Current Approaches to Nocturnal Enuresis: Pearls for the Family Doctor

1
Current Approaches to Nocturnal Enuresis
Pearls for the Family Doctor
2
Patients Perspective

• A survey reported that 68 of parents said that
  their childs paediatrician or primary care
  provider had never addressed bedwetting during a
  routine visit, regardless of the childs age1
• Most parents believe that NE is not a physical
  condition and are uncomfortable initiating a
  dialogue with physicians1

Adapted from Dunlop et al., Clinical Pediatrics
200544297-303 1.
3
Patients Perspective

• Inadequate treatment of NE has psychological
  ramifications including impaired personal, social
  and emotional behaviour1,2
• Only parental fighting and divorce are perceived
  by patients as worse than bedwetting3

Adapted from Fergusson et al. Pediatrics 1986
78 884 1 Butler et al. BJU intern 2002 Vol 89
issue 3295-7 2 Van Tijen et al. British
Journal of Urology 1998 81 Suppl 398-9 3.
4
Parents Perspective

• Most parents (80) believe that children wet the
  bed because they are stressed or worried, or in
  some cases simply out of laziness1
• A survey by the Enuresis Resource Information
  Centre (ERIC) ,UK-based charity

Adapted from http//www.eric.org.uk/Home/tabid/36/
Default.aspx 1
5
Physicians Perspective

• MDs maintain the notion that patients will
  outgrow the problem and defer treatment1
• Family Physician residents receive limited
  training in NE
• Not on the curriculum for post graduate students
  in the 6 Ontario medical schools2
• Health Canada recently issued a safety bulletin
  that directly impacts a common treatment option
  for NE3

Adapted from Gimble et al. Clin Pediatr (Phila).
199837(1)23-9 1. Personal communication 2 .
http//www.hc-sc.gc.ca/dhp-mps/medeff/advisories-a
vis/prof/_2008/desmopressin_hpc-cps-eng.php 3
6
Definition of NE1

• Involuntary discharge of urine at night by
  children old enough to be expected to have
  bladder control
• Persists beyond the age of 5 years
• Total bladder control never achieved or relapsed
• Incidence of more than twice weekly
• Continent during the day
• Types of nocturnal enuresis
• PNE when bladder control has never been attained
• SNE previously dry for a at least six months

Adapted from Canadian Pediatric Society.
Management of primary nocturnal enuresis.
Paediatrics Child Health 200510(10) 611-4 1
7
Prevalence1,4
NE affects twice as many boys than girls3
NE resolves spontaneously at a rate of 15 a year2
Nocturnal Enuresis ()
Age (years)
Adapted from Fergusson et al., Pediatrics 1986
78(5)884-90 1 Robson et al. Curr Opin Urol
2008,18425-30. Klackenberg et al., Acta
Paediatr Scand 198170453 3 Yeung et al. BJU
Int 2006971069-73.
8
Etiology

• Genetic predisposition1
• Family history one parent 44, two parents 77
• Excessive urine production2
• Due to inadequate amount, or response to ADH at
  night
• Deep sleep and arousal disorder3
• Lack of awareness of a full bladder during sleep

Adapted from Von Gontard et al. J Urol 2001 Vol.
166, 243843. 1 Rittig et al. Am J Physiol 1989
256(4 Pt 2)F664-71.2 Wolfish NM. J Urol 2001
166(6) 2444-7. 3
9
Etiology

• Diminished functional bladder capacity1
• Slow development of bladder control1
• Emotional and behavioural issues are not
  causative, but may influence treatment outcome2

Adapted from Wolfish NM. J Urol 2001 166(6)
2444-7 1 CPS-management of primary nocturnal
enuresis (revised Aug 2007)2
10

Causes of Enuresis A Triad1
Bladder Contractions
Urine Volume
Sleep Arousal
ENURESIS
Adapted from Wolfish et al., J Urol 2001 Vol.
166, 24447.
11
Circadian Urine Production
Plt0.001
ml/hour
Mean variation in urinary excretion rate
Adapted from Rittig et al. Am J Physiol 1989
Apr256(4 Pt 2)F664-71.
12
Circadian ADH Production
Plt0.001
P avp (pg/ml)
Mean variation in plasma antidiuretic hormone
(ADH)
Adapted from Rittig et al. Am J Physiol 1989
Apr256(4 Pt 2)F664-71.
13
Impact of Enuresis on Children

• Psycho-social impact1,2
• Low self-esteem
• Shame, embarrassment
• Guilt
• Parents become intolerant of the bedwetting2
• Interferes with age appropriate peer activities1,2

Adapted from Hägglöf et al., Scand J Urol Nephrol
199731533-6. 1 Butler et al, BJU intern 2002
Vol 89 issue 3 295-7.2
14
NE Its NOT the Childs Fault1

• Bedwetting is a medical condition
• It is mostly caused by the lack of naturally
  occurring messenger that reduces urine production
  to a non-bedwetters volume at night2
• Leads to an overproduction of urine, often more
  than a childs small bladder can hold1
• As the children grow, most will eventually stop
  wetting the bed

Adapted from Butler et al, BJU Intern 2002 Vol
89 issue 3 295-7 1 Djurhuus et al., Scand J
Urol Nephrol Suppl 19921417-17 discussion 18-9
2
15
Diagnosis

• Screen for NE as most patients are uncomfortable
  initiating dialogue1
• Investigate history, conduct physical examination
  and urinalysis2
• Urinanalysis not always needed
• Investigate family history
• Establish if NE is primary or secondary
• Primary NE started at birth is continuous
• Secondary NE previously dry for at least six
  months

Adapted from Dunlop et al., Clinical Pediatrics
2005 1Canadian Pediatric Society. Management of
primary nocturnal enuresis. Paediatrics Child
Health 200510(10) 611-4 2
16
Diagnosis

• Rule out other possible conditions1
• Structural or neurological problems
• Storage or voiding dysfunctions
• Daytime wetting
• Urinary tract infection
• Polyuric conditions
• Diabetes mellitus, diabetes insipidus, chronic
  renal failure, renal tubular acidosis, renal
  dysplasia, Bartters syndrome

Adapted from Hjalmas et al. J Urol
20041712545-61
17
Treatment Goals

• Increase the number of dry nights1
• Minimize the emotional impact of NE1
• Establish a positive environment to help the
  child become dry
• Protect improve self-esteem as NE is not the
  childs fault. Minimize feelings of guilt shame
  
• Note
• Therapy is a stepwise process
• Partial response better than no response
• May require years of continuous therapy

Adapted from Canadian Pediatric Society.
Management of primary nocturnal enuresis.
Paediatrics Child Health 200510(10) 611-4.
18
Common Management Strategies1

• Child to empty the bladder at bedtime
• Limit fluid consumption eliminate caffeine
• Late afternoon and onwards
• Clarify the goal of getting up / using the toilet
• Take the child out of diapers
• Consider pull-ups or training pants
• Include child in morning cleanup in a
  non-punitive manner

Adapted from Canadian Pediatric Society.
Management of primary nocturnal enuresis.
Paediatrics Child Health 200510(10) 611-4
(REVISED AUG 2007)
19
Treatment Approaches1

• Non-pharmacological
• Wet alarm ?
• Behavioural therapy X
• Pharmacological
• Desmopressin acetate ?
• Tricyclic antidepressants X / ?
• extreme caution
• Anticholinergics, amphetamine, ephedrine,
  atropine, furosemide, diclofenac X

Adapted from Canadian Pediatric Society.
Management of primary nocturnal enuresis.
Paediatrics Child Health 200510(10) 611-4.
20
Treatment Approaches Supported

• Approaches recommended by both the Canadian
  Paediatric Society1 and the WHO2
• Wet alarm
• Desmopressin acetate

Adapted from Canadian Pediatric Society.
Management of primary nocturnal enuresis.
Paediatrics Child Health 200510(10) 611-4.1
van Gool JD, et al. International Consultation
on Incontinence 1998Monaco WHO487-550. 2
21
Patients Involvement

• Appropriate care for the individual patient needs
  to consider patient preferences
• Better treatment outcomes are achieved when
  parents / patient are involved in making the
  decision about choice of treatment1
• Treatment modalities require consistent support
  and cooperation from the child and the family and
  are unlikely to succeed in their absence2

Adapted from Monda et al, J Urol. 1995
Aug154issue 2, 745-8. 1 Tarun Gera et
al.,Nocturnal Enuresis In Children. The Internet
Journal of Pediatrics and Neonatology. 2001.
Volume 2 Number 1.2
22
Wet Alarm

• Cure rate lt 501
• Up to 2 months needed to see improvement
• Main drawbacks with wet alarm
• High noncompliance rate 30 of patients may
  discontinue use within 3 weeks2
• Alarm rings during NREM sleep, the deepest and
  most difficult time for arousal3,4
• Success highly dependent on motivation of both
  parents and child1

Adapted from Canadian Paediatric Society
Positioning Statement, 2007. 1 Tietjen et al.
Mayo Clin Proc 199671857-62. 2 Wolfish et al.
J Urol 2001 Vol. 166, 24447. 3 Butler RJ et
al. Scand J Urol Nephrol. 200236(4)268-72. 4
23
Wet Alarm

• Most appropriate for older, motivated children gt
  7 or 8 years of age with motivated families1
• Wet alarm therapy requires a commitment from
  other siblings as often all members of the
  household are wakened when the alarm goes off2
• Often the family wakes up, not the bed wetter2

Adapted from Canadian Pediatric Society.
Management of primary nocturnal enuresis.
Paediatrics Child Health 200510(10) 611-4 .1
Butler et al. BJU Intern 2002 Vol 89 issue 3
295-7. 2
24
Wet Alarm

• The alarm goes off when the child starts to void.
  It may teach the child to wake up to the alarm
  and then, by extension, transfer the waking to
  the sensation of a full bladder1
• Nocturia could replace night time wetting2

Adapted from Canadian Pediatric Society.
Management of primary nocturnal enuresis.
Paediatrics Child Health 200510(10)611-4.1
Bonde et al. Scand J Urol Nephrol
199428(4)349-52.2
25
Desmopressin Acetate

• Synthetic analogue of ADH
• Efficacy while treated gt 801
• Suitable for children 5 years of age and older2
• Response to treatment seen within 7 days2
• Duration continue for 3 months when the child is
  dry and stop for one week. Re-initiate at the
  same dose/duration if needed2

Adapted from Janknegt et al., Dutch Enuresis
Study Group. J Urol 1997157(2)513-7.1 Ferring
Pharmaceuticals, Product Monograph, desmopressin
(DDAVP)2
26
Clinical Response to Desmopressin 0.2 mg Tablets1
lt 50 reduction wet nights
gt 50 reduction wet nights
gt 90 reduction of wet nights
Response rate 84
Adapted from Janknegt et al. J Urol
1997157(2)513-7.
27
Removal of NE Indication Spray Rhinyle

• In July 2008 Health Canada with support from
  Ferring, revised the product monograph for all
  intranasal formulations of desmopressin acetate
• Bedwetting treatment indication for both spray
  rhinyle are now contraindicated
• The central diabetes insipidus indication remains
  unchanged

Adapted from http//www.hc-sc.gc.ca/dhp-mps/medeff
/advisories-avis/prof/_2008/desmopressin_hpc-cps-e
ng.php
28
Desmopressin Formulations

• Desmopressin spray rhinyle
• Contraindicated for NE1
• Desmopressin tablet 200 µg
• Typically requires fluid intake
• Desmopressin MELT 120 µg and 240 µg
• Does not require water
• Physiologic activity matches childs duration of
  sleep3

Adapted from http//www.hc-sc.gc.ca/dhp-mps/medeff
/advisories-avis/prof/_2008/desmopressin_hpc-cps-e
ng.php 1 Lottmann et al. Int J Clin Pract
20071742-1241. 2 Vande Walle et al. BJU
International 2006 97 603309.3
29
Duration of Action
11
Hours
Average duration of sleep in PNE children2
7
Tablet
Melt
Spray
MELT matches sleep period of children 5 years of
age
Adapted from Product monographs. Vande Walle et
al. BJU International 2006 97603309.
30
Dosing Desmopressin Melt

• Start with one 120 µg Melt 1 hour before bedtime
  for 3 nights
• If not dry, increase by 120 µg Melt every 3
  nights to a maximum of 360 µg Melts
• Treatment should persist as long as symptoms
  exist
• Drug holidays every 3 months to evaluate
  treatment effect

Adapted from product monograph Desmopressin
acetate (DDAVP) 2008
31
Preference Trial Melt vs. Tablets

• Comparison of Melt and tablet in NE children /
  adolescents aged 515 years1
• Primary result
• Melt is statistically significantly preferred by
  children aged lt12 years
• Secondary results
• Efficacy same number of wet nights
• Tolerability same as tablets
• Compliance improved vs. tablets

Adapted from Lottmann et al. Int J Clin Pract
2007 , doi 10.1111/j.1742-1241.01493.x
32
Efficacy Number of Wet Nights
Adapted from Lottmann et al., Int J Clin Pract
2007 1742-124.
33
Desmopressin Melt No Water

• No fluid required
• Swallowing 57 mL of fluid with a tablet is
  equivalent to about 25 of the expected bladder
  capacity of a 7-year-old1
• Desmopressin Melt eliminates the need for water
  intake thus reducing an enuretic childs liquid
  burden

Adapted from Robson WLM, Parkhurst Exchange 2007.
34
Desmopressin Melt vs. Tablets

• Same efficacy, side effect profile, indication,
  dosin
• Matches the average duration of a night sleep in
  children with PNE
• No fluid required
• Preferred by children lt 12 years of age
• Better compliance
• Eliminates tablet swallowing difficulties
• Lower dose (120 µg melt 200 µg tab)

35
Pearls For Practice

• Bedwetting significantly impacts self esteem and
  instils guilt and shame in childre
• Bedwetting needs to be diagnosed as part of
  routine examination
• Annual physical, routine visits
• Children and their parents need to be actively
  involved in the treatment

36
Pearls For Practice

• Wet alarm is viable for older, very committed
  children highly motivated family
• Cure rate lt 50
• Desmopressin MELT is safe effective for
  children of all ages
• Lower dose, mimics duration of sleep, no water
• Efficacy while treated gt 80