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The New Zealand Medical Journal

 Journal of the New Zealand Medical Association, 19-May-2006, Vol 119 No 1234

Nocturia in adults: draft New Zealand guidelines for its assessment and management in primary care
Mark Weatherall, Ted Arnold
Abstract
Nocturia is a common bothersome condition. An ad hoc group of interested clinicians from a variety of backgrounds has developed draft guidelines for the assessment and management of this condition in primary care in New Zealand. The guidelines propose four steps in the assessment and management: clinical evaluation; simple investigations; assignment of a provisional diagnosis; and management based on the provisional diagnosis.
For nocturnal polyuria-associated nocturia, the draft guidelines recommend that: lifestyle measures should be used as part of the management; if a patient complaining of nocturia has other features of overactive bladder, then bladder retraining and/or anticholinergics can be used; hypnosedatives should not be used to treat nocturia in older adults because of the increased risk of falls; loop diuretics given in the afternoon should be considered for the treatment; and desmopressin can be considered in the management of nocturnal polyuria associated nocturia but that it should be used cautiously in people aged over 65 because of the risk of hyponatraemia. A draft algorithm based on international guidelines is presented.

Nocturia has been defined recently by the International Continence Society (ICS) as a complaint whereby the individual has to wake at night one or more times to void.1
The prevalence of nocturia in the community is high and it increases with age in both sexes, although the literature in this area must be considered carefully as rarely does the study definition of nocturia correspond to that of the ICS and different studies use a variety of different methods to ascertain nocturia.
In a study from the Netherlands using the current ICS definition, nocturia was experienced by 17% of men aged 18–34, by 34% of men aged 35–54, by 62% of men aged 55–74, and by 80% of men aged over 75 years. The figures for women similarly increased with age. Nocturia was noted by 36% of women aged 18–34, by 51% of women aged 35–54, by 86% of women aged 55–74, and by 77% in women aged over 75 years.2 Similar findings, albeit with different definitions of nocturia, have been demonstrated in other studies.3–7
Nocturia is a bothersome condition and the impact of nocturia may be substantial. In surveys where the individual symptoms are rated according to degree of ‘bother’, nocturia is rated almost as highly as incontinence. For those with the problem, around two-thirds rate it as at least a bit of a problem.8–14 Moreover, questions about nocturia are a common feature of lower urinary tract, condition-specific, quality of life questionnaires.11,15–17
Nocturia has been associated with falls,18 poor sleep patterns,19,20 and mortality.21 In addition, evidence shows that nocturia affects quality of life.22 There is likely to be considerable individual variation in the impact of nocturia however.
The purpose of these guidelines is to propose a framework for the assessment and management of nocturia in adults, together with a clinical algorithm to form the basis for guidelines for management in primary care in New Zealand.

Methods

These New Zealand guidelines have been developed by an ad hoc committee of interested clinicians with backgrounds in general practice, urology, geriatrics, urotherapy and continence advice, nephrology, and clinical pharmacology. Membership details are provided in Appendix 1.
These guidelines and their recommendations are concordant with the international guidelines developed by a group of international interested urologists, gynaecologists, endocrinologists, geriatricians, general practitioners, urotherapists and continence advisors, and experts in sleep disorders and their management, who participated in the International Consultation on Nocturia conference in London in 2002, as well as a second one in Malta in 2003.
Definitions and terminology used are as recommended by the International Continence Society and its Standardisation Committees.
Treatments for nocturnal polyuria, to be discussed in the body of the guideline, were assessed using levels of evidence for treatment, graded according to the Oxford classification.24

The guidelines

We propose a four-step approach to the assessment and management of nocturia:
  • Clinical evaluation.
  • Investigations.
  • Assign a provisional diagnosis.
  • Specific management.

Clinical evaluation

The following clinical factors should be assessed in people complaining of nocturia. History-taking may identify these factors. Fear of cancer (particularly of prostate cancer in men) may need an appropriate clinical evaluation.
Ageing is associated with nocturnal polyuria, an overactive bladder, and changes to anti-diuretic hormone (ADH) production, as well as with other sodium ion homeostatic mechanisms.25–29
The presence of other lower urinary tract symptoms (LUTS) should prompt consideration of bladder outlet obstruction, chronic urinary retention, overactive bladder, detrusor over-activity with impaired contraction,30 neurological disorders, and other pathological processes affecting the lower urinary tract.
Haematuria is an important symptom that may require further urological or nephrology investigation. Sleep-disordered breathing can be associated with altered atrial natriuretic peptide (ANP) secretion,31,32 and nocturia. Pregnancy33,34 and the menopause are associated with nocturia, although the role of the hormone replacement therapy for the nocturia associated with the menopause is uncertain.35
Although urinary tract infections can cause nocturia, symptoms should resolve between infections. Bacteriuria without symptoms is quite common in older women and this may cause diagnostic difficulty.
Other health problems such as congestive heart failure, peripheral oedema, chronic renal disease, and sleep disorders may all be associated with the complaint of nocturia. Pelvic pathology such as pelvic organ prolapse may account for nocturia,36,37 and pelvic masses or tumours in adjacent organs may be associated with LUTS including nocturia. Some clear-cut causes of excess urine production include diabetes mellitus, diabetes insipidus, and hypercalcaemia. Medication and other ingested substances may also cause nocturia.
Clinical evaluation should then include a physical examination. This should include both a general physical examination relevant to nocturia, and targeted examination to further assess features identified by history-taking.
The clinical examination should specifically include (where appropriate) assessment of the presence of heart failure or peripheral oedema, an abdominal examination for the presence of a distended bladder or other abdominal and pelvic masses, and a focussed neurological examination. The neurological examination must include assessment of the plantar reflexes. A pelvic examination should be performed in women, although it is recognised in primary care that not all practitioners are confident in the full assessment of prolapse as it might reveal atrophic changes in the post-menopausal patient. In men, a digital rectal examination is particularly important in the assessment of the prostate gland.

Investigations

Urinalysis and simple blood tests are recommended in all people complaining of nocturia. A bladder diary is recommended if the clinical evaluation, urinalysis, and simple investigations do not result in a provisional diagnosis. If other disorders are identified by the clinical evaluation then these should be investigated as appropriate.
Urinalysis—An abnormality on urinalysis should be further investigated and managed depending on the pattern of abnormality. Symptomatic urinary tract infections should be treated although as noted the prevalence of asymptomatic bacteriuria is high in older women. It is particularly important to evaluate haematuria as it may have an important urological cause such as malignancy. Haematuria may also indicate a renal abnormality.
Simple blood tests—These should include glucose and calcium levels to identify these substances causing solute (osmotic) diuresis.
Bladder diary—This is a record of the time and volume of all urine passed during 24 hours. Any incontinence episodes should also be recorded. To overcome daily variations, keeping this diary for 3 consecutive days and nights is preferred.

Assign a provisional diagnosis

A provisional diagnosis can often be made based on the results of the clinical evaluation and simple investigations. If these fail to provide a diagnosis, then a bladder diary can distinguish between global polyuria, nocturnal polyuria, or reduced functional bladder capacity, as discussed below.
Global polyuria—The bladder diary may show global polyuria defined as a 24-hour output of more than 2.8 litres.38 An alternative definition is urine output exceeding 40 ml/kg/day, for example 3.2 litres for an 80 kg adult. Global polyuria can be caused by a water or solute (osmotic) diuresis, which can secondarily increase the thirst and hence the water intake.
The best way to distinguish between water and solute diuresis is the urinary osmolality, which will be greater than 1010 mosmol/kg in solute diuresis and less than 1010 mosmol/kg in water diuresis. It can also be caused by excessive thirst and drinking, dipsogenic polyuria, which is usually psychogenic or behavioural.

Water diuresis—

Primary dabetes insipidus. Failure of pituitary secretion of ADH results in failure of the kidneys to retain water appropriately—with consequent polyuria. It responds to administration of desmopressin, and modest fluid restriction.
Nephrogenic diabetes insipidus. This can result if the renal collecting tubule becomes insensitive to the circulating ADH. Prescribing desmopressin produces no benefit.
Dipsogenic diabetes insipidus. This is caused by excessive thirst, which may be psychogenic or behavioural, and the large urine output is a physiological response to the huge water intake. Prescribing desmopressin is dangerous in this condition as the patient will keep on drinking and the antidiuretic effect prevents the elimination of the excess water that is needed. Water intoxication may follow. Treatment usually requires psychiatric and endocrinology expertise.
Solute diuresis. Osmotically-active substances such as glucose, albumin, and calcium may induce a solute diuresis—the associated water loss tends to produce dehydration, and thirst to correct it. This may need to be quantified in a 24-hour output study, as well as measuring these substances in the blood.
Nocturnal polyuria—The bladder diary may show nocturnal polyuria. Nocturnal urine production is measured as the volume of urine produced excluding the voided volume immediately before retiring, but including the volume of the first void in the morning. There is no widespread agreement as to the definition of nocturnal polyuria. One definition of nocturnal polyuria included a night-time output of more than 0.9 ml/minute,39 where night is defined as time spent in bed with the intention of sleeping, as recommended by the ICS.
Another definition includes adjustment for body weight, for example as greater than 10 ml/kg of urine produced during the night.40 This would mean a rather large volume (greater than 800 ml) for an 80 kg person, compared to around 450 ml by the definition of greater than 0.9 ml/minute.
Other definitions are based on relative criteria. For example by dividing the full 24 hour period into one 16-hour period and one 8-hour period: (0600–2200, and 2200–0600). The ICS definition suggests that the nocturnal volume should be approximately 22% of the total 24-hour output in younger patients, but this should be less than 33% in older subjects.41 The relative definition is appropriate only if the 24-hour volume is within normal limits.39
Reduced functional bladder capacity—The bladder diary may show nocturia without polyuria. This suggests a reduced functional bladder capacity (FBC). The normal range of FBC is 300–450 ml, smaller for older adults and slightly higher for women than men. The causes of reduced FBC include detrusor over-activity, bladder inflammation with or without fibrosis, and other pelvic pathology, such as pelvic masses.

Specific management

Specific management should reflect a specific diagnosis. The ad hoc committee did not rate management based on specific diagnoses, for example global polyuria associated with ADH deficiency due to pituitary disease, or nocturia related to bladder outlet obstruction in men. However the ad hoc committee felt it important to rate some commonly used treatments in primary care for nocturnal polyuria-associated nocturia. These treatments include lifestyle measures, management of the overactive bladder, sleep enhancement strategies, loop diuretics, and desmopressin.
Lifestyle measures—Although the principle of fluid restriction by type (for example tea, coffee, and alcohol) and volume near retiring to bed seems sensible, studies to confirm the effectiveness of this strategy could not be identified.25,35
The recommendation of the International Consultation on Incontinence35 was that: conservative management of nocturia, whilst lacking hard data appear nonetheless to be effective or helpful to many patients.
Recommendation 1: Lifestyle measures should be used as part of the management of nocturnal polyuria associated nocturia. (Grade of Recommendation D, Level of evidence 5.)

Management of the overactive bladder—

Bladder retraining. Several studies have found a reduction in nocturic episodes for patients on bladder retraining programs, supplemented at times with anticholinergic drugs.42,43
Recommendation 2: If a patient complaining of nocturia has other features of overactive bladder then retraining can be used. (Grade of Recommendation C, Level of Evidence 4.)

Antimuscarinic drugs. These include oxybutynin, and tolterodine (Detrusitol). Tolterodine is not publicly funded in New Zealand. It has an efficacy similar to oxybutynin, but has fewer adverse effects; hence more patients can tolerate the drug in the longer term. Both drugs are effective for nocturia as part of the management of the overactive bladder.44
Recommendation 3: If a patient complaining of nocturia has other features of overactive bladder then anticholinergic agents can be used. (Grade of Recommendation A, Level of evidence 1.)

Sleep enhancement—General measures to improve sleep include avoidance of stimulants like coffee or alcohol close to retiring, and treatment of specific mental health conditions such as depression and anxiety. If sleep-disordered breathing is present, it should be treated appropriately.45
The use of psychoactive drugs, such as hypnosedatives and tricyclic antidepressants, has been considered;46 however, these agents are associated with an increased risk of falls particularly in older adults.47 Indeed, one randomised controlled trial discovered that withdrawal of psychoactive medication decreased the rate of falls.48
Recommendation 4: Hypnosedatives should not be used to treat nocturia in older adults because of the increased risk of falls. (Grade of Recommendation B, Level of evidence 2.)

Loop diuretics—Diuretics in the afternoon, about 6 hours before retiring, might enable excess body water to be eliminated before the person retires.49,50
The International Consultation on Incontinence35 recommended that use of loop diuretics given in the afternoon to get rid of any postural oedema should be considered for further therapeutic trial since it is a simple and effective treatment in some patients provided they are screened and monitored for postural hypotension and electrolyte disturbances.
Recommendation 5: Loop diuretics, given in the afternoon, should be considered for the treatment of nocturnal polyuria-associated nocturia. (Grade of recommendation B, Level of Evidence 2.)

Desmopressin—Desmopressin is an analogue of vasopressin with effects like anti-diuretic hormone (ADH) but without any vasopressor effects. Its use has been recommended for persistent primary nocturnal enuresis in children, and for healthy younger adults with nocturnal polyuria, where no treatable cause is found.51
Both nasal desmopressin and oral desmopressin (which has poor oral bioavailability) have been used in randomised controlled trials of the treatment of nocturia,52,53 with reductions in the nocturnal urine volume and the number of nocturnal voids. However there is a risk of hyponatraemia associated with the use of desmopressin particularly in older adults.54 The manufacturers do not recommend its use in adults aged over 65 years.
Hyponatraemia with the use of desmopressin can occur at any age. Symptoms suggesting the possibility of hyponatraemia include headaches, nausea, vomiting, fatigue, dizziness, weight gain, and ataxia. Caution is required when desmopressin is used in the presence of renal failure or hepatic disease. Desmopressin should not be used in psychogenic polydipsia. Drug-drug interactions can occur with diuretics, anti-depressants (tricyclic anti-depressants and serotonin uptake inhibitors), chlorpromazine, carbamazepine, and non-steroidal anti-inflammatory drugs (NSAIDs).
Recommendation 6: Desmopressin can be considered in the management of nocturnal polyuria associated nocturia. (Grade of recommendation A, Level of evidence 1.)
Recommendation 7: Desmopressin use is associated with hyponatraemia in older adults, and (if used) should be used with extreme caution and close monitoring in adults over age 65 years. (Grade of recommendation A, Level of evidence 1.)

Conclusion

Nocturia in adults is a common bothersome condition, particularly in older adults. The New Zealand ad hoc committee recommends a simple four-step assessment and management strategy for nocturia. Appropriate treatment of identified disorders has the potential to reduce the impact of the symptom for patients.55
Author information: Mark Weatherall, Associate Professor, Rehabilitation Research and Teaching Unit, Department of Medicine, Wellington School of Medicine and Health Sciences, Otago University, Wellington; Edward P Arnold, Associate Professor, Christchurch School of Medicine and Health Sciences, Otago University, Christchurch
Correspondence: Dr Mark Weatherall, Senior Lecturer, Department of Medicine, Wellington School of Medicine and Health Sciences, Private Bag 7343, Wellington South, Wellington. Fax: (04) 389 5427; email: markw@wnmeds.ac.nz
Appendix 1. Membership of the ad hoc New Zealand Nocturia Guideline Committee
  • Chair: EP Arnold, Urologist, Christchurch School of Medicine and Health Sciences, Christchurch
  • J Boulton, Urologist, Auckland
  • J Brown, Urotherapist, Hamilton
  • A Catherwood, General Practitioner, Auckland
  • T Croker, General Practitioner, Auckland
  • R Harris, Geriatrician, Auckland
  • SD Mark, Urologist, Christchurch
  • R Robson, Renal Physician, Christchurch
  • M Weatherall, Geriatrician, Wellington School of Medicine and Health Sciences, Wellington
Appendix 2
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