Recommendations for research
3.2 Evidence Base
3.5.2 Conclusions and recommendations
Pathophysiology of nocturia can be divided into five categories and associated with several risk factors (Level 2 evidence, Grade of Recommendation [GOR] B)
1. Bladder storage problems
2. Nocturnal polyuria
3. Global polyuria
4. Sleep disorders
5. Mixed mechanisms
Research into pathophysiology remains a priority:
Mechanisms underlying nocturia are poorly understood.
Establishing why some patients manifest nocturia and others don’t with apparently similar predisposing factors.
Basic research into age-related circadian rhythms.
Effects on sleep quality, and the relationship between nocturia and restorative stages of sleep (107).
TABLE 2 Potential causes or associated risk factors for nocturia (211) Bladder Storage Problems Nocturnal Polyuria Sleep Disturbance &
Primary Sleep Disorders Other Potential Factors Reduced functional bladder
capacity Congestive heart failure Insomnia Medical disorders
- Cardiac failure - COPD
- Endocrine disorders
Bladder pain syndrome OSA Sleep apnea Psychiatric conditions
- Depression - Anxiety Bladder outlet obstruction
(i.e. BPH, BPO) Peripheral edema - Venous stasis - Hepatic failure
Periodic leg movements Neurological conditions - Parkinson’s disease - Dementia - Epilepsy Nocturnal detrusor
overactivity Excess evening fluid intake Narcolepsy Chronic pain disorders
Neurogenic bladder Circadian defect in secretion/
action of AVP Arousal disorders
Sleepwalking Nightmares
Alcohol/drug use
(consumption or withdrawal) Cancer of bladder, prostate,
or urethra Medications
- Corticosteroids - Diuretics
- β-Adrenergic antagonists Learned voiding dysfunction 24-hour polyuria
Bladder or ureteric calculi DM DO/OAB (idiopathic or
neurogenic) DI
Voiding problems/ post-void
residual Primary polydipsia
Urogenital aging (estrogen deficiency)
3.6 Assessment
A summary algorithm is presented in Figure 2.
Nocturia
Measures for nocturia include questionnaires and urinary diaries. This paragraph focuses on the validation of nocturia questionnaires, including frequency-related questions and quality-of-life measures, and on the methodological aspects of urinary diaries.
Questionnaires
Most generic LUTS-related questionnaires, such as the IPSS and the ICS Male questionnaire, include a question on nocturia. The ICS Male questionnaire included a validation of this question (212), whereas the IPSS did not (187). Subsequently, the Nocturia, Nocturnal Enuresis and Sleep-interruption Questionnaire (NNES-Q) has been validated as a symptom-specific questionnaire (105).
The main problem with the use of questionnaires, as well as history taking during consultation, is recall bias. This will be present particularly for patients who don’t visit the physician with a specific symptom. Men with nocturia as the main symptom (or reason for the visit) may have registered their nocturnal frequency in a better manner, than those presenting with other (main) symptoms.
The (negative) impact of nocturia on quality of life can be estimated using specific questionnaires.
The International Prostate Symptom Score – Quality of Life (IPSS-QoL) questionnaire is not appro-priate for specific assessment of nocturia impact, as it reflects opinion on general LUTS-related QoL.
Even in patients with a predominant complaint of nocturia, such an approach to QoL scoring may be confounded by other LUTS.
The Nocturia Quality-of-Life Questionnaire (N-QoL) has been validated as a symptom-specific QoL measure (70). It has been adopted as one of the International Consultation on Incontinence Questionnaire (ICIQ) modular tools (188) and is now known as ICIQ N-QoL. Linguistic validation for 16 languages has been performed (189), but currently it has yet to be validated for populations other than outpatient department patients.
It should be stressed that such specific questionnaires have a limited value for daily practice, as they can’t be used for treatment decisions. These questionnaires bring detailed information important in research studies.
Urinary charts and diaries
It is generally thought that collecting information from urinary diaries is not hampered by recall bias, as patients report actual data. Previous reports showed the large difference between FVC-derived nocturnal frequency and questionnaire-derived nocturnal frequency, both in patients referred to a urology outpatient department (190) and in men from the general population (38). This was thought to be the result of recall bias present in questionnaire data, but it may also reflect the differences in time frames used for either measure, or the presence of a fluctuation of nocturnal frequency. With questionnaires, patients report the average nocturnal frequency representative of the preceding week or month, whereas with FVCs they prospectively collect data. This was already noticed in the valid-ation of the ICS Male questionnaire: allowing the discrepancy between questionnaire and FVC data with plus or minus one category increased the exact crude agreement from 68% to 97% (186).
Three approaches to recording micturition events have been categorized by the ICS (2):
1. Micturition charts, on which only the times of micturitions are recorded, day and night, for at least 24 hours.
2. Frequency volume charts, on which the volumes voided and the time of micturition are recorded, day and night, for at least 24 hours.
3. Bladder diaries (BDs), which combine the FVC data collection with any additional information required for the clinical context.
For example, in people with incontinence this would include leakage episodes, pad usage, degree of urgency, degree of inconti-nence, and fluid intake.
The three approaches have their own premises. Micturition charts have limited value in clinical prac-tice, as the collected data are restricted to frequency only, with no additional information. Frequency volume charts also provide information such as the volumes voided. For most patients with nocturia, this may be the appropriate approach to recording micturition events, as an FVC can ascertain the presence or absence of NP. Bladder diaries are more laborious for patients and will generally be applied where additional information is key to fully understanding the clinical situation, particularly in patients with urgency and incontinence symptoms. Also, in patients with nocturnal or global polyuria, the additional registration of fluid intake may be helpful.
The majority of experts involved in the ICIQ bladder diary validation process indicated volume of fluid intake to be an essential parameter (191). Surprisingly, registration of time of awakening and time of going to bed was considered essential only by a small minority, yet it is vital information in the analysis of nocturnal frequency and nocturnal urine production.
Recently, Bright et al. summarized the evidence for the development and validation of diary content, format, and duration (192). While a survey revealed numerous urinary diaries in use, none was formally validated. Accordingly, they performed a first phase of validation of an ICIQ urinary diary (191). In this phase, patient and clinician opinion on diary format, duration, and content was studied, using interviews and questionnaires. In addition, four draft diary formats were evaluated, and final consensus was reached on the single preferred format. The validity, reliability, and responsiveness of this diary will be further evaluated for contextual validation.
In various reviews of the literature, the best estimates for FVCs are presented, mainly focusing on the ideal duration (186,192). Charts of longer duration may increase reliability of nocturnal frequency estimates, but for patients it is more labour intensive and may impair patient compliance with accur-ate or complete recording. Shorter charts will generally achieve higher compliance, though this is dependent on the individuals completing the charts. Previous analyses on this topic were based on correlation coefficients between consecutive nights completed on the charts (193). High correlation coefficients were thought to reflect high reliability. This does not, however, take into account that nocturnal frequency may differ between nights, for a variety of reasons. In the analyses of short-dur-ation FVCs, a difference between 2 nights is considered to be larger than a difference of 1 night compared with 4 or 5 other nights on a longer chart. It should be stressed that this only reflects a mathematical difference.
In the absence of an undisputed gold standard measurement, finding evidence for the correct duration of FVCs appears technically challenging. From the available literature, and based on logic, it seems that 3 or 4 consecutive days is the best compromise between information detail and patient compliance (Level of Evidence [LOE] 2) (186,192,194). This should include 2 or 3 complete nights, and allow for the need to identify normal variation in nocturnal frequency and voided volumes.
Importantly, it must be clear what information should be collected by patients, both in daily practice and for research. Frequency volume charts should include volume of each single void, time of each single void, time of going to bed, and time of rising in the morning.
From this information, the following measures can be read or calculated:
24-Hour urine volume
24-Hour frequency, daytime, and nighttime frequency
Maximum voided volume of a single void
Nocturnal MVV
Nocturnal voided volume (all voids during sleeping time, plus the first morning void)
Nocturnal polyuria index