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Nocturnal Bladder Emptying for Reversing Urinary Tract Deterioration Due to Neurogenic Bladder Stephen Canon, MD, Seth Alpert, MD, and Stephen A. Koff, MD Corresponding author Stephen A. Koff, MD Section of Pediatric Urology, Children’s Hospital, R oom # ED314, Education Building, 700 Children’s Drive, Columbus, OH 43205-2696, USA. E-mail: [email protected] Current Urology Reports 2007, 8:6065 Current Medicine Group LLC ISSN 1527-2737 Copyright © 2007 by Current Medicine Group LLC Although daytime clean intermittent catheterization with urotropic medications is often sufficient therapy to relieve urinary retention and elevated intravesical pres- sures, neglecting the bladder affected by neuropathy or other significant pathologies during sleeping hours can lead to overdistension of the bladder and its deleterious consequences. The effect of this seemingly inconsequen- tial clean intermittent catheterization interlude for some patients on an ideal daytime-only management protocol can lead to a syndrome of nighttime overdistension of the bladder, which can result in recurrent urinary tract infections, worsened incontinence, decreased bladder compliance and capacity, and progressive hydrouretero- nephrosis and renal insufficiency. Fortunately, nocturnal bladder emptying has emerged as a specific antidote for the syndrome of nighttime overdistension of the bladder, and because nocturnal bladder emptying can reverse or prevent bladder and upper tract deterioration, it is suggested that conventional therapies performed only during the daytime may have been inadequate for certain subgroups of patients who require a new therapeutic paradigm for their optimal management. Introduction The child born today with spina bifida still faces the daunting task of maintaining normal upper urinary tract function and anatomy because of their neurogenic bladder (NGB), which can cause bladder overdistension, induce sustained elevated end filling pressures within the bladder, and lead to hydroureteronephrosis (HUN) and renal deterioration [1–4]. With improved understanding of NGB dysfunction, clean intermittent catheterization (CIC) with urotropic medications has been employed therapeutically and even prophylactically to treat or pre- vent these deleterious effects [5–7]. Although CIC allows for regular bladder emptying and prevents bladder over- distension during the daytime, it is typically not utilized at night when the patient and family sleeps and thus may fail to decompress the bladder for a significant portion of the 24-hour day. Insufficient nighttime bladder emptying coupled with the bladder insensitivity (as occurs in NGB) has been proposed to induce a syndrome of nighttime overdistension of the bladder (SNOB) [8••]. The effect of a seemingly inconsequential nighttime CIC interlude for the patient on an otherwise ideal daytime-only manage- ment protocol can be significant and result in recurrent urinary tract infections (UTIs), worsened incontinence, decreased bladder compliance and capacity, and progres- sive HUN and renal insufficiency. Fortunately, the use of nocturnal bladder emptying (NBE) has emerged as a specific antidote for the SNOB in patients with NGB, and its evolution and development, application, and outcome in reversing urinary tract deterioration due to NGB is discussed further. NBE in the Valve-bladder Syndrome Historically, the valve bladder syndrome (VBS), defined as persistence or progression of HUN despite optimal medi- cal management in boys whose posterior urethral valves (PUV) were successfully eradicated, was first thought to be caused by irreversible alterations of the bladder (ie, changes in compliance, capacity, and contractility) secondary to obstruction, which permanently interfered with its function. However, patients with VBS and renal failure leading to renal transplantation have not been observed after renal trans- plantation to develop renal transplantation deterioration over long-term follow-up [9,10]. This surprising discovery suggested that renal deterioration, which occurred in PUV patients, was likely not a consequence of permanent bladder dysfunction, may be related to acquired renal dysfunction, was malleable and reversible after transplantation, and warranted further investigation.

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Page 1: Nocturnal bladder emptying for reversing urinary tract deterioration due to neurogenic bladder

Nocturnal Bladder Emptying for Reversing Urinary Tract Deterioration

Due to Neurogenic BladderStephen Canon, MD, Seth Alpert, MD, and Stephen A. Koff, MD

Corresponding authorStephen A. Koff, MDSection of Pediatric Urology, Children’s Hospital, Room # ED314, Education Building, 700 Children’s Drive, Columbus, OH 43205-2696, USA.E-mail: [email protected]

Current Urology Reports 2007, 8:60–65Current Medicine Group LLC ISSN 1527-2737Copyright © 2007 by Current Medicine Group LLC

Although daytime clean intermittent catheterization with urotropic medications is often sufficient therapy to relieve urinary retention and elevated intravesical pres-sures, neglecting the bladder affected by neuropathy or other significant pathologies during sleeping hours can lead to overdistension of the bladder and its deleterious consequences. The effect of this seemingly inconsequen-tial clean intermittent catheterization interlude for some patients on an ideal daytime-only management protocol can lead to a syndrome of nighttime overdistension of the bladder, which can result in recurrent urinary tract infections, worsened incontinence, decreased bladder compliance and capacity, and progressive hydrouretero-nephrosis and renal insufficiency. Fortunately, nocturnal bladder emptying has emerged as a specific antidote for the syndrome of nighttime overdistension of the bladder, and because nocturnal bladder emptying can reverse or prevent bladder and upper tract deterioration, it is suggested that conventional therapies performed only during the daytime may have been inadequate for certain subgroups of patients who require a new therapeutic paradigm for their optimal management.

IntroductionThe child born today with spina bifida still faces the daunting task of maintaining normal upper urinary tract function and anatomy because of their neurogenic bladder (NGB), which can cause bladder overdistension, induce sustained elevated end filling pressures within the bladder, and lead to hydroureteronephrosis (HUN) and renal deterioration [1–4]. With improved understanding

of NGB dysfunction, clean intermittent catheterization (CIC) with urotropic medications has been employed therapeutically and even prophylactically to treat or pre-vent these deleterious effects [5–7]. Although CIC allows for regular bladder emptying and prevents bladder over-distension during the daytime, it is typically not utilized at night when the patient and family sleeps and thus may fail to decompress the bladder for a significant portion of the 24-hour day. Insufficient nighttime bladder emptying coupled with the bladder insensitivity (as occurs in NGB) has been proposed to induce a syndrome of nighttime overdistension of the bladder (SNOB) [8••]. The effect of a seemingly inconsequential nighttime CIC interlude for the patient on an otherwise ideal daytime-only manage-ment protocol can be significant and result in recurrent urinary tract infections (UTIs), worsened incontinence, decreased bladder compliance and capacity, and progres-sive HUN and renal insufficiency. Fortunately, the use of nocturnal bladder emptying (NBE) has emerged as a specific antidote for the SNOB in patients with NGB, and its evolution and development, application, and outcome in reversing urinary tract deterioration due to NGB is discussed further.

NBE in the Valve-bladder SyndromeHistorically, the valve bladder syndrome (VBS), defined as persistence or progression of HUN despite optimal medi-cal management in boys whose posterior urethral valves (PUV) were successfully eradicated, was first thought to be caused by irreversible alterations of the bladder (ie, changes in compliance, capacity, and contractility) secondary to obstruction, which permanently interfered with its function. However, patients with VBS and renal failure leading to renal transplantation have not been observed after renal trans-plantation to develop renal transplantation deterioration over long-term follow-up [9,10]. This surprising discovery suggested that renal deterioration, which occurred in PUV patients, was likely not a consequence of permanent bladder dysfunction, may be related to acquired renal dysfunction, was malleable and reversible after transplantation, and warranted further investigation.

Page 2: Nocturnal bladder emptying for reversing urinary tract deterioration due to neurogenic bladder

NBE for Reversing Urinary Tract Deterioration Due to NGB Canon et al. 61

In 2002, Koff et al. [11] studied 52 boys with PUVs without urinary diversion or bladder defunctionalization (mean age, 11.1 years) who after valve ablation were treated for bladder dysfunction for a 15-year period with a combination of frequent and timed voiding, double voiding, anticholinergic medications, and (when necessary) intermittent catheterization. Unfortunately, even this aggressive daytime regimen failed to prevent the persistence or inappropriate progression of HUN in 18 boys who developed the VBS. The first six patients underwent urinary diversion or bladder augmentation to successfully treat the VBS with improvement or resolu-tion of HUN. After ensuring that their valve ablation was successful and excluding anatomic obstruction as a potential etiology of HUN, the remaining 12 patients began a program of NBE that added bladder emptying at night to their daytime regimen by utilizing a combi-nation of an indwelling nighttime catheter, intermittent nocturnal catheterizations, and/or frequent nocturnal double voiding.

The results were prompt and dramatic, and radio-graphic evidence revealed that HUN improved or resolved in all 12 patients after initiation of NBE (Table 1). The improvement noted was comparable in degree to the radiographic findings observed in the initial six patients in the series treated with urinary diversion or bladder augmentation. This outcome suggested that the HUN observed after daytime-only management of the VBS was a result of sustained nighttime bladder overdistension, which was due to a combination of sequelae of in-utero valvular obstruction (eg, polyuria in 10 boys, impaired bladder sensation in 18 boys, and residual urine volume in 14). Contrary to the previously held notion that the bladder itself was the primary cause of renal deterioration in the VBS, the improvement in HUN and normalization of bladder capacity and function in this series of patients indicated that polyuria, bladder insensitivity, and residual urine volumes worked synergistically to form the SNOB, and together, they were the actual mechanisms respon-sible for its pathophysiology.

NBE in NGBAlthough the VBS appears to be produced by polyuria, bladder insensitivity, and residual urine volume, which cause high-pressure bladder overfilling (especially at night), this pathophysiology (that can result in damage to the upper urinary tract) does not appear to be unique to this syndrome; similar pathophysiologic changes can occur in children with NGB who are on daytime treat-ment programs employing CIC. These children with NGB are particularly prone to develop SNOB because they lack not only the sensation needed to recognize bladder over-distension but also the ability to voluntarily empty their bladder at nighttime. Consequently, the application of NBE to patients with NGB in an attempt to ameliorate

their HUN and renal deterioration appeared to be a logical extension in the application of nighttime therapy to children whose daytime management was successful but ineffectual [8••,12••,13].

The results of applying NBE to children with NGB by Koff et al. [8••] are outlined in Table 1. There were 19 children (mean age, 10.4 years) with NGB who dete-riorated despite being managed with optimized CIC and urotropic medications. Seventeen had NGB secondary to myelomeningocele (MMC), and two were diagnosed with nonneurogenic neurogenic bladder. When deterioration in the form of decreased bladder capacity, progression or development of HUN, recurrent urinary tract infections (UTIs), or worsened incontinence between catheteriza-tions occurred, NBE was initiated. Nguyen et al. [12••] subsequently used NBE to treat NGB caused by a variety of etiologies associated with poorly compliant bladders and impaired renal function, worsened upper tract dilatation, or recurrent UTIs (Table 1).

Although there is only anecdotal evidence of sustained improvement in renal function (ie, serum creatinine [Scr] or glomerular filtration rate [GFR]) after initiating therapy, in both of these studies the benefit of NBE for improv-ing HUN was clear. In the Koff et al. [8••] series, seven of seven patients who began NBE because of persistent or worsening HUN demonstrated improvement or complete resolution of upper tract dilatation. Nguyen et al. [12••] noted improvement of HUN in seven of eight patients with upper tract dilatation after commencing NBE (four with complete resolution and three with improved HUN).

Preventing nocturnal overdistension of the bladder also resulted in urodynamically proven increased bladder capacity in both series. Koff et al. [8••] observed increased bladder capacity ranging from 80 mL to 220 mL, with a mean improvement of 147.5 mL. Of particular importance was the fact that this improvement in capacity was sufficient to avoid planned bladder augmentation in five children. In Nguyen et al. [12••], the increase in bladder capacity ranged from 0 to 150 mL, with a mean improvement of 64.5 mL.

Symptomatic UTI is another common problem children with NGB face and is especially problematic and potentially severe in those with SNOB. Following the introduction of NBE, both of the previous series demonstrated a decrease in the frequency and severity of UTI (Table 1). Koff et al. [8••] reported reduced frequency of UTI in six of eight patients, and Nguyen et al. [12••] reported elimination of febrile UTI in all three patients with previous UTI who started NBE. Montane et al. [13] demonstrated an even more definitive benefit in the prevention of UTI after NBE. Mean hospitalizations for febrile UTI decreased from 1.7 to 0.4 in the first year of NBE (P = 0.03), and there was complete cessation of admissions for febrile UTI by the 2nd year (P < 0.01).

Incontinence between catheterizations and during sleeping hours commonly occurs in patients with NGB despite anticholinergic therapy. These patients also respond well to NBE when their incontinence is due to

Page 3: Nocturnal bladder emptying for reversing urinary tract deterioration due to neurogenic bladder

62 New Techniques

Tabl

e 1.

Noc

turn

al b

ladd

er e

mpt

ying

in d

isor

ders

of b

ladd

er e

mpt

ying

Seri

esN

Mea

n ag

e (y

)M

ean

NB

E du

rati

on (y)

Impr

oved

H

UN

U

rina

ry t

ract

in

fect

ion

Ren

al f

unct

ion

impr

ovem

ent

Inco

ntin

ence

Path

olog

y

Koff

et a

l. [1

1]

1811

.1N

ot r

epor

ted

18/1

8 (1

00%

)N

ot r

epor

ted

Scr i

mpr

oved

in 6

, st

abili

zed

8, w

orse

ned

4N

ot r

epor

ted

*Val

ve-b

ladd

er s

yndr

ome

Mon

tane

et a

l. [1

3]

712

4.9

Not

rep

orte

dA

dmis

sion

s pe

r ye

ar d

ecre

ased

1.

7 to

0

Stab

ilize

d G

FR in

5N

ot r

epor

ted

† PU

V (2

), oc

hoa

synd

rom

e, r

eflux

ne

phro

path

y, N

GB,

oc

ulo-

cere

bral

-ren

al-s

yndr

ome,

ur

ogen

ital s

inus

Koff

et a

l. [8

••]

1910

.41.

97/

7 (1

00%

)Fr

eque

ncy

decr

ease

d in

6/8

Not

rep

orte

d3/

3 re

solv

edM

MC

(17)

and

NN

GN

GB

(2)

Ngu

yen

et a

l. [1

2••]

117.

52.

37/

8 (8

8%)

Febr

ile U

TIs

elim

inat

ed in

3/3

No

chan

ge in

mea

n Sc

r6/

9 re

solv

ed3/

9 im

prov

ed

PUV,

NN

GN

GB

(4),

MM

C (2

), ne

urob

last

oma,

prun

e-be

lly, t

rans

vers

e m

yelit

is,

and

sacr

al a

gene

sis

*Six

trea

ted

with

bla

dder

aug

men

tatio

n an

d co

mpa

red

with

NB

E.† F

ive

of s

even

pat

ient

s ha

d bl

adde

r au

gmen

tatio

n be

fore

NB

E.

GFR

—gl

omer

ular

filtr

atio

n ra

te; H

UN

—hy

drou

rete

rone

phro

sis;

MM

C—

mye

lom

enin

goce

le; N

BE—

noct

urna

l bla

dder

em

ptyi

ng; N

GB

—ne

urog

enic

bla

dder

; NN

GN

GB

—no

nneu

roge

nic

neur

ogen

ic b

ladd

er; P

UV

—po

ster

ior

uret

hral

val

ve; S

cr—

seru

m c

reat

inin

e; U

TIs—

urin

ary

trac

t inf

ectio

ns.

Page 4: Nocturnal bladder emptying for reversing urinary tract deterioration due to neurogenic bladder

NBE for Reversing Urinary Tract Deterioration Due to NGB Canon et al. 63

nocturnal bladder overdistension (Table 1) [8••]. One hundred percent of patients in Koff et al. [8••] had complete resolution of urinary incontinence between CIC, whereas Nguyen et al. [12••] reported complete resolution of incontinence in six of nine patients and improvement of continence in the remainder.

NBE and Postobstructive DiuresisIn contrast with PUV patients, children with NGB gener-ally do not have significant polyuria, and residual urine volumes are usually low after catheterization [8••]. How-ever, Nguyen et al. [12••] observed what they interpreted to be a profound diuresis during urodynamics in a select group of patients with poorly compliant bladders in whom daytime intermittent bladder drainage had failed. After emptying the bladder with a catheter at the start of urodynamics and then filling the bladder, the amount drained was much greater than the amount filled. Their interpretation that this was a postobstructive diuresis (POD) is based upon the observations made during uro-dynamic evaluation of this select group of patients using the following formula: POD (mL/kg/h) = (volume drained - volume filled)/ weight/ duration of study.

POD was based on the premise that residual urine volumes were greater than should be expected based upon the degree of the HUN, and therefore, another causative mechanism must be present, presumably POD. For the entire cohort, no statistically significant difference was noted between the pre- and post-NBE POD volumes (4.8 vs 4.4 mL/kg/h, P = 0.29). How-ever, a select group of patients with high volume POD (three of eleven patients) were found to have significant changes in their POD volumes before and after NBE (8.6 vs 4.4, P = 0.035).

Unfortunately, without confirming complete blad-der and upper tract emptying using ultrasonography in these patients before starting urodynamics, con-cern exists that the POD may in actuality represent undrained residual urine in the upper tracts that persisted after initial placement of the urodynamics catheter. This might represent residual urine either as a pseudoresidual (refluxing urine) or alternatively, a pseudo-pseudoresidual (urine contained within a non-refluxing HUN), which is capable of promptly refilling the bladder immediately after emptying, as was observed in the VBS population [11]. Nguyen et al. [12••] did note that one patient had vesicoureteral reflux, which was treated with bilateral ureteral reimplantation during their study, but the presence or absence of vesicoureteral reflux in the remainder of the patients was not reported. Therefore, the presence of upper tract urine either from reflux or HUN, which refills the bladder quickly, may be a confounding factor that potentially invalidates the concept of postobstructive diuresis in these patients and remains to be excluded.

NBE and Stabilization of Renal FunctionMontane et al. [13] studied the effect of NBE in seven chil-dren with NGB and progressive renal disease, including five patients with previously created bladder augmentations before initiation of NBE. These seven patients had an aver-age age of 12 years at the onset of NBE and a mean duration of NBE of 4.9 years. The underlying etiology for bladder dysfunction in the series was varied and included PUV (2), ochoa syndrome, reflux nephropathy, NGB, oculo-cerebral-renal-syndrome, and urogenital sinus with obstruction. NBE was initiated only after daytime management was optimized and progressive worsening of renal function occurred. All patients were polyuric with a mean urine output of 2370 mL per day. Both GFR and 1/Scr were assessed before and after NBE commencement. Using regression analysis of 1/Scr versus time, the intersection of 1/Scr and the timeline served as a reliable predictor of the age at which dialysis would be necessary. Six patients demonstrated benefit from NBE with significant attenuation of the slope of renal func-tional decay curve (P = 0.02). This indicated a significant amelioration of renal functional deterioration by NBE, though it cannot be proven that NBE actually improved GFR because only two of seven patients had improved GFR of more than 5 mL/min/1.73 m2. Two patients with GFRs that decreased by more than 5 mL/min/1.73 m2 were both transplanted preemptively. Also, the presence or absence of HUN along with improvement or lack thereof after NBE was not reported in this series. Presumably, improvement or stabilization of GFR as a result of NBE would be accompa-nied by improvement in HUN, and therefore, the presence of HUN would be a useful variable to monitor before and after NBE. Without a control group with which to compare these observations, it is difficult to determine exactly what impact NBE had upon renal functional decay. Nevertheless, the assessment of GFR and renal functional decay (1/Scr) in the setting of NBE remain valuable tools to critically assess the impact of NBE on function and potential deterioration of the upper tracts.

Surgically Altered Leak Point Pressure, SNOB, and NBE Other researchers have observed pathologic upper tract changes after surgically induced alterations in the dynamics of bladder emptying. Roth et al. [14] studied the effects of artificial urinary sphincter (AUS) placement upon continence and upper urinary tract function. In 47 children treated with AUS, 11 patients were observed to have transient HUN. Despite having preoperative radiologic evaluation and in most cases preoperative urodynamic evaluation, 11 patients inexplicably developed HUN: five with urinary retention (group 1) and six patients without urinary retention but with worsened bladder compliance (group 2). HUN resolved in four or five patients in group 1 with CIC and urotropic medication alone. One patient in group 1 had short-term HUN resolution but subsequently demonstrated

Page 5: Nocturnal bladder emptying for reversing urinary tract deterioration due to neurogenic bladder

64 New Techniques

recurrent HUN. In group 2, medical therapy alone was insufficient leading to bladder augmentation in five of seven patients. Although urodynamic evaluation before AUS placement was not performed in every patient in this series, the available preoperative radiologic information suggested sufficient bladder capacity and compliance to permit low-pressure urinary storage, and thus, the new development of bladder capacity and compliance deterioration appeared to the authors to represent a conundrum.

On closer analysis, however, the clinical scenarios in this subgroup of patients after AUS placement appear to be caused by the SNOB. Due to the artificial elevation of leak point pressure in an attempt to achieve continence, these children who were on a program of daytime-only management, especially in the setting of reduced bladder sensation, were predisposed to unrecognized nocturnal bladder overdistension, which in some patients may lead to decreased bladder compliance and HUN. As in some NGB patients, initiating CIC and urotropic medications may effectively reverse upper tract dilatation, as was seen in group 1 of the Roth et al. [14] study. However, in more severe cases or when the bladder is insensate, the SNOB may develop when the elevated filling pressures (due to bladder overdistension) cannot be alleviated by daytime therapy alone; this can lead to upper tract deterioration and altered bladder compliance as was seen in group 2. Due to the potential for developing the SNOB after implantation of an artificial sphincter, placement of a fascial sling around the bladder neck, or even after blad-der neck reconstruction, the surgeon must ensure by regular bladder drainage during the daytime and at night that bladder volume does not exceed bladder capacity. In addition, these patients must be carefully monitored for any adverse symptomatology or bladder and/or upper tract changes, which must be promptly assessed and appropriately treated, keeping in mind that SNOB might be the underlying etiology.

Bloom et al. [15] observed essentially the opposite clini-cal scenario in which a group of 18 patients with MMC underwent urethral dilatation for elevated leak point pressures. Among 350 children with MMC, 18 children (average age, 2.9 years) found to have leak point pressures greater than 40 cm H2O underwent urethral dilation with immediate pre- and postprocedure confirmation of a low-ered leak point pressure (decreased from mean 55.75 cm to 31 cm). Subsequent mean leak point pressure at follow-up decreased to 19.2 cm H2O. They observed inexplicably that bladder compliance improved dramatically with the mean leak point initial compliance ratio decreasing from 4.69 to 0.69 and the mean leak point terminal compliance ratio decreasing from 105.13 to 10.44 after urethral dilation. On closer examination, the explanation appears to reflect satisfactory treatment of the SNOB. Thus, by reducing leak point pressures in this population, these individuals’ bladders were no longer overdistended at night and no longer stored large volumes of urine at high pressure; not

surprisingly, bladder compliance improved. Bloom et al. [15] later revisited this patient population with 25 patients evaluated over a 15-year period and found that urethral dilatation in combination with medical therapy was suf-ficient to obviate the need for bladder augmentation in 21 of 25 (84%) patients [16]. Unfortunately, five of 25 patients (20%) initially demonstrated safe leak point pressure but later experienced recurrent high leak point pressures and upper tract deterioration. Four of these patients eventually required bladder augmentation. Also, seven of 21 patients (33%) without bladder augmentation were incontinent after urethral dilation. In light of the need for bladder augmenta-tion in some and iatrogenic incontinence in others in this series, one wonders whether alternative therapy with NBE instead of urethral dilation might have achieved the same or more beneficial effect in preventing bladder augmentation without adversely affecting urinary sphincter function and inducing urinary incontinence.

Tolerability of NBEThe tolerability of NBE is a topic briefly discussed in each of the series outlined in Table 1. Intolerance to NBE has been anecdotal. One patient in the Nguyen et al. [12••] series “did not tolerate (NBE)” in the form of a continuous overnight indwelling catheter. It is unknown whether nocturnal intermittent cath-eterization or nocturnal double voiding was attempted. Furthermore, Montane et al. [13] also alluded to one patient whose “compliance with intermittent cath-eterization and (NBE) was questionable.” This child showed no improvement after initiating NBE and had demonstrated noncompliant behavior before initiation of NBE. In the Koff et al. [8••] series, NBE was “readily accepted by all children and families and was free of complications in 19 patients.” Koff et al. [11] noted that some boys who would not initially permit an indwelling nocturnal urethral catheter came to accept its use when aids, such as anesthetic lubricants, low-friction cath-eters, and curved-tip catheters were used. Patients and parents were also made aware that nocturnal emptying might be an alternative to a surgical therapy, urinary diversion, or bladder augmentation, which might render them unable to voluntarily void. Catheters were prefer-entially taped rather than held in place by a balloon to prevent the risk of balloon inflation in the urethra and to reduce the intravesical foreign surface area. In addition, 10 hours or less of indwelling catheter time per night did not appear to induce UTI, irritative symptoms, or adverse effects.

Overall, the patients in each of the series demonstrated a high rate of compliance, with the collective compli-ance rate for all series outlined in Table 1 totaling 47 of 49 (96%). Granted, three patients in the series of Nguyen et al. [12••] performed NBE via a catheterizable channel and, therefore, would likely tolerate NBE even better than

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NBE for Reversing Urinary Tract Deterioration Due to NGB Canon et al. 65

a child performing NBE via the urethra. Furthermore, a significant portion of patients presented in Table 1 likely do not have urethral sensation, which may play a role in the tolerability of NBE. Montane et al. [13] reported that most patients had subjective benefits from the NBE regimen including the following: uninterrupted sleep with continu-ous nocturnal indwelling catheter; decreased bed soilage as a result of decreased urinary leakage; and elimination of morning intermittent catheterization before school. Formal analysis with a validated questionnaire would be helpful in further understanding the impact of NBE on quality of life and the compliance of this technique.

ConclusionsThe SNOB appears to be a heretofore unappreciated, yet significant determinant of urologic disease progression and morbidity in patients on maximal daytime catheterization and medical therapy. It appears to unify a group of seem-ingly unrelated urologic problems, which actually share a common pathophysiology and respond to the same simple therapy, namely NBE. The SNOB explains urinary upper tract deterioration in VBS and in NGB patients on idealized daytime bladder emptying programs, and it likely explains the decreased bladder capacity and compliance observed after AUS and fascial sling placement and the improve-ment in compliance in children with NGB who undergo urethral dilation therapy. Is the occurrence of bladder changes or upper tract deterioration in children with PUV or NGB simply the natural progression of their underlying disease process, or is it preventable, representing a failure to recognize and treat the SNOB? Because NBE can reverse bladder and upper tract deterioration caused by nighttime overdistension and can reverse bladder contraction and improve bladder compliance, it is suggested that conven-tional therapeutic protocols performed to date utilizing daytime bladder emptying and urotropic medications have been inadequate. These observations mandate that a new therapeutic paradigm that directs attention to the behav-ior of the bladder during the night be considered for this challenging patient population. It further suggests that the occurrence of bladder deterioration should no longer be considered to be an expected outcome in the natural history of PUV or NGB but viewed instead as an unfavorable out-come of the unrecognized SNOB, which is treatable and may even be preventable with NBE.

Because NBE is safe, has demonstrated benefit in the reduction of UTI and improvement in HUN, incontinence, and renal function, and is compatible with catheterizable stomas, it appears to represent an antidote for the SNOB. Use of NBE should be considered therapeutically and perhaps prophylactically in any high-risk clinical setting in which bladder insensitivity and overdistension coexist and especially before more invasive and irreversible measures, such as bladder augmentation, are considered or undertaken. Further research and controlled trials are

needed to fully understand and define the precise thera-peutic and prophylactic role of NBE in this challenging group of patients.

References and Recommended ReadingPapers of particular interest, published recently, have been highlighted as:• Of importance•• Of major importance

1. McGuire EJ, Woodside JR, Borden TA, Weiss RM: The prognostic value of urodynamic testing in myelodysplastic patients. J Urol 1981, 126:205–209.

2. Bauer SB, Hallet M, Khoshbin S, et al.: The predictive value of urodynamic evaluation in the newborn with myelodysplasia. JAMA 1984, 152:650–653.

3. Sidi AA, Dykstra DD, Gonzalez R: The value of urodynamic testing in the management of neonates with myelodysplasia: A prospective study. J Urol 1986, 135:90–93.

4. Teichman JMH, Scherz HC, Kim KD, et al.: An alternative approach to myelodysplasia management: Aggressive observation and prompt intervention. J Urol 1994, 152:807–811.

5. Geranoitis E, Koff SA, Enrile B: Prophylactic use of clean intermittent catheterization in treatment of infants and young children with myelomeningocele and neurogenic bladder dysfunction. J Urol 1988, 139:85–86.

6. Kasabian NG, Bauer SB, Dyro FM, et al.: The prophylactic value of clean intermittent catheterization and anticholinergic medication in newborns and infants with myelodysplasia at risk of developing urinary tract deterioration. Am J Dis Child 1992, 146:840–843.

7. Edelstein RA, Bauer SB, Kelly MD, et al.: The long-term urologic response of neonates with myelodysplasia treated proactively with intermittent catheterization and anticholinergic therapy. J Urol 1995, 154:1500–1504.

8.•• Koff SA, Gigax MR, Jayanthi VR: Nocturnal bladder emptying: a simple technique for reversing urinary tract deterioration in children with neurogenic bladder. J Urol 2005, 174:1629–1631.

Primary source material for NBE in NGB.9. Ross JH, Kay R, Novick AC, et al.: Long-term results of

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