Sleep and nocturia

Authors


P. Jennum, MD, DrMedSci, Consultant, Associate Professor, Sleep Laboratory, Department of Clinical Neurophysiology, University of Copenhagen, Glostrup Hospital, Ndr. Ringvej, DK-2600 Glostrup, Denmark.
e-mail: poje@glostruphosp.kbhamt.dk

Introduction

Nocturia is an annoying and potentially damaging symptom affecting a significant proportion of the adult population; it occurs with increasing prevalence in both sexes with age. As nocturia disturbs sleep, it may give rise to adverse consequences [1]. This paper focuses on sleep, nocturia and the effect of nocturia on daytime functioning; it will also consider the potential effect on sleep patterns of the treatment of nocturia caused by nocturnal polyuria.

Sleep architecture and physiological changes during sleep

Sleep is an essential, recurrent physiological state of unconsciousness and inactivity of the voluntary muscles that follows a characteristic circadian rhythm in all biological individuals, including humans [2]. Sleep is an active process regulated by several brain regions including the brain stem, reticular activating system, thalamus, hypothalamus and other brain areas. Sleep has a profound effect on several physiological processes including brain metabolism and electrical activity, neuroendocrine function, muscle tone, autonomic nervous system, and regulation of respiration. Normal sleep pattern varies between non-rapid eye movement (NREM) sleep and REM sleep, typically with a rhythmicity of 90–100 min. The deepest sleep stages, NREM stages 3 and 4, also called slow wave sleep (SWS) dominate the first third of sleep, whereas lighter sleep (NREM stage 2) and REM dominate the latest part of nocturnal sleep [3]. Age has a profound effect on the sleep pattern; sleep length, REM and SWS diminish with age [4]. During the sleep cycle, there are usually short awakenings or arousals; most are a result of normal movements and go unnoticed by the sleeper [3].

The purpose of sleep is not fully understood, but there is evidence that several processes are involved. These include restitution and rehabilitation, energy conservation, cognitive processing (including memory consolidation, brain reorganization and rebuilding) and, furthermore, sleep quality has an effect on life expectancy [5–7]. Thus, sleep is fundamental and essential to well-being and daytime functioning.

Sleep fragmentation

Sleep fragmentation and disruption causes daytime sleepiness, tiredness, mood changes, and cognitive dysfunction with poor concentration and performance. This is partly a result of changes in sleep pattern when sleep is disrupted [8]. A classical example is in patients with sleep apnoea, who experience nocturnal sleep disruptions, reducing SWS and REM sleep because of the respiratory arrest [9]. However, sleep fragmentation is increasingly common with age and is associated with chronic insomnia, daytime symptoms and impaired performance [10]. Sleep fragmentation can be a result of several medical, neurological and psychiatric diseases, and also medications like corticosteroid or diuretic treatment (Table 1) [11]. Depending upon severity, nocturia is a potential cause of sleep disruption and fragmentation, especially in the elderly [1].

Table 1.  Common reasons for arousal and sleep fragmentation
GroupReason
Sleep disordersSleep apnoea
 Periodic leg movements
 Narcolepsy
 Arousal disorders: sleepwalking and
 sleep terror
Medical disordersCardiac insufficiency
 Chronic obstructive lung disease
 Endocrine diseases: thyrotoxicosis,
 acromegaly
Neurological diseasesParkinson's disease
 Dementia
 Epilepsy with nocturnal seizures, e.g.
 paroxysmal awakenings
Nocturia
Psychiatric diseasesDepression
 Anxiety diseases
Pain, e.g.Rheumatological disorders
 Arthrosis
 Low back pain
MedicationCorticosteroids
 Diuretics
 β-blockers
 Discontinuation of benzodiazepines
Alcohol consumption 
and withdrawal syndromes 

Sleep disorders, sleep compliance, sleep quality (including sleep length and insomnia) and daytime symptoms like hypersomnia are all known to be associated with an increased risk of traffic accidents, morbidity, mortality and significant health costs to both the patient and the healthcare provider [11–13]. Recent studies have further suggested that nocturia is also associated with increased morbidity and mortality [14]. Whether this is caused by sleep fragmentation or the association between nocturia and other medical and neurological disorders needs to be clarified.

Nocturia

Nocturia is defined as the need to wake at night to urinate [15]. Nocturia should not be confused with enuresis, which is a condition that results in night-time urination whilst still asleep. Nocturia is a common condition, particularly in older groups; it has been reported that 58% and 66% of women and men, respectively, aged 50–59 years experience nocturia [16].

Nocturia is a complex medical condition and can result from several factors, including reduced bladder capacity, the excessive production of urine at night (nocturnal polyuria), or a combination of these two causes (Table 2). Underlying morbidity is often associated with nocturia; e.g. in patients with Parkinson's disease who, in addition, often have various sleep disorders like sleep apnoea, fragmented sleep, restless legs syndrome and periodic leg movements, nocturia was shown to be one of the most significant causes of sleep disruption [17]. In some patients nocturia is associated with polyuria, as in cardiovascular diseases and sleep-disordered breathing, including sleep apnoea [18,19]. However, in patients with sleep fragmentation from other causes, nocturia can be secondary to the awakening and sleep fragmentation rather than to nocturnal polyuria [15].

Table 2.  The causes of nocturia
Major causeDetail
Ageing 
Nocturnal polyuriaPsychogenic and behavioural, e.g.
 increased fluid
intake, caffeine
 Medical disorders, e.g.
 cardiovascular diseases,
 pulmonary diseases, etc.
 Neurological disorders, e.g.
 Parkinson's disease,
multiple sclerosis,
 hypothalamic lesions and tumours
 Sleep disorders, e.g.
 sleep apnoea, periodic leg
movements?
 Idiopathic
Bladder dysfunctionDecline in function and capacity
Prostate problemsHypertrophic prostate
Combinations of the above

Impact of nocturia on daytime functioning

Nocturia is inevitably associated with sleep fragmenta–tion and impairment of daytime functioning might be expected. However, despite the occurrence of the symptom, there is little information about the effect that nocturia has on quality of life and daytime functioning [1,20].

To address this issue, the impact nocturia on productivity at work, vitality and quality of life was recently assessed among professionally active individuals in Sweden [21]. Over 200 individuals reporting, on average, more than two voids per night were compared with a group of age- and gender-matched controls without nocturia. This study clearly showed that lack of sleep caused by excessive night-time voiding leads to lower energy levels (vitality), impaired work-related productivity and reduced quality of life compared with controls.

The implications of these findings in terms of potential tangible and intangible costs are considerable. There is therefore a strong case for considering the treatment of nocturia, particularly where sleep is markedly affected.

Desmopressin for nocturia and nocturnal polyuria

Desmopressin, a structural analogue of vasopressin (an antidiuretic hormone), is well established as a treatment for children and adults with primary nocturnal enuresis or vasopressin-sensitive diabetes insipidus, and has been suggested for the treatment of nocturia. Also, it has been used for patients with nocturia associated with multiple sclerosis.

The role of desmopressin in the management of nocturia has now been investigated in several studies [22–24]. A double-blind, placebo-controlled study of elderly men and women with nocturia (≥ 2 voids/night) and a urinary output of ≥ 0.9 mL/min showed that treatment with oral desmopressin reduced nocturnal urine production, reduced nocturnal micturitions and increased the time to first awakening by 1.4 h [24].

Whether desmopressin could change the sleep pattern of adults with nocturia was investigated in phase III studies [25,26] (Abrams et al., page 32–36). Nocturia was defined as ≥ 2 voids/night and a nocturnal urinary output that exceeded the maximum functional bladder capacity. Treatment with oral desmopressin (0.1, 0.2 or 0.4 mg/day) significantly increased the duration of the first sleep period compared with placebo, for both men and women (Table 3). Sleep disturbance occurred within 3 h for 60% of placebo-treated patients, compared with 14% of desmopressin-treated patients. Importantly, 34% of patients receiving desmopressin achieved an undisturbed sleep lasting at least 5 h, compared with just 4% of patients receiving placebo.

Table 3.  The effect of desmopressin on the mean duration of the first sleep period in adult patients with nocturia caused by nocturnal polyuria [ 25,26 ]
Mean (sd)
variable
BaselineDesmopressinBaselinePlacebo
  • *

    P  < 0.001.

Females
N72 72 
Mean duration of first sleep period, min
 142 (49)272 (103)*144 (53)181 (75)
% change + 78 + 20
Males
N86 65 
Mean duration of first sleep period, min
 161 (51)269 (89)*149 (54)175 (64)
% change + 59 + 21

Conclusions

Sleep is an essential biological process that is both highly regulated and very complex. Disturbances to the normal pattern of sleep lead to daytime symptoms (fatigue, sleepiness, mood changes), and increased morbidity and mortality. Nocturia, a very common condition that has many causes, results in sleep fragmentation and a reduced quality of life. Recent evidence suggests that in professionally active individuals, nocturia can lead to activity impairment and reduced productivity at work.

Desmopressin, administered orally, prolonged the first period of undisturbed sleep in most patients with nocturia caused by nocturnal polyuria, by reducing nocturnal urine production and the need to void. In about a third of patients, desmopressin normalized the duration of sleep. These findings support earlier studies showing that desmopressin is effective in patients with nocturnal polyuria in reducing nocturnal diuresis and improving sleep [23]. It is currently not known whether desmopressin improves the sleep pattern and to what extent daytime functioning is improved, which is why further studies are awaited.

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