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77

The Underactive Detrusor


Christopher R. Chapple, MD, FRCS (Urol), and Nadir I. Osman, PhD, MRCS

Terminology, Definitions, and Symptoms

Diagnosis

Epidemiology

Management

Etiopathogenesis

Conclusions

n impaired ability to empty the bladder is common in both


men and women with aging. It may be attributable to increased
resistance of the bladder outlet and/or a reduction in the
ability to generate an efficient bladder contraction, referred to as
detrusor underactivity (DUA) by the International Continence Society
(ICS), although the symptomatic condition could be labeled the
underactive bladder. Increased bladder outlet resistance, far more
common in men because of the effect of benign prostatic hyperplasia (BPH) with aging, has been the target of most therapeutic interventions for lower urinary tract symptoms (LUTS) in men. By
contrast, DUA mostly lacks any effective treatment other than catheterization (preferably by intermittent self-catheterization [ISC]),
when the postvoid residual (PVR) is raised. Despite its common
prevalence, which increases with age, in patients with LUTS referred
to urologists, the underlying cause and pathophysiologic mechanisms are poorly understood. Recently there has been a resurgence
of interest in this poorly understood condition (van Koeveringe
etal, 2011; Miyazato etal, 2013; Osman etal, 2014). In this chapter
we summarize and discuss the contemporary evidence relating to
symptomatology, epidemiology, cause, diagnosis, and management
of the underactive bladder.

nomonic of the underlying detrusor abnormality. In particular


the symptoms of DUA are diverse and overlap significantly with
those seen in OAB and associated with bladder outlet obstruction (BOO). During the voiding phase, patients may experience
weak stream, intermittency, hesitancy, and straining. After
voiding, some report a feeling of incomplete bladder emptying.
In the storage phase, some experience urinary frequency and
nocturia whereas others may have a loss of the normal urge to
void (the opposite of urinary urgency) and report infrequent
voiding. In the presence of a very large PVR, patients may experience incontinence (especially during sleep). One could speculate
that the reason for these very different clinical pictures is related to
the degree of residual bladder sensation, with patients with very
poor sensation typically being infrequent voiders and those with
intact sensation voiding frequently in the presence of a raised PVR
(Fig. 77-2). A further problem at present relates to the lack of consensus over what represents a clinically significant residual volume
in the bladder, with the suggestion being that the threshold is more
than 40% of the functional capacity (volume voided + residual).

EPIDEMIOLOGY
TERMINOLOGY, DEFINITIONS, AND SYMPTOMS
A confusing multitude of terms are used to describe impaired
bladder voiding function, including impaired detrusor contractility,
detrusor areflexia, and detrusor failure. The ICS standardization document in 2002 termed the problem DUA defined on the basis of
a urodynamic study (UDS) as a contraction of reduced strength
and/or duration, resulting in prolonged bladder emptying and/
or failure to achieve complete bladder emptying within a normal
time span (Abrams etal, 2002) (Fig. 77-1A). What constitutes
reduced strength, reduced length of contraction, or prolonged
emptying is not specified. If no contraction occurs, the term
acontractile detrusor is used (see Fig. 77-1B). In clinical practice it
is important to distinguish this from an isolated inability to void
during a UDS (or bashful bladder), which is common and often
can be correlated with a history of being unable to void in public
restrooms.
Defining DUA in purely urodynamic terms is problematic,
because this currently necessitates an invasive test that is neither
available nor appropriate in all health care settings. These were
some of the reasons why the overactive bladder (OAB) symptom
complex was introduced as an adjunct to the urodynamic concepts.
Nevertheless the two situations are not entirely analogous, because
OAB can be defined by the presence of urinary urgency (albeit variably correlated to detrusor overactivity (DOA). A symptom syndrome of underactive bladder is difficult to define because of the
absence of individual symptoms that can be considered pathog-

Epidemiologic studies have demonstrated that LUTS have a high


prevalence in the population, increasing significantly with age.
However, the extent to which DUA is a contributing factor is
unknown. The Epidemiology of LUTS (EpiLUTS) study, conducted
in the United Kingdom, United States, and Sweden, included
30,000 participants over 40 years of age and showed that storage
LUTS (occurring at least sometimes) are present in 45.7% of men
and 66.8% of women. Voiding LUTS (occurring at least sometimes)
were documented in 57.1% of men and 48% of women (Sexton
etal, 2009). Postmicturition symptoms occur with a similar prevalence in both men and women. Although it is clearly likely that
multiple factors contribute to this clinical picture, it is difficult
to establish on a population basis to what extent DUA is a cause
of these symptoms because of the lack of a simple noninvasive
marker.
In men, voiding LUTS, raised PVR or reduced urinary flow rate,
individually or collectively, cannot be used as proxy measures for
DUA, because they could be attributed to BOO. Similarly, in
women, voiding LUTS such as straining often can occur in the
context of frequency and low voided volumes associated with OAB.
However, if voiding LUTS occur in association with more objective
evidence such as reduced flow rate and raised PVR, underlying DUA
becomes more likely as a result of the extremely low incidence of
BOO in women (2.7% to 8% of those referred for UDS) (Carr and
Webster, 1996).
In the absence of epidemiologic data, clinical studies indicate
that in patients with LUTS referred for urodynamic assessment DUA

1807
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1808

PART XII Urine Transport, Storage, and Emptying


8:45

9:00

9:15

9:30

9:45

10:00

10:15

10:30

10:45

11:00

11:15

11:30

11:45

12:00

12:15

12:30

12:45

13:00

13:15

13:30

13:45 LABORIE
13966min
100 Pabd
31
188 ^
0 cm H2O
100 Pves
31
173 ^
0 cm H2O
100 Pdet
1
88 ^
0 cm H2O
50 Flow
0
75 ^
0 mL/sec

A
0

1:40

3:20

5:00

6:40

8:20

10:00

11:40

13:20

15:00

16:40

18:20

20:00

B
Figure 77-1. Urodynamic traces. A, A 67-year-old man with benign prostatic enlargement and
predominant voiding lower urinary tract symptoms. Voiding phase demonstrates low detrusor
pressure, prolonged detrusor contraction, and prolonged voiding time. The postvoid residual
was 100mL, and the diagnosis is detrusor underactivity. B, A 29-year-old woman with a history
of lower back injury and urinary retention managed with intermittent self-catheterization. The
diagnosis is acontractile detrusor. Pabd, abdominal pressure; Pdet, detrusor pressure; Pves,
intravesical pressure.

Voiding LUTS
Slow flow
Intermittency
Hesitancy
Straining

Reduced sensation of
bladder emptying

Detrusor
underactivity

Asymptomatic

Bladder sensation

Absent

Preserved

Normal intervoid
interval

Infrequent voiding

Incomplete bladder
emptying
Incontinence

Feeling of incomplete emptying


Frequency
Nocturia
incontinence

Figure 77-2. Lower urinary tract symptoms (LUTS) in detrusor underactivity (DUA). DUA may
manifest with a spectrum of voiding, storage, and postmicturition LUTS or cause no symptoms.
Patients with significantly impaired bladder sensation void infrequently and, if bladder emptying
is reduced, may have incontinence, typically more pronounced during nighttime (urethral relaxation during sleep). Patients who have preserved bladder sensation can have a normal intervoid
interval provided bladder emptying is normal. If bladder emptying is poor, these patients typically experience a sensation of incomplete emptying after voiding, urinary frequency, and
nocturia incontinence. This wide variation in symptomatology and its overlap with LUTS/
benign prostatic hyperplasia and overactive bladder hampers the development of a reliable
symptom-based definition.

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LAVORIL
19960min
100 Pabd
29
219 ^
0 cm H2O
100 Pves
22
206 ^
0 cm H2O
100 Pdet
6
48 ^
0 cm H2O
50 Flow
0
77 ^
0 mL/sec

Chapter 77 The Underactive Detrusor

1809

TABLE 77-1 Prevalence of Detrusor Underactivity in Clinical Studies

SIZE

AGE RANGE
OR MEAN
AGE (yr)

STUDY

POPULATION

Fusco etal, 2001

Male

541

26-89

Kuo, 2007b

Male

1407

46-96

Nitti etal, 2002

Male

85

18-45

Wang etal, 2003

Male

90

18-50

Kaplan etal, 1996

Male

137

18-50

Karami etal, 2011


Abarbanel and
Marcus, 2007
Jeong etal, 2012

Male
Male
Female
Male
Female

456
82
99
632
547

18-40
>70
>70
>65
>65

Resnick etal,
1989

Male

17

Female
(institutionalized)

77

Resnick etal,
1996

Female
(institutionalized)

97

Groutz etal, 1999


Valentini etal,
2011

Female
Female

206
442

87

87.6

62.6 15.8yr
>55

DIAGNOSTIC CRITERIA

PREVALENCE
OF DUA + (% OF
ACONTRACTILE
DETRUSORS)

Pdet@Qmax 30cm H2O and Qmax


12mL/sec
Relaxed sphincter EMG with open
membranous urethra during voiding
and low flow rate
Bladder outlet obstruction index
<20cm H2O and uroflow <12mL/sec
Pdet@Qmax <30cm H2O and Qmax
<15mL/sec
Pdet@Qmax <45cm H2O and Qmax
<12mL/sec
ICS definition
Pdet@Qmax <30cm H2O and Qmax
<10mL/sec
Bladder contractility index <100 (men)
Qmax 12mL/sec and Pdet@Qmax
10cm H2O (women)
In the absence of obstruction,
underactive detrusor: Failure to
empty in the absence of an increase
in abdominal pressure
DHIC: Involuntary detrusor contraction
that emptied less than half of volume
instilled
Reproducible failure of the involuntary
contraction to empty at least half of
bladder contents in the absence of
straining, urethral obstruction, and
detrusor-sphincter dyssynergia
ICS definition
Impaired detrusor contraction leading
to prolonged voiding time and high
residual volume

10
10.6

9
10
23 (5)
12.9 (10.5)
48
12
40.2
13.3
41.2

37.7

45

19
13.8

DUA, detrusor underactivity; EMG, electromyography; ICS, International Continence Society.


From Osman NI, Chapple CR, Abrams P, etal. Detrusor underactivity and the underactive bladder: a new clinical entity? A review of current
terminology, definitions, epidemiology, aetiology, and diagnosis. Eur Urol 2014;65:38998.

is very common, particularly in the older age groups (Table 77-1).


DUA is diagnosed in 9% to 28% of males under 50 years of age
and 48% in those over 70 years. In females, DUA is present in
12% to 45%, being more common in elderly nursing home residents who often have concomitant DOA, an entity described as
detrusor hyperactivity impaired contractility (DHIC) (Resnick
etal, 1989). It must be borne in mind that these data cannot be
extrapolated to the general population and are limited by the inconsistency in definitions used in these studies, the populations studied,
and the post-hoc data interpretation.
One of the largest clinical urodynamic series demonstrated
that DUA often coexists with other LUT dysfunctions (LUTDs) in
the elderly (Jeong etal, 2012). In their study of 1179 patients older
than 65 years, 46.5% of males with DUA also had DOA or BOO
and 72.6% of the females with DUA also had DOA or urodynamic
stress urinary incontinence (Fig. 77-3). In our opinion this is further
support for the case for urodynamic assessment before surgical
intervention for LUTS in this group.
Very little is known of the natural history of DUA. In a 10-year
study of 69 men with non-neurogenic DUA (with a maximal urinary
flow rate [Qmax] of <15mL/sec and detrusor pressure [Pdet] at
Qmax [Pdet@Qmax] of <40cm H2O) managed conservatively,

there was minimal symptomatic or urodynamic progression


(Thomas etal, 2005b). In this cohort, 11 patients underwent transurethral resection of the prostate (TURP), 3 for acute urinary retention and 8 for worsening LUTS (all of whom showed no change in
Qmax preoperatively compared to the baseline values).

KEY POINTS: TERMINOLOGY, DEFINITIONS, AND


SYMPTOMS, AND EPIDEMIOLOGY
DUA is a common clinical problem associated with a range
of storage, voiding, and postmicturition LUTS.
The population prevalence of DUA is not known, because
of the lack of a noninvasive marker.
DUA affects 9% to 28% of men under 50 years of age and
48% in those over 70 years undergoing UDS and is more
prevalent among the institutionalized elderly.
In women DUA is found in 12% to 45% undergoing UDS
and is more prevalent among the institutionalized elderly.
DUA commonly coexists with other LUTDs.

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PART XII Urine Transport, Storage, and Emptying

60

Males
Females

50
40
30
20
10

U
A
+B +D
O O
O A
D
U
+U A+D
SU O
I A

SU
A+
D

A+
U
D

BO

O
D

A+

on
A
U
D

ly

% of total no. of patients with DUA

1810

Urodynamic findings
Figure 77-3. The overlap between detrusor underactivity (DUA),
detrusor overactivity (DOA), and bladder outlet obstruction (BOO) in
1179 patients (632 men and 547 women) older than 65 years in a
Korean clinical series of urodynamic studies. DUA was defined as a
bladder contractility index less than 100 in men and Qmax 12mL/sec
or less and Pdet@Qmax 10cm H2O or less in women. In total, 40.2%
of men and 13.3% of women were classified as having DUA. The data
suggest a significant overlap between DUA and other urodynamic
diagnoses. USUI, urodynamic stress urinary incontinence. (Raw data
provided by Dr. Sang Eun Lee. From Jeong SJ, Kim HJ, Lee YJ, etal.
Prevalence and clinical features of detrusor underactivity among
elderly with lower urinary tract symptoms: a comparison between
men and women. Korean J Urol 2012;53:3428.)

ETIOPATHOGENESIS
DUA occurs in both sexes and diverse clinical groups. Several distinct etiologic factors are recognized, such as diabetes mellitus and
cauda equina compression. In clinical practice many patients do
not have any obvious cause for DUA, neurologic or otherwise,
suggesting that DUA may occur secondary to common agerelated changes. In particular, an age-related decline in detrusor
function with normal aging is likely, although it has not been
conclusively demonstrated.
Direct measurement of the contractility of bladder muscle strips
from rodents, comparing younger to older animals, has yielded
contradictory results that are difficult to extrapolate to humans
because of differences in functional innervation. The few studies
that used human bladder muscle strips often have failed to demonstrate a decline in contractile responses to electrical stimulation and
a variety of agonists (Mark etal, 1992; Yoshida etal, 2001; Fry etal,
2011). Some clinical urodynamic data suggest an age-related reduction in Pdet and flow rate accompanied with an increase in PVR
(Pfisterer etal, 2006; Smith etal, 2009; Valentini etal, 2011). Most
studies have included symptomatic individuals with probable
underlying pathophysiologic abnormalities that could be expected
to progress with time. It is to be expected that there would be a
more pronounced decline in detrusor contractility in men
because of bladder wall changes (increased connective tissue and
reduced smooth muscle) occurring as a result of BOO; however,
these changes are also seen in women suggesting that they may
be partly attributable to normal aging (Lepor etal, 1992; Holm
etal, 1995) (Fig. 77-4A to C).
The mechanisms by which different causes result in DUA can
be classified as (1) myogenic, affecting the cellular functions of
detrusor myocytes or the surrounding extracellular matrix; or (2)
neurogenic, affecting the afferent pathways, efferent pathways, or
brain circuits involved in the micturition reflex. (These mechanisms and the probable major etiologic factors are summarized in
Fig. 77-5.)

Myogenic Factors
Processes that alter the normal structure and function of the
detrusor muscle extracellular matrix may result in diminution of
transmitted contractile force. The intrinsic ability of detrusor
muscle cells to generate contractile activity may be compromised
by dysfunction of cellular mechanisms (e.g., ion storage/exchange,
excitation-contraction coupling, calcium storage, energy generation) such that even in the presence of normal extrinsic neuronal
activity, a reduced contraction may occur (Brierly etal, 2003).
Morphologic changes have been reported to occur in the detrusor with normal aging and disease. Elbadawi and colleagues
(1993a, 1993b, 1993c) proposed that distinct ultrastructural patterns observed by electron microscopy characterized the normally
contractile aging detrusor and different bladder dysfunctions,
including DUA. Although the applicability of this classification
system is disputed, other groups have noted similar findings
(Hindley et al, 2002; Brierly et al, 2003). This degeneration
pattern, which consists of widespread disrupted detrusor myoctyes
and axonal degeneration, has been associated with DUA (Elbadawi
et al, 1993a). Whether detrusor myocyte disruption is the cause
of DUA or a consequence of a pathologic insult is not clear (see
Fig. 77-4D to E).

Neurogenic Factors
Brain Circuits
The central neural control mechanism governing micturition
involves key processes including perception and integration of
storage and voiding that, if disturbed, may result in DUA (Suskind
and Smith, 2009). The micturition reflex is facilitated by the spinobulbo-spinal pathway passing through the sacral parasympathetic
nucleus and the pontine micturition center (PMC). The PMC
receives input from higher centers in the cerebral cortex and in
particular the limbic system. Many insights have been gained from
functional neuroimaging studies in animals (de Groat etal, 1998;
Sugaya etal, 2003, 2005). Certain populations of PMC neurons
(direct neurons), appear to become activated immediately before
and during reflex bladder contractions, whereas outside these
periods they are completely inactive. A large number of these
neurons pass to the lumbosacral spinal cord, suggesting a role in
the micturition reflex. Human functional neuroimaging suggests
similar areas of the brainstem and cortex are implicatedthe insula,
hypothalamus, periaqueductal gray, and PMC (Blok etal, 1997).
Any lesion affecting these regions could in theory result in DUA,
albeit a clinical correlation between the site of a neurologic lesion
and the urodynamic finding is not always apparent in all diseases
(Kim etal, 1998).

Bladder Efferent Pathways


Interruption or impairment of efferent signaling in the sacral
cord, sacral roots, and pelvic nerves may manifest as absent or
reduced detrusor contraction. There is evidence to suggest that a
reduction in autonomic innervation occurs in human bladders as
a consequence of normal aging (Gilpin etal, 1986). A range of
diseases and injuries can result in disturbance of efferent signaling
(discussed later in this section).

Bladder and Urethral Afferent Pathways


Intact bladder sensation is critical to the functioning of the efferent limb of the micturition reflex. Bladder afferents monitor both
volumes during bladder filling in the storage phase of the micturition cycle and the magnitude of detrusor contractions during
the voiding phase. Urethral afferents have an important role in
the perception of both flow through the urethra and detrusor
contraction (Feber etal, 1998; Bump, 2000). An impairment in
afferent function (from bladder or urethra) is likely to reduce or
prematurely end the micturition reflex, leading to impairment or

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Chapter 77 The Underactive Detrusor

F
Figure 77-4. Morphologic detrusor changes in aging and disease. Light microscopy: A to C.
A, Normal detrusor. B, Man with bladder outlet obstruction, showing an increase in muscle
mass and increase in fibrous tissue deposition inside and between muscle bundles. C, Elderly
woman without lower urinary tract symptoms showing similar deposition of fibrous tissue
suggesting extracellular matrix changes also occur with aging. Electron microscopy: D to F.
D, Normal detrusor muscle showing two muscle bundles, a wide collagen-rich septum dividing
the bundles is seen. Within the bundles are individual fascicles separated by a thin microseptum
(magnification 6000). E, Normal muscle cells at higher power magnification; smooth intact
sarcolemma with a thin interstitium between adjacent cells. F, Degeneration pattern. A disruptive cell, with a shriveled appearance and sarcolemma breakdown, with debris and collagen
deposition in the interstitium. (A to C from Nordling J. The aging bladder: a significant but
underestimated role in the development of lower urinary tract symptoms. Exp Gerontol
2002;37:9919; D to F from Brierly RD, Hindley RG, McLarty E, etal. A prospective controlled
study of ultrastructural changes in the underactive detrusor. J Urol 2003;169:13748.)

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1811

PART XII Urine Transport, Storage, and Emptying

Brain circuits

Efferent pathways

Afferent pathways

Muscle

PMC
PAG
Limbus
Hypothalamus
Prefrontal cortex

Sacral cord
Sacral nerves
Pelvic nerves
Postganglionic neurons

Peripheral afferents
Anterolateral white
column
Posterior column

Detrusor myocyte
Extracellular matrix

Neurologic disease or injury

Mechanism

Major etiologic factors

Site of dysfunction

1812

Diabetes mellitus

?Bladder outlet obstruction due to BPH


?Normative aging

Failure of integration
or processing

Impaired activation
of detrusor

Early termination of
voiding reflex

Loss of intrinsic
contractility

Detrusor underactivity
Figure 77-5. Etiopathogenesis of detrusor underactivity (DUA). The mechanisms by which the
likely major etiologic factors lead to DUA. Bladder outlet obstruction and normative aging are
probable rather than definite factors. BPH, benign prostatic hyperplasia; PAG, periaqueductal
gray; PMC, pontine micturition center.

loss of voiding efficiency (Suskind and Smith, 2009). There is


evidence that normal aging is associated with a decline in sensory
function in the LUT. In support of this, an age-related increase in
the thresholds for reaching bladder capacity was observed in women
(Pfisterer etal, 2006, 2007) and functional magnetic resonance
imaging in asymptomatic older people has shown a reduced
response to bladder filling in the insula (the region that maps visceral sensation).
Given that both tissue changes and a decline in sensory function appear to occur with aging, it is likely that both factors contribute to DUA in the elderly. An interesting hypothesis that
integrates both aspects has been proposed (Smith, 2010). It is
based on the concept that afferent outflow is a function of bladder
wall stress and suggests that increased connective tissue deposition
and smooth muscle disruption results in a loss of bladder elasticity
that leads to changes in the normal passive compliance curve.
There would also be impairment of normal sensory innervations
resulting from connective tissue infiltration into the bladder wall.
Conceptually the bladder progressively loses the property of receptive relaxation and becomes more akin to a stiff balloon. Such a
stiff-walled bladder will exhibit a precipitous rise in wall stress
with physiologic filling. Clinically this would be manifested by
delayed bladder sensation and soon after this the sensation of
urgency as the functional bladder capacity is reached. After a small
volume of urine is passed, wall stress is dramatically reduced, with
a reduction in afferent stimulation resulting in premature termination of the detrusor contraction before the bladder is emptied and
an increased PVR. This is a potential explanation for the finding
of DHIC, which has been described to occur with aging (Resnick
and Yalla, 1987).

Specific Etiologic Factors


See Box 77-1.

Bladder Outlet Obstruction


DUA also may occur as consequence of a series of changes in the
detrusor induced by the increased work requirements to overcome
bladder outlet obstruction (BOO). In rodent models of partial
BOO, the sequence of events leading to DUA is well described and
has been separated into three stages. Initially a surgically created
BOO (e.g., ring or ligature) increases bladder outlet resistance and
results in bladder distention. The detrusor muscle then undergoes
compensatory hypertrophy and hyperplasia, with bladder weight
increasing sharply over the next few weeks before stabilizing. During
this time tissue blood supply also increases. The contractile function
at this point is almost normal, and the bladder is said to have
entered the compensated stagein which mass and function
remain relatively stable. After a period of variable length, detrusor
contractile function declines and bladder emptying is impaired,
marking the decompensation phase (Levin etal, 1992, Saito etal,
1997). This is characterized by reduced response to electrical stimulation and agonists and replacement of bladder muscle with connective tissue (fibrosis). Typically, if the obstruction is not relieved
before the stage of decompensation and connective tissue deposition, permanent contractile dysfunction ensues. In such an
obstructed bladder, laser Doppler estimation of blood flow has
demonstrated this to be decreased, further contributing to the
bladder wall dysfunction by a direct effect on both neural and
muscular dysfunction (Greenland and Brading, 1996). Other work
has demonstrated that there is denervation of the bladder as a consequence of BOO in both humans and an animal model (Harrison
etal, 1987; Sibley, 1987).
Clearly the hypothesis for the sequential changes observed in
animals centers on ischemic/reperfusion injury and pathologic
connective tissue infiltration consequent on increased intravesical
pressure being necessary to overcome outlet resistance. This results
in increased bladder wall tension during contraction (the law of

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Chapter 77 The Underactive Detrusor

1813

BOX 77-1 Etiologic Factors


IDIOPATHIC
Normal aging
Unknown factor in younger people

MYOGENIC
Bladder outlet obstruction
Diabetes

NEUROGENIC INJURY AND DISEASE


Vascular
Stroke (early phase)
Degenerative
Parkinson disease
Multisystem atrophy
Demyelinating neuropathies
Multiple sclerosis
Peripheral neuropathies
Guillain-Barr syndrome
Neurosyphilis (tabes dorsalis)
Herpes-zoster and herpes simplex
Diabetes mellitus
Acquired immunodeficiency syndrome
Spinal cord and cauda equina
Intravertebral disk prolapse
Cauda equina lesions
Spinal cord tumors
Spinal canal stenosis
Spinal cord injury
Sacral fracture
Pelvic fracture
Pudendal nerve injury (bilateral)

IATROGENIC
Radical pelvic surgery
Radical prostatectomy
Radical hysterectomy
Anterior resection, abdominoperineal resection
Detrusor myomectomy
Intravesical phenol injections
Radiation therapy

Laplace). This leads to compression of bladder wall vessels, tissue


ischemia, and hypoxia. Cycles of ischemia and reperfusion during
the micturition cycle (as the bladder empties and then fills) lead to
generation of reactive oxygen species (Erdem etal, 2005) and
release of free intracellular calcium. These factors cause activation
of proteases, phospholipases, and membrane lipid peroxidation,
which damages cellular and subcellular membranes, including
nerve cells, synaptic membranes, mitochondria, and sarcoplasmic
reticulum. The outcome of these processes is impaired cellular function and denervation, leading to decompensation of detrusor function (Schroder etal, 2001).
Relating the insights from this work to humans is problematic,
because the animals studied are usually immature and often female;
the obstruction is acute and certainly not representative of the clinical scenario. Indeed, the sequential changes that have been
described, with consistency, do not correlate with the diverse outcomes men with BOO experience clinically. In addition, this
sequence of events is not seen in patients presenting with a urethral
stricture and does not explain the genesis of the similar bladder
dysfunction seen clinically in female patients.
A longitudinal study has demonstrated that prolonged BOO
commonly does not necessarily result in clinical decompensation.
In a cohort of 170 men with BOO followed for a mean of 13.9
years, no significant deterioration was found in urodynamic parameters (no change in pdet@Qmax (detrusor pressure at maximum
flow) and a reduction in Qmax (maximum flow rate) of only 1mL/
sec) and only 17% required any form of intervention (Thomas etal,
2005a). Of men who decompensate their bladders acutely (i.e.,
develop acute urinary retention), most have preserved detrusor
function. Even among men with chronic retention there are some
who have preserved contractility and typically poor compliance and
upper renal tract changes (high-pressure chronic retention) (George
etal, 1983, Djavan etal, 1997). The pathophysiologic explanation
for these divergent clinical outcomes remains unknown.

FUNCTIONAL
Fowler syndrome
Dysfunctional voiding
PHARMACOTHERAPY
Drugs with anticholinergic effects
Antimuscarinics
Antihistamines
Antipsychotics
Anti-Parkinson medications
Antispasmodics
Tricyclic antidepressants
Opioids

Some aspects of the pathophysiology relating to BOO remain


unclear. Animal models do not predict or explain what is seen
in the clinical setting. It is likely that the clinical picture in any
individual patient is multifactorial and thus unlikely to be
explained by any single hypothesis.

Diabetes Mellitus
Diabetes mellitus may impair detrusor function through a combination of myogenic and neurogenic mechanisms. Diabetesinduced bladder dysfunction (DBD), classically termed diabetic
cystopathy, results in a reduction in emptying efficiency in a timedependent fashion during the course of the disease (Lee etal,
2004; Lifford etal, 2005). This is traditionally attributed to an
autonomic neuropathy occurring as a result of axonal degeneration
and segmental demyelination resulting in diminished bladder sensation (Hill etal, 2008). The mechanisms underlying this process
are thought to occur as consequences of hyperglycemia. These
include activation of the polyol pathway, increases in the generation
of free radicals, activation of protein kinase C, and formation of
advanced glycated end products (Daneshgari etal, 2009; Miyazato
etal, 2013). It has been suggested that a reduction in nerve growth
factor (essential for maintaining normal sympathetic and sensory
nerve function) is also implicated in DBD. In support of this,
studies in streptozotocin-induced diabetes mellitus in rats have
shown reduced levels of nerve growth factor in the dorsal root
ganglia associated with increased PVR and bladder capacity (Hellweg
etal, 1994; Sasaki etal, 2002).
DBD also may result from detrusor myocyte dysfunction occurring as a result of alterations in intercellular connections and excitability, intracellular signaling, receptor density, and distribution.
These mechanisms are poorly understood; most insights are derived
from animal studies, which have demonstrated both increases
and reductions in bladder contractility. Daneshgari and colleagues

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1814

PART XII Urine Transport, Storage, and Emptying

(2009) suggested this may be explained by time-dependent changes


occurring in the bladder wall, the DBD temporal theory. This theory
postulates that initially osmotic diuresis induced by hyperglycemia
causes bladder wall stretching, which with increased intravesical
pressure results in compensatory bladder hypertrophy. This stage
would correspond clinically to storage symptoms early in the
disease time course. It is suggested that as the disease progresses,
accumulation of toxic products of oxidative stress results in bladder
decompensation, clinically manifested as poor bladder sensation
and impaired voiding function with associated LUTS.

Neurologic Disease or Injury


A range of neurologic diseases or injuries affecting the brain, spinal
cord, or peripheral nerves can lead to DUA (see Box 77-1). Although
neurogenic DOA is the most common chronic urologic sequela of
cerebrovascular accident, in the acute phase approximately half of
patients develop urinary retention (attributed to cerebral shock);
75% of these have acontractile detrusors (Burney etal, 1996). Similarly in Parkinson disease DUA is far less common than DOA,
occurring in less than 20% of cases (Araki etal, 2000).
Anticholinergic parkinsonian medication may be an important
contributor; in a study in which these were withdrawn before urodynamic assessment, DUA was not demonstrated in any patient
(Stocchi etal, 1997). Multisystem atrophy, otherwise known as
Shy-Drager syndrome, is a condition often confused with Parkinson
disease, in which 52% to 95% of patients demonstrate DUA on
UDS (Bloch etal, 2010; Yamamoto etal, 2014) as a result of atrophy
of efferent parasympathetic nerves, and clinically the majority of
these patients develop urinary retention. DUA occurs in 20% of
patients with multiple sclerosis (Litwiller etal, 1999), particularly
when plaques affect the lumbosacral cord.
Injury at the level of lumbosacral spinal cord, the cauda equina,
and sacral and pelvic nerves can occur as a result of trauma or a
prolapsed intervertebral disk and also commonly results in DUA
related to cauda equina syndrome. In particular, radical pelvic
surgery can lead to injury to the pelvic plexus (located near the

anterolateral wall of the lower rectum) or postganglionic fibers that


traverse the lateral wall of the upper vagina.
A systematic review found that the overall incidence of LUTD
after radical hysterectomy was 72% (Plotti etal, 2011). Although
high incidences were reported in older series of patients undergoing
rectal cancer surgery, more recently lower rates have been reported
(<5%) (Maurer etal, 2001), which can be attributed to the adoption
of nerve-sparing techniques. The true incidence of DUA in this
context is difficult to define because of the lack of studies correlating
preoperative and postoperative urodynamic findings. Nevertheless
many patients appear to recover bladder function by 1 year after
surgery. In support of this, a study of feline pelvic plexus extirpation
suggests this may be due to restitution of intrinsic cholinergic nerves
and muscle cell regeneration after an initial injury-related degeneration (Elbadawi, 1988).
In neurologic disorders associated with infective causes, DUA
can be either entirely reversible, such as in Guillain-Barr syndrome
and herpes zoster (shingles), or permanent, as seen with progressive
problems such as acquired immunodeficiency syndrome or neurosyphilis (tabes dorsalis) as was common in the preantibiotic era.

DIAGNOSIS
The only accepted modality for clinically estimating detrusor
voiding function is an invasive UDS; however, there are currently
no universally agreed criteria for diagnosing DUA. Current
methods of estimating detrusor voiding function almost exclusively focus on detrusor contraction strength (Table 77-2),
neglecting other potentially important aspects such as the speed
and sustainability of a detrusor contraction.

Detrusor Contraction Strength


A detrusor contraction generates both pressure and flow (Griffiths,
2003); thus many authors have used two parameters to diagnose
DUA: Qmax and Pdet@Qmax. Reductions in both are considered

TABLE 77-2 Summary of Diagnostic Methods and Criteria


TYPE

METHOD

ADVANTAGES

LIMITATIONS

Mathematical
calculations

Watts factor

1. Lengthy and complex calculation


2. No validated thresholds
3. Does not measure sustainability of
contraction

Detrusor shortening velocity

1. Measure of bladder power


2. Minimally dependent on volume
of urine
3. Not affected by presence of BOO
1. May identify early-stage DUA

Indices

Detrusor contraction
coefficient (DECO)
Bladder contractility index
(BCI)

1. Simple to use
2. Measurement easy to obtain
3. Estimation of isovolumetric
contraction

1. Does not measure sustainability of


contraction
2. May not be applicable to other
groups

Occlusion testing

Voluntary stop test


Mechanical stop test
Continuous occlusion

1. Real-time indication of
isovolumetric contraction
strength
2. No calculations

1. Uncomfortable or painful for patients


2. Impractical
3. No information on sustainability of
contraction in (in continuous
occlusion)
4. May underestimate isovolumetric
pressure (stop test)
5. Unusable in some patient groups

Ranges of
urodynamic
measurements

Pdet@Qmax (e.g., <40)


Qmax (e.g., <15)

1. Simple to use

1. No widely accepted normal ranges


2. Underestimate contraction strength
3. Does not conceptually consider
coexistence of BOO and DUA

BOO, bladder outlet obstruction; DUA, detrusor underactivity; Pdet, detrusor pressure.
From Osman NI, Chapple CR, Abrams P, etal. Detrusor underactivity and the underactive bladder: a new clinical entity? A review of current
terminology, definitions, epidemiology, aetiology, and diagnosis. Eur Urol 2014;65:38998.
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Chapter 77 The Underactive Detrusor


200

KEY POINTS: EITOPATHOGENESIS

to be below the lower limits of the normal ranges for the particular
patient group. For men these ranges were derived from series of
patients undergoing bladder outlet surgery (Abrams and Griffiths,
1979; Schfer etal, 1989). In healthy men and women these ranges
are less well characterized (Schmidt etal, 2002; Pfisterer etal, 2006;
Rosario etal, 2008).
There are two limitations with this approach. First, it is likely to
underestimate the contraction strength because of bladder outlet
relation (BOR), the normal inverse relationship between Pdet and
urine flow (Griffiths, 1973). The BOR is an adaptation of the Hill
equation for actively contracting muscle and can be summarized as
during voiding when flow is low the pressure is high and vice versa.
On this basis the Pdet@Qmax actually represents the point of least
pressure. Second, the variability in bladder outlet resistance that
also can affect flow rate is not considered. The clinical implications
of this are that when Pdet is low, a low Qmax also can be attributed
to increased outlet resistance (e.g., BOO caused by BPH) or alternatively a normal Qmax can result from reduced outlet resistance
(e.g., postprostatectomy incontinence).
To more accurately assess contraction strength, methods that
estimate isovolumetric pressure were developed. These are based
either on post-hoc mathematical calculations or volitional or
mechanical interruption to the flow of urine during UDS
(Griffiths, 2004). Many of these are complicated, time-consuming,
or impractical limiting their use in clinical practice.
The Watts factor (WF) is an estimate of the power per unit area
of bladder surface that is generated by the detrusor, corrected for
the finite power required for either isometric contraction or for
shortening against no load. It is calculated by the formula: WF =
[(Pdet + a) (Vdet + b) ab]/2 where Vdet is detrusor shortening
velocity and a and b are fixed constants (a = 25cm H2O, b = 6mm/
sec), derived from experimental and clinical data (Griffiths, 1991).
Throughout micturition the WF varies because of the variation in
Pdet and Vdet; the points proposed to best represent detrusor contraction strength is the point at which the WF peaks, the maximal
WF (WFmax). The major advantages of the WF are that it minimally
depends on volume (Griffiths, 1991) and that it is not affected by
increased outlet resistance (Lecamwasam etal, 1998). However, as
of yet there are no validated cutoffs for the normal range, but based
on expert opinion a WFmax of 7 W/m2 was deemed to represent
the threshold for reduced contractility (van Koeveringe etal, 2011),
although some authors use a value of 10 W/m2 (Mitsui etal, 2012).
Ultimately the WF found little use in everyday clinical practice
because of the complexity of the calculation and as with all current
measures it does not consider the sustainability of a contraction.
Schfer (1995) proposed an alternative method of estimating
isometric contraction strength that is based on superimposing
the BOR on his pressure-flow nomogram. The BOR is simplified
to a straight line and projected back to the y-axis (Pdet) from
the point representing Pdet@Qmax to obtain the isovolumetric

Strong
Pdet (cm H2O)

The etiopathogenesis of DUA is incompletely understood; a


diverse range of factors and pathophysiologic mechanisms
are likely to be implicated.
Confirmed etiologic factors include neurologic injury/
disease and diabetes mellitus; BOO and normal aging are
probable rather than definite contributory factors.
These factors may cause DUA by impairing or disrupting
processes that are essential for the generation of an efficient
voiding contraction.
The pathophysiologic mechanisms can be classified as
follows:
Myogenic: Affecting detrusor myocytes or their surrounding extracellular matrix
Neurogenic: Affecting the central neural control mechanisms governing the voiding reflex by an action on either
afferent or efferent nerves

1815

Projected
isovolumetric
pressure

Normal

100

Point marking
Pdet@Qmax

Weak

Very weak

0
0

10
Qmax (mL/sec)

20

Figure 77-6. Method of determining the projected isovolumetric


pressure. The point marking the detrusor pressure (Pdet) @Qmax is
plotted on Shfers contractility nomogram and is projected back to
the y-axis. In this case the pressure is 130cm H2O, which is in the
normal contractility range.

pressure (Fig. 77-6). This projected isovolumetric pressure (PIP)


can be calculated by the formula PIP = Pdet@Qmax + KQmax,
where K is a fixed constant representing the slope of the BOR
(Schfer, 1995). The value of K depends on the specific population
studied. In men with BPH it is taken as 5cm H2O/mL/sec, whereas
in older women 1cm H2O/mL/sec was found to be more accurate
(Griffiths, 2004).
Based on this the suggested formula for use in men in clinical
practice is as follows:
PIP = Pdet @Qmax + 5 Qmax
A PIP greater than 150 represents strong contractility, 100 to 150
normal contractility, 50 to 100 weak contractility, and less than
50 very weak contractility. The corresponding BORs at these cutoffs
were plotted on the Schfer pressure-flow nomogram, to give subdivisions for contractility (see Fig. 77-6).
Although there are two other reported variations of PIP, all three
are essentially the same. The detrusor coefficient is the PIP divided
by 100, where a value less than 1 signifies weak contraction.
PIP = Pdet@Qmax + 5 Qmax /100
The bladder contractility index, described by Abrams, is calculated using the same formula as PIP and includes three groupings (strong > 150, normal 100 to 150, and weak < 100) (Abrams,
1999). Evidently all these methods are fairly easy and quick to
calculate but tend to overestimate PIP, because such adjustments
need to be made for use in different populations. Although testretest reliability is thought to be acceptable, it is less consistent
than measures that directly record isovolumetric pressures (Tan
et al, 2003).
Isovolumetric pressure can be measured directly by mechanically obstructing the flow of urine (Sullivan, 2007). This can be
achieved through either (1) a stop test, interruption of urine flow
after it has begun, or (2) continuous occlusion test, in which the
urine outflow is blocked before and during the course of the
voiding contraction.
There are two types of stop test: a voluntary stop test, in which
the patient voluntary contracts the urethral sphincter, and a mechanical stop test, in which the bladder outflow is occluded by the
investigator (e.g., by tugging a catheter balloon against the bladder
neck). These techniques correlate well with each other in both sexes

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1816

PART XII Urine Transport, Storage, and Emptying

(Tan etal, 2003), but the voluntary stop test tends to produce a
lower value for isovolumetric pressure by approximately 20cm
H2O. This is probably explained by the reflex detrusor inhibition
induced by urethral sphincter contraction (Sullivan etal, 1995).
The voluntary stop test is difficult and sometimes impossible to
conduct in patients with urethral sphincter weakness. The continuous occlusion testing has greater test-retest reliability and allows
assessment of sustainability of contraction, although the consequence is that a representative flow measurement during that particular contraction is not obtained. Although it correlates well with
the ability of bladder to empty (Sullivan and Yalla, 1996), continuous occlusion is potentially painful and has found little applicability outside of a research setting.

Detrusor Contraction Speed


A bladder that contracts more slowly could in theory result in clinical symptoms, although this is not part of the ICS definition. A
reduction in detrusor shortening velocity (calculated by the formula
Vdet = Q/2[3/(V + Vt)/4]0.66, where Q represents the flow rate
[milliliters per seconds], V represents bladder volume [in milliliters], and Vt represents the volume of noncontracting bladder wall
tissue) was found to precede reduction in WF in series of longitudinal studies in both males (Cucchi etal, 2007, 2010) and females
(Cucchi etal, 2008).

Detrusor Contraction Duration


A detrusor contraction of reduced duration is suggested by the ICS
as part of the definition of DUA (Abrams etal, 2002); however, the
limits of a normal voiding detrusor contraction are not defined.
There are only a few studies that assess contraction duration as a
urodynamic parameter. In a study of men with BPH, unobstructed
patients with poor contractility actually had significantly longer
contraction durations than those with no obstruction and normal
contractility (Ameda etal, 1998). It is likely that the contraction
duration reflects the underlying pathophysiologic mechanismsfor
example, an early termination of the micturition reflex could presumably lead to a shorter duration. A standardized method for
measuring duration of the detrusor contraction is needed before
any conclusions can be reached.

Bladder Sensation
An assessment of bladder sensation is clearly relevant to the
evaluation of DUA because the afferent nerves play such a central
role in the initiation and maintenance of a detrusor contraction.
This is most commonly undertaken using the patients perceptions of bladder filling (first sensation, first desire, strong desire,
and capacity).
Thresholds in normal individuals are available (Wyndaele,
1998), although this method can be criticized because patients may
report bladder sensation even when the bladder is not being filled
(Erdem etal, 2004; De Wachter etal, 2008); as with any subjective
measure, there is substantial individual variation because of the
circumstances of a UDS and the anxiety level of the study subject.
Testing sensory responses to the passage of electrical current through
the bladder wall (current perception threshold testing) may provide
a more objective measure but is clearly rather an invasive approach
and is as yet an unvalidated research technique.

Ambulatory Urodynamics
Patients often fail to void during UDS because of anxiety or a socalled bashful bladder. It is thought this arises as a result of poor
pelvic floor relaxation and reflex detrusor inhibition. Alternatively
the patient may have true DUA or acontractile detrusor. A careful
history is usually sufficient to differentiate the two situations. Where
doubt exists, ambulatory UDS may be useful (Rosario etal, 2000).
van Koevering and colleagues (2010) demonstrated that 84% of
patients who failed to generate a detrusor contraction during

standard UDS had evidence of demonstrable contraction during an


ambulatory study.

KEY POINTS: DIAGNOSIS


There is no published consensus on the diagnostic criteria
for DUA.
Most available criteria focus on the strength of contraction
as determined by the Pdet during UDS.
Several indices and formulas to estimate isometric detrusor
strength are available, most of which are unvalidated and are
not applicable to all patient groups.
Urodynamic stop and occlusion tests are more reliable but
may be painful and impractical.
The significance of other aspects of detrusor contraction
such as speed and duration is unclear.

MANAGEMENT
The goals of managing the patient with DUA are to improve
symptoms and quality of life and reduce the risk for the complications of impaired bladder emptying. These include urinary
tract infections (UTIs), bladder stones, ureteric reflux leading
to back-pressure on the upper urinary tract, and skin damage
from urinary overflow incontinence associated with chronic
retention. There is a profound lack of effective treatments to
improve detrusor function and thereby facilitate bladder emptying. Thus management commonly entails bladder drainage techniques (e.g., catheterization) or therapies aimed at reducing
bladder outlet resistance, for example, by relaxing the external
urethral sphincter mechanism. The clinical approach and therapies that are available in contemporary clinical practice as well as
potential experimental approaches are reviewed in the next sections
(Fig. 77-7).

Initial Assessment
The assessment of patients with symptoms suggestive of DUA
entails routine urologic evaluation (bladder diary, digital rectal
examination, urinalysis, uroflowmetry, PVR estimation using
ultrasound) and neurologic assessment (sacral dermatomes anal
tone, the bulbocavernosal reflex, lower limb reflexes). Neurologic
deficits require further specialist evaluation; magnetic resonance
imaging of the spine is commonly performed in particular to
assess the lumbar spinal cord and cauda equina. A careful drug
history should be taken to identify medications that impair
bladder contractility (agents with anticholinergic or opioid
effects) (see Box 77-1) or that increase outlet resistance (e.g.,
-adrenoreceptor agonists). Fecal impaction/constipation may
contribute to poor bladder emptying by a direct obstructive
effect, and, if identified, its treatment may facilitate improved
bladder emptying (Charach etal, 2001).

Conservative Management
Behavioral interventions in patients with DUA aim to reduce the
symptoms and complications of incomplete bladder emptying.
Scheduled voiding can be instituted to increase the frequency of
voids in patients with sensory impairment. Double voiding to
improve bladder emptying may help reduce bothersome frequency, and patients often use this strategy before seeking treatment. Bladder expression techniques such as Valsalva voiding or
the Cred maneuver are used in only very specific neurogenic
situations (i.e., DUA with incompetent sphincter) and are otherwise not recommended because of the risk for generating high
vesical pressure, causing vesicoureter reflux or reflux into the
prostate and seminal vesicles.
Pelvic floor physiotherapy and biofeedback have been used
to successfully treat children and adults with dysfunctional

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Chapter 77 The Underactive Detrusor

Detrusor function

Outlet resistance

Drainage

In routine clinical use

Experimental

Not recommended

Time voiding/double voiding

Compression

Catheterization

Reflex voiding

Urine diversion

Valsalva voiding

Pelvic floor physiotherapy


and biofeedback
-Blockers

1817

Intrasphincter botulinum toxin

Muscle relaxants

Bladder outlet surgery

Sacral neuromodulation

Intravesical prostanoids

Anticholinesterase

Intravesical electrotherapy
Anterior sacral root stimulator

Detrusor myoplasty

Muscarinic agonists

Reduction cystoplasty
Figure 77-7. Management options in detrusor underactivity.

voiding (de Jong et al, 2007; Minardi et al, 2010). In this group,
poor relaxation of the pelvic floor muscles and the external
urethral sphincter mechanism may obstruct urine flow and
cause reflex inhibition of detrusor contraction. In a study by
van Koeveringe and colleagues (2010), 24% of patients with acontractile detrusors on conventional UDS who subsequently demonstrated contractility on ambulatory studies were successfully treated
with physiotherapy.
ISC is the preferred method of establishing bladder drainage
in patients with problematic high PVR. Provided cognition and
dexterity are adequate, this method is safe and effective, with lower
infection rates than with indwelling catheters. Specific problems
include urethral bleeding (one third of patients) (Webb etal, 1990)
and production of false passages. Additionally, the technique may
be time-consuming and socially restricting; some patients may be
unable to overcome the psychological barriers such as a fear of
inflicting harm or infection (Mangnall, 2012). An indwelling urethral catheter is best avoided in the long term, and in this context
a suprapubic catheter is the best long-term option in patients
unwilling or unable to perform ISC.

Pharmacotherapies
Parasympathomimetics for Underactive Bladder
Acetylcholine is the principal neurotransmitter mediating bladder
contraction, acting on muscarinic (M3) receptors. Parasympathomimetic agents, including direct muscarinic receptor agonists or
anticholinesterases, have been used with the aim of increasing
bladder contractility. Bethanechol and carbachol, the most
common compounds studied, are quaternary amines that are
selective for the muscarinic receptor but not receptor subtype
selective. In mechanistic terms these compounds are more likely to
be effective if the problem is reduced or absent contractile stimulus
(e.g., reduced efferent input, impaired acetylcholine release from
parasympathetic nerves, increased acetylcholine breakdown). Anti-

cholinesterases (e.g., distigmine) would require the presence of at


least some endogenous acetylcholine, to amplify its effect. Conversely if the underlying cause is reduced tissue responsiveness to
stimulation (e.g., detrusor muscle cell dysfunction, bladder wall
fibrosis), parasympathomimetics are less likely to benefit. Similarly,
if the problem is loss of the detrusor muscle, no pharmacotherapy
is likely to be effective.
The efficacy of parasympathomimetics has been assessed in a
small group of heterogeneous studies, mainly for the prevention
and treatment of postoperative urinary retention. A systematic
review of this literature (Barendrecht etal, 2007) found only 4 of
10 randomized clinical trials included (two of the four in patients
with DUA) showed a significant benefit over placebo. However, all
of these studies could be considered to be underpowered. Bethanechol was used in all four (dose of 10 to 50mg up to four times
daily). A further three studies failed to show any advantage with use
of this agent. One study found that distigmine (5mg) actually
increased PVR compared to placebo. It was concluded there is little,
if any, benefit in using parasympathomimetics.
When bethanechol is given to neurologically normal individuals
it causes a rise in bladder wall stiffness and sensory perception (De
Wachter and Wyndaele, 2001). De Wachter and associates (2003)
also noted that women with DUA responding to bethanechol demonstrated significant reductions in bladder sensory thresholds.
Hence, intact sensory pathways may be a prerequisite for improvement in voiding with muscarinic agonists, which may explain their
lack of efficacy in unselected groups. Alternatively it could be that
the doses used are simply too low because of the concern with side
effects. Parasympathomimetics are associated with significant
dose-dependent systemic side effects, including nausea, bronchospasm, abdominal cramping, diarrhea, increased salivation,
flushing, and visual disturbance. A rare but potentially lethal side
effect is severe cardiac depression resulting in cardiac arrest. In
contemporary practice, parasympathomimetic agents are generally avoided because of their questionable efficacy and potentially serious side effects.

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PART XII Urine Transport, Storage, and Emptying

-Adrenoreceptor Antagonists
-Adrenoreceptor antagonists have been used to reduce bladder
outlet resistance in children and adults with both neurogenic
bladder and dysfunctional voiding. Chang and associates (2008)
studied the use of tamsulosin (0.2mg) in 52 women with DUA
(Pdet@Qmax <10cm H2O), finding 38.5% had a greater than 50%
improvement in voiding LUTS, 53.8% had a greater than 30%
improvement in Qmax, and 32.7% were judged to have had a good
therapeutic response (Chang etal, 2008). Combination therapy
with an -adrenoreceptor antagonist and a parasympathomimetic has long been considered a therapeutic possibility (Khanna
and Gonick, 1975). In a prospective single-blind randomized study
of 119 patients with DUA, urapidil alone did not result in a reduction in Qmax in either sex and led to a reduction in PVR in women
only (Yamanishi etal, 2004). By contrast a combined regimen of
urapidil (60mg) with either bethanechol (60mg) or distigmine
(15mg) led to significantly improved flow rates (by 2.66mL/sec in
women, P < .01, and 4.33mL/sec in men, P < .05) and significantly
reduced PVR in women (by 54.1mL/sec, P < .01) (Yamanishi etal,
2004).

Prostanoids
Prostanoids are a subclass of signaling molecules that may be
implicated in the micturition reflex. The efficacy of prostanoids
in treating DUA is not clear. Most clinical studies have evaluated
the effect of intravesical prostaglandin (PG) instillation in the
prevention of postoperative urinary retention.
There are five principal endogenous prostanoids (PGE2, PGF2,
PGI2, PGD2, and thromboxane A) that are all synthesized in the
bladder wall and released into the general circulation when the
bladder is stretched (Maggi, 1992; Rahnamai etal, 2012). Detrusor
contraction in response to acetylcholine and adenosine triphosphate stimulation is enhanced by prostanoid production. Conversely, nonsteroidal anti-inflammatory agents (inhibitors of
prostanoid synthesis) cause a loss of tone in the isolated bladder
that is reversed with the administration of prostanoids. PGF2,
PGE1, and PGE2 all enhance detrusor contraction; PGE1 and PGE2
cause urethral relaxation, and PGF2 results in urethral contraction
(Rahnamai etal, 2012).
The clinical studies conducted to date have demonstrated mixed
outcomes (Wagner etal, 1985; Tammela etal, 1987; Koonings etal,
1990; Bergman etal, 1992, 1993); however, a recent pooled analysis of the results of two randomized trials assessing PGE2 and a third
assessing PGF2 demonstrated a statistically significant association
between instillation and successful voiding (risk ratio 3.07) (Buckley
and Lapitan, 2010). Both PGE and PGF series also stimulate contraction of the uterus, a potential side effect of treatment (OBrien,
1995).

Future Prospects in Pharmacotherapy


In the absence of any effective compound, there are several avenues
aimed at increasing bladder contractility that can be explored, as
follows:
Parasympathomimetics could yet be an option; however, their
side-effect profile is concerning. Development of a bladderspecific agent could avoid these effects permitting dose escalation. However, this is unlikely to be possible based on
contemporary knowledge.
Novel muscarinic receptor manipulation such as postsynaptic
allosteric receptor enhancement or the presynaptic M2-receptor
antagonist could be promising.
Exogenous prostanoids require further investigation; agents with
selectivity for the urinary tract over the uterus and gastrointestinal tract are under development; however, whether they will be
effective if taken orally is an important question.
Agonists of transient receptor potential (TRP) channels, such as
TRPV4 agonist GSK1016790A, can increase contractility and are
worthy of further investigation.

Treatments of analogous conditions affecting other organ


systems, such as cardiac inotropes in cardiac failure or prokinetics for intestinal dysmotility, could provide alternative options
to increase contractility.
Improving bladder sensation using sensory sensitizers could
hypothetically help patients with impaired afferent signaling.
To develop effective drug therapies there is a need to better
understand the pharmacologic principles that underpin normal
detrusor contraction and the mechanisms of detrusor dysfunction underlying DUA.

Electrical Stimulation
A variety of electrical stimulation techniques have been applied in
DUA of different causes. Brindley and associates (1982, 1986)
developed the sacral root stimulator for patients with complete
spinal cord injury to activate the anterior sacral roots and achieve
volitional bladder emptying. For the procedure to be successful
there is a need for intact peripheral efferents and the absence of
myogenic dysfunction. This is confirmed by the presence of reflex
detrusor contractions on bladder filling preoperatively. The anterior
sacral roots are stimulated through an implantable receiver, stimulation wires, and external transmitter. Stimulation also activates
urethral somatic efferents; this is overcome by using intermittent
stimulation patterns that exploit the longer relaxation time of
smooth muscle compared to skeletal muscle to generate a sustained
detrusor contraction with short intermittent periods of sphincter
contraction. Clinically this results in an interrupted void pattern.
Sauerwein (1990) subsequently modified the technique by combining it with total sacral root rhizotomy, thereby abolishing all reflex
activity.
Katona and Berenyi (1975) popularized the technique of applying electrical current to the bladder wall through a transurethral
electrode in 1958, termed intravesical electrotherapy (IVE). The
bladder is filled with saline, and current is passed through an electrode (cathode) at the tip of the catheter; the circuit is completed
by a neutral electrode applied to the skin in an area of normal
sensation. Daily sessions of stimulation are undertaken, usually of
1 hour or more, with 10 to 15 sessions considered a trial period.
Animal experiments have shown that IVE activates mechanosensitive bladder afferents (myelinated A fibers) and, as a consequence, central reflex activation of the detrusor (Ebner et al,
1992). It is postulated that repeat activation of this pathway
upregulates its performance during bladder filling and volitional voiding, resulting in improved sensation and emptying.
On this basis, where the underlying cause is complete denervation or bladder wall fibrosis, IVE is considered unlikely to be
successful.
IVE has been studied primarily in the pediatric age group,
with some encouraging results, but is still considered a controversial therapy. There is considerable heterogeneity in inclusion
criteria and technical aspects, and most studies include only
small numbers, limiting definitive conclusions as to efficacy. In
children with both neurogenic and idiopathic DUA, voiding was
normalized after treatment in as many as 85% of cases (Gladh,
2002). In adults with predominately neurogenic DUA, 39% of
those without a detrusor contraction and 75% without bladder
sensation before treatment experienced a restoration of these
parameters (Primus etal, 1996). Several studies have failed to show
benefit, including the only sham controlled randomized prospective study (Boone etal, 1992). Moreover, IVE often is undertaken
alongside an intensive bladder training/biofeedback regimen,
which may partially explain the positive outcomes (Madersbacher,
1990). Although not associated with significant complications
(except a small risk for UTI), its principal limitations are the
significant time and resource requirements. An average of 47
sessions was required for a durable effect in a cohort of children
followed for 10 years after treatment (Kaplan, 2000).
Sacral neuromodulation (SNM) was first introduced over 30
years ago by Tanagho and Schmidt (1982). It has been used with
good efficacy in the group of patients with nonobstructive

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Chapter 77 The Underactive Detrusor


urinary retention and DUA (Everaert etal, 1997; Swinn etal,
2000). It is postulated that abnormal afferent signals generated
from the urethral sphincter (because of pelvic floor/sphincter disorders) have an inhibitory effect on bladder afferents at the level of
the sacral spinal cord, preventing their transmission in the periaqueductal gray and higher brain centers. SNM is thought to inhibit
urethral afferent signals and allow restoration of normal afferent
flow to the brain and the resumption of normal bladder sensation and detrusor contractions. A direct effect on bladder efferents
is possible but less likely (DasGupta and Fowler, 2004).

Botulinum Toxin
Botulinum neurotoxin A (BoNT-A) injected into the urethral
sphincter has been used to reduce outlet resistance and improve
bladder emptying in patients with detrusor-sphincter dyssynergia (Dykstra etal, 1988; Schurch etal, 1996; Phelan etal, 2001).
The potential rationale for its use in DUA is to relax the urethral
sphincter mechanism, thereby overcoming reflex inhibition of
detrusor function (Park etal, 1997), or to facilitate Valsalvainduced voiding.
Kuo (2003) reported the results of urethral BoNT-A (50U in
4mL of normal saline) in 20 patients with DUA of mixed causes.
The toxin was injected cystoscopically in men and periurethrally in
women. Seven patients who previously required indwelling catheters could void with low PVRs (150mL). In the 7 patients performing ISC at baseline it could be stopped or reduced in frequency after
injection. The same author also reported the effects of urethral
BoNT-A (50U or 100U in 4mL and 8mL of normal saline, respectively) in 27 patients (5 men and 22 women) with idiopathic detrusor underactivity (low or no Pdet and Qmax of <10mL/sec and PVR
>150mL) (Kuo, 2007a). An increase in Pdet and Qmax with a
decrease in PVR occurred in 13 patients (48%), all of whom could
void without abdominal straining. Analysis of baseline characteristics identified the responders as having significantly better bladder
sensation. Patients with evidence of poor sphincter relaxation
before treatment were more likely to improve (87%) compared to
patients with DUA only (33%) or DHIC (30%).
The evidence available suggests that the action of BoNT-A
when injected into the urethral sphincter mechanism is shortlived, and to date no adequate clinical studies have been conducted to evaluate the appropriate dose. In this context it is not
licensed for use and cannot be used outside of a clinical trial
setting.

Surgery
Bladder Outlet Surgery
The role of bladder outlet surgery in the management of men
with non-neurogenic DUA is a controversial topic in which there
is a lack of high-level evidence to guide clinical decision making.
It is important to differentiate between two common clinical
scenarios: the patient with DUA with a low or minimal PVR whose
primary complaint is symptoms and the patient with DUA who is
catheter dependent (i.e., chronic retention). In the former, although
BOO cannot be definitively excluded, because of the limitations of
urodynamic analysis discussed earlier, it is generally less likely to
be significant as the patient is able to empty the bladder with a low
Pdet. In this situation, outlet surgery is generally considered to be
unlikely to significantly improve voiding LUTS. This supposition is
supported by a study that followed 22 men with DUA treated with
TURP for a mean of 11.3 years (Thomas etal, 2004). The majority
of patients underwent TURP on the basis of symptoms (3 of 22 after
acute retention). There was no significant improvement in any
symptoms. A small reduction of questionable clinical significance
in the BOO index (BOOI = Pdet@Qmax 2 Qmax) did occur but
was not associated with an improvement in flow rate or voiding
efficiency. It can be concluded that when compared to patients
with DUA undergoing conservative treatment, outlet surgery
confers no significant improvement in symptoms or urodynamic

1819

parameters. Other studies with shorter follow-up support these


findings (Rollema and Van Mastrigt, 1992; Javle etal, 1998).
In the situation in which the patient with DUA is catheter dependent and has arguably reached a later stage of detrusor decompensation, even less evidence is available as to the benefit of outlet
surgery. Surgery is performed with the aim of reducing outlet resistance enough to permit bladder emptying, albeit the flow rate and
PVR rarely return to normal in this scenario. Predictors of poor
outcome include low voiding pressures (<45cm H2O) (Ghalayini
etal, 2005), older age (>80 years), and high residual volume
(>1500mL) (Djavan etal, 1997). Although the limited evidence
suggests men with DUA and chronic retention do less well after
bladder outlet surgery (Ghalayini etal, 2005), a significant proportion resume spontaneous voiding (Monoski etal, 2006). In
the absence of any other effective treatments some advocate
surgery in the younger, medically fit patient who wishes to
become catheter free.
The use of urethral dilation for women with DUA and significant residuals has been advocated but lacks an adequate evidence
base to permit clear conclusions to be drawn (Basu and Duckett,
2010). Resection or incision of the bladder neck in women with
DUA is not recommended, because this may lead to significant
problems with either incontinence or bladder neck stenosis.

Urinary Diversion
Because of the general acceptability and safety of both ISC and
indwelling catheterization techniques, urinary diversion is rarely
performed for DUA outside of the neurogenic population. When
urethral clean intermittent catheterization is not possible and the
patient wishes to avoid a suprapubic catheter, as is often the case
in young women with idiopathic urinary retention refractory to
SNM, a continent catheterizable stoma can be performed. An incontinent diversion (e.g., ileal conduit) is occasionally performed when
there are signs of renal deterioration resulting from obstruction to
the intramural ureters secondary to a thick-walled bladder.

Reconstructive Surgery
Few reports of reconstructive surgical procedures for DUA are available. Stenzl and colleagues (1998) reported the first series of latissimus dorsi detrusor myoplasty in patients with DUA in 1998. The
muscle is harvested, and its pedicle is anastomosed to the inferior
epigastric vessels, with the nerve coapted to the intercostal branch.
The muscle is wrapped in a spiral configuration around the bladder,
covering over three quarters of its surface. It is then anchored to the
pelvic floor fascia and ligaments. The long-term outcomes of this
technique in 24 catheter-dependent patients with acontractile
detrusor have been reported (Gakis etal, 2011). Seventeen patients
recovered the ability to void (mean PVR = 25mL). The mean
bladder contractility index increased from 20.1 7.6 to 176.2
25.4 (P < .001). Complications occurred in a third of patients,
including thromboembolism, pelvic abscess, and wound infection,
though there were no long-term problems. Partial cystectomy (or
reduction cystoplasty) has been reported as an alternative approach,
in a few series (Weinberg etal, 1974; Klarskov etal, 1988), with no
recent reported studies and is no longer considered in contemporary practice.

CONCLUSIONS
DUA is a not uncommon problem that can pose a difficult challenge for both patients and physicians because of the lack of simple
and effective treatments. This problem has received little attention
in clinical and basic science research in comparison to other
common LUTD such as OAB and DOA. Defining the problem in
symptom-based terms is difficult because of the wide spectrum of
manifesting symptoms, underlying clinical conditions, and absence
of accurate noninvasive markers. Clinical studies suggest that the
problem is highly prevalent in both men and women with LUTS

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1820

PART XII Urine Transport, Storage, and Emptying

KEY POINTS: MANAGEMENT


There are no effective pharmacotherapies for the treatment
of DUA.
Parasympathomimetic agents have questionable efficacy, are
associated with potentially fatal systemic effects, and are not
used in routine practice.
Intravesical electrotherapy has shown promising results in
restoring detrusor contraction; however, it is time- and
resource-consuming.
SNM is effective in restoring voiding in patients with DUA
associated with urethral sphincter/pelvic floor disorders.
Bladder outlet surgery has a high risk for failure in men with
DUA not reliant on catheters. Men with DUA and chronic
retention dependent on catheter drainage experience poorer
outcomes than those with normal detrusor function;
however, they still may benefit from surgery.

presenting to urologists. A variety of causes are implicated, affecting


all aspects of the micturition reflex. There is a lack of any simple
and effective treatments. Preserved bladder sensation appears to
predict better responses to treatment. There is need for a greater
understanding of the mechanisms governing normal detrusor con-

traction and how these are affected by disease. Until this is achieved
it will be difficult to develop compounds that enhance detrusor
strength and duration of contractility or enhance bladder sensation.
In the future developments in regenerative medicine, stem cell and
gene therapy may provide interesting avenues for further research,
but a prerequisite for this will be to develop a better understanding
of both normal structure and function of the LUT and the way in
which this is altered in cases of DUA.

REFERENCES
The complete reference list is available online at www.expertconsult.com.

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Chapter 77 The Underactive Detrusor 1820.e1

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