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Evidence Based Management of
Enuresis
Dr Girish C Bhatt
Assistant Professor
Pediatrics
AIIMS, Bhopal
Enuresis
Definition
ICD-10/ DSM -5: Bedwetting in children≥5 years
Exclusion of organic causes
Many subtypes of elimination disorders, varied
symptoms, aetiologies and specific treatment
options
DSM-5 criterion did not integrate these new
approaches
Enuresis
Definition
International Children’s Continence
Society(ICCS): discrete episodes of urinary
incontinence during sleep in children ≥5 years
of age
Used regardless weather there is a daytime
incontinence or other lower urinary tract
symptoms
J Urol. 2006;176(1):314
Nocturnal Enuresis
Classification
Monosymptomatic :
•Used for child
without any lower
urinary tract
symptoms
•Further classified
into primary and
secondary
Non-monosymptomatic:
• Enuresis in children with other lower urinary tract symptoms
J Urol. 2006;176(1):314
Lower Urinary Tract
Symptoms •Frequency
•Daytime incontinence
•Urgency/Hesitancy
•Straining
•Weak stream
•Holding maneuvers
•Post micturition dribble
Primary Enuresis •Children who have never
achieved a satisfactory
period of nighttime dryness
•80%
Secondary Enuresis • Children who develop
enuresis after a dry period
of at least six months
Pediatr Nephrol 1999;13:662
Prevalence of NE
Prevalence 3.8% to 20%
India •NE-12.7%
•PMNE-8.2%
•Secondary enuresis-3.6%
•Non-monosyptomatic enuresis-0.5%
7
BEDWETTING •Genetic
predisposition
Developmental delay
Abnormal circadian rhythm of
antidiuretic hormone (AVP) secretion
Psychosomatic manifestation
Sleep-arousal disturbances
Bladder detrusor/sphincter
dysfunction
Abnormal bladder reservoir function
PATHOPHYSIOLOGY OF BEDWETTING
AVP, arginine vasopressin
Pre-treatment Evaluation
Detailed History •Frequency of bedwetting
•Period of dryness
•Associated daytime symptoms
•Constipation and encopresis
•Sleep disordered breathing
Voiding Diary •Timing of daytime voids
•Volume of voided urine
•Lower urinary tract symptoms
•At least 24 hours
Time Urine
(volume)
Fluids Accidents
Urge Straining/interrupted stream
0700 70
0800 90 150
0900 50
1100 90 100
1300 80 75
1530 70
1700 30 150
4
Total 650 650
Expected bladder capacity=[30+(AgeX30)]
Nocturnal polyuria-Nocturnal UO >130%
J Urol. 2006;176:314–24
Sleep disordered breathing & Enuresis
Sleep disordered breathing was independently
associated with MNE-(OR 3.38, (95% CI -2.06–5.54)
Systematic review of 14 studies
•Significant improvement with adenotonsillectomy
Pre-treatment Evaluation
Physical Examination •Full neurological evaluation
•Blood pressure measurement
•Examination of genitalia
•Examination of lumbosacral spine
At least one urinalysis(including specific gravity)-
Morning
Investigations
Routine USG is not recommended-For MNE
J Urol 2010; 183:441.
Urologic imaging is reserved for children who have
significant daytime symptoms
Pediatr Nephrol.2014;29:1189–94.
Renal sonography in MNE children
• 279 children bladder abnormalities in 12.54% of enuretic
children as compared to controls(5.38%)(p=0.04)
•Majority of the clinical findings were insignificant
•Enuretic children with RBUS abnormalities - more resistant to
treatment than enuretic children with normal RBUS (P = 0.002)
Management
Non Pharmacological
•Motivational therapy
•Alarm therapy
Pharmacological
•Desmopressin
•Anticholinergics
•Combination therapy
Goals of the treatment
•To stay dry on particular occasions(e.g
sleepovers)
•To reduce the number of wet nights
•To reduce the impact of enuresis on the child
and family
•To avoid recurrence BMJ Clin Evid 2007; 2007.
Management
Fluid management
•Minimized during evng
•7am-12 pm-40%
•12pm-5pm-40%
•After 5pm-20%
•Avoid sugar and
caffeine particularly
during evening
Motivation therapy
•First line therapy for
younger children(5-7
yrs)
•Initial award –for agreed
upon behavior
• No Penalties
Motivation therapy
•Successful in 25% of the cases(14 dry nights)
•Significant improvement in >70%(80% reduction)
•Relapse rate-5%
Motivational therapy fails after three to six months, the
addition of active interventions may be warranted
Simple behavior methods are superior to no active
treatment but inferior to alarm
Enuresis Alarm
•First line therapy for non responders to fluid intake
and motivation therapy
•Meta-analysis of 56 RCT with 3257 children(2412 alarm
gr)
•66% children-dry for14 consecutive nights
•Nearly half of the children who continue to use alarm
remained dry after treatment
Enuresis Alarm
Monitoring Response
•Scheduled follow up visit at 1-2 weeks
•Rx should be continued until the child
has had a minimum of 14 consecutive
dry nights
•This usually takes between 12 and 16
weeks
•Therapy should be initiated for relapse(>2 wet
nights in 2 weeks)
Limitations of alarm therapy
•Motivation of the parents and child needed
•High failure rates of alarm therapy in winter
E-190 Naraina Vihar New Delhi India 110028 *
Ph: 91-11-45033581, 91- 9953706025
Desmopressin
•Desmopressin is a synthetic vasopressin analogue
•Most efficient in children with nocturnal polyuria
•Other indications: •Failure of alarm therapy
•Non compliant with alarm therapy
•For rapid and short improvement (sleepovers)
J Urol 2010; 183:441.
Efficacy
• 30 percent of patients achieve total dryness
using desmopressin
•40 percent exhibiting a significant decrease in
nighttime wetting Arch Dis Child 1986; 61:30.
Desmopressin
•47 RCTS with 3448 children(2210 received DDAVP)
•Compared with placebo, desmopressin reduced
bedwetting by 1.34 nights per week
•Treatment effect not sustained and failure rate was 65 in
DDAVP group and 45% alarm
•Evidence generated was “low grade”
Desmopressin
•Open label prospective phase IV study in 30 enuretic children
•Significant decrease in periodic limb movements during sleep
(PLMS) and a prolonged first undisturbed sleep period
•Amelioration of sleep and psychological functioning through
successful treatment of enuresis.
Desmopressin
Administration and Adverse affects
•Administered during late evening
•Starting dose is 0.2 mg(one tablet) 1 hr before bedtime
• For no response dose increased to a maximum of 0.4mg
After 10-14 days
• Oral melt tablets are given 30 to 60 minutes before
bedtime
•Initial dose of melt tablet is 120ug upto a maximum 240ug
J Urol. 2010;183(2):441.
Desmopressin
Adverse affects
•Adverse effect of DDAVP uncommon
•Dilutional hyponatremia-Excessive fluid intake during
evening
•Limit fluid intake-240 ml 1 hr before and 8 hrs post
•Rx interrupted during episodes of electrolyte imbalance
•Routine measurement of weight, serum electrolyes, BP.,
osmolality not indicated
U.S. Food and Drug Administration, 2007
Desmopressin
•Systematic review-42 studies and post marketing safety
data
• 48 cases of hyponatremia(21 publications) all due to
intranasal formulation
•Post marketing safety data-151 cases of hyponatremia •145(96%)cases treated with intranasal DDAVP
•6 (3.9%)cases with oral formulations
Intransal formulation is no longer indicated for the
treatment of enuresis U.S. Food and Drug Administration, 2007
Desmopressin
Assessing response
•1-2 weeks
•Rx continued for 3
months if there are signs
of improvement
•Withheld for 1 week
every 3 months
Sleeep-overs or camps
•Start 6 weeks prior
•Titrate the dose to
make it effective
Discontinuation •Dose should be tapered and not discontinued abruptly
•Provide half of the daily dose for 2-4 weeks
•Tapering the dose may decrease rate of relapses
Desmopressin
•4 RCTS with 500 subjects
•Sustained response improved with structural withdrawal
(57 versus 42 percent; pooled relative risk [RR] 1.4, 95%
CI 1.2-1.6)
•Subgroup analysis-decreasing dose prevented relapses and
not increasing the interval
Treatment of relapses
•Relapse-more than one wet night per month
after a period of dryness
•Reinitiate the effective intervention
•Try a tapering dose of desmopressin
•Combination therapy i.e alarm and DDAVP may
be beneficial for>1 recurrence following
successful treatment with alarm.
•4 trials reported this outcome
• Combination therapy associated with fewer wet
nights(MD—0.83,95% CI-1.11—0.55)
•Failure and relapse rate did not differ
•75 patients with MNE randomized to 3 arms: alarm,
desmopressin, combination desmo+alarm
•The three therapeutic modalities equally efficacious
• High dropout rates with alarm 9/75
Anticholinergic drugs
•Monotherapy with anticholinergics-Not helpful in PMNE
•Used, if associated symptoms of overactive bladder are
present
•Oxybutynin- 5mg per day along with DDAVP
•If responsive ,drug should be continued until
the child is free of symptoms for 4 months
•48 patients of enuresis and OAB •Success rate oxybutynin alone -54%
•Combination of oxybutynin and DDAVP-71%
Eur Urol 1993; 24:92.
Tricyclic Antidepressants
•Given the safety and efficacy of Alarm therapy and
DDAVP ,TCA are considered as third line for MNE
•Mechanism of action: •Decrease the amount of time spent in REM sleep,
•Stimulate vasopressin secretion, and
•Relax the detrusor muscle
•Systematic review with 4 trials/ 347 participants
•Associated with reduction of approximately 1 wet night /week
• 20 % dry with imiprimanine vs 5% with placebo
•Relapse rate 96% after discontinuation of therapy
Refractory Enuresis
•Nonresponsive-<50% improvement in symptoms
•Possible reason for lack of response includes:
•Bladder dysfunction
•Underlying disease
•Incorrect use of alarm
•Occult constipation
•Sleep apneas
•Social & emotional factors
Treatment
modality
Advantages Disadvantages
Motivational therapy Better long-term
success rate, best in
younger children
Not useful for immediate
relief
Alarm therapy First-line management
option, higher cure
rate, persistent effect
Requires high motivation
Desmopressin(0.2-0.4 mg) High initial response
rate, best for episodic
use
Relapses after
discontinuation
Oxybutynin
(5-10 mg)
Useful in patients with
daytime urgency/
frequency
Anticholinergic side effects
Imipramine
(<9 yrs-25 mg at bedtime
>9 yrs 50 mg at bedtime)
Uses in resistant case Sleep disturbance,
headache, tremors
Summary of treatment modalities for enuresis