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MONOSYMPTOMATIC ENURESIS NOCTURNA

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Title: MONOSYMPTOMATIC ENURESIS NOCTURNA


1
MONOSYMPTOMATIC ENURESIS NOCTURNA
2
  • Johan,
  • Have you had any thoughts about the workshop?
  • We could both play the devils advocate,
  • Me for the Evidence Based
  • And you for the scientific aproach
  • Jonathan

3
Some questions
  • Johan,
  • Have you had any thoughts about the workshop?
  • We could both play the devils advocate,
  • Me for the Evidence Based
  • And you for the scientific aproach
  • Jonathan

4
Some questions
  • Johan,
  • Have you had any thoughts about the workshop?
  • We could both play the devils advocate,
  • Me for the Evidence Based
  • And you for the scientific aproach
  • Jonathan

5
WHAT IS EVIDENCE
  • UK is the wettest country of Europe
  • Is A. Watson the devil (??)
  • A. Watson wins a golf-tournement in Palermo, the
    day that he is organizing this meeting
  • Is the evidence based medecine evident?
  • NO because none of the old publications does
    follow the new ICCS-standardisation, thereby have
    extremely heterogeneous study-populations.

6
(No Transcript)
7
WHAT IS EVIDENCE
  • UK is the wettest country of Europe
  • Is A. Watson the devil (??)
  • A. Watson wins a golf-tournement in Palermo, the
    day that he is organizing this meeting
  • Is the evidence based medecine evident?
  • NO because none of the old publications does
    follow the new ICCS-standardisation, thereby have
    extremely heterogeneous study-populations.
  • All studies are performed in primary care
    patients, and not in the hardcore patients that
    we see

8
WHAT TO DO WITH THERAPY REFRACTORY MNE?
  • J. Vande Walle
  • PUNC Ugent Belgium
  • Palermo 2006

9
Use it as national monument
10
You have to nod it
Je zou er moeten
11
(No Transcript)
12
What is a refractory MNE?
  • After exclusion of NMNE
  • No response after at least 1 y
  • on conventional therapy
  • lege artis,
  • as described in the EBM paper of Hjalmas 2004
  • including
  • Cognitive training
  • dDAVP
  • Alarm
  • Urotherapy
  • And combination-therapy
  • an ad hoc definition for this talk

13
Refractory MNE ?
  • The major reason for not responders is
  • that the initial intake was not performed
    appropriately,
  • that patients according to the new
    ICCS-standardisation should be considered as
    NMNE.
  • READ THE NEW ICCS-STANDARDISATION
  • Pray for forgiveness to Neveus, Von Gontard,
    Hoebeke that you did not follow their advice
  • REDO THE FULL SCREENING

14
1.Symptoms suggestive for underlying OAB
  • REDO THE FULL SCREENING
  • history of incontinence diurna (ID)
  • diurnal symptoms after the age of 3,5 years,
  • high /low frequency, postponing during normal
    fluid intake
  • are very suggestive for OAB dysfunction.
  • Low fluid intake is suggestive for a defense
    mechanism

15
1.Symptoms suggestive for underlying OAB
  • Bladder dysfunction symptoms in OAB are masked by
  • the low fluid intake as compensatory mechanism
  • Are not mentioned by parents
  • Repeat questioning,
  • Perform a bladder diary during standardized
    fluid intake 1,5ml/1.73m²/day can give
    additional information.
  • Take your time for the firstintake

16
1. Symptoms suggestive for underlying OAB
  • Both measurement of max. voided volume and
    uroflow during forced fluid-intake and diuresis
    may give additional information, because symptoms
    of OAB may become detectable during fast filling
    of the bladder.
  • Values of diuresis and enuresis-volume overnight
    may give indices on a possible role of
    OAB-contractions overnight.
  • (Incontinentia) enuresis nocturna with only
    drops (new ICCS)
  • early night wetting with small enuresis -and low
    overnight diuresis-volume
  • therapy resistance correlates with
  • Thick bladder wall (Yeung)
  • small bladder volume for age. (but only voided
    volume available)

residue for a small BV
17
2. Symptoms suggestive for dysfunctional voiding
and/or UAB
  • History of UTI, constipation
  • Absence of daytime symptoms does not exclude
    dysfunctional voiding perform an uroflow and
    ultrasonography for residue (3x)
  • Large BV with high compliance or UAB (lazy
    bladder) is frequent associated with nocturnal
    polyuria and may therefore be a consequence of
    it.
  • To make the Urotherapy effective for the UAB
    bladder, nocturnal polyuria should be treated to
    avoid the overnight distention.

18
3. DDAVP-therapy partial responder nocturnal
polyuriaA) poor compliance
  • Not taking the drug consider to let the patient
    fill in a drug-diary. Register the number of
    prescriptions
  • If the child forgets to void before sleeping, you
    start already with a full bladder
  • the minimum time to reach maximum concentrating
    capacity is one hour, and therefore the drug
    should be taken at least one hour before the last
    void before sleeping.

19
Effet anti-diurétique maximale rapide
effet anti-diuretique maximale rapide
Pharmacodynamic studies of dDAVP melt during
water-load Vande Walle JG et al. BJU Int
200697(3)6039
20
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21
Capacité de concentration maximale rapide /- 1h
Pharmacodynamic studies of dDAVP melt during
water-load Vande Walle JG et al. BJU Int
200697(3)6039
22
3. DDAVP-therapy partial responder nocturnal
polyuria B) poor pharmacokinetic and dynamic
characteristics
  • The 3 formulations (tablet, melt spray) have a
    poor biodisponibility ( 0,2-2- 4)
  • but with a rather large SD.
  • Only for the melt are dose-response-data and
    proper pharmacodynamic and kinetic data in
    children available.
  • Rationale that it might be worse for
  • - spray nasal congestion (higher or lower
    resorption)
  • - tablet interference of nutrition

23
/- 1SD
24
/- 2SD
25
/- 2SD
26
3.DDAVP-therapy partial responder nocturnal
polyuria B) poor pharmacokinetic and dynamic
characteristics
  • This high SD might be the explanation of the
    documented prolonged bioactivity (J.Dehoorne J
    Urol 2006)
  • resulting not only in side-effects,
  • but it can also lead to apparent dDAVP
    resistance.
  • Only for the melt are proper dose-response-studies
    and pharmacodynamic and kinetic data in children
    available.
  • Rationale that it might be worse for the spray
  • nasal hyperaemia increased resorption
  • insufficient dosing or overdosing ( PWP ICCS
    2006)

27
/- 1SD
28
/- 2SD
29
4. DDAVP-therapy resistant nocturnal polyuria A)
poor pharmacodynamic characteristics lack of
anti-diuretic and enuretic effect
  • Renal diabetes insipidus
  • X-linked RDI partial forms in heterozygotic
    girls
  • Renal diseases are associated with decreased
    renal concentrating capacity
  • Only in minority of patients,
  • since the kidney is able to concentrate urine
    normally, although the values do vary between
    800 to gt1200 mosmol/l (range of normal
    concentrating capacity).

30
EVIDENCE OF PARTIAL dDAVP RESPONSE RELATED TO
POORPHARMACODYNAMIC EFFECTS OF dDAVP NASAL
SPRAY A. Raes ICCS Antalya 2006 long oral
  • Significant number does not reach values gt 850
    mosmol/l
  • Is fluid-intake dependent
  • Loss of dDAVP-activity after lt 7h
  • 30 higher U osmol results in 30 higher
    diuresis-rate

p lt O.O1
dDAVP 2 nasal spray
31
DDAVP-therapy resistant nocturnal polyuria 3)
despite appropriate dDAVP-response good
concentrating capacity, no anti-diuretic effect
  • 24 h urinary excretion
  • high sodium excretion,
  • Kuzenetsova in random population Yes
  • Kamperis (JAmPhys 2006) No
  • Hypercalciuria
  • Chiozza,Valenti, Italian studies yes, yes yes
  • Neveus No
  • A. Raes (J Urol 2006) probably related to tubular
    sodium-handling disorder
  • High osmotic excretion (J. Dehoorne J Urol 2006)
  • Dietary advice is logical, should always be apart
    of urotherapy, but data on the effectiveness are
    insufficient.(Rittig Iccs 2006)

32
DDAVP-therapy resistant nocturnal polyuria 3)
despite appropriate dDAVP-response good
concentrating capacity, no anti-diuretic effect
  • Abnormal circadian rhythm of
  • sodium excretion, prostaglandins
  • Kamperis (JAmPhys 2006) yes
  • Indication for indomethacin?
  • Indication diuretics ?
  • GFR (A. Deguchtenaere ICCS 2006)

33
DDAVP-therapy resistant nocturnal polyuria 3)
despite appropriate dDAVP-response good
concentrating capacity, no anti-diuretic effect
  • High osmotic excretion (J. Dehoorne J Urol 2006)
  • Group 1
  • high 24 h intake, high 24 h excretion of sodium
    and water
  • Obese children
  • Group 2
  • (high) Normal 24 h intake, normal 24 h excretion
  • But high nocturnal excretion of osmol and water
  • high osmotic load in the evening
  • group 3
  • normal 24 h intake, normal 24 h excretion
  • But high nocturnal excretion of osmol and water
  • Small bladder volume
  • Low fluid intake during daytime (defense
    mechanism)
  • Low osmotic excretion during daytime
  • Dietary advice is logical, should always be apart
    of urotherapy, but data on the effectiveness are
    insufficient.

34
Refractory MNE Psychological and social
disturbance
  • Primary cause NO (?) A. Von Gontard ICCS 2006  
  • Secondary effect PNE may have a profound
    psychological and social impact on the affected
    child and their families.
  • Comorbidity Children with enuresis have
    significantly more behavioural and psychological
    problems, worse self-esteem
  • more attention problems, anxiety and depression,
    thought problems, internalizing and externalising
    signs, delinquent and aggressive behaviour.
  • Although uncertain if they play a major role in
    the pathogenesis, they do play a major role in
    therapy-resistance.
  • Psychological screening and approach is indicated
    in therapy-resistant children

35
Refractory MNEconclusion
  • Did you follow the ICCS-standardisation ?
  • Is there any evidence for underlying
    bladderdysfunction not included in de ICCS.
    Consider cystomanometry.
  • dDAVP-partial responders nocturnal polyuria
  • Improve compliance
  • Titrate dDAVP (by performing simple PD-tests)
  • Switch to the best biodisponible form
  • Reduce fluid intake in the evening (and not only
    at night)
  • dDAVP resistance
  • Consider fluid intake, osmotic load,
    hypercalciuria, indomethacin, diuretics
  • Consider psychological problems, ADHD, ADD
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