Nocturia in older people: A review of causes, consequences, assessment and management

Nocturia in older people: A review of causes, consequences,assessment and management

A. ALI ,1 J . SNAPE2

SpR Geriatric Medicine,1 Consultant Geriatrician,2 King’s Mill Hospital, Mansfield Road, Sutton in Ashfield, Notts

SUMMARY

Nocturia is common in older people and it may be bother-

some for both patients and carers. It is most commonly

related to bladder storage difficulties and nocturnal polyuria.

The former results most frequently from an uninhibited

overactive bladder. The latter occurs as a consequence of

age-associated changes in the circadian rhythm of urine

excretion. The management of an overactive bladder includes

both behavioural and drug treatment. The management

options for nocturnal polyuria include an afternoon diuretic

and desmopressin, but caution is required, particularly with

the latter, as it can cause significant hyponatraemia.

Keywords: Nocturia; nocturnal polyuria; bladder storage

problems

� 2004 Blackwell Publishing Ltd

INTRODUCT ION

The purpose of this article is to explore the causes and impact

of nocturia in older patients and their carers, to discuss its

assessment and diagnosis and to go on to look at the manage-

ment of some of the conditions which lead to nocturia. The

standardisation subcommittee of the International Con-

tinence Society has recently agreed to the standardisation of

terminology in relation to nocturia (1) (Figure 1).

We will concentrate on nocturnal polyuria (NP) and bladder

storage problems, briefly mentioning other conditions that

might appear in the differential diagnosis of nocturia.

DEF IN IT IONS

Nocturia

Nocturia is the complaint that a patient has to wake at night

to void, on one or more occasions (1). It particularly affects

older individuals (2,3). Four per cent of children aged 7–15

years were reported as suffering from regular nocturia (4)

whereas in men and women aged 50–59 years the prevalence

was 66 and 58%, respectively (5). In those over 80 years 91%

of men and 72% of women reported nocturia (5).

Nocturia needs to be distinguished from nocturnal enuresis

(which is not considered here) where voiding occurs during

sleep. The first morning void is not included as a night time

void, as it is the natural expulsion of urine produced during the

night (1). Patients with nocturia may or may not be bothered

by it, and this will determine whether or not they seek help.

Nocturnal Polyuria

NP is defined as the production of an abnormally large

volume of urine during sleep. This includes all urine pro-

duced after going to bed plus the first morning void. If the

24-h urine volume is normal, the output during sleep can be

expressed as a percentage of the total (1). Healthy adults aged

21–35 years excrete about 14% of their total urine at night

(6) whereas older people pass about 34% (7). About 25%

of nursing home residents in one study were passing more

than 50% of their total daily output at night (8).

Therefore, younger people producing more than 20% of

their urine during sleep and older individuals who produce

more than 33% of their daily total during the same time are

defined as suffering from NP (1). The causes of NP will be

considered below.

Bladder Storage Problems

Patients with reduced structural bladder capacity (e.g. due to

fibrosis, previous radiation therapy or carcinoma in situ) orwith reduced functional bladder capacity including those

with uninhibited overactive bladder or with significant post-

void residuals among others, may have bladder storage

problems which tend to present with frequency, urgency, urge

incontinence and nocturia. They may have several episodes of

nocturia but the volumes passed were small (9). The diagnosis

can be clarified by using a frequency/volume (F/V) chart.

Correspondence to:Dr J. Snape, MB, FRCP, Consultant Geriatrician, King’s Mill

Hospital, Mansfield Road, Sutton in Ashfield, Notts, NG17 4JL

Tel.: 144 (1623) 785100

Fax: 144 (1623) 785230

Email: [email protected]

ª 2004 Blackwell Publishing Ltd Int J Clin Pract, April 2004, 58, 4, 366–373

REVIEW

Polyuria

Patients with urine output exceeding 40ml/kg body weight/

24 h are suffering from polyuria. They may present with

nocturia. The polyuria should be further investigated to see

whether it is due to water diuresis (e.g. diabetes insipidus or

excessive fluid intake) or a solute diuresis (e.g. diabetes mellitus).

Sleep Disorders

Some patients may seem to have bladder storage problems

when the F/V chart is studied, but their real problem is one of

the sleep disorders (e.g. insomnia, obstructive sleep apnoea or

periodic leg syndrome).

Patients who are constantly waking up at night for other

reasons may feel the need to void on each occasion and void a

small volume. Further investigations in a sleep laboratory may

be necessary.

Consequences of Nocturia to Patient and Care Given

Nocturia is one of the commonest causes of sleep interruption

and lack of sleep. It is associated with unrefreshing sleep and

daytime fatigue. Concentration, co-ordination, problem-solving

skills and creativity are reduced. There may be mood alteration

and muscle stiffness (10). Lack of sleep has also been associated

with reduced natural killer cell numbers and cytokine levels in the

blood – the result of which is an increased incidence of infection

(11). Nocturia is also a risk factor of falls and fractures; the risk

increases proportionally to the frequency of nocturia (12).

The combination of postural hypotension resulting in

impaired balance and nocturnal awakenings for frequent visits

to the toilet increases the risk of falls-related injury. Urgency

at night also increases the risk (13). Nocturia, in general,

causes poor health in older people. There is increased need

for emergency care, independent of the presence of heart

disease, asthma and renal problems. Older people who voided

N O C T U R I A

Patient desires treatment Patient does not desire treatment

Screen

Lifestyle advice

Further investigations

Polyuria Nocturnal polyuria Apparent bladderstorage problems

Primary sleep disorders

Examples of causes related to bladder storage problems:

Detrusor overactivityReduced functional bladder capacity (e.g. significantpost void (PV) residualBladder outlet obstruction with PV residual

Figure 1 Algorithm for assessment of

patients with nocturia [adapted and

reproduced with the permission of the

International Continence Society (1)]

NOCTURIA IN OLDER PEOPLE 367


three or more times at night had a greater mortality over a

54-month period (14). Heart disease (e.g. cardiac failure and

hypertension) and autonomic dysfunction may be respon-

sible, it was suggested.

In a Dutch study, older women with poor health were more

likely to suffer with nocturia.

Nocturia can also be a very bothersome symptom and have a

deleterious effect on everyday activities (15). Although not every-

body who reports nocturia, considers it problematic, some con-

sider it to be a part of normal ageing. Currently, there is no

dedicated instrument to measure the prevalence and impact of

nocturia in terms of quality of life, although there are several

valid and reliable questionnaires that include nocturia (16,17).

Seventy per cent of care givers have cited sleep-related problems

(nocturia being the most frequent complaint) of older relatives as

a major reason for deciding to institutionalise them (18).

FACTORS WHICH AFFECT URINE PRODUCT ION

IN THE AGED

Circadian Urine Production

A circadian rhythm of urine production is usually established

by 5 years of age. Seven-year olds produce 2–3 times the

amount of urine during the day than they do at night (19).

In adults, 25% or less of the daily urine output occurs during

the hours of sleep (20). After 60 years, a shift to more

nocturnal urine production occurs, and with increasing age,

the ratio of day to night time urine flow falls until the

latter equals or exceeds the former (7) The total 24-h urine

excretion, however, does not change with age (21).

Arginine Vasopressin

Arginine vasopressin (AVP) (otherwise anti-diuretic hor-

mone) is the main hormone responsible for the regulation

of urine production. Ageing does not affect the nuclei of the

hypothalamus either in terms of cell loss or synthetic ability.

There remains some confusion about the effect of ageing on

daytime blood AVP levels. Some studies have suggested an

increase in daytime basal plasma level of AVP in older people

(22,23,24), whereas others indicated that basal levels were not

affected by age (25,26). Further studies have reported lower

daytime plasma AVP concentrations in healthy older subjects

when compared with young subjects (27). During the hours

of sleep, however, it seems clear that there is a circadian

rhythm of AVP with peak concentration occurring at night

(28). It appears to be related to the wake/sleep cycle rather

than the time of day (29). With ageing, there is a blunting of

the nocturnal AVP secretions, so that, levels of hormone are

similar during the day and night (21,30). Impairment of

nocturnal AVP release accompanying with NP has been

demonstrated in multiple system atrophy (MSA) (31) and

Alzheimer’s disease (32).

Asplund (33) found that there was a difference between

older men and older women with a two-fold higher plasma

AVP in the former. This finding has so far not been

confirmed (24,25).

Atrial Natriuretic Hormone

Atrial natriuretic hormone (ANH) [previously known as atrial

natriuretic peptide (ANP)] through its action on the kidney

results in natriuresis and consequent diuresis. ANH levels have

been shown to increase with age (34) fivefold higher in older

nursing home residents compared to younger controls (35).

ANH has been shown to interact with the renin-angiotensin-

aldosterone system, high levels suppressing renal renin

secretion, plasma renin activity and thus plasma aldosterone

via plasma angiotensin II (36). A slow intravenous infusion of

ANH, causing minimal increase (within the physiological

range) in ANH, inhibits angiotensin II-provoked aldosterone

release (37). ANH, moreover, seems to suppress aldosterone

secretion directly (38). ANH also opposes AVP action in the

kidney and inhibits central AVP release (55). Therefore,

ANH, through its impairment of renal sodium conservation

and concomitant water loss (via the direct natriuretic effect

and through its suppression of aldosterone) and also

through its effect on AVP, may contribute to age-related

changes in urine excretion. Subclinical heart failure may also

be contributing to elevated ANH levels, resulting in nocturnal

diuresis. This was suggested by a study of patients present-

ing to a urology clinic. It was found that patients with NP

had a significantly higher level of ANH compared to controls,

and that they had significant cardiomegaly on chest X-ray

(39).

Another study looked at ANP levels in geriatric patients

with nocturia and nursing home residents with nocturnal

incontinence. Whilst ANP levels were elevated, NP was not

associated with higher levels. The study concluded that ANP

levels were unlikely to be a primary cause of nocturia but they

may contribute (along with other factors such as low AVP

levels) to the problem in some older patients (40).

RENAL FACTORS AND AGE

Water Loss

There is a fall in renal-concentrating ability with age. A fall in

maximum urine osmolality with age occurred in a study when

hospitalised males (aged 23–72 years) underwent 24 h of fluid

deprivation (40). Similarly healthy males aged 40–101 years

demonstrated a fall in urine-specific gravity from 1.03 at

40 years to 1.023 at 89 years when exposed to 24-h water

deprivation (41). This decline in renal-concentrating ability

was felt to be related to impaired renal tubular responsiveness

to AVP (40). In effect, this represents a mild form of acquired

nephrogenic diabetes insipidus.

368 NOCTURIA IN OLDER PEOPLE


Sodium Loss

Normal ageing is associated with increased renal sodium loss.

The ability of the aged kidney to conserve sodium in response to

salt restriction is impaired (42). Natriuresis in older people is

associated with an osmotic diuresis which is more evident when

in the recumbent position. The ability of the kidney to conserve

sodium is partly dependent on the renin-angiotensin-aldosterone

system, which is affected by ageing. Renin secretion in

response to stimuli, such as low-dietary sodium and upright

posture, falls with age. This results in reduced aldosterone

secretion and therefore reduced renal sodium conservation

(43,44,45).

Age and Urine Storage

Community-based studies suggest that with normal ageing,

bladder capacity and bladder compliance fall as do urinary

flow rates and maximal urethral closure pressure. Frequency

of inhibited detrusor contractions and post-void residual

increase (46,47,48). These factors interfere with the bladder’s

ability to store urine successfully. In the presence of signifi-

cant lower urinary tract problems in old age, such as detrusor

overactivity (of whatever cause), this reservoir function may

be further impaired leading to frequency, urgency, urge

incontinence and nocturia. In men, the progressive enlarge-

ment of the prostate with age greatly influences the behaviour

of the bladder and urinary outflow tract contributing to lower

urinary tract symptoms including nocturia (49).

ASSESSMENT OF NOCTURIA

Several different urinary and extra urinary problems can lead to

nocturia. Its assessment is laid out in the algorithm (Figure 1).

The initial assessment should include a complete history, detail-

ing lower urinary tract symptoms (e.g. urgency may suggest an

overactive bladder; nocturia, hesitancy, poor stream and a feel-

ing of incomplete emptying in a male would indicate the

possibility of prostatic hyperplasia). A detailed medical history

including a known history of conditions, such as Parkinson’s

disease, multiple sclerosis, Alzheimer’s disease, diabetes mellitus,

congestive cardiac failure and obstructive sleep apnoea, is

important. The presence of chronic neurological conditions

may indicate an overactive bladder secondary to loss of central

inhibition of the detrusor muscle. It may also, in more advanced

conditions, suggest the presence of a hypotonic bladder.

In multiple system atrophy and Alzheimer’s disease,

reduced nocturnal AVP secretion can cause NP. Diabetes

may indicate polyuria secondary to poor glycaemic control

or hypotonic bladder due to autonomic neuropathy. Oedema

as a consequence of, for example, congestive cardiac failure or

hepatic disease, can provoke nocturia by the mobilisation of

large quantities of fluid at night when the patient is supine

(56). Obstructive sleep apnoea is a condition which results in

NP, thought to be a consequence of raised ANH levels at

night (21), hence, symptoms of this condition should be

sought. A review of symptoms may provide clues as to other

conditions leading to nocturia (e.g. constipation). A history of

previous surgical or gynaecological attention should be

sought. Drug history is important: diuretics in the evening

may cause nocturia, anti-cholinergics may cause retention and

overflow and lithium may cause nephrogenic diabetes insipi-

dus. The patient’s attitude to their problem (is it bother-

some?) is also vital when considering management. Details

of sleep pattern should be sought. A complete physical exam-

ination is mandatory and may provide evidence of congestive

cardiac failure, urinary retention, faecal impaction, neuro-

logical deficits or other conditions that may provide clues as

to the cause of nocturia.

Laboratory evaluation should include urinalysis, urine cul-

ture and sensitivity, blood urea, electrolytes, calcium and

glucose. These tests may indicate the presence of a urinary

tract infection (UTI) or a cause of polyuria that may explain

nocturia. Treatment of a UTI is only likely to be helpful if the

patient has symptoms and signs of infection. A chest X-ray,

ECG and echocardiogram may indicate overt or incipient

heart failure, which could be implicated as a cause of nocturia.

Further evaluation crucially includes the F/V chart, which

should include of the voided urine (volume and time) over at

least 72 h (50). The chart should also include information on

the volume and type of fluid ingested, the bed time and time

of rising and subjective idea of each night’s sleep (good or

bad). The F/V chart is likely to identify patients with NP.

Measurement of post-void residual volume by non-invasive

ultrasound scan will identify patients with urinary retention

caused either by outlet obstruction or by neurogenic bladder.

Measures of quality of life (see above) may be appropriate in a

research setting. Serum ANP and AVP levels are not routinely

used in clinical practice. Patients with bladder storage problems

causing nocturia may also be identified from the F/V chart,

although some patients may require further urodynamic assess-

ment (e.g. filling and voiding cystometry). If a sleep disorder is

suspected, a nocturnal polysomnography should be considered.

Polyuria is defined as a 24-h voided volume in excess of

2800ml (i.e.> 40ml/kg in a 70 kg person). The F/V chart

should identify excessive fluid intake. Fasting blood glucose

and a fluid deprivation test should diagnose diabetes mellitus

or diabetes insipidus. Serum calcium and blood urea and

creatinine should identify hypercalcaemia and renal failure

(other possible causes of polyuria).

MANAGEMENT OF NOCTURIA

Lifestyle Advice

General lifestyle advice, such as reducing alcohol and caffeine

intake and limiting food/liquid intake after 7:00 PM, can be a

successful strategy in some patients. While it is recognised



that in nursing homes, the sleep of residents is very disrupted

by noise, light and nursing practices (51) and that improving

sleep quality may improve nocturia, (52) attempts to try and

improve the sleep of residents by strategies to reduce noise

and light or by introducing a physical activity programme

have so far failed (53,54).

An interesting finding was that older people who were

treated with hypnotic excreted a smaller volume of urine at

night than those not so treated (52). It seemed that not only

spontaneous sleep but also sleep induced by medication

reduces nocturnal urine output. It has also been suggested

that the use of daytime compression stockings may be useful

in oedematous patients with NP and also afternoon nap (9),

but further research is needed.

Nocturnal Polyuria

Apart from lifestyle changes, three areas have been considered

for the pharmacological management of NP. Firstly, forcing

more urine output during the day in the hope that nocturnal

production would fall as a consequence. It has been observed

that nursing home patients taking diuretics had smaller noc-

turnal volumes than non-diuretic-taking controls (8). Diure-

tics taken 6 h before bedtime have been shown in two trials to

reduce nocturnal urine volume in some patients (57,58).

The mechanism may be diuretic induced reduction in the

intravascular volume and reduced renal blood flow. Improve-

ment in incipient cardiac failure resulting in decreased ANH

secretions is another possibility. Clearly, the risks of dehydra-

tion in older people when using such treatment should be

remembered.

Secondly, blocking or lowering nocturnal ANH production

has been suggested (59), but apart from the use of afternoon

diuretics, we found no studies in man that attempted to lower

ANH levels or block ANH receptors. However, it has been

proposed that NP and essential hypertension share a defect in

the nitric oxide pathway leading to resetting of the pressure-

natriuresis relation in the kidney, sodium retention and

compensatory nocturnal natriuresis (60). These authors pre-

dict that concentrations of urodilatin (a natriuretic peptide

produced by the kidney, which may be more important than

ANH in regulating sodium excretion) (61) and ANH will be

increased in patients with NP. Moreover, while they feel that

giving diuretics in the daytime in this situation to alleviate

sodium overload is a logical approach, measures to increase

the production of nitric oxide (such as dietary supplements

of L-arginine) may be more effective. They point out that

anti-hypertensive agents have not been systematically assessed

in the treatment of NP.

The third approach to reducing NP is the administration

of AVP before sleep, to restore the normal nocturnal rise.

Desmopressin has been used in a number of small studies in

different clinical settings. In a double blind placebo-

controlled crossover study of 25 women with nocturia

aged 41–76 years, 20 mg of desmopressin was given intra-

nasally to the treatment group. Two weeks of treatment

resulted in a significant fall in nocturnal urine output from

a mean of 438–267ml. Also, nocturnal frequency fell from

3.2 to 1.9 episodes (62).

Asplund and Aberg looked at short-term (2 weeks) and

long-term (2 months) use of desmopressin given intranasally

in 20 women with nocturnal diuresis (mean age 71 years) and

observed a significant decrease in nocturnal urine production,

which was sustained (63,64).

More recent studies have looked at the use and safety of

oral desmopressin in older subjects with NP. Asplund, in

1999, reported on a double blind randomised crossover trial

of 2 weeks of oral desmopressin vs. placebo in a group of

mixed gender with NP (mean age 67.7 years). It showed

significantly reduced nocturnal diuresis and number of

nocturnal voids. Also, longer uninterrupted sleep was demon-

strated. No serious adverse effects were observed (in particular

no significant hyponatraemia) (65). In a study reported in

2002, 30 patients (mean age 75.4 years) with nocturia on

three or more occasions or NP refractory to medication were

treated with 0.1mg desmopressin at bedtime for 4 weeks.

Twenty patients reported a good response with significantly

reduced nocturnal frequency (mean of 5.2 vs. 2.24 times/

night) and urine volume (mean of 956 vs. 528ml). Five

patients had side-effects including one with hyponatraemia

(66).

The benefits of desmopressin in geriatric patients with NP

and other problems such as dementia remain a concern. In a

placebo-controlled study, Seiler et al. treated nine patients

(mean age 82 years) who had dementia and nocturnal incon-

tinence, with intranasal desmopressin 10–40 mg daily. He

observed a significant reduction of urine volume from 10 to

50% of the original total. Also, long-term treatment with

10 mg daily restored the night time continence without

adverse effects (67).

There remains concern, however, about the possibility of

serious hyponatraemia occurring in association with the use of

desmopressin in older patients (60).

In a study, seven of 20 older men treated with 20–40 mgintranasal desmopressin for 2–4 weeks suffered adverse effects

(including profound hyponatraemia) (68). The British

National Formulary advise ‘considerable caution’ in prescrib-

ing desmopressin to patients with cardiovascular disease or

hypertension and recommends it be avoided in elderly

patients with nocturia (69).

BLADDER STORAGE PROBLEMS

Bladder storage problems may be caused by such conditions

as detrusor overactivity (from whatever cause), reduced

structural bladder capacity, reduced functional bladder



capacity with increased post-void residual and bladder

outlet obstruction. These problems may present with

nocturia and appropriate management may improve the

nocturia.

Habit retraining, timed voiding and prompted voiding

are the techniques that may be employed in patients with

overactive bladder during the daytime and have beneficial

effects on night-time symptoms (70). Anti-cholinergic drugs

such as oxybutynin and tolterodine are effective in increasing

functional bladder capacity and reducing symptoms (includ-

ing nocturia) in patients with overactive bladders (71). Both

drugs have extended release preparations that seem to have

benefits in terms of efficiency and fewer side-effects.

Imipramine, a tricyclic anti-depressant, has long been

known to have anti-cholinergic effects, which can benefit

patients with overactive detrusor (72), as well as alpha-

adrenergic stimulant effects, which can be beneficial in

patients with stress or mixed continence.

But also Hunsballe et al. (73) described an anti-diuretic

effect of this drug, which they felt, resulted from increased

sensitivity of the renal collecting ducts to AVP or from

decreased solute excretion.

Patients with bladder outlet obstruction secondary to

benign prostatic hypertrophy (BPH) are more likely to have

both NP and polyuria as a cause of nocturia (9). Some

symptomatic benefits may be derived from alpha-adrenergic

blocking drugs in patients with BPH. However, orthostatic

hypotension is a common side-effect of these drugs, and in

combination with nocturia, the risks of night-time falls

is high. Patients should be warned. Tamsulosin is a more

selective alpha blocker which is less likely to cause postural

hypotension (74). Five alpha reductase inhibitors can also be

helpful, but they take several months to produce clinical

effects – working better on larger glands (75).

Patients with reduced functional bladder capacity and

increased post-void residual, once inappropriate medication

has been stopped (e.g. those with detrusor hyperreflexia and

impaired contractility) (76) and also in those with hypotonic

bladder (e.g. due to diabetic autonomic neuropathy) may

benefit from clean intermittent catherisation (77). This may

be particularly useful in reducing nocturia when performed

just before bedtime. Cholinergic drugs (e.g. bethanechol) in

this situation tend to be disappointing.

POLYURIA

The cause of polyuria (e.g. diabetes mellitus, diabetes insipidus

– pituitary or renal origin or primary polydipsia) should be

established and appropriate treatment instigated. No further

details will be included here, but treatment of the cause of

polyuria is likely to improve nocturia. Of course, more than

one cause of nocturia may coexist in the same patient.

CONCLUS ION

Terminology in relation to nocturia has recently been

standardised (1). This common symptom of older people causes

problems not only for patients but also for their carers. Careful

assessment should allow a cause for the nocturia to be identified.

As a result of an age-related fall in renal concentrating ability,

sodium conservation and secretion of renin-angiotensin-

aldosterone, together with impairment of the circadian rhythm

of AVP secretion and increased output of ANH, there is an

age-associated change in the circadian rhythm of urine excre-

tion leading to NP.

The most common causes for bladder storage problems in

old age are an uninhibited overactive bladder, bladder outflow

obstruction and infection; and for polyuria, it is diabetes

mellitus. Sleep disorders may need to be considered.

Management of nocturia should include general lifestyle advice

and specific treatment for causes of polyuria (e.g. diet, oral

hypoglycaemic drugs or insulin in the case of diabetes mellitus).

Bladder storage problems should be defined and treated

appropriately (e.g. habit retraining and anti-cholinergic

drugs in inhibited overactive detrusor muscle).

In the case of NP treatment, options are limited. Both for

an afternoon diuretic and night-time desmopressin, there is

some evidence of benefit, but the trials that have been carried

out are small and short-term and considerable caution is still

required when using the latter in older patients, because of the

danger of significant hyponatraemia.

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Paper received May 2003, accepted August 2003



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Nocturia in older people: A review of causes, consequences, assessment and management