Nocturnal enuresis in children and adolescents

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Classification and
epidemiology
Pathophysiology
Investigations
Treatment
The authors
Dr Aniruddh Deshpande
fellow, department of urology and
Centre for Kidney Research, the
Children’s Hospital at Westmead;
and PhD student, school of public
health, Sydney Medical School,
University of Sydney, NSW.
Nocturnal enuresis
in children and
adolescents
Dr Patrina Caldwell
staff specialist, department of
nephrology, the Children’s Hospital
at Westmead; and senior lecturer,
discipline of paediatrics and child
health, Sydney Medical School,
University of Sydney, NSW.
Background
medical advice for their condition.1
involvement. More significantly,
NOCTURNAL enuresis, or bedwetthe single most important predictor
ting, is a common problem in childChildren with nocturnal enuof therapeutic success is the child’s
ren. It is a source of considerable
resis beyond six years of age merit
desire to become dry.
anxiety to the child and the family,
therapy since many of them are
The evidence underpinning the
and can affect self-esteem, relationunlikely to grow out of the problem
evaluation and treatment for nocturships with peers and schooling,
until their late teens and will expernal enuresis has grown significantly.
with affected children often missience negative psychosocial effects
This has resulted in an improved
ing opportunities to attend school
of the wetting if left untreated. The
understanding of the pathophysiolcamps and sleepovers. Despite its
parents and the child need to be an
ogy and an increased precision in
high prevalence, it is estimated that
integral part of the decision-making
A D one-third
2 8 4 0 _ of
D children
e p _ b awith
n n noce r . p process,
df
P aasg the
e various
1 2 3 /treatments
1 1 / 1 2 , therapy.
2 : 2 8 The
P MInternational Childonly
ren’s Continence Society (see Online
turnal enuresis in Australia seek
require different degrees of family
resources, page 25) has played a leading role in streamlining the available
research, standardising the terminology for lower urinary tract function
and generating useful treatment algorithms.2
In this article, we have summarised
the latest advances in the nomenclature, pathophysiological understanding and the management of nocturnal
enuresis in children and adolescents.
cont’d next page
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19
How To TREAT Nocturnal enuresis in children and adolescents
Classification and epidemiology
Definitions
THE International Children’s
Continence Society (ICCS) has
classified nocturnal enuresis into
primary and secondary nocturnal enuresis (table 1). Nocturnal
enuresis in children can be further
classified into monosymptomatic
and non-monosymptomatic nocturnal enuresis.2 Children with
monosymptomatic nocturnal enuresis do not have daytime urinary
symptoms while those who have
urgency, frequency or daytime urinary incontinence in association
with nocturnal enuresis are said to
have non-monosymptomatic nocturnal enuresis.
Children who have been dry at
night (for at least six consecutive
months) before resuming bedwetting at night are classified as having secondary nocturnal enuresis.
Children with secondary nocturnal
enuresis are more likely to have an
identifiable cause for their incon-
Table 1: ICCS recommended terminologies and their explanations
Terminology
Description/ definition
Urinary
incontinence
Involuntary leakage of urine
Types: intermittent (includes enuresis or daytime urinary
incontinence) and continuous urinary incontinence
Daytime
incontinence
Uncontrollable intermittent leakage of urine during the
day
Enuresis (nocturnal
enuresis)
Intermittent urinary incontinence during sleep in the
absence of physical disease beyond the age of five
years
Primary nocturnal
enuresis
A child who has never been dry at night for more than
six months
Secondary
nocturnal enuresis
Enuresis in a child who has previously been dry
for more than six months. This is more likely to be
associated with an organic or a psychological cause
Nonmonosymptomatic
nocturnal enuresis
Nocturnal enuresis with daytime symptoms such as
urgency, frequency or daytime wetting
tinence although management of
this subgroup is similar to those
for primary nocturnal enuresis.
Prevalence
Although nocturnal enuresis is a
common problem, the exact prevalence is often under-reported. Nevertheless, large epidemiological studies
have suggested prevalence rates of
15-20% for five-year-olds, 7% for
seven-year-olds and 5% for 10-yearolds.1 The spontaneous remission
rate is 14% per year. The chance of
enuresis persisting into adulthood
is about 1-2%.3 Traditionally, it is
believed that only a quarter of children with nocturnal enuresis have
non-monosymptomatic nocturnal
enuresis, however, the true proportion of non-monosymptomatic nocturnal enuresis may be higher than
previously reported, as parents have
been shown to under-report daytime urinary symptoms in enuretic
children.1
Genetics
A genetic link has been long suspected for nocturnal enuresis
based on the finding of a higher
incidence of the condition among
family members. If a child wets
the bed, there is a 20-40% chance
of a parent and about a 60-70%
chance of a second- or thirddegree relative having also been
bedwetters.4
The risk of severe nocturnal
enuresis is three times greater in
a child whose mother had nocturnal enuresis, whereas the risk for
a child whose father had nocturnal enuresis is doubled, suggesting
that although nocturnal enuresis
is more common among males
(60%), females are more likely to
‘pass on’ enuresis to their children.4
Analyses suggest that nocturnal
enuresis is a genetically heterogenous condition with about 30%
of cases being sporadic and 50%
following an autosomal dominant
pattern.5 However, specific genes
responsible for this transmission
have not yet been identified.
Pathophysiology of nocturnal enuresis
ALL children are born incontinent
and there are various stages in
development of continence. Becoming continent involves the ability
to store urine in the bladder at low
pressure and the ability to release
urine periodically. Filling and emptying of the bladder are dependent
on the activity of smooth and striated muscles of the bladder, urethra
and the external urethral sphincter,
and are controlled by the central
and peripheral nervous system.
During voiding, the pelvic floor
muscle and striated urethral muscles must relax completely and
the bladder and detrusor muscle
must contract, allowing free flow
of urine to occur until the bladder
is completely empty. It was previously thought that a simple reflex
arc was responsible for voiding in
babies. However, babies have been
found to have cortical arousal
before voiding, hence are usually
awake when they void. Children
will normally have achieved day
dryness by 3-4 years, and night
dryness a little later. Voiding after
this age is initiated voluntarily by
the cerebral cortex. Bladder capacity increases over time in children.
Children will normally void
between four and seven times a
day and have an expected bladder
capacity of (30mL × age) + 30mL
up to 12 years of age. A child’s
maximum bladder capacity is considered to be within normal limits if
it is between 65% and 150% of the
expected bladder capacity for age.
Nocturia (having to wake at night
to void) is not uncommon among
school-age children, with a small
percentage waking habitually to
void. In most people, the circadian
variation in the level of antidiuretic
hormone (ADH) released by the
pituitary gland at night results in
increased urine concentration and
decreased urine volume overnight,
which allows them to sleep during
the night without the need to void.
Why do children develop
nocturnal enuresis?
The aetiology of nocturnal enuresis is multifactorial. Many theo-
20
| Australian Doctor | 7 December 2012
nocturnal polyuria who have a
defective sleep arousal response
are likely to wet during sleep when
their bladder is full. Similarly
children who have a small bladder
capacity and a defective arousal
response may have enuresis. There
are also children who have nocturnal detrusor overactivity, resulting
in urinary leakage while asleep.
Assessment of the child’s bladder storage capacity and nocturnal
polyuria is best achieved by asking the family to complete a bladder diary that gives an estimate of
the maximum voided volume and
total overnight urine production
(which can be calculated by measuring the urine loss in the nappy
plus the first morning void).
Is nocturnal enuresis more
common with specific
disorders?
ries have been proposed to explain
the causation, including the delay
in maturation of the micturition
centre. The symptom of enuresis is
now accepted to be caused by the
interplay between the three factors: nocturnal urine production,
sleep and arousal patterns and
bladder capacity. These factors
interact to produce symptoms in
each patient.
When the amount of urine produced exceeds the bladder storage
capacity, an urge to void resulting
in arousal is experienced by nonenuretic children. This response is
defective in many enuretic children, who have a high arousal
threshold.6 It is uncertain why this
occurs but some have suggested
that chronic overstimulation of the
arousal centre in the brain results
in a paradoxical suppression and
an inability to waken when the
bladder is at capacity, resulting in
bedwetting. It has been postulated
that the increased frequency of
cortical stimulation from the bladder (either stimulation from a full
bladder or from uninhibited bladder contractions) leads to lightening of sleep, but not to full arousal.
Well-documented studies indicate
that enuretic episodes occur in
all sleep stages, although children
with monosymptomatic nocturnal
enuresis usually wet during the
early phases of sleep.7
Other studies including sleep
studies and self-reports from the
children with nocturnal enuresis
demonstrate other sleep disturbances including: higher sleep
latency (increased time to onset of
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sleep), lower sleep efficiency (ratio
of time spent asleep to the time
spent in bed), and increased frequency of movements during sleep
or periodic limb movements.7 The
suggested abnormality in these
children is that frequent small sleep
disturbances cause a reduction in
deep sleep and/or sleep quality
that reduces the child’s capacity to
awaken fully in response to a full
bladder, resulting in enuresis.
Nocturnal polyuria can be a
result of variation in the daily
rhythmic secretion of ADH. These
children do not secrete adequate
ADH at night, resulting in production of large amounts of relatively
dilute urine. It has been estimated
that about two-thirds of enuretic
children have varying degrees of
nocturnal polyuria. Children with
The incidence of nocturnal enuresis is higher in children with
constipation,
upper-airway
obstruction
(including
sleep
apnoea) and ADHD. In addition,
some children with obstructive
sleep apnoea showed improvement or resolution of their nocturnal enuresis when their obstructive
sleep apnoea was treated.8 It is
believed that obstructive sleep
apnoea causes nocturnal enuresis
by altering sleep mechanisms as
well as influencing secretion of
hormones such as atrial natriuretic
peptide, aldosterone and ADH, all
of which are responsible for water
balance.
Constipation has also been
associated with an increased risk
of nocturnal enuresis, probably
because of the impact of constipation on bladder function. One
study found that one-third of children with chronic constipation
had nocturnal enuresis. The relief
of constipation resulted in the
resolution of nocturnal enuresis in
two-thirds of patients.9 Therefore,
in a child with nocturnal enuresis it
is important to determine whether
the child may be constipated and if
so, to instigate treatment.
cont’d page 22
How To TREAT Nocturnal enuresis in children and adolescents
Investigations
NOCTURNAL enuresis has a
widespread impact on the lives
of the child and the family. It can
cause parental fatigue, disruption
to sleep of family members and
limitations on the family’s choice
of holidays and social events. More
important is the negative impact of
bedwetting on the child’s psychosocial development. Studies using a
bladder-specific quality of life tool
have confirmed the negative impact
of bedwetting on children, especially on their self-esteem and mental health. It has also been shown
that girls, children from a non-Caucasian background and older children are more significantly affected
by their enuresis.10 Thus, although
the prevalence of nocturnal enuresis may be lower in adolescents,
its impact is more significant in this
group. Health practitioners need to
be aware of the impact of bedwetting on the quality of life of different children and the importance of
effective investigation and management of the condition.
Figure 1 displays a management
algorithm for nocturnal enuresis in
children.
Figure 1: Management algorithm for children with nocturnal enuresis.
Child with nocturnal enuresis
Detailed history-taking
Secondary nocturnal enuresis:
investigate for underlying causes
Primary nocturnal enuresis
without daytime urinary syptoms
(monosymptomatic nocturnal
enuresis)
Primary nocturnal enuresis with daytime
urinary symptoms (non-monosyptomatic
nocturnal enuresis): treat daytime
symptoms first
History and examination
A thorough history is essential in
the evaluation. It is important to
identify the type of enuresis and
also any risk factors that may contribute to the enuresis or treatment
response (table 2).
As somatic and psychological
comorbid conditions (such as UTIs,
types 1 and 2 diabetes mellitus and
diabetes insipidus, stress, sexual
abuse and disorders of the bladder) are more common in secondary nocturnal enuresis; these need
to be sought in the history-taking.
It is also important to differentiate
monosymptomatic and non-monosymptomatic nocturnal enuresis,
as treatment for the daytime bladder symptoms should precede treatment for the nocturnal enuresis.
Physical examination in children with nocturnal enuresis is usually normal. Examination should
include urinalysis (to identify UTI,
kidney disease and diabetes), examination of the spine (for neurological
abnormalities such as spina bifida
occulta), the abdomen (to assess
for constipation) and the external
genitalia (to assess for urogenital
abnormalities). Rectal examination
is usually not necessary.
Bladder diary
A bladder diary (frequency volume
chart) measuring the time and volume of all fluid intake and urine
output in a 24-hour period is one
of the most useful tools for assessing nocturnal enuresis. It provides
information about the child’s fluid
intake, frequency of voiding during the day, bladder capacity (estimated from the volume of each
void measured by parents using a
measuring jug), and total overnight
urine production.
Nocturnal polyuria (defined
as urine production greater than
1.3 times the maximum bladder
capacity for age) should alert the
practitioner to the possibility of
the need for desmopressin therapy
in conjunction with alarm training.
On the other hand, small voided
cont’d page 24
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| Australian Doctor | 7 December 2012
General assessment, physical examination (abdominal examination, spine
and neurological examination), assessment of constipation, bladder diary
(assessment of nocturnal urine production and maximum voided volume).
Baseline renal ultrasound, urinalysis, uroflowmetry and assessment of
post-void residual (whenever possible) (figure 2, next page)
General assessment, physical
examination (abdominal examination,
spine and neurological examination),
assessment of constipation, bladder
diary (assessment of nocturnal urine
production and maximum voided volume)
Urgency, high daytime urinary
frequency, daytime urinary
incontinence
Consider overactive bladder
Education, urotherapy, bedwetting
alarm therapy
Desmopressin if nocturnal polyuria or if
alarm therapy not indicated
Health practitioners
need to be aware
of the impact of
bedwetting on the
quality of life of
different children.
Anticholinergic, urotherapy
Initiate therapy for nocturnal enuresis
after control of daytime symptoms
Urgency, holding postures, high postvoid residuals, recurrent UTIs
Consider dysfunctional voiding
Urotherapy pelvic floor training,
timed voiding
Initiate therapy for nocturnal enuresis after
control of daytime symptoms
Table 2: History-taking in nocturnal enuresis
Assess for type of enuresis
Rationale
Primary or secondary?
Look for causes of secondary nocturnal enuresis. Did occurrence of wetting
coincide with any major event?
Monosymptomatic or nonmonosymptomatic?
Treat bladder symptoms first if non-monosymptomatic
History of daytime voiding habits
Is there urgency, frequency, holding
manoeuvres? Is there an interrupted
or weak urine stream, continuous
urine leakage or the use of abdominal
pressure to void?
Assess for bladder dysfunction (for example a history of continuous daytime
urinary leakage which may need treatment or referral to a specialised centre for
further management
History of nocturnal enuresis
How often does it occur?
Assess for severity of nocturnal enuresis at baseline to compare treatment
response
Does the child wake to void during the
night?
Nocturia would indicate that the child is not extremely difficult to wake during
the night, suggesting that arousal is not the main cause of the nocturnal
enuresis
History of fluid intake
Does the child drink adequate fluid?
Inadequate fluid intake can contribute to constipation
Does the child have a high evening
fluid intake?
High evening fluid intake can cause nocturnal polyuria
Does the child drink too many
caffeinated drinks?
Caffeine can cause bladder dysfunction in some children
Assess for comorbid conditions
Does the child have constipation or
faecal incontinence?
Bladder and bowel function are closely interrelated. Treatment of bowel
disorder is important for optimising enuresis therapy
Does the child have ADHD?
Children with ADHD may need treatment for it together with enuresis therapy
Does the child have sleep-disordered
breathing?
Relief of upper airway obstruction may improve nocturnal enuresis
Assess for the general health of the
child
Childhood illness including kidney disease and diabetes can impact on bladder
function and nocturnal enuresis
What strategies have the family
previously tried for their nocturnal
enuresis?
If previous treatments have been tried, it is important to assess that they were
used correctly
Adapted from Neveus et al., 2010.18
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How To TREAT Nocturnal enuresis in children and adolescents
from page 22
volumes may need aggressive urotherapy and anticholinergic medications in an attempt to increase
the bladder capacity in order to
increase the likelihood of success of
alarm therapy. Urotherapy consists
of fluid advice, voiding posture,
timed voiding and a bowel program.
Figure 2: Bladder scanner for measurement of post-void residual urine.
Urotherapy consists
of fluid advice,
voiding posture,
timed voiding and a
bowel program.
Figure 3: Body-worn nocturnal enuresis bedwetting alarm.
effect lasting for 10-12 hours.
Oral desmopressin comes in the
form of tablets and two strengths
of melts available in Australia
(120µg and 240µg). The usual
dose is 200-400µg for tablets
(1-2 tablets), 120-24µg for lysate
(melts) (1-2 melts) or 10-40µg for
the nasal spray (1-4 puffs), which
does not vary with age or weight.
The medication can be used sporadically or continuously, and can
be stopped without weaning.
There is a higher risk of side
effects with the nasal formulation
and therefore the tablet or lysate
formulation is preferable. Most
common adverse effects reported
are nasal irritation and nose bleeds
with the nasal formulation. Many
cases of water intoxication were
reported spontaneously by physicians and children before 1993.
Since then the guideline of restricting fluid intake to below 250mL
from one hour before until eight
hours after administration has
dramatically reduced the incidence
of water intoxication.
Desmopressin has a definite role
in treatment of enuresis. Although
alarm treatment has a more sustained effect, desmopressin is
particularly useful when a rapid
response is required (such as for
sleepovers or school camps) and
for use when alarm training is
difficult or problematic (such as
children who cannot comply with
alarm training, children living in
foster care or where parents are
not supportive of alarm training).13
In addition, there may be financial
constraints with the purchase or
hire of alarms (with costs ranging
from $50-$1000, depending on
the type and make of alarm).
Desmopressin is a safe and relatively affordable treatment and is
also sometimes used in conjunction with other therapies and in
children with treatment resistance.13 Four trials appear to suggest that desmopressin combined
with alarms is more effective than
alarm monotherapy.13
Urine culture
A urine culture to exclude a UTI
is the only investigation indicated
for nocturnal enuresis. An ultrasound of the child’s kidneys and
urinary tract is usually not warranted, unless there are daytime
urinary symptoms, suggestion of
underlying bladder dysfunction or
suspicion of associated urological
anomalies.
Treatment
TREATMENT of a child with
nocturnal enuresis is more likely
to be successful if the child and
parents want the child to achieve
night-time continence, have a positive attitude to address the wetting
problem and are motivated to
engage in treatment.
Non-pharmacological treatment
Urotherapy
Urotherapy includes all forms of
non-surgical and non-pharmacological interventions undertaken
to improve or rectify voiding habits in children with micturition
disorders.2 Standard urotherapy
covers a wide array of interventions and advice.
The foremost component is to
educate the child and family about
their child’s lower urinary tract
function (that the bladder stores
urine, signals the brain when it is
full, and expels urine under conscious control, and the explanation
of the impact of constipation, fluid
intake and void withholding on
bladder function) and the aims of
treatment. The next step includes
advice regarding voiding postures.
This can include advice to undress
appropriately (for boys) or sit
securely on the toilet (for girls)
with buttock support, foot support and comfortable hip abduction
to ensure no activate abdominal
muscles and pelvic floor musculature contraction. Appropriate
advice should also be given on regular voiding (timed voiding every
2-3 hours), optimising fluid intake
(about 50mL/kg/day up to 2.5L
per day maximum) and treatment
of constipation.2 The child should
be encouraged to void 5-7 times a
day without straining.
Most experts dealing with enuresis believe that urotherapy should
be an integral part of management
of primary nocturnal enuresis.
Standard urotherapy (fluid advice,
voiding posture, timed voiding
and bowel program) can be started
under the supervision of a GP and
is likely to substantially increase the
efficacy of the definitive therapies
offered concurrently.
Bedwetting alarms
Bedwetting alarms are the first line
of treatment for children with primary nocturnal enuresis, and usually recommended in a child older
than six years. Alarms are used to
train the child to withhold urina-
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| Australian Doctor | 7 December 2012
tion while asleep or to wake to
void, which avoids activating the
alarm. Alarms were used as early as
1938. The first alarms were placed
on the bed (bell and pad), and rang
in response to contact with urine.
This underlying principle of a bedwetting alarm remains unchanged.
The newer alarms are smaller and
worn on the body (a ‘body-worn
alarm’), and both types appear to
be equally effective.
Alarms should be used until the
child experiences 14 consecutive
dry nights, and children should
be encouraged to wake and void
on alarm signal (even if they had
already emptied their bladder into
the bed). If using a bell and pad
(bed) alarm, pants (including underwear) should not be worn as they
delay the alarm signal. The sensor
is attached to the underpants in
body-worn alarms (figure 3). Children who cannot sleep without pants
should therefore use the body-worn
alarm.
Alarms produce a gradual but
more sustained decrease in the frequency of wet nights when compared to desmopressin therapy or
other behavioural interventions.11
The short-term effect of desmopressin appears to be better than
alarm therapy but the rate of relapse
after stopping treatment is high.11
Overlearning (giving additional
fluids at bedtime) in a child who
has responded well to alarm therapy can further reduce the relapse
rates by training the child to wake
to a full bladder signal rather
than just inhibiting voiding during sleep.11 Alarm therapy usually
takes 2-4 months to be fully effective, and can take much longer
in children with developmental
delay.
Other behavioural interventions
Interventions such as lifting (taking the child to the toilet during
sleep), waking, reward systems,
retention control training (asking the child to “hold on” when
they feel the urge to urinate) and
dry bed training (strict schedule of
waking the child repeatedly during
the night) continue to be used in
the treatment of primary nocturnal enuresis. Although they are
more effective than no treatment,
alarms and medication are more
effective than these simple behavioural therapies.
Complementary and alternative
therapies
These techniques continue to be
commonly used in some parts of
the world. Evidence based on a
handful of trials of doubtful methodological quality suggests that
hypnotherapy, acupuncture, chiropractic adjustments and medicinal
herbs may be effective for treating nocturnal enuresis.12 Large
randomised trials are needed to
confirm these findings as well as
to assess the adverse effects and
cost-effectiveness of these interventions.
Pharmacological treatment
A large number of medications have
been trialled in the past to treat nocturnal enuresis. Pharmacotherapy is
now used in children where alarm
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therapy has failed or is unlikely to
be successful by itself. Pharmacotherapy should be used sparingly
in children, given the risks of side
effects. Drugs commonly used in
the treatment of nocturnal enuresis
are discussed below.
Desmopressin
Desmopressin is a synthetic analogue of the pituitary hormone,
ADH. It exerts an anti-diuretic
effect through its action on the
renal tubules and results in reabsorption of water from the kidney.
When administered at bedtime, it
helps reduce nocturnal urine production with a beneficial effect on
the symptom of enuresis in a large
proportion (70%) of children with
nocturnal enuresis.13
It was first trialled in 1972, and
the initial results were impressive.
However, a high rate of relapse
after discontinuation of therapy
has been consistently observed,
as desmopressin only reduces the
nocturnal urine production without permanently altering the associated causative factors of reduced
bladder capacity.13 Although some
authors believe that desmopressin
improves arousability in children
with nocturnal enuresis, the finding has been challenged by other
authors.
Desmopressin is administered
via two common routes: oral (in
a tablet or lysate form) or nasal.
The bioavailability of oral, melt
and intranasal desmopressin is
about 0.5%, 0.8% and 10% of
parenteral routes with the peak
reached within an hour and the
Imipramine and other tricyclic
antidepressants
The tricyclic antidepressant imipramine is one of the oldest medications used to treat nocturnal
enuresis in children. The mechanism of action is uncertain, but
thought to be related to its anticholinergic effects.
The reduction in wet nights
using imipramine is modest with
response rates in the range of
20%.14 The rate of relapse after
discontinuing treatment is high.
The major concern with the use
of imipramine is the risk of potentially life-threatening side effects
such as arrhythmias, heart block
and convulsions. Surprisingly,
none of these side effects have
been reported in the trials of imipramine for treating nocturnal
enuresis.14
Given the potential risk and
the availability of better and safer
treatment options (alarms and
desmopressin) tricyclic antidepressants are now recommended
as third line, to be used as monotherapy or in combination with
other treatments, particularly
with treatment failure with monotherapy.
Oxybutynin and other
anticholinergic drugs
Some children have nocturnal
enuresis as a result of nocturnal
detrusor overactivity (with or
without daytime detrusor overactivity). Those with lower urinary
tract symptoms in the daytime
are now classified as having nonmonosymptomatic nocturnal enuresis according to the recent ICCS
standardisation guidelines.2
Anticholinergic
medications
are often indicated in this group
as they can have a dual effect
through their action of relaxing
the smooth muscle of the bladder, which inhibits detrusor overactivity and can increase bladder
capacity. In enuretic children with
a small bladder capacity who are
refractory to therapy, the addition of anticholinergic medications to treatment is particularly
beneficial.15 Anticholinergics can
be used in combination with other
treatments such as alarm training
or desmopressin in treating resistant nocturnal enuresis, and has
delivered encouraging results.16
An upcoming Cochrane review
provides early evidence of the
increased efficacy of combination therapy using anticholinergics compared with established
monotherapy (personal communication). Although the evidence
underpinning this observation is
currently weak, this is a significant finding that needs to be studied further.
Oxybutynin is the most commonly used anticholinergic medication. It also is the most potent
one. It is generally used for children who are shown to have a
small maximum voided volume
or are strongly suspected of having detrusor overactivity (which
can be evaluated by a urodynamic
study performed by urologists).
Side effects of oxybutynin are four
times more common in children
than in adults, necessitating withdrawal of treatment in about 10%
of cases.
These include dry mouth,
diplopia, flushed face, headache,
inability to concentrate and constipation. For some children,
transdermal oxybutynin in the
patch form is a good option, as it
has a sustained release of medication, resulting in fewer side effects.
Alternatively tolterodine is an
anticholinergic that has fewer side
effects than oxybutynin because it
is more bladder selective. Newer,
safer anticholinergic medications
like darifenacin or solifenacin are
currently being trialled in children
and early reports are encouraging.
Other drugs used in the treatment of
nocturnal enuresis
In the past, more than 30 drugs
have been trialled in the treatment of nocturnal enuresis (table
2, page 22).13,14,17 Other than
desmopressin,
anticholinergics
and tricyclic anti-depressants,
few have been found to be effective.17 In a comprehensive review,
only indomethacin, diclofenac,
diazepam and atomoxetine were
superior to placebo based on isolated, small studies.17 None of
these trials gave information on
the relapse rates after stopping
the therapy. Besides, these medications are associated with many
side effects and hence are rarely
used in practice.
Referral to specialist centres
In children aged six or above, the
treatment of nocturnal enuresis can
be started by their GP. Children
who have failed initial treatment
after 3-6 months should be referred
to specialised incontinence services.
It is important to confirm that the
child is motivated to achieve dryness and that the family is ready to
co-operate in the proposed therapy.
Children who have infrequent
voiding (three or fewer times a
day), a history of recurrent UTIs,
suspicion of congenital or structural problems, or neurogenic
abnormalities require more urgent
urological assessment and should
be referred to appropriate specialists.
Summary of management approach to treatment of a child with
nocturnal enuresis
• Check whether enuresis is primary or secondary. If secondary, look
for causes (such as UTIs, types 1 and 2 diabetes mellitus and diabetes
insipidus, stress, sexual abuse and bladder dysfunction).
• Take a thorough history to differentiate between monosymptomatic and
non-monosymptomatic nocturnal enuresis.
• Collect objective data on maximum voided volume, nocturnal urine
production and underlying diseases.
• Advise on basic urotherapy.
• Begin alarm therapy when appropriate.
• Choose pharmacotherapy on a case-by-case basis.
Case study
MARK is a seven-year-old boy who has been
bedwetting all his life. He wears pull-up pants
to bed, and the pull-up can be soaked or lightly
wet in the morning. Mark is usually unaware
of when he wets overnight and he never wakes
spontaneously to void. Although his parents
have tried taking him to the toilet during the
night it has not helped his bedwetting.
Mark does not have any daytime urinary
incontinence, although his parents often
observe him “doing the wee dance” with voidwithholding symptoms despite denying the
need to void. He voids 7-8 times a day. He
opens his bowels daily passing normal consistency stools but occasionally strains and also
complains of pain when passing stool. He does
not have faecal incontinence. Mark drinks
approximately 3-5 cups of fluid per day, and
likes caffeine-containing drinks such as chocolate milk. His fibre intake is reasonable.
Mark had been well in the past. His developmental milestones were normal and he was
toilet trained by three years of age. There is no
family history of nocturnal enuresis.
Mark’s physical examination was normal although hard faeces were palpable on
abdominal examination. His urinalysis was
normal. We performed a uroflow (figure 4)
on Mark when he felt a strong urge to void,
cont’d next page
Figure 4: Uroflowmeter used for nocturnal enuresis patients.
Key points
• The understanding of
the pathophysiology of
nocturnal enuresis has
improved greatly, with
resultant improvements in
treatment strategies.
• Bedwetting alarms remain
the first line therapy for
primary nocturnal enuresis.
• Basic urotherapy should
be initiated in all children
with nocturnal enuresis,
especially in those with
non-monosymptomatic
nocturnal enuresis.
• Desmopressin is the most
common drug used in the
treatment of nocturnal
enuresis and should be
used if alarm therapy is
not feasible or ineffective
or as an adjuvant to alarm
therapy. Anticholinergic
agents like oxybutynin or
tolterodine should be used
in children with a small
maximum voided volume
or detrusor overactivity.
• Pharmacotherapy should
be used sparingly and with
due diligence in children
with nocturnal enuresis
due to the risk of side
effects.
References
1. Bower WF, et al. The epidemiology of
childhood enuresis in Australia. British
Journal of Urology 1996; 78:602-06.
2. Neveus T, 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.
Journal of Urology 2006; 176:314-24.
3. Yeung CK, et al. Characteristics of
primary nocturnal enuresis in adults: an
epidemiological study. BJU International
2004; 93:341-45.
4. Von Gontard A, et al. Family history of
nocturnal enuresis and urinary incontinence:
results from a large epidemiological study.
Journal of Urology 2011; 185:2303-06.
5. Arnell H, et al. The genetics of primary
nocturnal enuresis: inheritance and suggestion
of a second major gene on chromosome 12q.
Journal of Medical Genetics 1997; 34:360-65.
6. Kawauchi A, et al. Changes in the structure
of sleep spindles and delta waves on
electroencephalography in patients with
nocturnal enuresis. British Journal of Urology
1998; 81(Suppl 3):72-75.
7. Cohen-Zrubavel V, et al. Sleep and sleepiness
in children with nocturnal enuresis. Sleep
2011; 34:191-94.
8. Basha S, et al. Effectiveness of
adenotonsillectomy in the resolution of
nocturnal enuresis secondary to obstructive
sleep apnea. Laryngoscope 2005;
115:1101-03.
9. Loening-Baucke V. Urinary incontinence and
urinary tract infection and their resolution
with treatment of chronic constipation of
childhood. Pediatrics 1997; 100:228-32.
10. Deshpande AV, et al. Factors influencing
quality of life in children with urinary
incontinence. Journal of Urology 2011;
186:1048-52.
11. Glazener CMA, et al. Alarm interventions
for nocturnal enuresis in children.
Cochrane Database of Systematic
Reviews 2005; Issue 2.
12. Huang, T, et al. Complementary and
miscellaneous interventions for nocturnal
enuresis in children. Cochrane Database of
Systematic Reviews 2011; Issue 12.
13. Glazener CM, Evans JH. Desmopressin for
nocturnal enuresis in children. Cochrane
Database of Systematic Reviews 2002;
Issue 3.
14. Glazener CMA, et al. Tricyclic and related
drugs for nocturnal enuresis in children.
Cochrane Database of Systematic Reviews
2003; Issue 3.
15. Yeung CK, et al. Reduction in nocturnal
functional bladder capacity is a common
factor in the pathogenesis of refractory
nocturnal enuresis. BJU International 2002;
90:302-07.
16. Austin PF, et al. Combination therapy
with desmopressin and an anticholinergic
medication for nonresponders to
desmopressin for monosymptomatic
nocturnal enuresis: a randomized, doubleblind, placebo-controlled trial. Pediatrics
2008; 122:1027-32.
17. Glazener CM, et al. Drugs for nocturnal
enuresis in children (other than desmopressin
and tricyclics). Cochrane Database of
Systematic Reviews 2003; Issue 4.
18. Neveus T, et al. Evaluation of and
treatment for monosymptomatic enuresis:
a standardization document from the
International Children’s Continence Society.
Journal of Urology 2010; 183:441-47.
Online resources
NICE clinical guidelines
Nocturnal Enuresis: The Management of
Bedwetting in Children and Young People
publications.nice.org.uk/nocturnalenuresis-cg111
International Children’s Continence Society
www.i-c-c-s.org
The Continence Foundation of Australia
www.continence.org.au
The Australian Continence Exchange
www.continencexchange.org.au
Department of Health and Ageing’s Bladder
Bowel Website
www.bladderbowel.gov.au/
www.australiandoctor.com.au
7 December 2012 | Australian Doctor |
25
How To TREAT Nocturnal enuresis in children and adolescents
from previous page
and he voided 73mL (with a staccato-shaped uroflow) and had no
post-void residual urine on bladder
ultrasound.
Our initial clinical impression
was of non-monosymptomatic nocturnal enuresis on the background
of mild constipation. We felt Mark
may have a small bladder capacity
as he needed to void at 73mL.
We put Mark onto increased fluids, with reduced caffeine intake.
We also suggested an increase in
fibre to reduce his constipation. We
educated his parents about lower
urinary tract function. His parents were asked to monitor bowel
movements and undertake a complete time and volume chart for
urination.
After a month, Mark returned.
He had increased his fluid intake
and treated his constipation. He
continued to wet every night.
Mark’s time and volume chart
showed that his largest daytime
void was 230mL and his overnight
urine volume was 250mL (figure
5).
Mark was started on alarm training and became dry at night after
10 weeks. He was sleeping through
the night every night. His alarm
training was stopped.
Four months later, we saw
Mark again. Although at the
previous visit he was completely
dry every night, his bedwetting
gradually returned one month
after alarm training stopped. He
reported that he was now wetting
about 2-3 nights per week. On
those occasions, the size of the
wet patch was moderately large
(wetting his pyjamas and sheets),
and he was usually unaware that
he had wet. On the nights he was
dry, he slept through the night.
He admitted that over the winter months, his fluid intake had
reduced and he was not eating as
much fruit as during summer.
His relapse of occasional nocturnal enuresis appeared to be due
to reduced bladder volume (from
reduced fluid intake and possibly
constipation) combined with the
inability to wake to void. Again,
we encouraged him to increase
fluid and fibre intake and went
through the function of the lower
urinary tract again. We also instituted further alarm training with
overlearning.
Mark returned two months later.
At this time he was completely dry
at night, and occasionally could
wake to void during the night if
needed.
Figure 5: Time and volume chart for Mark.
How to Treat Quiz
Nocturnal enuresis in children and
adolescents — 7 December 2012
1. Which TWO questions regarding
classification of nocturnal enuresis are
correct?
a) Ninety per cent of patients with nocturnal
enuresis seek medical advice for their
condition
b) Children with monosymptomatic nocturnal
enuresis do not have daytime urinary
symptoms
c) Non-monosymptomatic nocturnal enuresis
is defined as children who have urgency,
frequency or daytime urinary incontinence
in association with nocturnal enuresis
d) Children who have been dry at night
for at least three consecutive months
before starting to wet the bed at night are
classified as having secondary nocturnal
enuresis
2. Which TWO statements regarding the
epidemiology and genetics of nocturnal
enuresis are correct?
a) The prevalence rate of nocturnal enuresis in
10-year-olds is 1%
b) The spontaneous remission rate in children
with nocturnal enuresis is 14% per year
c) In children with nocturnal enuresis, there
is a 10% chance of a parent having had
enuresis
d) Nocturnal enuresis is a genetically
heterogenous condition with about 30% of
cases being sporadic and 50% following an
autosomal dominant pattern
3. Which TWO statements regarding
continence are correct?
a) Continence involves the ability to store
urine in the bladder at low pressure and the
ability to release urine periodically
b) The peripheral nervous system alone
controls the process of filling and emptying
the bladder
c) Children will normally have achieved day
dryness by the age of one year
d) Voiding after achieving daytime dryness is
initiated voluntarily by the cerebral cortex
4. Which TWO statements are correct?
a) Children have an expected bladder
capacity of [(30mL × age) + 30mL] up to 12
years of age
b) A child’s maximum bladder capacity is
considered to be within normal limits if it is
between 65% and 150% of the expected
bladder capacity for age
c) Nocturia (having to wake at night to void) is
very rare among school-age children
d) Circadian variation in the level of
antidiuretic hormone (ADH) released by the
pituitary gland at night results in decreased
urine concentration and increased urine
volume overnight
5. Which THREE statements regarding the
pathophysiology of nocturnal enuresis
are correct?
a) The three factors thought to cause enuresis
are nocturnal urine production, sleep and
arousal patterns and bladder capacity
b) The response of the urge to void when the
Seeking clinical trial
participants
TIMED voiding (voiding on a
scheduled program during the
day) is an established treatment
for adults with daytime urinary
incontinence. However, it is
more difficult for children to
achieve. The Children’s Hospital
at Westmead is currently
conducting the WATCH Study to
test a personalised alarm watch
for treating daytime wetting
in children. Children will be
randomised to either an alarm
watch or a non-alarm watch. The
study is open for recruitment to
children aged 5-13 with daytime
wetting at least twice a week for
the past six months. It is open
until the end of 2013.
If you or your patients would
like to know more about this
study, please email Marianne
Kerr at marianne.kerr@health.
nsw.gov.au or call 0429 468 883
for more information.
Instructions
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amount of urine produced exceeds the
bladder storage capacity is defective during
sleep in many enuretic children
c) Enuretic episodes occur only during delta
wave (deep) sleep
d) The child’s bladder storage capacity and
nocturnal polyuria can be assessed by
keeping a bladder diary
6. Which TWO of the following conditions
are associated with nocturnal enuresis?
a) Constipation
b) Eczema
c) Upper airway obstruction
d) Chronic otitis media
7. Which TWO statements regarding
history, examination and investigation
are important in assessing an enuretic
child?
a) Questions about comorbid conditions such
as diabetes (mellitus or insipidus), stress,
sexual abuse and UTIs are an important
aspect of the medical history
b) Rectal examination to assess for
constipation is essential
c) A urine culture to exclude a UTI should be
performed
d) All enuretic children need an ultrasound of
their kidneys and urinary tract
8. Which TWO statements regarding nonpharmacological treatments are correct?
a) Urotherapy should be an integral part of
management of primary nocturnal enuresis
b) Urotherapy should only be conducted by a
paediatric urologist
c) Bedwetting alarms are the second
line of treatment and should follow
pharmacotherapy
d) Alarms should be used until the child
experiences 14 consecutive dry nights
9. Which THREE statements regarding
desmopressin are correct?
a) Desmopressin is a synthetic analogue of
the pituitary hormone ADH
b) Desmopressin results in excellent longterm control of nocturnal enuresis once
treatment has stopped
c) There is a risk of water intoxication in
children treated with desmopressin
d) Desmopressin is very useful when a rapid
response is required
10. Which TWO statements regarding
treatment with tricyclic antidepressants
and anticholinergic drugs are correct?
a) Response rates with imipramine are in the
range of 45%
b) There is a risk of potentially life-threatening
side effects with the use of imipramine in
children
c) Anticholinergic medications are often
indicated in the group of children with
nocturnal enuresis and lower urinary tract
symptoms in the daytime, classified as
non-monosymptomatic nocturnal enuresis
d) Side effects from the anticholinergic drug
oxybutynin are minimal
CPD QUIZ UPDATE
The RACGP requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2011-13 triennium. You can
complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept the quiz by post or
fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online.
how to treat Editor: Dr Barbara Tink
Email: barbara.tink@reedbusiness.com.au
Next week While about 50% of infants and preschoolers will have an episode of wheezing, only a small proportion will go on to have asthma. The next How to Treat aims to clarify the diagnostic maze
for the different types of wheeze and asthma. The author is Professor Craig Melllis, associate dean and head, Central Clinical School, Royal Prince Alfred Hospital, Camperdown and Sydney Medical
School, University of Sydney, NSW.
26
| Australian Doctor | 7 December 2012
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