Nocturia in Elderly

Dr. BC TongMBBS(HK), MRCP(UK), FHKCP, FHKAM(Med), FRCP(Edin and Glasg)

Specialist in Geriatric MedicinePrincess Margaret Hospital

Nocturia

is the complaint that the individual has to wake at night one or more times to void

International Continence Society Definition

ICS Standardisation of Terminology Report 2002

Neurourol Urodyn 2002; 21:179-83

Wein A, Lose GR, Fonda DBJU Int 2002; 90(suppl 3) 28-31

Swithibank LV, Abram PBJU Int 2000; 85(suppl 2):19-24

Consequence of NocturiaSleep deprivation

Middelkoop HAM et alJ Gerontol A Biol Sci Med 1996; 51:108-15

Fall

Stewart RB et al.JAGS 1992; 40(12):1217-20

Asplund RBJU Int 1999; 84:297-301

Man > 3 nocturnal voiding episodes

All men

Women > 3 nocturnal voiding episodes

All women

Survival

Etiology of nocturiaNocturia polyuria NP(Nocturia urine vol >35%)

7%

Nocturnal detrusor NDOoveractivity

57%

Mixed(NP+NDO)

36%

Polyuria(24 hour urine output> 2.5L)

23%

Weiss JP, Blaivas JG et al.Neurourol Urodynam 1998; 17:467-72

Circadian Urine Production

Established at 5 years of age7-year-old: 2-3 times the amount of urine during the day c.f. nightAdult: 25% or less during hours of sleep– 70-80 ml/h during waking period and 30-40

ml/h during sleepAfter 60 years: a shift to more nocturnal urine production; with increasing age, ratio of day to night time urine flow fallsTotal 24 hour urine secretion remains unchanged

Healthy adult aged 21-35 years excreted ~14% of total urine output at nightOlder people ~34%

Nursing Home residents: around ¼ produced substantially more urine at night

No.

Ouslander J, Schnelle J et al.JAGS 1993; 41:371-6

Total night (9p-7a) urine volume

Total day and night (9p-7a and 9a-7p) urine volume

Age related changes

Water diuresis– Arginine vasopressin– Renal concentrating ability

Solute diuresis– Renal sodium loss– Atrial natriuretic hormone– Renin-angiotensin-aldosterone system

Miller MJAGS 2000; 48:1321-29

Arginine vasopressin

Daytime blood AVP level: no consistent age-related changeGreater response of AVP to– Hypertonic saline infusion– Water deprivation– Intravenous metoclopramide– Cigarette smoking

Diurnal release of AVP– Peak blood concentration occurs during

the hours of sleep– Blunting of the nocturnal phase of AVP

Renal concentrating ability

Decline of renal concentrating ability– Water deprivation: unable to alter urine

flow or osmolalityImpaired renal tubular response to AVP– Acquired form of partial nephrogenic

diabetes insipidus

Renal sodium loss

Impaired ability of the kidney to retain sodium– Acute water load caused exaggerated

natriuresis– Took a longer time for reduction of urine

sodium excretion after salt restriction

Renin-angiotensin-aldosteronesystem

Lower level of plasma renin activity and aldosterone in supine positionLower increase in plasma renin activity and aldosterone after stimulation by low dietary sodium intake or upright posture

Atrial natriuretic hormone

ANH concentration increase with age Exaggerated increase after normal saline infusionIncrease renal response to ANHHigh ANH suppress renal reninsecretion, plasma renin activity, plasma angiotensin II and plasma aldosterone

Noctural polyuria syndromeUrine output during sleep >33% of total 24 hr volumeNight time urine flow >0.9 [1.3] ml/min7p to 7a urine volume >50% of total 24 hour volume

Disease MechanismMultiple sclerosisSpinal cord injuryAlzeihmer’s diseaseCerebrovascular diseaseAutonomic dysfunctionObstructive sleep apnoea High ANH concentrationCongestive heart failureEdematous state

Redistribution of third space fluid

Altered circadian rhythm of AVP

Nocturnal polyuria of disease state

Lancet 2000; 355:486-8

Age related impairment of endothelial NO release. The resultant increase in urodilatin secretion causing a lost of its circadian rhythm causing natriuresisAge related impairment of endothelial NO release also cause HT

Management of Nocturnal Polyuria

Life styleDiureticsDesmopressinImipramineOthers

Lifestyle modification

Fluid restriction after dinnerCompressive deviceLate afternoon naps with legs elevatedAvoidance of caffeine and alcoholImprovement of sleep quality Asplund R Gen Pharmac1995; 1203-9

Management of Nocturnal Polyuria

Life styleDiureticsDesmopressinImipramineOthers

Diuretics

Heart failure and edematous state

Frusemide 40 mg 6 h before bedtime in non-heart failure patient

Parameter Tx vs Placebo P

Night-time frequency -0.5 vs 0 0.014*

Daytime frequency +1.9 vs –0.1 <0.001*0.0640.002*

24 h urine output 1780 vs 1663 0.2

Night-time voided volume -120 vs +9 mlDaytime voided volume +365 vs -31

No relationship between severity of NP and reduction in night-time frequency

Reynard JM, Cannon A, Yang Q, Abram PBr J Urol 1998; 81:215-8

Management of Nocturnal Polyuria

Life styleDiureticsDesmopressinImipramineOthers

Desmopressin

Drugs 2005; 65:99-107

Abram P, Mattiasson A, Lose GR, Robertson GIBJU Int 2002;90(Suppl 3):32-6

Nocturia Study GroupAm J Obstet Gynecol 2003; 189:1106-13

Mattiasson A, Abram P, Kerrebroeck V, Walter S, Weiss JBJU Int 2002; 89:855-62

Short term results: 3 weeks

Primary end-point: > 50% reduction of nocturnal void– Men: 34% vs 3% (p<0.001)– Women: 46% vs 7% (p<0.001)

Drugs 2005; 65:99-107

Secondary end-point

Long term results: 10-12 months

Lose G, Mattiasson A et al.J Urol 2004; 172:1021-5

Adverse event: short term study

Adverse event: long term study

Hyponatremia 35/248 (14%)– 33/35 >130 mmol/L– 2(one male and one female)/35= 125-130 mmol/L

Desmopressin studies on Elderly

Desmopressin reduced nocturnal diuresis in polyuric elderly subject and this reduction, occurring with doses of 0.1 mg given at bedtime, does not increase in a dose dependent way

BJU Int 2003; 91:642-6

Sensitivity to change in serum sodium- mean serum sodium level during treatment deviate by more than 5 units from the baseline: 6/72

Sensitivity to hyponatremia

Increasing age (>77 y)Concomitant cardiac disease (angina, AF, previous MI)Increase baseline 24 h urine outputGreater effect on 24 h diuresis

Cautions: see under Vasopressin; less pressor activity, but still considerable caution in renal impairment, in cardiovascular disease and in hypertension (not indicated for nocturnal enuresis or nocturia in these circumstances); elderly (avoid for nocturnal enuresis and nocturia in those over 65 years); also considerable caution in cystic fibrosis; in nocturia and nocturnal enuresis limit fluid intake to minimum from 1 hour before dose until 8 hours afterwards; in nocturia periodic blood pressure and weight checks needed to monitor for fluid overload; pregnancy (Appendix 4)

HYPONATRAEMIC CONVULSIONS. The CSM has advised that patients being treated for primary nocturnal enuresis should be warned to avoid fluid overload (including during swimming) and to stop taking desmopressinduring an episode of vomiting or diarrhoea (until fluid balance normal). The risk of hyponatraemic convulsions can also be minimised by keeping to the recommended starting doses and by avoiding concomitant use of drugs which increase secretion of vasopressin (e.g. tricyclic antidepressants)

Protocol for desmopressin10 ug/0.1mg desmopressin increased by 10 ug/0.1mg every third nightSeen next afternoon – for symptom of headache, N/V, lightheadedness,

visual disturbance– check electrolyte

Recheck electrolyte 1 week laterPatient / caregiver taughter to monitor daily BW, presence of edema and symptom of hyponatremiaSharply reduce evening water intake

Weiss JP, Blaivas JGJ Urol 2000; 163:5-12

Desmopressin excluded in

History of hyponatremia while on thiazide or other drugsRenal failureCongestive heart failureCirrhosisSuspected primary polydipsiaLow basal sodium level

Abram P, Mattiasson A, Lose GR, Robertson GIBJU Int 2002;90(Suppl 3):32-6

Management of Nocturnal Polyuria

Life styleDiureticsDesmopressinImipramineOthers

Imipramine15 monosymptomatic enuretic patient (15-37y) and 8 controls (25-32y)6 with nocturnal polyuria– Single dose Imipramine 50 mg

• decrease in urine output (0.67+ 0.45 ml/kg/h vs 1.14+ 0.24 [P 0.007])

• reduced osmolal (Na, K, urea) clearance (1.27+ 0.38 ml/kg/h vs 1.82 + 0.47 [P 0.02])

Effect not observed at non-polyuric / controlIncrease alpha-adrenergic stimulation in proximal tubules with a secondary increase urea and water reabsorption more distally in the nephron

Hunsballe JM, Rittig S et al

J Urol 1997; 158:830-6

Imipramine

Daily dose 25-100 mg per dayComplicated mechanism of action: CNS modulation, anticholinergic, beta-adrenergic, alpha-adrenergic, direct smooth muscle relaxation, increase ADH secretionConflicting results from evaluation of its clinical efficacy on urge incontinence and stress incontinenceProven effect in nocturnal enuresis

Urol Res 2001;29:118-25

Management of Nocturnal Polyuria

Life styleDiureticsDesmopressinImipramineOthers

Other observation

Dry fruit Thomas DV J Urol 2003; 170:1956-7

Aspirin Le Fanu J BJU Int 2001; 88:126-7

Take home messageIn elderly nocturic, multiple pathologies interactNoctural polyuria is commonMechanism for NP can be age-related changes and/or pathology-relatedA precise frequency volume chart is the key for diagnosisLife style change can help some of the patientsDiuretics 6 hours before bed-time can help edematous patientDesmopressin can be use in otherwise healthy elderly but close monitoring is essential