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Nocturnal enuresis
By
Dr. Turky Al-MouhissenR4 Urology
OUTLINE:
Introduction & definition Epidemiology & natural history Physiology of bladder maturation Causes Evaluation Management
INTRODUCTION & DEFINITION
Enuresis defined as involuntary voiding
When it occurs at night it is termed nocturnal enuresis
daytime incontinence is termed diurnal enuresis
At 5 yrs of age, 15 % of children remain incompletely continent of urine
Most of these children have isolated nocturnal enuresis ( monosymptomatic enuresis )
Monosymptomatic enuresis divided into 1ry & 2ndry
1ry enuresis: who never achieved a satisfactory period of nighttime dryness 80 % of nocturnal Enuresis
2ndry enuresis: who had a period of dryness, usually for at least 6 mo. before the onset of wetting begins 20 % of noc. Enuresis Often associated with unusually stressful
event
20 % of children who have nocturnal enuresis also have daytime symptoms
Daytime symptoms may be limited to urgency and frequency, but often include incontinence (diurnal enuresis)
Urologic and neurologic disorders (eg, detrusor instability, recurrent UTI, spinal dysraphism) more common among children with diurnal symptoms
Nocturnal enuresis + daytime symptoms =
complex or complicated enuresis ( dysfunctional voiding )
[ Noc. Enuresis + Urinary & bowel
symptoms =
dysfunctional elimination syndrome
EPIDEMIOLOGY AND NATURAL HISTORY
5 years: 16 % 6 years: 13 % 7 years: 10 % 8 years: 7 % 10 years: 5 % 12 to 14 years: 2 - 3 % 15 years: 1 - 2 %
Boys = twice girls
resolves spontaneously at a rate of 15
% / year
The longer the enuresis persists, the lower the probability that it will spontaneously resolve
IN A STUDY BY THE COLLEGE OF MEDICINE IN DAMMAM, SAUDI ARABIA
cross-sectional population-based study Data were collected using a self-administered
questionnaire 644 school children aged 6-16 years were
selected randomly Enuresis prevalence was
16.3% among boys and 13.8% among girls The overall prevalence was 15%
The 83 children who had enuresis during sleep, 25 (30.1%) wet their beds during day time sleep
: Acta Paediatr. 1996 Oct;85(10):1217-22. LinksEnuresis: prevalence and associated factors among primary school children in Saudi Arabia
Kalo BB, Bella H.
BLADDER MATURATION
Normal bladder function entails a complex interrelation btwn autonomic and somatic nerves
They are integrated at various sites in spinal cord, brain stem, midbrain, and higher cortical centers
The complex coordination permits urine storage at low pressure with high outlet resistance and voiding with low outlet resistance and sustained detrusor contraction
Central organization of mic. Reflex by centers in cerebrum, posterior hypothalamus, midbrain,
pontine, sacral spinal cord Parasymp. Supply by pelvic nerve arising
from S 2-4, to the detrusor muscle Symp. Supply by hypogastric n. from t 10-12
innervating bladder neck & urthral smooth m. Somatic supply. By pudendal n. innervating
ext. urethral sphinter
At birth, bladder function is coordinated through the lower spinal cord and/or primitive brain centers
Voiding at this stage is efficient but uncontrolled: uninhibited contraction is caused by progressive and sustained bladder filling
Voiding in the newborn also may be initiated by neurologically stimulating activities such as feeding, bathing, tickling, etc.
The newborn voids approx. 20 times per day During the first 3 yrs, bladder capacity
increases disproportionately relative to body surface area
At 3 yrs, No. of voids per day decreases to approximately 11, while mean voided volume increases nearly fourfold
At 4 years, most children void 5-6 times/day
Development of bladder control appears to follow a progressive maturation child first becomes aware of bladder filling subsequently develops the ability to
suppress detrusor contractions voluntarily finally learns to coordinate sphincter and
detrusor function These skills usually are achieved, at least
during the day, by 4 yrs of age.
Nighttime bladder control is achieved months to years after daytime control, but is not expected until 5 – 7 yrs of age
Incomplete development of bladder control results in more complex wetting problems that almost always associated with diurnal enuresis uninhibited bladder of childhood bladder sphincter dyssynergy recurrent UTI some cases of vesicoureteral reflux
CAUSES:
Maturational delay Genetics Functional small bladder capacity Abnormal diurnal secretion of vasopressin (
antidiuretic hormone, ADH) Nocturnal polyuria Detrusor instability Sleep disorders Psychological issues
MATURATIONAL DELAY
In almost all cases, monosymptomatic nocturnal enuresis resolves spontaneously
This suggests that delayed maturation of a normal developmental process plays a role
Some studies have demonstrated increased incidence of delayed language & gross motor development and slowed motor performance among children with enuresis
GENETICS
Monozygotic twins twice that among dizygotic twins (68 versus 36 %)
One parent have h/o prolonged nighttime wetting, ½ of the offspring are affected
Both parents affected, ¾ the offspring are affected When neither parent has a history of nocturnal
enuresis, only 15 % of offspring are affected An autosomal dominant form was identified in Danish
families and linked to a locus on chr. 13q13-q14.3 Additional genetic loci for enuresis have been
identified on chr. 12q and 22q11 [
SMALL BLADDER CAPACITY
At birth, bladder volume approx. 60 mL
it increases with age at a relatively steady rate of approximately 30 mL per year
Children with noc. enuresis, even who do not have daytime symptoms, have noted to have smaller bladder capacity than age-matched children who do not have nocturnal enuresis
In a study showed, the reduced bladder capacity appears to be functional rather than anatomical
In another study, the maximal bladder capacity during the daytime was similar between children with enuresis and controls However, among children with enuresis, the
maximal voided vol. during night was significantly smaller than the maximal daytime bladder capacity
NOCTURNAL POLYURIA AND ADH
It has been suggested that increased nighttime U.O.P may play a role in nocturnal enuresis
In children who don`t have enuresis, U.O.P. during the night bcs the secretion of ADH and other regulatory hormones follows a circadian pattern, with increased secretion at night
studies have indicated that nocturnal enuresis children have decreased nocturnal secretion of ADH increased U.O.P. One of the reasons may be small bladder
capacity, since ADH secretion is thought to increase with bladder distension
The relationship between ADH secretion and nighttime urinary flow rates remains controversial
Abnormalities in ADH secretion appear to play a role in at least some pts with noct. enuresis.
However, whether these abnormalities are primary or secondary (eg, to bladder capacity or maturational delay) is not clear
DETRUSOR INSTABILITY
Urodynamics in children who have diurnal incontinence demonstrates significant functional detrusor abnormalities
No clear pattern of UDN abnormality demonstrated in children with primary monosymptomatic noct. Enuresis
Most studies suggest that the incidence of uninhibited bladder activity in children with 1ry monosymptomatic noct. enuresis is similar to the incidence in normal children ( 3-5% )
bladder dysfunction should be considered in children who have refractory monosymptomatic primary nocturnal enuresis
When UDN studies performed during sleep, the only difference between enuretic and nonenuretic children is the increased rate of bladder contractions in enuresis
SLEEP DISORDERS
Parents often describe their children with enuresis as excessively deep sleepers
Excessively deep sleep appears to contribute to nocturnal enuresis in adolescents and adults
Sleep studies show that sleep patterns among children with and without enuresis are similar
Nocturnal sleep and bladder monitoring studies by Robert and others (1993) have been able to distinguish 3 types of enuretic episodes:
Type 1: Gradually elevations in bladder pressure culminate in
wetting; . •associated with prominent somatic and visceral
reactions• tachycardia, body movements, increasing
respirations, and progressive awakening. •The awakening reaction is strong, and the child
struggles to keep from wetting.
Type 2A very quick micturition is associated with minimal
body movement and visceral signs.• The awakening reaction is very brief, and the struggle
to keep from wetting is very limited
Type 3Complete parasomnia, a total lack of CNS reaction
and response to bladder contraction, occurs• neither bladder filling nor bladder contraction registers
on the EEG• involuntary voiding occurs without any modification of
sleep.
These three patterns appear to reflect the various stages in the normal development of nocturnal urinary control and suggest wetting during sleep is to a great
extent determined by CNS maturation.
These findings suggest sleep patterns of enuretics are not different
from those of normal children most enuretics neither have a disorder of
arousal nor wet as a consequence of sleeping too deeply
Enuresis is related to delay in CNS development or, more accurately, a dual delay in the development of the perception and inhibition of bladder filling and contraction by the CNS (Koff, 1995).
PSYCHOLOGICAL
Although psychologic abn. have been considered to play a role in noct. enuresis, this relationship has not been proven
perceived adjustment problems tend to improve after resolution of enuresis, suggesting behavioral abnormalities are a result, rather than a cause of the enuresis
DEFERENTIAL DIAGNOSIS:
Unrecognized underlying medical disorders (eg, SCD, seizures, DM, DI , hyperthyroidism)
Encopresis or constipation Dysfunctional voiding (usually associated
with daytime symptoms) Urinary tract infection Chronic renal failure Spinal dysraphism Psychogenic polydipsia
EVALUATION:
History
Presence of daytime wetting or symptoms
Any prolonged period of dryness Family history of nocturnal enuresis Frequency and trend of nocturnal
enuresis
Fluid intake diary Voiding diary Stooling diary Medical history ( diabetes, sickle cell disease
or trait, urinary tract infection, gait or neurologic abnormalities)
Social history ( important in secondary enuresis)
Effect of problem on child & family which interventions the family has tried
PHYSICAL EXAMINATION
Usually normal
CONDITIONS WHICH REFLECT MEDICAL ETIOLOGY FOR ENURESIS INCLUDE:
Palpation of stool in the abdomen suggests constipation or encopresis.
Perianal excoriation or vulvovaginitis may indicate pinworm infection
Poor growth and/or hypertension may indicate renal disease.
Presence of abnormalities of the lower lumbosacral spine or neurlolgical abnormalities
Detection of incomplete bladder emptying
Urinalysis screen for diabetic ketoacidosis, diabetes insipidus, water
intoxication, and/or occult urinary tract infection
Imaging —
Urologic imaging is reserved for who have significant daytime complaints h/o UTI not previously evaluated signs and symptoms of structural urologic abnormalities
Neurologic imaging (MRI spine) is indicated in children who have abnormalities of the lower lumbosacral spine on neurologic examination of the perineum and lower extremities
MANAGEMENT OF NOCTURNAL ENURESIS IN CHILDREN
GENERAL PRINCIPLES — age at which enuresis is considered to be a
"problem" varies depending upon the family For the child, nocturnal enuresis usually
becomes significant only when it interferes with his or her ability to socialize
As a general rule, children younger than seven years of age may be managed expectantly, as the majority will resolve spontaneosly
Parents must clearly understand that nocturnal wetting are involuntary on the part of the child
Parent education that Rx may be prolonged, associated with relapses, and may fail in the short term
The parents must be willing to participate, and the family environment must be supportive
The child must be highly motivated to participate in a treatment program
TREATMENT MODALITIES
Motivational therapy Bladder training Fluid management Behavioral alarms Pharmacological agents
Rx is rarely indicated in a child younger than 7yrs motivational therapy, bladder retention exercises,
fluid management are usually tried for 3-6 mo. in motivated family & child
More active intervention (eg, arousal alarm systems, pharmacotherapy) should be considered as the child gets older, social pressures increase, and self-esteem is affected
Pharmacologic agents can be effective in the short-term (eg, for sleepovers or camp attendance), but enuresis alarms are the most effective long-term therapy
MOTIVATIONAL THERAPY
Rewards given to a child for longer period of dryness
leads to significant improvement > 70 % relapse rate (more than two wet nights in two wks
) is 5 % Motivational therapy is a good 1st line of therapy
for 1ry noct. enuresis, particularly in younger children
If motivational therapy fails to lead to improvement after 3-6 mo., other methods should be tried
BLADDER TRAINING
children with noct. enuresis have a functionally small bladder capacity
Bladder retention training exercises may be undertaken to increase bladder capacity
Bladder training therapy leads to significant improvement 60 %
Successful in 35 % a trial of this simple behavioral method is
recommended before alarms and pharmacologic agents are tried
FLUID MANAGEMENT
Some authors recommend to drink 40 % of their total fluid in the
morning 40 % in the afternoon only 20 % in the evening beverages consumed in the evening caffeine-
free Isolated nighttime fluid restriction, should
be compensated in daytime fluid consumption
ENURESIS ALARMS
Enuresis alarm is the most effective means of controlling nocturnal enuresis
Enuresis alarms are activated when a sensor, placed in the undergarments or on a bed pad, detects moisture; the arousal device is usually an auditory alarm and/or a vibrating belt or pager
Alarm works through conditioning: the patient learns to wake or inhibit bladder
contraction in response to the neurologic conditions present before wetting
The child should F/U 1-2 wks after starting the alarm and then at the end of an 8 -week trial
Therapy with the alarm can be reinitiated for relapse (more than two wet nights in two weeks).
30 % of pts discontinue the alarm for various reasons
Alarms appeared to be less immediately effective than desmopressin, but more effective in preventing relapse
Alarms were more effective than tricyclic antidepressants during and after treatment
Relapse rate after stopping therapy is much lower with alarms than with desmopressin
ALARM CLOCKS
It may be possible to condition some children to wake to void by using an alarm clock
Many authors concluded that an ordinary alarm clock is safe Effective noncontact treatment that does not require an
episode of bedwetting to initiate a conditioning
PHARMACOLOGIC THERAPY
desmopressin acetate (DDAVP) tricyclic antidepressants (TCAs) Other drugs may be beneficial
DESMOPRESSIN:
mechanism of action unclear Suggested that DDAVP acts on a different
receptor, possibly the vasopressin 1b receptor in the brain
Dose given late evening to reduce urine production during sleep
The drug is given either intranasally or orally It is relatively expensive A normal functional bladder capacity is
necessary for response to desmopressin
Dose usually titrated to best effect, increasing the dose every 10 days to the maximum recommended dose
The process usually takes a total of 30 days The oral tab. is given at 0.2 mg initially (1
tab.) and may be increased to 0.6 mg (3 tab.) as needed over a 2-week trial
The nasal spray is usually begun at 20 micrograms at bedtime, and titrated to max. of 40 micrograms at bedtime
25 % achieves total dryness using desmo.
50 % had significant decrease in nighttime wetting
Similar to TCAs, stopping the medication
is associated with high rates of relapse 60-70 %
SYSTEMATIC REVIEW OF 41 RANDOMIZED TRIALS INVOLVING 2760 CHILDREN COMPARING DESMOPRESSIN TO OTHER DRUGS OR
ALARMS IN THE TREATMENT OF NOCTURNAL ENURESIS
Compared with placebo, desmopressin (20 microgram nasal spray) reduced bedwetting by 1.34 nights per week (95% CI 1.11-1.57).
Compared with placebo, children treated with desmopressin (20 microgram nasal spray) were more likely to become dry (ie, no episodes for 14 nights) (RR 1.19, 95% CI 1.10-1.27).
In contrast to arousal alarms, treatment effects were not sustained after discontinuation of therapy.
Desmopressin and TCA appear to be equally effective.
Adverse effects of desmopressin uncommon Nasal form occasionally causes mild rhinitis The most serious adverse effect is dilutional
hyponatremia, occurs when excess fluids are taken in the evening hours To prevent this complication, it is recommended
that fluid intake be limited to 240 mL on any evening that desmopressin is given
TRICYCLIC ANTIDEPRESSANTS:
Imipramine, Amitriptyline, and desipramine have been recognized as a useful adjunct in the Rx of enuresis since 1960
Although imipramine is the drug most often used, other TCAs are also effective
TCAs decrease the amount of time spent in REM sleep, stimulate vasopressin secretion, and relax the detrusor muscle.
The dose of imipramine is 0.9 - 1.5 mg/kg per day, bedtime
On average, the bedtime dose is 25 mg for children 5-8 years of age and 50 mg for older children
The dose should not exceed 50 mg in children between 6 -12 yrs of age and 75 mg in children 12 years of age
The Effect of imipramine is quick if the dose is adequate
Imipramine should be discontinued if there is no improvement after a three-week trial (at an adequate dose); it may be discontinued abruptly
Adverse effects of TCA therapy are relatively uncommon
5 % develop neurologic symptoms including nervousness, personality change, and disordered sleep
The most serious adverse effects of TCAs, involve CVS, including the risk of cardiac conduction disturbances and myocardial depression, particularly in cases of overdose.
OTHER DRUGS
Indomethacin: Rarely used One small randomized controlled trial found
that indomethacin suppository versus placebo significantly increased the number of dry nights in children with primary nocturnal enuresis who were treated for 3 wks
Possible mechanisms of action include removal of the normal inhibitory effect of prostaglandins on the response to vasopressin
ANTICHOLINERGIC DRUGS:
such as oxybutynin, are not effective in treating monosymptomatic nocturnal enuresis
May be useful in children who also present with significant daytime urgency
combination of anticholinergic therapy and desmopressin may be used in these children in an attempt to increase bladder capacity during sleep
Other drugs, including phenmetrazine, amphetamine sulfate, ephedrine, atropine, furosemide, diclofenac, and chlorprotixine have been tried
none of the drugs was better than desmopressin
RECOMMENDATIONS IN THE RX OF MONOSYMPOTOMATIC NOCTURNAL ENURESIS
children < 7yrs therapy should consist primarily of reassurance that spontaneous resolution is likely
Once the child is able to be partially responsible for Rx, motivation and simple behavior therapies are recommended include reinforcement for dry nights (eg, a sticker calendar) bladder training exercises, fluid management, as described above combination of these
Enuresis alarms or pharmacologic therapy should be considered in children who failed to improve after 3-6 months of behavioral interventions
Enuresis alarms are preferred to pharmacologic therapy bcs their effects are sustained after discontinuation and bcs they are associated with fewer S/E
Desmopressin is an effective short-term alternative to the enuresis alarm in patients who are unresponsive to the alarm
Similar to desmopressin, TCA are an effective short-term therapy for nocturnal enuresis their high relapse rate and potentially
severe adverse effects make them less appealing than alarm or desmopressin therapy
Thank you
REFERENCES
www.uptodate.com www.pubmed.com Campbell`s Urology