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Received: 12 July 2017 Accepted: 11 September 2017 DOI: 10.1111/ijcp.13027
CONSENSUS
A practical approach to the management of nocturia Matthias Oelke1 | Stefan De Wachter2 | Marcus J. Drake3 | Antonella Giannantoni4 | Mike Kirby5
| Susan Orme6 | Jonathan Rees7 | Philip van Kerrebroeck1 |
Karel Everaert8 1 Department of Urology, University of Maastricht, Maastricht, The Netherlands
Summary
2
Aim: To raise awareness on nocturia disease burden and to provide simplified aetio-
Department of Urology, University of Antwerp, Antwerp, Belgium
logic evaluation and related treatment pathways.
3
Department of Urology, University of Bristol, Bristol, UK
Methods: A multidisciplinary group of nocturia experts developed practical advice and recommendations based on the best available evidence supplemented by their own
4 Department of Surgical and Biomedical Sciences, Urology and Andrology Unit, University of Perugia, Perugia, Italy
experiences. Results: Nocturia is defined as the need to void ≥1 time during the sleeping period of
5
The Centre for Research in Primary and Community Care, The University of Hertfordshire and The Prostate Centre, London, UK
the night. Clinically relevant nocturia (≥2 voids per night) affects 2%-18% of those aged 20-40 years, rising to 28%-62% for those aged 70-80 years. Consequences include the following: lowered quality of life; falls and fractures; reduced work productivity; depres-
6 Department of Geriatric Medicine, Barnsley Hospital NHS Foundation Trust Hospital, Barnsley, UK
sion; and increased mortality. Nocturia-related hip fractures alone cost approximately €1 billion in the EU and $1.5 billion in the USA in 2014. The pathophysiology of nocturia
7
Backwell and Nailsea, North Somerset, UK
is multifactorial and typically related to polyuria (either global or nocturnal), reduced
8
Department of Urology, Ghent University Hospital, Ghent, Belgium
bladder capacity or increased fluid intake. Accurate assessment is predicated on frequency-volume charts combined with a detailed patient history, medicine review and
Correspondence Karel Everaert, Ghent University Hospital, Ghent, Belgium. Email:
[email protected]
physical examination. Optimal treatment should focus on the underlying cause(s), with lifestyle modifications (eg, reducing evening fluid intake) being the first intervention. For patients with sustained bother, medical therapies should be introduced; low-dose,
Funding information Ferring
gender-specific desmopressin has proven effective in nocturia due to idiopathic nocturnal polyuria. The timing of diuretics is an important consideration, and they should be taken mid-late afternoon, dependent on the specific serum half-life. Patients not responding to these basic treatments should be referred for specialist management. Conclusions: The cause(s) of nocturia should be first evaluated in all patients. Afterwards, the underlying pathophysiology should be treated specifically, alone with lifestyle interventions or in combination with drugs or (prostate) surgery.
1 | INTRODUCTION
men and women of all ages, with higher rates in older populations.3-5 It is
Nocturia is a highly prevalent lower urinary tract symptom (LUTS), de-
also in younger age groups, reduced quality of life (QoL), mainly due to
fined by the International Continence Society (ICS) as “the complaint
fragmented sleep, and an increased prevalence of depressive symptoms,
that the individual has to wake at night one or more times to void …
particularly in younger men and women.5-13 Nocturia also places a con-
associated with falls and fall-related injuries, primarily in the elderly but
1,2
each void is preceded and followed by sleep.”
Nocturia equally affects
siderable economic burden on the individual and healthcare services, in
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2017 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd Int J Clin Pract. 2017;e13027. https://doi.org/10.1111/ijcp.13027
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OELKE et al.
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terms of direct (falls and fractures), indirect (decreased work productivity and activity levels) and intangible costs (reduction in QoL).5,14 Although very common, nocturia remains an underreported, undertreated and poorly managed medical and social problem in adults.15,16 Nocturia was oftentimes considered a symptom associated with functional issues, such as overactive bladder syndrome (OAB) and/or benign prostatic hyperplasia (BPH), with treatments focused on increasing bladder capacity and/or lowering bladder outlet obstruction. However, because nocturia is often associated with nocturnal polyuria—the overproduction of urine during the night—such treatments will not be effective for all patients and appropriate patient selection is essential.17-19 As such, it is essential that physicians and other healthcare professionals understand the aetiology, burden and the most effective methods for diagnosing, assessing and treating nocturia. The treatment of nocturia should be according to its causative factors and aetiology where possible, as recommended in the European Association of Urology guidelines on the treatment of male LUTS20; however, specific guidelines for nocturia have not yet been published as a journal article.
What’s known • A non-systematic review of the relevant literature was undertaken, supplemented by studies identified by the authors. All recommendations were predicated on the best available evidence combined with practical insights from the authors’ extensive experiences in managing patients with nocturia. What’s new • Nocturia is a bothersome and serious medical condition affecting men and women of all ages, which can negatively impact quality of life and increase morbidity and mortality. Frequency-volume charts are essential for accurate assessment. Treatment should be tailored to the individual patient based on the underlying pathophysiology, with lifestyle interventions always considered. Medical therapies, such as desmopressin in patients with idiopathic nocturnal polyuria, can provide effective and safe relief for patients with persistent bother.
1.1 | Aim
vary considerably between individuals. Nocturnal polyuria has been
The aim of this expert paper was to raise awareness and increase rec-
defined as a nocturnal urine output of >20% of a 24-hour urine vol-
ognition of nocturia as a medical condition and provide straightfor-
ume in younger adults, and >33% in older adults (morning void being
ward, practical recommendations for its diagnosis and management.
included in nocturnal urine output).2
3.2 | Epidemiology of nocturia
2 | METHODS
Nocturia is one of the most bothersome LUTS according to most The paper was developed by a multidisciplinary group of experts on
epidemiological studies.7,25,26 The prevalence of nocturia is high and
nocturia, including urologists, general practitioners and a geriatrician
broadly similar in men and women, affecting 28%-93% of those aged
with a special interest in nocturia. A non-systematic review of the
40 years or older.27-29 The prevalence varies depending on the defi-
relevant literature retrieved in the PubMed/Medline database was
nition (from 1 to 3 voids per night). A review of 43 epidemiological
undertaken, which was supplemented by studies identified by the au-
studies reported prevalence rates of 11%-35% for ≥1 void per night
thors. All recommendations were based on the best available evidence
and 2%-17% for ≥2 voids per night for men aged 20-40 years, whilst
combined with the authors’ experiences in managing nocturia. The au-
for women in the same age group, rates of 20%-44% for ≥1 void per
thors intend that the recommendations and practical advice provided
night and 4%-18% for ≥2 voids per night were reported.27 The preva-
herein will improve confidence in the management of nocturia and
lence of nocturia in the community increases with age, with rates of
help define when specialist referral is appropriate.
29%-59% for men aged 70-80 years and of 28%-62% for women of the same age (≥2 voids per night).27 Other studies have reported rates of 16% in men and 21% in women aged over 20 years (≥2 voids per
3 | RESULTS AND DISCUSSION
night),29 and 34% for men and 28% for women (>2 voids per night) aged over 40 years.28 In another study, reporting a prevalence of 34%
3.1 | Terminology
in women aged >40 years, it was found that 40% of those with noc-
In 2002, the ICS defined nocturia as the need to void one or more times 1,2
This
In terms of incidence, a recent meta-analysis of 13 studies re-
; however, nocturia often
ported a rate of 0.4% per year among adults (men and women) aged
during the night, with each void preceded and followed by sleep. definition is currently a topic of debate
turia had no other urinary tract symptom.26
21,22
only becomes clinically relevant when it causes comorbidities or
40 mL/kg
storage symptoms. Nocturia occurs when the bladder capacity is ex-
body weight,33 which equates to >2800 mL/24 hours for a reference
ceeded by the amount of urine entering the bladder during the night.33
person with a body weight of 70 kg. It can be seen in patients with
Reduced bladder capacity may indicate detrusor overactivity (primary
diabetes insipidus, diabetes mellitus, increased fluid intake, hypercal-
[idiopathic] or secondary, eg, due to neurogenic bladder dysfunction),
caemia or primary polydipsia, or it can be drug-induced.33
Pathophysiology of nocturia
Bladder capacity
Fluid intake
24 h Anatomical capacity
Funconal capacity
Too much fluid
Causes, for example:
Causes, for example:
Causes, for example:
• Bladder wall fibrosis • Post-radiaon fibrosis augmentaon • Bladder surgery
Primary: • Detrusor overacvity • Postvoid residual due to bladder outlet obstrucon or detrusor underacvity • Bladder hypersensivity • Intersal cyss
• Iatrogenic polydipsia • Psychogenic polydipsia • Dipsogenic polydipsia
Secondary: • Urinary tract infecon • Bladder stone • Bladder cancer • Foreign body
F I G U R E 1 Pathophysiology of nocturia (adapted from Oelke et al32)
Evening/night Wrong me of fluid intake Causes, for example: • Excessive drinking in the evening • Alcoholism • Iatrogenic
Diuresis
24 h
Night
Global polyuria
Nocturnal polyuria
Causes, for example:
Causes, for example:
• Diabetes mellitus (I/II) • Diabetes insipidus (pituitary, renal, gestaonal) • Renal insufficiency • Oestrogen deficiency in women • Hypercalcaemia • Polyuria due to polydipsia
• Nocturnal arginine vasopressin (AVP) ↓ • Atrial natriurec pepde (ANP) ↑ • Cardiac insufficiency, congesve heart failure • Obstrucve sleep apnoea • Evening use of diurecs • Chronic venous insufficiency of the lower extremies
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Nocturnal polyuria
sleep, often considered the most restorative stage of sleep.44 Long-
Nocturnal polyuria (night-time urine output >20% of total daily urine
term loss of N3 sleep as occurs in nocturia could have potentially
output for younger adults or >33% for older adults) is the most fre-
deleterious impact on daytime alertness, health and well-being.44,45
quent cause of nocturia, having been shown in studies to be respon-
The negative effect of nocturia on sleep outcomes appears to be
sible for up to 88% of cases.2,38,39 Nocturnal polyuria is thought to
stronger in adults aged >65 years.46 As nocturia causes activity at
result from an abnormality of the circadian rhythm of secretion of the
night when a patient may not be fully awake, it is also an important
antidiuretic hormone, arginine vasopressin (AVP). It is a heterogene-
cause of falls and fall-related fractures in the elderly population.5,8
ous condition, in which water diuresis, solute diuresis or a combina-
A population-based epidemiologic survey also found a strong as-
tion of both is the underlying cause.40 Water diuresis is represented
sociation of nocturia with depression in both men and women, with
by high free water clearance and low osmolality at night. For solute
a significant trend in increased odds of depression with more voids
diuresis, the driving force seems to be increased sodium clearance
nightly.13 The magnitude of this association was larger in younger age groups, especially among women aged 2 h before bedme) • Treat alcoholism
F I G U R E 3 Management algorithm for patients with nocturia/nocturnal polyuria (adapted from Oelke et al32)
pattern could be indicated as this would act to lower nocturnal urine production.
40
have been developed, although not all formulations and doses are available in every country. Each of these has specific pharmacological
Desmopressin has shown to be an efficacious and well-tolerated
properties and doses. For example, the sublingual melt formulation
treatment for patients with nocturia due to nocturnal polyuria, with
has a time to maximum plasma concentration of 0.5-2.0 hours and a
females requiring lower effective doses compared to males.67-70 Nasal
serum half-life of around 2.8 hours, meaning that its effect lasts for ap-
spray, oral tablet and sublingual melt formulations of desmopressin
proximately 8 hours.78 A once-daily, low-dose, gender-specific formulation of desmopressin has lately become available: 25 μg for women
T A B L E 3 Potentially beneficial lifestyle modifications for patients with nocturia20,32,52,53,63-65
and 50 μg for men.79 This formulation has the benefit of reducing the
• Minimising fluid intake at least 2 h before going to bed, particularly caffeine and/or alcohol • Restricting total fluid consumption to