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