1 / 47

Nocturia: Causes, Consequences and Clinical Approaches

Nocturia: Causes, Consequences and Clinical Approaches. Jeffrey P. Weiss, MD, FACS Professor and Chair Department of Urology SUNY Downstate College of Medicine Brooklyn, NY. Nocturia. Definition: voiding during (nocturnal) sleep time Preceded and followed by sleep (ICS guidelines)

reed-zamora
Download Presentation

Nocturia: Causes, Consequences and Clinical Approaches

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Nocturia: Causes, Consequences and Clinical Approaches Jeffrey P. Weiss, MD, FACS Professor and Chair Department of Urology SUNY Downstate College of Medicine Brooklyn, NY

  2. Nocturia • Definition: voiding during (nocturnal) sleep time • Preceded and followed by sleep (ICS guidelines) • Normal: nocturia < 1x* • Scientific problems: • How to define sleep time • Is patient awakened by the need to void, or, • Do patients void because they’re awake *van Kerrebroeck et al Neurourol and Urodyn 21:179-183, 2002

  3. What triggers nocturia*? 50 men and women mean # nocturia=2.6 Nocturia awakenings attrib’d to urge vs not 78% nocturic voids prec’d by urge to void In the remainder the pt awakened for some other reason, then voids out of habit or convenience before going back to sleep The etiology and treatment of these two groups is likely different • *Blaivas JG, Amirian M, Weiss JP et al: Why do people void at night?. SUFU abstract 2010

  4. Nocturia • Medical/Renal? • Nocturnal polyuria • Polyuria • Urological/Lower tract dysfunction? • Diminished global/nocturnal bladder capacity

  5. Nocturia – at least 1 void/night

  6. Nocturia: Consequences • Mediated by Sleep Deprivation

  7. Nocturia is associated with increased mortality • Summary of 3 major new studies • Nakagawa et al.1 (788 men and women, 70-97 yrs): significantly increased mortality risk in elderly patients with 2, 3, and 4 vs. 1 voids/night • Kupelian et al.2 (15,988 men and women, ≥20yrs): significantly increased mortality risk with 2+ vs. <2 voids/night • Magnitude of the nocturia and mortality association was greater in those younger than 65 years and in those without baseline comorbidities • Lightner et al.3 (2,447 men, 40-79 yrs): significantly increased mortality risk and CHD risk in younger patients (40 to 59 yrs) with ≥3 voids/night • Nakagawa et al. J Urol 2010;184: 1413-1418. • Kupelian et al. J Urol Vol. 185, 571-577, February 2011 • Lightner et al. AUA 2010

  8. Nocturia: Evaluation • Simple arithmetic analysis of 24 hour voiding diary • First AM voided volume included in NUV • First AM void diurnal, not nocturnal

  9. Diary Assessment • NPi (Nocturnal polyuria index = NUV/240 volume): • NPi > 33% = Nocturnal polyuria • Ni (Nocturia index = NUV/MVV): • Ni >1: Nocturia occurs because functional bladder capacity (maximum voided volume) is exceeded

  10. Diary Assessment: NBCi • NBCi (Nocturnal Bladder Capacity index) > 0: Diminished nocturnal bladder capacity • Higher NBCi >> Nocturia occurs at voided volumes < MVV

  11. Diary Assessment: NBCi • NBCi = ActualminusPredicted # nightly voids (ANV-PNV) • PNV = Ni - 1 • Example: Patient with Nocturia (ANV) x7 NUV = 750 ml MVV = 250 ml Ni = NUV / MVV = 3 PNV = 3-1 = 2 NBCi = ANV-PNV= 7-2 = 5

  12. Formulas for evaluation of nocturia

  13. Summary • Classification of nocturia through use of the voiding diary “unlocks” up to 17 significant underlying medical conditions which potentially contribute to its genesis • Efficacy of nocturia treatment based upon this analysis is unproven

  14. Nocturia:Classification • Nocturnal polyuria (NP) • Diminished global/nocturnal bladder capacity (NBC) • Mixed (NP +  NBC) • Polyuria

  15. Nocturnal polyuria: “medical” cause for nocturia • NUV > 6.4 ml / kg* • Nocturnal diuresis  0.9 ml/min (54 ml/hr) • Krimpen study (Bosch): Men 50-78: mean NUV=60 ml/hr • Suggest NP cutpoint >90 ml/hr** • NUV/24h urine ≥ 0.33 (ICS) • <25 years: mean NPi=0.14 • >65 years: mean NPi=0.34*** *Matthiesen, T.B., et al: J. Urol., 156: 1292, 1996 **Blanker, M. H. et al: J. Urol., 164: 1201, 2000 ***Kirkland J.L. et al: Br Med J., 287: 1665, 1983

  16. Sleep Disordered Breathing / Nocturia • Sleep apnea: Sudden cessation of respiration due to airway obstruction during sleep • Older adults with severe SDB have a greater number of nocturia episodes Yalkut, D., et al.: J. Lab. Clin. Med., 128: 322, 1996 Endeshaw, YW et al: J Am Geriatrics Soc. 52(6):957-60, 2004

  17. Sleep Apnea: Rx with nasal CPAP (continuous positive airway pressure) • *Nocturia in 88 men studied with OSA: avg. x3.8 ± 0.4 • Diminished to x 0.7 ± 0.27 after Rx with nasal CPAP* • **Nocturia in 196 women: median 3 episodes > 0 episodes per night (p<.001) with CPAP • “Nocebo” effect of CPAP machine obviates lack of placebo • Greater contribution to nocturia etiology in younger pts*** *Guilleminault C, Lin CM, Goncalves MA and Ramos E: J Psychosomatic Res 56:511-515, 2004 **Fitzgerald MPet al: Am J Obstet Gynecol. 2006;194:1399-1403. ***Moriyama Y, Miwa K, Tanaka H et al. Urology 2008; 71:1096-8

  18. Remember: Patients are on many agents which may cause nocturia

  19. Pharmacological treatment of nocturnal polyuria (Timed) Diuretics • Prevent water accumulation by forcing water out of the system • May be helpful in patients with lower limb venous insufficiency or congestive cardiac failure • Level 2 evidence, Grade C recommendation (ICI 2005) • Bumetanide 1mg po in afternoon (Pederson PA et al BJU 1988) • Furosemide 40mg po in afternoon (Reynard JM et al BJU 1998) (Timed) Antidiuretics • Helps retain water until a more appropriate time • Reduce nocturnal voids and voided volume • Level 1 evidence, Grade A recommendation • Desmopressin 0.1mg po titrated to 0.4mg (van Kerrebroeck PE et al: Desmopressin in the treatment of nocturia: a double-blind, placebo-controlled study. Eur Urol 2007; 52: 221.) • No direct bladder effect • No direct cardiovascular actions • Hyponatremia main potentially adverse effect

  20. Nocturia:Classification • Nocturnal polyuria (NP) • Diminished global/nocturnal bladder capacity (NBC) • Mixed (NP +  NBC) • Polyuria

  21. Causes of Low global/NBC: Urologic • Infravesical obstruction • Idiopathic nocturnal detrusor overactivity • Neurogenic bladder • Cystitis: bacterial, interstitial, tuberculous, radiation • Cancer of bladder, prostate, urethra

  22. Drug effects

  23. Low global/NBC: Treatment • Dx & Rx of remediable conditions • Empiric Rx

  24. Nocturia persists despite prostate surgery • Third National Health and Nutrition Examination Survey (NHANES III) in the USA showed • Amongst those who undergo TURP, Nocturia (≥2 voids per night) persists for • 41% of 60–69 year olds • 50% of ≥70 year olds Platz et al. Urology 2002;59;877–883

  25. TURP and nocturia • 118/138 (85.5%) BPO patients had nocturia before TURP • After treatment, 91 of these (77.1%) still reported nocturia • Mean improvement in nocturia score (1.0) significantly inferior to improvements for all other IPSS symptoms Yoshimura et al. Urology 2003;61:786–790

  26. 5 ARI : Little success α (-) : Occ statistical, not clinically 5 ARI + α (-) : Same as α - blocker Antimuscarinics : Some statistical, minimal clinical AntiM + α (-) : Some statistical, minimal clinical Optimal group: Large # N episodes, most due to severe urgency, no NP Likely that other types of therapy will be necessary to achieve a clinically significant reduction in nocturia Summary* * AJ Wein MD

  27. Nocturia:Classification • Nocturnal polyuria (NP) • Diminished global/nocturnal capacity (NBC) • Mixed (NP +  NBC) • Polyuria

  28. “Mixed” Nocturia etiology • Review of 194 consecutive patients with nocturia • 13 (7%) had NP, 111 (57%)  NBC, 70 (36%) had “mixed” etiology • Forty-five (23%) also had polyuria • NP = a significant component of nocturia in 43% of the patients • Conclude: Etiology of nocturia multifactorial and often unrelated to underlying urologic condition Weiss JP, Stember DS and Blaivas JG: Nocturia in adults: Classification and etiology. Neurourol Urodyn 16:401, 1997

  29. Nocturia:Classification • Nocturnal polyuria (NP) • Diminished global/nocturnal bladder capacity (NBC) • Mixed (NP +  NBC) • Polyuria

  30. Polyuria • Polyuria (24 hr urine output > 40 ml/kg) • Once steady state is reached polyuria is associated with excessive oral intake (polydipsia) • Results in both day and night urinary frequency due to global urine overproduction in excess of bladder capacity

  31. Common Causes of Polyuria • Diabetes mellitus • Diabetes insipidus • Polydipsia: Primary thirst disorder (dipsogenic, psychogenic)

  32. Diabetes Insipidus (DI) • Disorder of water balance • Inappropriate excretion of water leads to polydipsia to prevent circulatory collapse • Central vs Nephrogenic

  33. Central DI • Deficient ADH synthesis or secretion • Causes: Loss of neurosecretory neurons in hypothalamus or posterior pituitary gland

  34. Nephrogenic DI • ADH secretion normal • Kidneys are non-responsive (eg chronic renal failure)

  35. Polyuria: Diagnostic algorithm • Overnight water deprivation (OWD) • If normal, DDx is polydipsia, either dipsogenic or psychogenic • If OWD is abnormal, do renal concentrating capacity test (DDAVP) • If RCCT normal, Dx = central DI: Tx with DDAVP • If RCCT abnormal, Dx = nephrogenic DI: No specific treatment

  36. Primary polydipsia • Normal water deprivation studies • Dipsogenic vs. psychogenic • Dipsogenic polydipsia associated with Hx central neurologic abnormality such as Hx of brain trauma, radiation • Psychogenic polydipsia is long-term behavioral or psychiatric disorder

  37. Antidiuretics: Indications • Antidiuretic hormone vasopressin is important for urinary concentration • Antidiuretic therapy (desmopressin*) affects urine production. Proven benefit in treatment of polyuric conditions: • Pituitary diabetes insipidus • Primary nocturnal enuresis (PNE) • Nocturia * vasopressin analogue

  38. Desmopressin: mechanism of action • Desmopressin is a selective V2-receptor agonist: • Retains antidiuretic properties of vasopressin1 • Lacks unwanted pressor activity of vasopressin • Desmopressin, when bound to V2-receptorsin kidney: • Increases tubular water permeability • Enhances water reabsorption • Extracellular fluid = more dilute • Urine = more concentrated2 Recommendations for desmopressin in nocturia:ICI: Grade A (Level 1 evidence); EAU: Grade A (Level 1b evidence) References 1. Vilhardt H. Drug Investigation 1990; 2(Suppl. 5):2–8. 2. Hammer M and Vilhardt H. J Pharmacol Exp Ther 1985; 234(3):754–760.

  39. Desmopressin formulations • Intranasal: 10 mcg/spray; Max 40 mcg/day (CDI indication only) • Oral: 0.1 mg tablets; Max 0.6 mg/day for PNE • Melt: 60, 120, 240 mcg melt tabs • Melt in development: 25 mcg (women) and 50-100 mcg (men)

  40. Ferring US Nocdurna Study Results – All Subjects

  41. Summary of recommendations for potentialdesmopressin patients • All patients – use voiding diary • Global polyuria – exclude for further evaluation • Low volume per void and no nocturnal polyuria – other Rx? • ? Dosing differential between genders • Baseline sodium a good idea • Where does pediatric ”no need” to check Na+ end and adult ”need” begin? • Elderly (>65 years) with nocturnal polyuria • All need baseline serum sodium • Closely monitor serum sodium at 4 and 28 days after starting therapy or increasing dose • Monitor fluid intake • Use judgment: It’s always OK to check serum Na if you think it’s necessary

  42. Nocturia: Future Considerations • Outcome studies • Behavioral modification • Stockings • Targeted therapy • ? Desmopressin for nocturnal polyuria • ? Antimuscarinics for nocturnal urgency • Treatment of Nocturia irrespective of bother? • Is nocturia itself morbid or just a symptom of a morbid underlying condition? • Analagous to • HTN • Hypercholesterolemia

  43. Nocturia: Discussion/Questions

More Related