Diagnosis and Mangement of Nocturia in Adults Christopher Chapple Professor of Urology Sheffield Teaching Hospitals University of Sheffield Sheffield Hallam University UK 23 rd October 2015
Terminology Epidemiology Pathophysiology Measures & assessment Therapy Algorithm
Nocturia the symptom! International Continence Society standardisations! Abrams et al. Neurourol Urodyn 2002; 21: 167-178! Van Kerrebroeck et al. BJU Int 2002; 90 S3; 11-15! Nocturia; complaint that the individual has to wake at night one or more times to void, each void is preceded and followed by sleep! Night time frequency differs from nocturia, as it includes voids that occur after the individual has gone to bed, but before he/she has gone to sleep, and voids which occur in the early morning which prevent the individual from getting back to sleep as he/she wishes
Bother, quality of life and health Primarily mediated by sleep disturbance Need to allow for subjective difficulty discerning cause of waking Threshold of meaningful impact on well-being 2x/ night often used, and some evidence to support May be age-dependent Minimum important difference of severity reduction in treatment is not known Mortality in younger adults (<65) with N 2x shown in NHANESiii (Kupelian et al. J Urol 2011; 185: 581-7)
Polyuria Nocturia is a storage LUTS and a systemic symptom Global polyuria; production of more than 2.8L/ 24 hours in a 70kg adult Nocturnal polyuria (NP) is present when an increased proportion of the urine output is produced at night (usually while in bed) Normal range of nocturnal urine production differs with age and the normal ranges remain to be defined. Therefore, nocturnal polyuria is present when greater than 20% (young adults) to 33% (over 65 years) is produced at night.
Causes of nocturia: multi-factorial BPO Nocturnal polyuria Sleep disorders Detrusor overactivity Nocturia Primary polydipsia Reduced bladder capacity Uncompensated heart disease Untreated diabetes mellitus or insipidus Oestrogen deficiency
Nocturnal polyuria is present in most nocturia pts Europe 1 n=845 USA 2 n=934 Japan 3 n=41 males only 26% 12% 17% 74% 88% 83% NP Without NP Homeostasis and the upper urinary tract have a key role in nocturia 1. Abrams et al. Neurourol Urodyn 2004;23:466. 2. Weiss et al. J Urol 2009:181:538. 3. Chang et al. Urology 2006;67:541 544.
Nocturia is associated with increased mortality Percent survival % 100 95 90 85 1 2 3 4 HR=1.00 (n=425) HR=1.59 (n=219) HR=2.34 (n=99) HR=3.60 (n=41) 80 0 500 1000 1500 Days p for trend <0.01* * Adjusted for age, sex, BMI, diabetes, smoking status, history of coronary heart disease, renal diseases and stroke, use of tranquilizers, hypnotics, and diuretics. Nakagawa et al. J Urol 2010;183(4): e1-e2. Nakagawa et al. 2010
Epidemiology Systematic review of the key recent studies; race, socio-economic affect prevalence
Pathophysiology; key role of FVC Cornu J-N et al. Eur Urol 2012; E-pub
Measures of nocturia Questionnaires are unsuitable for the estimation of nocturnal voiding frequency (LOE4, Grade C) Nocturia-specific quality of life questionnaires can be used to determine impact of nocturia on quality of life (LOE4, Grade C) Urinary diaries are essential in the analysis of nocturia (LOE4, Grade C) The ICIQ bladder diary has been developed according to methodological requirements for assessment tools, and is proceeding with contextual validations (LOE2, Grade B)
Clinical assessment! Medication review is an important part of nocturia clinical assessment (Grade A)! Physical examination, flow rate testing and urinalysis are relevant to the assessment of LUTS help identify potential contributory mechanisms in some cases of nocturia (Grade C)! Post void residual measurement is directly relevant to nocturia (Grade C)! Routine use of invasive urodynamics, such as filling cystometry and pressure flow study, is not recommended (Grade D)! Blood chemistry examination is optional (Grade C~D)! Radiological examinations or cystoscopy should only be used where indicated by the medical context, such as suspected malignant disease (Grade D)
Behavioural/ conservative treatment! Lifestyle changes and behavioral modification are non-invasive, conservative methods that can successfully reduce the number of nocturia episodes (LOE 3).! Behavioral modification in conjunction with antimuscarinic pharmacotherapy is more effective at reducing nocturia episodes than either method alone (LOE 3).! Lifestyle changes, such as reducing intake of caffeine and alcohol, limiting night-time fluid intake and improving sleep hygiene help reduce nocturnal urine volume and episodes of nocturia (GOR C)! Behavioral modification with biofeedback-assisted pelvic floor muscles exercises may help reduce nocturia episodes (GOR C)! Consider using bladder training in conjunction with antimuscarinic medication (GOR C)
Alpha adrenergic antagonists! Most studies were undertaken in the context of men with LUTS and presumed BPE, using IPSS! Alpha blockers are more effective than placebo at reducing number of nocturia episodes in BPE (LOE 1)! Studies comparing efficacy of agents need to take into account dose equivalence/ population studied (LOE 3)! Alpha adrenergic antagonists may be offered to men with nocturia in association with LUTS and BPE (GOR A)! In the event of insufficient response to an alpha adrenergic antagonist, another may be offered to men with nocturia associated LUTS and BPE (GOR C)
Antimuscarinic drugs! can significantly reduce the number of nocturnal micturitions versus placebo (LOE 1)! are more effective than placebo at reducing OAB-related, but not non-oab nocturnal micturitions (LOE 1)! are not effective for reducing nocturia in nocturnal polyuria (LOE 1)! can be offered to men with OAB-related nocturnal micturitions, with suitable counseling in regard to potential adverse effects (GOR A)! should not be offered to men with nocturnal polyuria and no urgency symptoms (GOR B)
Combination therapies! Alpha blockers can be used in conjunction with 5 ARIs and may be more effective than each drug used separately (LOE1)! Combination of antimuscarinic and alpha blocker significantly reduces number of nocturnal micturitions over placebo (LOE1)! Alpha blockers may be more effective at improving nocturia when given with a PDE5 inhibitor (LOE 3)! Alpha blockers in conjunction with 5 ARIs may be offered to men with nocturia associated with LUTS and BPE (GOR A)! Alpha blockers with antimuscarinic drugs may be offered to men with nocturia in association with storage LUTS (GOR A)! Alpha blockers with PDE5 inhibitor may be offered to men with nocturia (GOR C) 16
Anti-diuretic therapy Desmopressin can safely decrease the frequency of nocturnal voids and decrease nocturnal diuresis (LOE 1) Clinically significant hyponatremia (serum Na<125 mmol/ L) is a rare but serious event; patients over 65 are at greater risk (LOE 1) Desmopressin can be prescribed to decrease nocturnal diuresis and night-time frequency in men (GOR A) Due to the risk of hyponatraemia, sodium testing is essential when starting desmopressin to exclude low sodium levels, particularly in patients over 65 (GOR A)
Diuretic therapy Men with nocturnal polyuria may benefit from diuretic therapy with furosemide 6 hours prior to sleep (LOE 2, GOR B) Bumetanide may reduce number of nocturnal voids, but is not beneficial in men with BPE (LOE 3, GOR C)
Change in LUTS after TURP IPSS domain Patients scoring 2 before TURP Patients scoring 2 after TURP Rate of response (%) Emptying 102 27 74.3 Voiding frequency 116 63 38.4 Intermittency 101 33 49.3 Urgency 103 70 37.0 Weak stream 122 35 63.0 Hesitancy 84 18 47.8 Nocturia 118 91 19.6 TURP is often not effective for nocturia other mechanisms involved Yoshimura et al. Urology 2003;61:786 790.
Surgery and nocturia Nocturia does not respond as well as voiding LUTS to surgery for relief of BOO (LOE 3) The number of nocturnal micturitions may reduce after TURP, TUMT, HIFU, TUNA and TUVP (LOE 3) Surgery to relieve BOO is not indicated for management of patients whose primary complaint is nocturia (GOR C) Comprehensive evaluation of the cause(s) of nocturia is essential before considering surgical approach (GOR C) Patients must be warned of potential non-response of nocturia and of risks associated with surgery (GOR C)
Nocturia Frequencyvolume chart Low nocturnal/ global bladder capacity Nocturnal polyuria: NPi >33% Polyuria: 24-hour volume >40 ml/kg Mixed Look for urological cause: prostatic obstruction nocturnal detrusor overactivity neurogenic bladder pharmacologic agents bladder/ureteral calculi Congestive heart failure Refer to cardiology Diabetes mellitus Obstructiv e sleep apnea suspected (snoring, obesity, short neck) Sleep studies Peripheral edema due to venous disease Excessive PM fluid intake Urine >800 m0sm/kg Primary polydipsia Overnight water deprivation Normal Dx central diabetes insipidus Urine <800 m0sm/kg Refer to endocrinolog y Renal concentrating capacity test Multiple incremental etiologies as per individual nocturia categories Abnormal Dx nephrogenic diabetes insipidus Chronic renal failure, lithium, tetracycline, hypercalcemia, hypokalemia