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## Complete Summary

#### GUIDELINE TITLE

Evidence-based clinical practice guidelines: primary monosymptomatic
nocturnal enuresis in primary care.

#### BIBLIOGRAPHIC SOURCE(S)

Asociación Española de Pediatría de Atención Primaria (AEPap).
Evidence-based clinical practice guidelines: primary monosymptomatic
nocturnal enuresis in primary care. Rev Pediatr Atencion Prim 2005
Oct;VII(Suppl 3):1-149.

#### GUIDELINE STATUS

This is the current release of the guideline.

### \*\* REGULATORY ALERT \*\*

#### FDA WARNING/REGULATORY ALERT

Note from the National Guideline Clearinghouse: This guideline
references a drug(s) for which important revised regulatory and/or
warning information has been released.

-   [December 04, 2007, Desmopressin Acetate (DDAVP, DDVP, Minirin, &
    Stimate)](http://www.fda.gov/medwatch/safety/2007/safety07.htm#Desmopressin):
    New information has been added to the existing boxed warning in
    Desmopressin\'s prescribing information about potential increased
    risk for severe hyponatremia and seizures.

### COMPLETE SUMMARY CONTENT

 \*\* REGULATORY ALERT \*\*\
 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Primary monosymptomatic nocturnal enuresis

#### GUIDELINE CATEGORY

Diagnosis\
Evaluation\
Management\
Prevention\
Treatment

#### CLINICAL SPECIALTY

Family Practice\
Pediatrics\
Urology

#### INTENDED USERS

Health Care Providers\
Nurses\
Physicians

#### GUIDELINE OBJECTIVE(S)

To provide evidence-based clinical practice guidelines that analyze the
evidence and help in the decision-making process of prevention,
diagnosis, and treatment of primary monosymptomatic nocturnal enuresis
(PMNE)

#### TARGET POPULATION

Children with primary monosymptomatic nocturnal enuresis (PMNE) (i.e.,
children 5 years of age or older, attended in Primary Care, who have not
had a dry period lasting for 6 months or longer)

#### INTERVENTIONS AND PRACTICES CONSIDERED

**Prevention/Risk Assessment**

1.  Toilet training strategies (for prevention of incontinence)

2.  Risk factor assessment (comorbid conditions such as chronic headache
    or attention-deficit hyperactivity disorder,
    constipation/encopresis, sleep apnea)

**Diagnosis**

1.  Clinical interview

2.  Clinical examination

3.  Bladder diary

4.  Dipstick urinalysis

**Treatment**

1.  Simple behavioral interventions

2.  Complex and educational behavioral interventions

3.  Alarm intervention

4.  Pharmacological treatment:

    -   Desmopressin (intranasal, oral)

    -   Desmopressin associated with anticholinergics (not recommended
        routinely)

5.  Follow-up and withdrawing treatment

#### MAJOR OUTCOMES CONSIDERED

-   Response to treatment assessed in terms of:

    -   Initial success (14 consecutive dry nights)

    -   Complete dryness (100% dry nights)

    -   Full response (\>90% decrease in wet nights versus baseline)

    -   Cure (initial success or full response, without relapse)

-   Quality of life

-   Patient and parental satisfaction

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Hand-searches of Published Literature (Secondary Sources)\
Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

**[Systematic Strategy for the Bibliographic Search]{.underline}**

The systematic review of the literature only covered studies reported in
Spanish, English and French. Searches were made in:

*Secondary Sources of Information*

[Major]{.underline}

1.  Cochrane Collaboration

2.  Clinical practice guides (CPGs):

    -   Centers that prepare CPGs: American Academy of Pediatrics, New
        Zealand Guidelines Group, Cincinnati Children\'s Hospital
        Medical Center

    -   CPG storage centers: National Guideline Clearinghouse, CMA
        Infobase, Primary Care Clinical Practice Guidelines, NeLH
        Guideline Finder

3.  Reports by Health Technology Assessment Agencies: Health Technology
    Assessment Database-HTA

[Minor]{.underline}

4.  Journals with structured abstracts: ACP Journal Club, Clinical
    Evidence on line, Bandolier

5.  Files of critically appraised topics: AEPap, CATs

[Global]{.underline}

6.  EBM databases: TRIP/SUMSearch and The Database of Abstracts of
    Reviews of Effectiveness-DARE)

*Primary Sources of Information*

1.  Traditional bibliographic databases: Medline with its electronic
    version PubMed, Embase, IME

2.  Traditional medical journals

3.  Textbooks

*Grey Literature/Manual Search*

**[Selection Criteria (Inclusion-Exclusion)]{.underline}**

Studies were selected according to the following criteria in the
searches:

-   They should deal with children and adolescents. PubMed goes up to 18
    years of age (in exceptional cases, and when there was no data
    exclusively obtained on children and adolescents, authors accepted
    mixed inclusion with adults, with explicit reference made in the
    text).

-   They should deal with primary monosymptomatic nocturnal enuresis
    (PMNE).

-   Outpatient setting: If specific information was not available
    according to these criteria, studies with general criteria were
    included (e.g., hospital setting, different types of enuresis), but
    this was always specified in the results.

-   Quality criteria: The highest quality articles have always been
    selected on each aspect evaluated.

-   Years of searches: Searches were made in databases from the lower
    limit of each one up to August 2004.

**[Types of Studies Included]{.underline}**

**Studies of Associated Factors in PMNE**

-   Systematic reviews

-   Cohort studies

-   Case-control studies

-   Case studies

-   Population surveys

**Diagnostic Studies**

-   Validation of diagnostic tests

-   Systematic reviews

-   Cohort studies

-   Case-control and cross-sectional studies

**Treatment Studies**

-   Systematic reviews and meta-analyses

-   Controlled clinical trials

-   Cohort and case-control studies

-   Case studies

The specific key words for each subject critically assessed are
described in Table IX of the original guideline document.  The details
of the search strategy for each subject are presented in Chapter 6 of
the original guideline document.

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2001)

  --------------------------------------------------------------------------------------------------------------------------------
  **Level**   ** **               **Therapy/Prevention   **Prognosis**     **Diagnosis**     **Differential      **Economic and
                                  Aetiology/Harm**                                           Diagnosis/Symptom   Decision
                                                                                             Prevalence Study**  Analyses**
  ----------- ------------------- ---------------------- ----------------- ----------------- ------------------- -----------------
  **I**       **At Least One                                                                                     
              Controlled Clinical                                                                                
              Trial Appropriately                                                                                
              Randomized**                                                                                       

              a                   SR (with               SR (with          SR (with          SR (with            SR (with
                                  homogeneity^a^) of     homogeneity^a^)   homogeneity^a^)   homogeneity^a^) of  homogeneity^a^)
                                  RCTs                   of inception      of Level 1        prospective cohort  of Level 1
                                                         cohort studies;   diagnostic        studies             economic studies
                                                         CDR^b^ validated  studies; CDR^b^                       
                                                         in different      with 1b studies                       
                                                         populations       from different                        
                                                                           clinical centres                      

              b                   Individual RCT (with   Individual        Validating^k^     Prospective cohort  Analysis based on
                                  narrow Confidence      inception cohort  cohort study with study with good     clinically
                                  Interval^c^)           study with \> 80% good^i^ reference follow-up^m^        sensible costs or
                                                         follow- up;       standards; or                         alternatives;
                                                         CDR^b^ validated  CDR^b^ tested                         systematic
                                                         in a single       within one                            review( s) of the
                                                         population        clinical centre                       evidence; and
                                                                                                                 including
                                                                                                                 multi-way
                                                                                                                 sensitivity
                                                                                                                 analyses

              c                   All or none^d^         All or none case  Absolute SpPins   All or none case    Absolute
                                                         series            and SnNouts^g^    series              better-value or
                                                                                                                 worse-value
                                                                                                                 analyses^j^

  **II**      **Cohort Studies                                                                                   
              and Studies of                                                                                     
              Final Outcomes**                                                                                   

              a                   SR (with               SR (with          SR (with          SR (with            SR (with
                                  homogeneity^a^) of     homogeneity^a^)   homogeneity^a^)   homogeneity^a^) of  homogeneity^a^)
                                  cohort studies         of either         of Level \>2      2b and better       of Level \>2
                                                         retrospective     diagnostic        studies             economic studies
                                                         cohort studies or studies                               
                                                         untreated control                                       
                                                         groups in RCTs                                          

              b                   Individual cohort      Retrospective     Exploratory^k^    Retrospective       Analysis based on
                                  study (including low   cohort study or   cohort study with cohort study, or    clinically
                                  quality RCT; e.g., \<  follow-up of      good^i^ reference poor follow-up      sensible costs or
                                  80% follow-up)         untreated control standards; CDR^b^                     alternatives;
                                                         patients in an    after derivation,                     limited review(s)
                                                         RCT; Derivation   or validated only                     of the evidence,
                                                         of CDR† or        on                                    or single
                                                         validated on      split-sample^f^                       studies; and
                                                         split-sample^f^   or databases                          including
                                                         only                                                    multi-way
                                                                                                                 sensitivity
                                                                                                                 analyses

              c                   \"Outcomes\" research, \"Outcomes\"                        Ecological studies  Audit or outcomes
                                  ecological studies     Research                                                research

  **III**     **Case-controls**                                                                                  

              a                   SR (with                                 SR (with          SR (with            SR (with
                                  homogeneity^a^) of                       homogeneity^a^)   homogeneity^a^) of  homogeneity^a^)
                                  case-control studies                     of 3b and better  3b and better       of 3b and better
                                                                           studies           studies             studies

              b                   Individual                               Non-consecutive   Non-consecutive     Analysis based on
                                  Case-Control Study                       study; or without cohort study, or    limited
                                                                           consistently      very limited        alternatives or
                                                                           applied reference population          costs, poor
                                                                           standards                             quality estimates
                                                                                                                 of data, but
                                                                                                                 including
                                                                                                                 sensitivity
                                                                                                                 analyses
                                                                                                                 incorporating
                                                                                                                 clinically
                                                                                                                 sensible
                                                                                                                 variations.

  **IV**                          Case-series (and poor  Case-series (and  Case-control      Case-series or      Analysis with no
                                  quality cohort and     poor quality      study, poor or    superseded          sensitivity
                                  case-control           prognostic cohort non-independent   reference standards analysis
                                  studies^e^)            studies^l^)       reference                             
                                                                           standard                              

  **V**                           Expert opinion without Expert opinion    Expert opinion    Expert opinion      Expert opinion
                                  explicit critical      without explicit  without explicit  without explicit    without explicit
                                  appraisal, or based on critical          critical          critical appraisal, critical
                                  physiology, bench      appraisal, or     appraisal, or     or based on         appraisal, or
                                  research or \"first    based on          based on          physiology, bench   based on economic
                                  principles\"           physiology, bench physiology, bench research or \"first theory or \"first
                                                         research or       research or       principles\"        principles\"
                                                         \"first           \"first                               
                                                         principles\"      principles\"                          
  --------------------------------------------------------------------------------------------------------------------------------

**Notes**:

Users can add a minus-sign \"-\" to denote the level of evidence that
fails to provide a conclusive answer because of:

-- EITHER a single result with a wide Confidence Interval (such that,
for example, an ARR in an RCT is not statistically significant but whose
confidence intervals fail to exclude clinically important benefit or
harm)

-- OR a Systematic Review with troublesome (and statistically
significant) heterogeneity.

-- Such evidence is inconclusive, and therefore can only generate Grade
D recommendations.

^a^ By homogeneity the guideline authors mean a systematic review that
is free of worrisome variations (heterogeneity) in the directions and
degrees of results between individual studies. Not all systematic
reviews with statistically significant heterogeneity need be worrisome,
and not all worrisome heterogeneity need be statistically significant.
As noted above, studies displaying worrisome heterogeneity should be
tagged with a \"-\" at the end of their designated level.

^b^ Clinical Decision Rule. (These are algorithms or scoring systems
which lead to a prognostic estimation or a diagnostic category.)

^c^ See note #2 for advice on how to understand, rate and use trials or
other studies with wide confidence intervals.

^d^ Met when all patients died before the Rx became available, but some
now survive on it; or when some patients died before the Rx became
available, but none now die on it.

^e^ By poor quality cohort study the guideline authors mean one that
failed to clearly define comparison groups and/or failed to measure
exposures and outcomes in the same (preferably blinded), objective way
in both exposed and non-exposed individuals and/or failed to identify or
appropriately control known confounders and/or failed to carry out a
sufficiently long and complete follow-up of patients. By poor quality
case-control study the guideline authors mean one that failed to clearly
define comparison groups and/or failed to measure exposures and outcomes
in the same (preferably blinded), objective way in both cases and
controls and/or failed to identify or appropriately control known
confounders.

^f^ Split-sample validation is achieved by collecting all the
information in a single tranche, then artificially dividing this into
\"derivation\" and \"validation\" samples.

^g^ An \"Absolute SpPin\" is a diagnostic finding whose Specificity is
so high that a Positive result rules-in the diagnosis. An \"Absolute
SnNout\" is a diagnostic finding whose Sensitivity is so high that a
Negative result rules-out the diagnosis.

^h^ Good, better, bad and worse refer to the comparisons between
treatments in terms of their clinical risks and benefits.

^i^ Good reference standards are independent of the test, and applied
blindly or objectively to applied to all patients. Poor reference
standards are haphazardly applied, but still independent of the test.
Use of a non-independent reference standard (where the \'test\' is
included in the \'reference\', or where the \'testing\' affects the
\'reference\') implies a level 4 study.

^j^ Better-value treatments are clearly as good but cheaper, or better
at the same or reduced cost. Worse-value treatments are as good and more
expensive, or worse and the equally or more expensive.

^k^ Validating studies test the quality of a specific diagnostic test,
based on prior evidence. An exploratory study collects information and
trawls the data (e.g., using a regression analysis) to find which
factors are \'significant\'.

^l^ By poor quality prognostic cohort study the guideline authors mean
one in which sampling was biased in favour of patients who already had
the target outcome, or the measurement of outcomes was accomplished in
\<80% of study patients, or outcomes were determined in an unblinded,
non-objective way, or there was no correction for confounding factors.

^m^ Good follow-up in a differential diagnosis study is \>80%, with
adequate time for alternative diagnoses to emerge (e.g., 1 to 6 months
acute, 1 to 5 years chronic)

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review\
Systematic Review with Evidence Tables

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Any content whose scientific evidence was insufficient is referred to
explicitly. In these cases, the recommendation was reached by consensus
on the basis of standard of care in the Primary Care setting. The
\"Centre for Evidence-Based Medicine\" (CEBM) of Oxford classification
was used to grade the evidence (see \"Rating Scheme for the Strength of
the Evidence\" above). The guideline authors considered potential
clinical differences between the target population of their guidelines
and studies reported in the literature; for example, when the reported
study\'s scenario was not the community but rather the hospital or any
other scenario different from Primary Care, or if the study reported on
a type of enuresis different from primary monosymptomatic nocturnal
enuresis (PMNE). In this case extrapolation criterion were applied to
grade recommendations.

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

Guidelines for the appropriate decision making process of prevention,
risk factors, diagnosis and treatment of primary monosymptomatic
nocturnal enuresis (PMNE) are based on critical review of the available
data and expert consensus.

**Formulation of Clinical Questions**

-   The clinical questions were clearly defined and all alternatives to
    the decision and expected outcomes were identified.

-   All existing evidence was located systematically, evaluated
    critically, and then classified according to evidence-based medicine
    criteria, summarizing the best scientific evidence on each aspect.

-   Each of the decision points was identified where it was necessary to
    integrate this valid evidence with the clinician\'s expertise and
    patient preferences. Hence, the present guide is not of a regulatory
    nature, it sets out to accurately identify the range of potential
    decisions and to provide evidence that, together with clinical
    judgment, patient values and expectations, and the center\'s
    conditions, should make it easier to make the most appropriate
    decision in each case.

The authors identified areas of uncertainty regarding associated
factors, diagnosis, and treatment of primary PMNE.

**Questions Identified**

The areas of uncertainty were specified in the following questions:

*Risk Factors Associated with Enuresis*

1.  Is there any physical condition that is associated with PMNE?

2.  Is there any psychiatric condition that is associated with PMNE?

*Diagnosis*

1.  Does a urine culture or dipstick urinalysis need to be performed on
    all children with PMNE seeking care at the Healthcare Center?

2.  Do other diagnostic tests need to be carried out in children with
    PMNE seeking care at the Healthcare Center?

*Treatment*

1.  How efficacious is behavioral therapy?

2.  How efficacious is alarm behavioral therapy for enuresis?

3.  How efficacious is drug treatment with desmopressin?

4.  Have risk factors for treatment failure been described for the
    different treatments?

*Follow-up*

1.  For how long should treatment be continued?

2.  What is the most effective treatment withdrawal guideline?

3.  What are the indications for referral to an urologist?

**Timeline of the Elaboration of the Guidelines**

The working meetings took place from January 2004 to May 2005,
approximately every two weeks and outside of working hours.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

**Grades of Recommendation**

A.  Consistent level 1 studies

B.  Consistent level 2 or 3 studies or extrapolations\* from level 1
    studies

C.  Level 4 studies or extrapolations\* from level 2 or 3 studies

D.  Level 5 evidence or troublingly inconsistent or inconclusive studies
    of any level

\*Extrapolations are when data is used in a situation which has
potentially clinically important differences than the original study
situation.

Phillips B, Ball C, Sackett D, Badenoch D, Straus S, Haynes B, Dawes M.
Levels of evidence and grades of recommendations, 1998. Review May 2001.
Center for Evidence-Based Medicine (CEBM) of Oxford Available in English
at: [http://www.cebm.net](http://www.cebm.net/index.aspx?o=1025).

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

External Peer Review\
Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

The external review took place between January and February 2005 and the
assessment of applicability to Primary Care is still pending completion.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

Definitions for the grades of recommendations (**A, B, C, D**) are
provided at the end of the \"Major Recommendations.\"

**[Prevention]{.underline}**

The following attitudes have been shown to be beneficial in achieving
daytime urinary continence at an earlier age and avoiding dysfunctional
voiding. Although it is not known if they will also bring about the
onset of nocturnal urinary continence, it is recommended **\[C\]**:

-   Start toilet training before the age of 18 months, perhaps when the
    child is able to wake up dry from his/her nap.

-   Use of a pot or potty chair that properly supports his/her thighs
    and feet.

-   Suggest to the child that they should urinate when you see or
    imagine that they feel the urge, so that they can do so on the first
    try. Do not keep the child seated on the pot until he/she urinates
    and do not insist that they strain if the first attempt fails.

-   Be persistent in this training, because the objective can be
    achieved in less than three months. Do not dilute the effort by
    continually changing the technique.

**[Risk Factors Associated with Primary Monosymptomatic Nocturnal
Enuresis (PMNE)]{.underline}**

(See Table II \"Factors Associated with Primary Monosymptomatic
Nocturnal Enuresis\" in the original guideline document.)

**Chronic Headache**

Inquiring about chronic headache in children with nocturnal enuresis is
recommended **\[B\]**.

**Epilepsy**

An electroencephalogram is not justified in the assessment of nocturnal
enuresis **\[B\]**.

**Attention Deficit-Hyperactive Disorder (ADHD)**

Given the high prevalence of these two conditions (ADHD and PMNE) and
their association, it is clinically important to know if there is
concomitant ADHD in enuretic children. Hence, ADHD symptoms in children
that present enuresis should be investigated **\[B\]**.

**Other Psychological Problems**

Early treatment of enuresis is recommended in Primary Care to improve
**\[A\]** or prevent low self-esteem **\[D\]**.

**Sleep/Arousal Disorders**

Although waking up plays an important role in the pathogenesis of
enuresis, no clinical implications have been found. Sleep patterns need
not be studied as part of the clinical history of a child with enuresis
**\[B\]**.

**Sleep Apnoea Syndrome**

It is recommended that a history of sleep apnoea symptoms in children
with PMNE be obtained, despite the fact that the level of evidence is
low **\[C\]**. It should always be ruled out in cases of secondary
enuresis **\[A\]**.

**Asthma/Allergy**

It is not recommended that the presence of asthma/allergy in children
with primary PMNE be specifically investigated **\[C\]**.

**Caffeine**

Although it has never been studied, it is reasonable to recommend that
caffeine-containing beverages should be avoided late in the evening
given their diuretic effect **\[D\]**.

**Encopresis/Constipation**

The presence/absence of constipation or encopresis is worth
investigating in all patients with enuresis; if present, treat the
constipation first **\[C\]**, since constipation is easy to diagnose on
clinical grounds (fewer than 3 bowel movements per week), and given the
possibility that constipation can be the cause of enuresis.

**Pinworm Infestation**

At present, and in the Primary Care setting, Graham\'s technique is not
justified in all children with primary PMNE **\[C\]**.

**Urinary Tract Infection/Bacteriuria**

In PMNE, adopting the same attitude toward urinary tract
infection/bacteriuria as in the general population is recommended
**\[B\]**.

**Diabetes Mellitus**

Routine testing to rule out diabetes mellitus in children with PMNE is
not recommended **\[C\]**.

**Diabetes Insipidus**

Routine testing to rule out diabetes insipidus in children with PMNE is
not recommended **\[D\]**.

**Detrusor Overactivity**

The usefulness of anticholinergics in PMNE should be evaluated in
clinical trials **\[C\]**.

**[Diagnosis]{.underline}**

It is recommended that medical professionals actively search for cases
(of PMNE) in all children 5 years of age or greater in any visit for
illness or routine check-up. **\[D\]**.

**Bladder Diary**

It is essential that the bladder diary be filled in for at least 3 days
**\[A\]**. It can be done conveniently over two weekends.

**Dipstick Urinalysis**

*Urinary Infection*

In monosymptomatic nocturnal enuresis, it is recommended that the same
attitude toward urinary tract infection as in the general population be
adopted **\[B\]**.

*Diabetes Mellitus and Diabetes Insipidus*

Routine testing to rule out diabetes mellitus in children with PMNE is
not recommended **\[C\]**.

It is not recommended that dipstick urinalysis be used as a screening
device for diabetes insipidus in children with PMNE **\[B\]**.

**[Treatment]{.underline}**

**How Efficacious Are Behavioral Interventions?**

*Simple Behavioural Interventions*

Bladder retention training by toileting schedule does not provide any
benefit in PMNE; hence, it is not recommended in Primary Care **\[B\]**.

Despite the lack of quality PMNE data, motivational therapy using charts
with stars, drawings\... helps to objectify the baseline situation
regarding the number of wet nights and can be recommended before and
together with other treatments, since it lacks adverse effects
**\[D\]**.

There are no data available that evaluate the efficacy of bladder
training by mid-stream urine interruption, and its use is not
recommended in light of the fact that it can predispose to dysfunctional
voiding **\[D\]**.

*Complex and Educational Behavioural Interventions*

Given the scant efficacy of complex and educational interventions, their
use is not recommended in Primary Care **\[B\]**.

**How Efficacious Is the Behavioral Intervention with Alarm Therapy?**

*Alarm/No Intervention*

Alarm intervention is a treatment option for PMNE if the family is
motivated and collaborative **\[B\]**.

*Alarm/Alarm Associated with Other Behavioral Interventions*

Associating bladder retention training by toileting schedule techniques
or dry bed training with alarm therapy is not recommended **\[B\]**.

The reinforcement technique should be recommended before completing
alarm therapy in children with PMNE **\[B\]**.

*Tolerability*

A change in treatment is recommended if, once alarm treatment has begun,
the child never wakes up **\[C\]**. Monitoring this response over a
minimum period of one month is recommended **\[D\]**.

**How Efficacious Is Drug Treatment?**

*Desmopressin*

Intranasal desmopressin should be administered at bedtime. Because
orally administered desmopressin has its onset of action 30 minutes
post-administration, it is recommended that it be taken 30 minutes
before the last void and going to bed **\[D\]**.

*Desmopressin versus Placebo*

Drug treatment with desmopressin is a therapeutic option in PMNE
**\[B\]**.

*Dosage*

Because the optimal dose of desmopressin is yet unknown, whether orally
or intranasally administered, it is recommended to customize treatment
to the minimum effective dose (0.2 to 0.4 mg oral and 10 to 40
micrograms intranasal). There are two trends: 1) to begin treatment with
the minimum dose and titrate up if the response is insufficient, or 2)
start directly with the higher dose, which can subsequently be titrated
down, although there are no data that provide guidance as to when to do
this **\[D\]**.

*Tolerability*

To prevent water intoxication, it is recommended that fluid intake the
evening that desmopressin is taken be limited to no more than 240 ml (1
glass of water), 1 hour before to 8 hours after **\[D\]**.

Without taking cost-effectiveness studies into account, the oral mode of
delivery is recommended because it is safer **\[A\]** and easier to
administer, which improves treatment compliance **\[D\]**.

*Treatment Duration*

If the objective is to cure the condition, discontinuation should be
started one month after attaining initial success **\[B\]**. In case of
prolonged treatments, withdrawing therapy periodically for 1-2 weeks in
order to re-evaluate is recommended **\[D\]**.

*Relapses after Treatment Completion*

Precipitous interruption of treatment with desmopressin that is
achieving good response is not recommended **\[B\]**.

Using a structured withdrawal plan (at full doses) when finishing
treatment with desmopressin is recommended **\[B\]**.

*Association with Other Treatments*

Except for specific situations in which there is great interest in
achieving a higher rate of dryness at the beginning of treatment,
routinely associating desmopressin and alarm is not recommended
**\[A\]**.

In the case of children who wet the bed more than once a night, the use
of desmopressin might be recommended with the aim of decreasing the
number of nocturnal micturitions to just one, to make alarm therapy more
tolerable **\[D\]**.

There is not enough evidence to recommend the association of
anticholinergics, although it might be an alternative after treatment
failures **\[D\]**.

*Strategy with Alarm Therapy following Desmopressin Failure*

Associating alarm therapy to desmopressin is not recommended in children
who have not responded to desmopressin **\[A\]**.

**Advantages and Disadvantages of Different Treatments**

(See Table III \"Advantages and Disadvantages of the Different Treatment
Options\" in the original guideline document.)

When the treatment objective is dryness in the short term, desmopressin
and not alarm therapy is recommended **\[A\]**. If the aim is to
maintain dryness without relapses when concluding treatment, alarm
therapy offers obvious advantages over desmopressin **\[A\]**.

**Prognostic Factors of Treatment**

(See Tables IV and V \"Predictive factors for alarm therapy\" and
\"Predictive factors for treatment with desmopressin\" in the original
guideline document.)

*Sex*

Gender is not a prognostic factor to be taken into account when
initiating therapy with alarm or desmopressin **\[A\]**.

*Age*

Age is not considered a decision criterion in treatment selection
**\[A\]**.

*Inheritance in Enuresis*

Family history of enuresis does not intervene in the choice of treatment
**\[B\]**.

It is recommended that alarm treatment not be started if low motivation
is detected in the family or child **\[B\]**. In this case, desmopressin
is the treatment of choice **\[B\]**.

*Number of Wet Nights*

Alarm therapy is a good treatment option when there is a high frequency
of wet nights **\[B\]**. Based on the data in the literature, it is not
possible to establish a precise number that defines \"high frequency of
wet nights\", although it has been observed that the greater the number
of wet nights, the better the response.

Desmopressin is a good treatment option when there are few wet nights
**\[B\]**, even in young children **\[B\]**.

*Number of Incidents Per Night*

Determining maximum daytime voided volume (MDVV) by filling in bladder
diaries is recommended **\[A\]**. Do not administer desmopressin in
children with a MDVV less than 75% of the amount calculated by Koff\'s
formula **\[B\]** and refer the child to the urologist if this volume is
less than 45% **\[C\]** because it is a poor predictor for response to
both treatments (desmopressin and alarm).

*Family or Child Attitudes*

It is recommended not starting alarm treatment if low motivation is
detected in the family or the child **\[B\]**. In this case,
desmopressin is the treatment of choice **\[B\]**.

*Neuropsychological/Psychiatric Problems*

In children with enuresis and the suspicion or diagnosis of ADHD or a
psychiatric condition, it is recommended starting treatment with
desmopressin instead of alarm **\[B\]**.

*Rey-Osterrieth Complex Figure Test*

Given the complexity of the test (time consuming and difficult to
interpret), the guideline developers do not consider it to be helpful in
clinical practice, and therefore do not recommend its use in Primary
Care **\[D\]**.

*Hypercalciuria*

There is not sufficient evidence to recommend urinary calcium
(Ca)/creatinine ratio determinations in children with PMNE and nocturnal
polyuria in Primary Care, although it could be examined in those
children who have failed on desmopressin **\[D\]**.

**[Definitions]{.underline}**:

**Grades of Recommendation\***

A.  Consistent level 1 studies

B.  Consistent level 2 or 3 studies or extrapolations from level 1
    studies

C.  Level 4 studies or extrapolations from level 2 or 3 studies

D.  Level 5 evidence or troublingly inconsistent or inconclusive studies
    of any level

\* See the \"Rating Scheme for the Strength of the Evidence\" field for
the definitions of the levels of evidence.

#### CLINICAL ALGORITHM(S)

A \"Diagnostic Algorithm\" and a \"Treatment Algorithm\" are provided in
the original guideline document.

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of supporting evidence is identified and graded for each
recommendation (see \"Major Recommendations\").

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

Appropriate treatment of nocturnal enuresis may eliminate many of the
negative repercussions for the child and his/her family, including
problems with the child\'s social relations, social performance, and
self-esteem.

#### POTENTIAL HARMS

Side effects of desmopressin are very uncommon and almost never require
treatment withdrawal. The adverse effect that can and must be prevented
is water intoxication. Since 1974, twenty-eight cases have been
reported, all with intranasal administration.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

The authors of the present guide assume that the healthcare
professionals will exercise their clinical discretion and general
knowledge in applying the general and specific recommendations to each
individual patient. The recommendations may not be appropriate in all
circumstances. All the recommendations contained in these guidelines
shall only be applied in the absence of contraindications, adverse
effects, or treatment interactions.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

#### IMPLEMENTATION TOOLS

Chart Documentation/Checklists/Forms\
Clinical Algorithm\
Quick Reference Guides/Physician Guides

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better

#### IOM DOMAIN

Effectiveness\
Patient-centeredness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Asociación Española de Pediatría de Atención Primaria (AEPap).
Evidence-based clinical practice guidelines: primary monosymptomatic
nocturnal enuresis in primary care. Rev Pediatr Atencion Prim 2005
Oct;VII(Suppl 3):1-149.

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2005 Oct

#### GUIDELINE DEVELOPER(S)

Spanish Association of Primary Care Pediatrics

#### SOURCE(S) OF FUNDING

Spanish Association of Primary Care Pediatrics

#### GUIDELINE COMMITTEE

Not stated

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

***Primary Authors***

**MI. Úbeda Sansano**, Primary Care Pediatrician. La Eliana Healthcare
Center. Valencia. Valencian Regional Government Health Authority.
Department 6

**R. Martínez García**, Urologist. Urinary Incontinence Unit. Urology
Department. Clinic Hospital. University of Valencia. Valencia. Valencian
Regional Government Health Authority. Department 5

**J. Díez Domingo**, Primary Care Pediatrician. Nazaret Healthcare
Center. Valencia. Valencian Regional Government Health Authority.
Department 5

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

All authors work for the Agencia Valenciana de Salud (Valencian Regional
Government Health Authority) of the Generalitat Valenciana (Valencian
Regional Government). They have no relationship whatsoever with private
commercial entities involved in the treatment of enuresis nor have they
received any external public or private assistance in relation to these
guidelines. These guidelines have been promoted and carried out by the
authors without any external financial support.

#### GUIDELINE STATUS

This is the current release of the guideline.

#### GUIDELINE AVAILABILITY

Electronic copies: None available

Print copies: Available from Exlibris Ediciones. C/ Infanta Mercedes,
92, bajo; 28020 Madrid; Tel.: 915717051; Fax: 915716913; Email:
<revistapap@pap.edu>

#### AVAILABILITY OF COMPANION DOCUMENTS

The following is available:

-   Asociación Española de Pediatría de Atención Primaria (AEPap). Quick
    reference guide. Evidence-based clinical practice guidelines:
    primary monosymptomatic nocturnal enuresis in primary care. Rev
    Pediatr Atencion Prim 2005 Oct;VII(Suppl 3):31-44

Annexes 2 and 3 of the original guideline document contain diagnostic
criteria for attention deficit hyperactivity disorder (ADHD) and a
diagnostic questionnaire for dysfunctional voiding.

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI Institute on August 27, 2008.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions.

### DISCLAIMER

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Date Modified: 11/3/2008