: Efficacy of desmopressin combined with alarm therapy for monosymptomatic nocturnal enuresis. J Urol 2001; 166: 2456. 14. Sukhai RN, Mol J and Harris AS: Combined therapy of enuresis alarm and desmopressin in the treatment of nocturnal enuresis. Eur J Pediatr 1989; 148: 465. 15. Naitoh Y, Kawauchi A, Yamao Y, Seki H, Soh J, Yoneda K et al: Combination therapy with alarm and drugs for monosymptomatic nocturnal enuresis not superior to alarm monotherapy. Urology 2005; 66: 632.