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Home , Nocturia, Primary polydipsia, Urinary retention

clinical A guide to assessment and management David Prince Kesley Pedler Prem Rashid

Epidemiology Background The prevalence of nocturia increases with age. More Nocturia is a common cause of disturbance affecting up to 40% of the than 70% of people aged 70 years and over are adult population. affected.8 A substantial proportion of younger adults Objective are affected with up to 30% of those aged 20–40 years This article provides a framework for the management of nocturia. Based on voiding at least once per night.6 Younger sufferers are the frequency volume chart, nocturia can be divided into three categories: more likely to be female, however, prevalence is similar global , nocturnal polyuria and bladder storage disorders. Differentiating in both genders in older patients.8,9 between these categories enables effective targeting of treatment. Discussion Circadian control of urine production Although nocturia is one of the most bothersome urinary symptoms, it hormone (ADH) is released by the posterior has generally been poorly understood and managed. Aetiology is often pituitary and increases water reabsorption at the renal multifactorial and includes systemic medical , lower urinary tract collecting tubule. Normally, ADH increases during sleep pathology, sleep disorders and behavioural and environmental factors. resulting in smaller volumes of concentrated urine.10 Keywords In elderly patients with nocturia this rhythm is often urological blunted with reduced nocturnal levels of ADH. This may be partly responsible for the increased prevalence that occurs with advancing age.11 Nocturia is ‘waking at night one or more times to void’. Each void is preceded and followed by Classification of nocturia sleep. ‘Night time’ is considered the hours of sleep Nocturia can be categorised into three clinical entities whenever they occur, day or night. Being in based on the pattern of 24 hour urine (Figure 1): but not asleep, does not constitute night time.1 • nocturnal polyuria • global polyuria The impact of nocturia on quality • bladder storage disorders. of life The frequency-volume chart • Nocturia has a profound impact on quality of life, being comparable to gout, , and angina in A frequency-volume chart (FVC) – or ‘voiding diary’ – terms of disease burden2 distinguishes between the three categories of nocturia. • Nocturia typically becomes bothersome to patients when Charts should include: it occurs more than two times per night3 • volumes and times of for a 24–72 hour • The severity of sleep impairment increases with the period1 number of nocturnal voids3 • beginning and end of sleep periods • Decreased sleep can cause daytime fatigue, poor • time, type and volume of fluids ingested.12 concentration, memory impairment, mood alterations and Giving clear instructions before patients complete the affects work performance4 chart improves compliance and eliminates the need for • Fall and hip fracture risk is increased in elderly patients multiple diaries. It is usally more convenient for patients with nocturia5 to choose a time when they are mostly at home to • Nocturia is a predictor of mortality, with higher mortality complete their voiding diary. The period recorded needs risk with increased number of nightly voids6 to be representative of the patient’s typical symptoms. • Nocturia affects bed partners and carers and can cause Once the diary has been completed by the patient, relationship disturbances.7 important values can be calculated (Table 1).

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Pathophysiology Nocturnal polyuria nocturnal ADH levels. This can occur from central Nocturnal polyuria (NP) is increased urine nervous system lesions that affect the hypothalamic- Global polyuria production at night. Nocturnal polyuria exists when pituitary axis, but it can also occur in elderly patients Global polyuria is continuously raised urine the nocturnal urine volume represents >20% of the without specific central nervous system pathology. output defined as >40 mL/kg/24 hours.1 The most 24 hour voided volume in younger adults and >33% Peripheral oedema can result in NP as the common cause is primary . Polydipsia in patients aged 65 years and over. The 24 hour accumulated fluid is redistributed to the intravascular can also be a compensatory mechanism for fluid voided volume is normal.13 Nocturnal polyuria is compartment once recumbent in bed. This excess fluid loss, such as the osmotic of uncontrolled present in up to 80% of patients with nocturia and is then excreted by the kidneys.11 diabetes mellitus. Global polyuria can also result can be easily overlooked if a FVC is not completed.7 Obstructive sleep apnoea (OSA) causes NP due to from .13 Nocturnal polyuria can be caused by low increased secretion of atrial natriuretic peptide, which induces a natriuresis.10,11

Nocturia Bladder storage disorders

Lower urinary tract pathology may present Increased total urine Increased urine Frequent small volume with frequent small volume voids often in production production at night voids +/– LUTS association with other lower urinary tract (>40 mL/kg/24 hours) (>20% of 24 hour urine symptoms (LUTS). Any structural or functional volume in young adults; pathology that affects the reservoir capacity >33% in older adults) of the bladder can increase voiding frequency. Potential pathologies are listed in Figure 1. Global polyuria Nocturnal polyuria Bladder storage disorders Bladder storage disorders tend to predominate among younger patients while NP predominates in older patients.14 The • Primary polydipsia • Oedematous states • Bladder outflow presence of other LUTS suggests lower urinary obstruction (eg. BPH, • Diabetes mellitus (eg. congestive cardiac tract pathology, however many patients , urethral • Diabetes insipidus failure, renal disease, (especially the elderly) have a mixed pattern hepatic failure) stricture disease) of disease with multiple contributing factors.15 • Obstructive sleep •  Nocturia in males should not be assumed to apnoea syndrome be due to benign prostatic hypertrophy (BPH). • Alcohol/ •  Nocturia is the least specific symptom of BPH • Excessive night time •  fluid intake • Calculi and prostatic pathology is unlikely to exist in • • Cystitis the absence of voiding symptoms such as poor 7 • Neurogenic bladder stream and hesitancy. dysfunction (, Parkinson disease) Sleep disorders • External compression Patients who constantly wake at night for (pelvic mass/pregnancy) other reasons may feel the need to void. Figure 1. Classification of nocturia These patients pass small volumes of urine and have a similar FVC to a bladder storage Table 1. Definitions of terms derived from the frequency-volume chart disorder.1 It is important to determine whether the primary reason for waking was to void.10 If a sleep Term Definition disorder is suspected, referral to a sleep physician Nocturia Number of voids recorded during a night’s sleep, each void is preceded and followed by sleep should be considered. Night time Time spent asleep Clinical evaluation 24 hour voided volume Total volume of urine voided in a 24 hour period It is important to enquire about nocturia as it is often First morning void The first void after waking with the intention of rising under reported. Many patients will not present with Nocturnal urine volume Total volume urine passed during the night: the complaint of nocturia, but with fatigue related • includes the first morning void symptoms. Some may not raise the issue as they feel • excludes the void before going to bed embarrassed, do not realise treatment is available or Maximum voided volume Largest single volume voided (usually between 300–600 mL) may perceive it as a normal part of ageing.9

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Given the wide range of possible aetiologies, Management Lifestyle modifications the key diagnostic tool is the FVC. History and Management should be directed to correctly Appropriate lifestyle modification should be examination give important clues to the underlying identifying the underlying aetiology. Most recommended (Table 4). The sleep environment pathological processes (Table 2). Medications can individual treatments reduce nocturia by less should be optimised with attention to room precipitate nocturia through several mechanisms, than one episode per night compared to placebo. temperature, noise, lighting and consistent times of hence review is warranted in all patients A combined approach consisting of behavioural, going to bed. Regular exercise can lead to deeper (Table 3).10 Investigations include screening for renal medical and surgical interventions, where sleep and increases the bladder volume arousal failure, and diabetes (Table 2).10 appropriate, has greater benefit.15 threshold.10 Dealing with psychological factors, financial and family issues have been shown to Table 2. Recommended clinical assessment of patients with nocturia improve sleep quality.16,17 Lower limb elevation History • Daily fluid consumption before going to bed is useful in patients with • Fluid consumption before going to bed peripheral oedema.15 Dosage times for • Alcohol and caffeine consumption should be moved from evening to mid afternoon. • Presence of other LUTS Sedatives are best reserved for sleep disorders • Voiding – hesitancy, weak stream, incomplete emptying rather than nocturia, although a short acting hypnotic • Storage – frequency, urgency • Incontinence may be beneficial for patients who wake early in the • Typical sleeping habits night and find it difficult to return to sleep.10 • Medical history – especially , renal failure, diabetes, obstructive sleep apnoea, gastro-oesophageal reflux, lung Specific treatment disease, endocrine evaluation (eg. disease) Global polyuria • Symptoms and signs of the above conditions • Symptoms of obstructive sleep apnoea – history of , Primary polydipsia can be effectively managed with collaborative history from partner fluid restriction. Patients with poorly controlled • Medications diabetes mellitus or diabetes insipidus will benefit Examination • from an endocrinology assessment. • Waist circumference and weight assessment • Cardiovascular examination – signs of congestive cardiac failure Nocturnal polyuria • Neurological examination of sacral integrity – perineal sensation/ Underlying medical causes (eg. congestive cardiac anal wink and other neurological evaluation (where indicated) • Digital rectal examination failure, chronic disease and obstructive sleep Investigations • Frequency-volume chart (voiding diary) apnoea [OSA]) should first be identified and treated. • Urinalysis +/– midstream urine If patients already have these conditions, new onset • , electrolytes and creatinine nocturia should prompt a management review. • Serum glucose Patients suspected of OSA will benefit from referral • Lipids to a sleep physician for a and tailored • Prostate specific antigen (if clinically relevant) • (if clinically relevant) treatment. Nasal (an antidiuretic hormone Table 3. Medications implicated in nocturia [ADH] analogue) is currently used in Europe for the treatment of NP. It is hypothesised to rectify Effect Medication defects in circadian secretion of ADH and has been Increased urine output • Diuretics shown to reduce the number of nocturnal voids in • SSRIs patients with NP.18 However, elderly patients are • Calcium channel blockers • Lithium (nephrogenic diabetes insipidus in 40% at risk of hyponatraemia and use is contraindicated of users) in congestive cardiac failure and renal failure.19 • Tetracylines Desmopressin is not currently listed for use in Precipitate and • Australia for treating nocturia, except where other central nervous • Centrally active antihypertensives (α-blockers, associated with diabetes insipidus. system effects β-blockers, methyldopa) • Bladder storage disorders • Psychotropic medications • Parkinsonian medications These patients require urological assessment. The • Phenytoin urologist may perform further investigations such as Precipitate LUTS • Ketamine uroflowmetry/postvoid residual urine measurement, • Cyclophosphamide urodynamics or , depending on the

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symptoms. 2011;77:183–6. Table 4. Recommended lifestyle modifications to manage nocturia 3. van Dijk L, Kooij DG, Schellevis FG. Nocturia in the Dutch • Avoid drinking caffeine and alcohol in the evening adult population. BJU Int 2002;90:644–8. 4. Burgio KL, Johnson TM, 2nd, Goode PS, et al. Prevalence • Limit excessive fluid and food intake 3 hours before and correlates of nocturia in community-dwelling older • Evening leg elevation adults. J Am Geriatr Soc 2010;58:861–6. 5. Asplund R. Hip fractures, nocturia, and nocturnal polyuria • Pre-emptive voiding in the elderly. Arch Gerontol Geriatr 2006;43:319–26. • Medication timing (moving doses to the mid-afternoon. Calcium channel 6. Kupelian V, Fitzgerald MP, Kaplan SA, Norgaard JP, Chiu blockers, especially hydropyridines, to be administered in the morning rather than GR, Rosen RC. Association of nocturia and mortality: evening for symptomatic patients) results from the Third National Health and Nutrition Examination Survey. J Urol 2011;185:571–7. • Optimisation of the sleep environment 7. Weiss JP, Blaivas JG, Bliwise DL, et al. The evaluation • Exercise program and treatment of nocturia: a consensus statement. BJU Int • Attention to psychological, financial and family concerns 2011;108:6–21. 8. Bosch JL, Weiss JP. The prevalence and causes of noc- turia. J Urol 2010;184:440–6. clinical scenario. and endocrine causes may be relevant. 9. Fitzgerald MP, Litman HJ, Link CL, McKinlay JB. The asso- In male patients with bladder outlet obstruction, • A multimodal approach to treatment yields ciation of nocturia with cardiac disease, diabetes, body mass index, age and diuretic use: results from the BACH treatments are less effective at improving nocturia the most effective results because aetiology is survey. J Urol 2007;177:1385–9. than for obstructive LUTS such as slow stream and often multifactorial. 10. Gulur DM, Mevcha AM, Drake MJ. Nocturia as a manifes- hesitancy.20,21 α-blockers (eg. prazosin, , • Appropriate behavioural modifications should tation of systemic disease. BJU Int 2011;107:702–13. 11. Asplund R, Aberg H. Diurnal variation in the levels ) have shown a modest improvement in be recommended to all patients. of antidiuretic hormone in the elderly. J Intern Med the number of nocturic episodes.20 Gains tend to 1991;229:131–4. be noticed almost immediately and correlate with Authors 12. Abrams P, Avery K, Gardener N, Donovan J. The David Prince is a medical student, University of International Consultation on Incontinence Modular the severity of nocturia.20 α-blockers must be New South Wales Rural Clinical School, Port Questionnaire: www.iciq.net. J Urol 2006;175(3 Pt prescribed with caution, especially in the elderly Macquarie, New South Wales. david.prince@ 1):1063–6; discussion 6. 13. Weiss JP, Weinberg AC, Blaivas JG. New aspects of the due to associated postural hypotension. student.unsw.edu.au classification of nocturia. Curr Urol Rep 2008;9:362–7. Prostatic (eg. transurethral resection Kesley Pedler BSc(Med), MBBS(Hons), is an accred- 14. Weiss JP, Blaivas JG, Jones M, Wang JT, Guan Z. Age of prostate [TuRP], laser ) in ited urology registrar, Department of Urology, Port related pathogenesis of nocturia in patients with overac- tive bladder. J Urol 2007;178:548–51. Macquarie Base Hospital, New South Wales appropriately selected patients with bladder outlet 15. Vaughan CP, Endeshaw Y, Nagamia Z, Ouslander JG, obstruction reduces episodes of nocturia.22 Surgery Prem Rashid MBBS, FRACGP, FRACS(Urol), PhD, Johnson TM. A multicomponent behavioural and drug appears to be more effective in younger patients is a urological surgeon and Conjoint Associate intervention for nocturia in elderly men: rationale and pilot results. BJU Int 2009;104:69–74. 10 Professor, Department of Urology, Port Macquarie and in those with more severe obstruction. 16. Torimoto K, Hirayama A, Samma S, Yoshida K, Fujimoto K, Base Hospital and University of New South Wales Surgical results are less successful in mixed Hirao Y. The relationship between nocturnal polyuria and Rural Clinical School, New South Wales. nocturia, especially those with NP. the distribution of body fluid: assessment by bioelectric Conflict of interest: A/Prof Prem Rashid has acted impedance analysis. J Urol 2009;181:219–24. A trial of antimuscarinic therapy (eg. , 17. Foley D, Ancoli-Israel S, Britz P, Walsh J. Sleep distur- as a consultant for Coloplast, AstraZeneca, Abbott, , , ) can be of bances and chronic disease in older adults: results of the Ipsen and Sanofi Aventis pharmaceuticals, as well 2003 National Sleep Foundation Sleep in America Survey. benefit to patients with symptoms suggestive as, the Neotract Corporation. He was a Preceptor J Psychosom Res 2004;56:497–502. of overactive bladder. Patients who derive most in Advanced Laparoscopic Urology with Professor 18. Mattiasson A, Abrams P, Van Kerrebroeck P, Walter S, Weiss J. Efficacy of desmopressin in the treatment of benefit are those whose nocturic episodes are Inderbir S. Gill, (then) Head of the Section of 7 nocturia: a double-blind placebo-controlled study in men. associated with urgency. Laparoscopic and Robotic Surgery and Chairman, BJU Int 2002;89:855–62. Glickman Urological Institute, Cleveland Clinic 19. Appell RA, Sand PK. Nocturia: etiology, diagnosis, and Key points treatment. Neurourol Urodyn 2008;27:34–9. Foundation via a 2006 grant from the Australasian 20. Johnson TM, 2nd, Jones K, Williford WO, Kutner MH, Issa • Nocturia is common over the age of 40 years Urological Foundation. MM, Lepor H. Changes in nocturia from medical treatment and its prevalence is similar in both males and of benign prostatic hyperplasia: secondary analysis of the Acknowledegments Department of Veterans Affairs Cooperative Study Trial. J females. Thanks to Dr Mohan Vattekad, Director of Urol 2003;170:145–8. • Nocturia can have a profound impact on quality Nephrology, Port Macquarie Base Hospital, for his 21. Johnson TM, 2nd, Burrows PK, Kusek JW, et al. The effect of life and has been shown to be a predictor of of , and combination therapy on helpful comments on the content of this article. nocturia in men with benign prostatic hyperplasia. J Urol mortality. 2007;178:2045–50. • Prostatic disease should not be assumed to be References 22. Margel D, Lifshitz D, Brown N, Lask D, Livne PM, Tal R. 1. Van Kerrebroeck P, Abrams P, Chaikin D, et al. the cause of nocturia in men. Predictors of nocturia quality of life before and shortly The standardization of terminology in nocturia: after prostatectomy. Urology 2007;70:493–7. • Nocturia may signify the presence of an report from the standardization subcommittee undiagnosed medical condition or suboptimal of the International Continence Society. BJU Int 2002;90(Suppl 3):11–5. management of a known medical condition. 2. Johnson TV, Abbasi A, Ehrlich SS, Kleris RS, Raison Cardiovascular, respiratory, renal, neurological CL, Master VA. Nocturia associated with depressive

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