A practical approach to the management of ... - Wiley Online Library

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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:



• 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



• 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