Nocturia in older people
Adrian Wagg
Professor of Healthy Ageing
1
Nocturia
the complaint that an individual wakes one or more
times to void urine at night
Kerrebroeck P et al. A standardization of
terminology in nocturia. Neurourol Urodyn
2002; 21: 179-183.
• The definition does not
ascribe any reason to the
need to awaken,
• “night” is defined according
to the sleeping habits of the
individual
Causes for nocturnal awakening to void
Bing MH, Moller LA, et al BJU Int. Sep 2006;98(3):599-604.
Symptom prevalence and age
Men
35
30
% (95%CI)
Nocturia (≥2 times/night)
25
Urgency
20
Frequency
UUI
15
MUI
10
SUI
5
0
0
1
<39
2
40-59
3
>60
Age group
Irwin DE, Milsom I, Hunskaar S, et al. Eur Urol. Dec 2006;50(6):1306-1314
Symptom prevalence and age
40
Women
35
% (95%CI)
30
Nocturia (≥2 times/night)
25
Urgency
20
Frequency
UUI
15
MUI
10
SUI
5
0
0
1
<39
age group
2
40-59
3
>60
Irwin DE, Milsom I, Hunskaar S, et al. Eur Urol. Dec 2006;50(6):1306-1314
Prevalence of nocturia (≥ 2) in a USA
community sample
men - red
Women - green
Coyne K et al. BJU Int 2003;92:948-54
Nocturia by age and sex in Finland
Prevalence of nocturia defined as
at least 1 void per night
Prevalence of nocturia defined as
at least 2 voids per night
Tikkinen KA et al. J Urol. 2006;175(2):596600.
Nocturia in Swedish men
90
80
70
60
%
50
40
30
20
10
0
45
50
55
60
65
70
75
80
85-89
≥90
age
n = 7763
Ulmsten et al. J Urol 1997;158:1733-1737
Prevalence and frequency in 60 – 80 year olds
Bing MH, Moller LA et al. BJU Int. Sep 2006;98(3):599-604.
Associated bother
Bing MH, Moller LA et al BJU Int. Sep 2006;98(3):599-604.
Impact
• Nocturia is associated with
–
–
–
–
accidental falls
injury and hip fracture
poor sleep quality
increased risk of depression and poor self-rated
health
• Adults with nocturia complain that nocturia “makes them feel
old” and they worry about falling at night
• Older individuals describe nocturia as debilitating,
frustrating, distressing and puzzling.
impact
• Associated with chronic medical conditions
–
–
–
–
–
–
–
–
–
hypertension
diabetes
advancing renal insufficiency
cardiovascular disease
sleep apnoea,
restless leg syndrome
moderate alcohol usage
poor nocturnal glycaemic control
Fitzgerald, M.P.Journal of Urology, 2007. 177(4): p. 1385-9.
increased mortality
Johnson, T.M.J Am Geriatr Soc, 2005. 53(6): p. 1011-6.
Plantinga, L. Am J Kidney Dis, 2011. 58(4): p. 554-64.
Hillier, P. Quarterly Journal of Medicine, 1980. 49(196): p. 461-78.
Rembratt, A. BJU Int, 2003. 92(7): p. 726-30.
Asplund, R. BJU International, 2002. 90(6): p. 533-6.
Weiss, J.P. BJU International, 2011. 108(1): p. 6-21
Sleep
• 1,424 elderly individuals, ages 55–84 were presented with a
checklist of symptoms that potentially disrupt sleep,
– nocturia was chosen by 53% of the sample as a selfperceived cause “every night or almost every night”.
– nocturia was cited four times as frequently as pain,
– bother from nocturia is related to the number of trips
to the bathroom,
– difficulty experienced in trying to return to sleep –
falls higher in this group
• other lower urinary tract symptoms are also highly correlated
with sleep disturbance.
Bliwise, D.L., et al Sleep Medicine, 2009. 10(5): p. 540-8.
Impact on well-being
• the most “bothersome” of lower urinary tract symptoms
• associated with
–an increased risk of falling
(risk increasing from 10 – 21% with ≥ 2 micturitions per night)
–Fracture
– Excessive daytime somnolence
– Nocturnal enuresis
Pathophysiology
• In older people
• the pathophysiology of nocturia is multifactorial
• In age-adjusted analyses from a large survey in Finland, no
single factor related to nocturia was present in greater than
50%
• The factors with the greatest impact at the population level
were
• urgency, benign prostatic hyperplasia, and snoring for men
• overweight and obesity, urgency, and snoring for women
Tikkinen, K.A., et al.American Journal of Epidemiology, 2009. 170(3): 361-8.
Pathophysiology
• The proportion of 24-hour urine volume produced at night
increases with age, even among healthy older adults free of
overt comorbid conditions
• Studies of frail elderly have shown that the proportion of
urine produced at night is close to 50%, rather than less
than 30% as in young healthy adults
• Nocturnal polyuria is more common in older compared to
younger nocturics
Ouslander, J.G., et al. Journal of the American Geriatrics Society, 1998. 46(4): p. 463-6.
Weiss, J.P. and J.G. Blaivas. Journal of Urology, 2000. 163(1): p. 5.
Abrams, P., et al. BJU International, 2002. 90 Suppl 3: p. 32-6.
• In some elderly people, this is due to mobilisation of excess
volume caused by peripheral oedema, which may be due to
venous insufficiency, medications, and/or heart failure.
• calcium channel blockers
• hydrocholorothiazide and loop-diuretics in men
Hall, S.A., et al. BJU Int, 2011.
Pathophysiology
• abnormality in the secretion and/or action of arginine
vasopressin (AVP)
• a loss of the normal diurnal rhythm (with inappropriately low
values at night)
• high atrial natriuretic peptide (ANP) levels at night however,
these investigators did not use echocardiography or brain
natriuretic peptide levels to detect occult heart failure.
Pathophysiology
• Sleep disordered breathing and sleep apnoea also
associated with nocturia and nocturnal polyuria
• Community-based elderly populations who have higher
levels of sleep disordered breathing (>25 breathing events
per hour), have nearly double the number of nocturia
episodes compared with those with low rates of sleep
apnoea
• Whether this relates to increased ANP production
mechanical forces on the bladder generated during apnoea
events or other mechanism(s) is unknown.
Umlauf, M.G., et al. Sleep, 2004. 27(1): p. 139-44.
Dahlstrand, C., et al.Lancet, 1996. 347(8996): p. 270-1.
Bliwise, D.L. Sleep, 2004. 27(1): p. 153-7.
Pressman, M.R. Arch Intern Med, 1996. 156(5): p. 545-50.
Diagnostic assessment
• A frequency-volume chart of at least 24 hours duration that
includes timing and volume of each void at night as well as
during the day
• a hand-held urinal or a receptacle to place in the toilet to
measure volumes, with clear markings and involvement of
caregivers may improve compliance and accuracy.
• Additional questions in the history that focus on the
possibility of a primary sleep disorder, such as asking about
sleep quality, daytime sleepiness, snoring, and leg
movements at night
• Additional history and focused physical examination related
to volume overload
Aetiology of nocturia
• Sleep disturbance
• Sleep
disturbance……and then
drinking
• Excess fluid intake
• Poorly controlled
Diabetes Mellitus
• Diabetes insipidus (rare)
•
•
•
•
Lithium therapy
Heart failure
Hypercalcaemia
Dependent oedema
• Venous insufficiency
• Hypoalbuminaemia
•
•
•
•
Late night diuretics
Calcium channel blockers
Obstructive sleep apnoea
Restless leg syndrome
Wagg, A., et al.Int J Clin Pract, 2005. 59(8): p. 938-45.
Treatment algorithm: nocturia
Nocturia
Bothersome?
Yes
No
Simple advice
Exclude
Co-morbidities
Medication effect
Blood tests
Sleep disorder
Environmental problem
Advice re sleep
hygiene
Overactive bladder
syndrome
Rx
Frequency-volume chart
Bladder outflow
tract obstruction
Rx
Polyuria/nocturnal
polyuria
bladder
diary
Rx
Wagg, A., et al.Int J Clin Pract, 2005. 59(8): p. 938-45.
Treatment
• treatment of nocturia in elderly patients should be based on
a holistic approach informed by identification of multiple
potential underlying causes.
• little high quality evidence for most treatments and combined
treatments- for nocturia in this age group.
• Cure, or the complete resolution of nocturia, is infrequently
achieved in either clinical practice or research.
• Some trials have reported the percent of participants who
achieving a 33% - 50% reduction in nocturia equal to 1.0
fewer mean nightly episodes of nocturia
Dubeau, C.E. J.P. Weiss, et al., Editors. 2012, Springer: New York. p. 147-155.
Weiss, J.P., et al.Neurourol Urodyn, 2012.
Johnson, T.M., 2nd, et al. Journal of the American Geriatrics Society, 2005. 53(5): p. 846-50.
Mattiasson, A. BJU International, 2002. 89(9): p. 855-62.
Treatment
• The use of specific behavioural strategies (e.g. altering fluid
intake, reducing sodium intake, leg elevation for oedema)
on nocturia in older patients have largely been made on the
basis of consensus.
• Using bedside commodes or urinals, and minimising the
distance necessary to reach a toilet and providing a safe,
adequately lit path may be helpful in reducing the risk of
night-time falls related to nocturia, especially in those with
underlying gait instability and other risk factors for falls.
Treatment
• pelvic floor muscle exercises and urgency suppression
strategies reduced nocturia in women (mean age 68) with
urgency-predominant UI. The median reduction of 0.5
episodes per night was significantly more effective than
drug treatment (0.3 episodes) or placebo (no reduction)
• No benefit of behavioural therapy when added to tolterodine
4 mg LA for nocturia.
• There are currently no trials of pelvic floor muscle exercises
or urgency suppression strategies where reduction in
nocturia is the primary outcome.
Antimuscarinic therapy
• Most patients with nocturia do not have
overactive bladder
• Most patients with OAB do have nocturia
• antimuscarinics are not usually efficacious for
nocturia
• antimuscarinics may be effective for nocturnal
voids due to urgency
Weiss, J.P., et al BJU International, 2011. 108(1): p. 6-21.
Antimuscarinics
• There are several trials examining the effect of
antimuscarinics for nocturia reduction; even when agents
from this category have shown statistically significant
reductions in nocturia, the net benefit of reduction in
nocturia (above that effect shown with placebo) is only by
0.0 to 0.3 episodes.
• Use of anticholinergic medications should be used with
caution in at-risk individuals as they may cause worsening
of confusion or delirium
Drugs for BPE
• Alpha-adrenergic agents used in patients with symptoms
suggestive of BPO have a modest impact on nocturia, with
a mean reduction of slightly less than one episode per
night.
• 5-alpha reductase inhibitors and saw palmetto have not
shown statistical benefit for nocturia except in one study
within one subset of participants age >70.
• This statistical advantage did not persist beyond one year,
and the net benefit compared to placebo was a difference
of < 0.2 fewer nocturia episodes.
DDAVP
• The value of classification of patients according to the
presence or absence of NP has not been demonstrated to
be a meaningful predictor of efficacy, or lack of benefit, for
any treatment, including desmopressin.
• Use of DDAVP results in significant reductions in nocturia
and nocturnal urine volume, and increases in mean
duration of self-reported first night-time sleep episode.
• Most individuals in DDAVP oral tablet trials were titrated up
to an oral dosage of 0.4 mg
• Older patients can have a significant reduction in night-time
urine with much lower doses of 0.1 or 0.2 mg orally.
• A major concern related to DDAVP treatment in elderly
patients is fluid retention and hyponatraemia
DDAVP
• Pharmacodynamic studies in younger older men (aged 5570) found that DDAVP had a prolonged half-life which was in
part responsible for hyponatraemia
• DDAVP is not useful in frail older persons in nursing homes
with nocturia and/or night-time UI because of the lack of
efficacy for reducing night-time voids and the very high rate
of hyponatraemia
• orally-disintegrating formulation of DDAVP data show that for
men, the minimal effective dosage is 100 micrograms (-1.38
versus -0.84 for placebo) and for women it 25 micrograms (1.22 versus -0.88 for placebo). Side effects depended upon
both age (older had higher side effects) and sex (women had
higher side effects).
DDAVP
• For those participants over 65 years of age, the following
percentages of participants had a reduction of sodium of
either 125-130 or <125: on 100 micrograms, 14.1% and 4.7%;
on 50 micrograms, 6.6% and 2.6%; for 25 micrograms, 2.6%
and 0%.
•
• There have also been trials with staggered DDAVP and
diuretics, which have greatly reduced nocturia, 5% of study
completers had hyponatraemia
Posterior Tibial Nerve Stimulation:
• Posterior tibial nerve stimulation has been used in OAB
trials.
• in 214 individuals nocturia reduction in the active treatment
group (2.9 at baseline to 2.1 with treatment) that was
statistically superior to the effect of sham (2.9 to 2.6, net
benefit of active over placebo -0.4 reduction)
• whether or not these gains are maintained without ongoing
treatment is not known
MacDiarmid, S.A., et al. J Urol, 2010. 183(1): p. 234-40.
Surgery
• Surgical approaches to treatment of nocturia have long
been recognized to be effective, yet overall symptoms to
improve more than does nocturia specifically.
• older patients with the highest symptom scores prior to
surgery benefit the most from transurethral resection of the
prostate yet nocturia often persists and may be the least
responsive symptom
Seki, N., et al.Neurourol Urodyn, 2009. 28(3): p. 197-201.
Simaioforidis, V., et al.Int J Urol, 2011. 18(3): p. 243-8.
Margel, D., et al., Urology, 2007. 70(3): p. 493-7.
Summary
• Late afternoon administration of a diuretic may reduce
nocturia in persons with lower extremity venous
insufficiency or congestive heart failure unresponsive to
other interventions. (Level 2)
• If OAB, DO, and/or urgency UI is felt to be a major
contributor to nocturia, antimuscarinic agents should be
considered. (Level 3)
• If nocturia is due to insomnia alone, then a very-short acting
sedative hypnotic may be considered. (Level 3)
• DDAVP should not be used in frail elderly because of the
risk of hyponatraemia. (Level 1)
Research recommendations
• Studies to elucidate the reason for awakening
• Ways in which to understand, and potentially diminish, the
robust effect of placebo/control arms
• Epidemiological research regarding studies of nocturia
involving the following aspects: incidence/natural history,
bother, effect on quality of life
• Research regarding what would be a clinically significant
improvement)
• Further clinical trials examining the impact of sleep focused
treatments
• Trials examining the effects of multiple incremental and
multicomponent therapies for nocturia
Wagg, A et al. 5th ICI chapter on frail elderly. 2012 in press
Other
• Melatonin showed only a trend towards reduction in
nocturia compared to placebo (-.03 and -0.05 episodes
from baseline 3.1 episodes, respectively) but did
significantly reduce reported bother.
• Reducing volume overload associated with lower extremity
venous insufficiency or congestive heart failure with a late
afternoon dose of a rapid acting diuretic may be helpful in
reducing nocturnal polyuria and nocturia in selected
patients.
• Treating sleep apnoea with continuous positive airway
pressure can reduce nocturia severity.