Nocturia

Nocturia is waking at night to void one or more times, with each void preceded and followed by sleep. It is common with age, and bothersome when two or more voids occur each night.

Mechanisms. Nocturnal polyuria (urine over a defined proportion of 24 hour volume at night), reduced nocturnal bladder capacity, global (24 hour) polyuria, sleep disorders, and mixed.

Definitions. Nocturnal polyuria: nocturnal urine volume over 20 percent of 24 hour output in younger adults (under 35 years), over 33 percent in adults over 65 years (a nocturnal polyuria index). Nocturnal polyuria is also defined as over 90 mL/hour of night urine or over 6.4 mL/kg of body weight. Global polyuria: over 40 mL/kg in 24 hours (over 3 L). Reduced nocturnal bladder capacity: nocturnal voids at small volumes and maximum voided volume under 33 percent of maximum 24 hour capacity.

Key distinctions. Large nocturnal volumes with a normal daytime pattern suggest nocturnal polyuria (heart failure, sleep apnoea, venous insufficiency, drugs, evening fluid intake). Frequent small volumes day and night suggest bladder cause or outlet obstruction. Large volumes throughout the day suggest global polyuria.

History. Number of nocturnal voids, timing, volume, effect on sleep and function, daytime frequency, urgency, incontinence, flow symptoms, thirst and fluid intake (evening and bedtime), alcohol, caffeine, snoring and witnessed apnoea, leg swelling, orthopnoea, diabetes symptoms, sleep pattern (insomnia, restless legs, pain, depression, shift work), medication timing, prostate symptoms, pregnancy, menopause, and falls at night.

Drug history. Diuretics (especially evening), lithium, sodium glucose cotransporter 2 inhibitors, calcium channel blockers (oedema), steroids, SSRIs and SNRIs (hyponatraemia with desmopressin), tetracyclines, antidiabetic agents, alcohol and caffeine.

Examination. Weight, body mass index, blood pressure (supine and standing), neck circumference, oedema, jugular venous pressure, heart and lung examination (heart failure), abdomen, rectal examination (prostate), genital and pelvic examination, and neurological examination.

Red flags

• Polyuria with thirst, weight loss or high glucose (diabetes), or high calcium
• Orthopnoea, breathlessness or leg swelling (heart failure)
• Snoring, witnessed apnoea, hypertension, and daytime sleepiness (obstructive sleep apnoea)
• Urinary retention, haematuria, or recurrent infection
• Neurological signs (spinal cord or cauda equina)
• Age over 65 with falls at night
• Nocturnal polyuria with hyponatraemia, or on desmopressin
• Pregnancy
• Renal impairment

Special groups. Women: menopause and prolapse. Men: benign prostatic enlargement. Older adults: falls, hip fracture and delirium risk with night voiding. Children: enuresis assessment. Region specific: schistosomiasis and tuberculosis.

Nocturnal polyuria

• Heart failure, venous insufficiency and oedema (redistribution on lying), nephrotic syndrome, chronic kidney disease, autonomic dysfunction, nocturnal polyuria syndrome (idiopathic, age related loss of circadian vasopressin secretion)
• Obstructive sleep apnoea (atrial natriuretic peptide), diabetes mellitus, diabetes insipidus, hypercalcaemia
• Drugs and habits (evening diuretics, alcohol, caffeine, high evening fluid intake, steroids)

Reduced bladder capacity and frequency

• Overactive bladder, bladder outlet obstruction (benign prostatic enlargement), urinary tract infection, interstitial cystitis, bladder stones, bladder tumour, radiation cystitis, urethral stricture, prostatitis
• Pelvic organ prolapse, pregnancy, and detrusor overactivity of neurological disease

Sleep and psychological

• Insomnia, restless legs and periodic limb movements, pain, depression and anxiety, shift work, and habitual waking

Reasoning. A 3 day frequency volume chart classifies nocturia into nocturnal polyuria, reduced bladder capacity or global polyuria. Then screen for the underlying systemic and urological cause.

First line. Frequency volume chart for 3 days, urine dipstick and culture, blood tests (glucose or HbA1c, urea, creatinine, electrolytes, calcium, full blood count), blood pressure, weight, and post-void residual (bladder scan) in men and older adults.

Targeted tests.

• Calculate the nocturnal polyuria index (night urine volume divided by 24 hour volume; over 33 percent in older adults) and nocturia index.
• B type natriuretic peptide or NT proBNP, echocardiography and chest radiograph for heart failure.
• Sleep study (home or in laboratory polysomnography; apnoea hypopnoea index 5 or more with symptoms indicates obstructive sleep apnoea, 15 or more is moderate to severe) and Epworth sleepiness score (over 10 abnormal) for suspected sleep apnoea.
• Urine protein to creatinine ratio, renal ultrasound, and estimated glomerular filtration rate for kidney disease.
• Water deprivation and desmopressin test, plasma and urine osmolality for suspected diabetes insipidus; parathyroid hormone for hypercalcaemia.
• Prostate specific antigen (after counselling), uroflowmetry, and cystoscopy or imaging as for urinary frequency; urodynamics when diagnosis is unclear.
• Serum sodium before and during desmopressin.
• Thyroid function and morning cortisol when clinically suggested.

Limitations. Frequency volume charts require patient adherence and vary between nights. Nocturnal polyuria thresholds vary with age and body size.

Address underlying disease (all patients). Optimise heart failure (diuretic timing, ACE inhibitor, beta blocker), diabetes, sleep apnoea (continuous positive airway pressure for moderate to severe disease, weight loss, avoid alcohol and sedatives), renal disease, and hypercalcaemia. Treat urinary infection and constipation. Stop or move culprit drugs to the morning (diuretics in the morning; avoid evening dosing), and review calcium channel blockers causing oedema.

Lifestyle and behavioural measures.

Limit fluid intake in the 2 to 4 hours before bed (total daily intake about 1.5 to 2 L, not excessively restricted).

• Avoid evening caffeine, alcohol and large meals.
• Treat evening oedema with leg elevation in the late afternoon and compression stockings in the daytime.
• Reduce salt intake.
• Address sleep hygiene (regular schedule, dark cool room, cognitive behavioural therapy for insomnia).
• Empty the bladder before bed (double voiding).
• Maintain physical activity in the day.

Safe night time access to the toilet with lighting, a commode or urinal, and falls prevention in older adults.

Nocturnal polyuria.

• Furosemide 20 to 40 mg orally in the mid or late afternoon (about 6 hours before bed) to promote diuresis before sleep; monitor potassium, sodium and renal function.
• Desmopressin acetate (oral lyophilisate) 25 micrograms (women) or 50 micrograms (men) sublingually 1 hour before bed, increased cautiously if no effect (maximum 50 micrograms in women and 100 micrograms in men by some labels), or intranasal 10 micrograms for those unable to use oral therapy. Check sodium at baseline, then at 3 days, 7 days, 1 month and then every 3 to 6 months; stop if sodium is under 130 mmol/L (or under 135 mmol/L with symptoms). Contraindicated in hyponatraemia or history of hyponatraemia, heart failure, polydipsia, creatinine clearance under 50 mL/min, syndrome of inappropriate antidiuretic hormone secretion, use of loop or thiazide diuretics, and with caution over 65 years (avoid in frail older adults, and limit fluids after the dose; restrict intake to a minimum from 1 hour before to 8 hours after the dose). Warn about symptoms of hyponatraemia (headache, nausea, confusion).
• Nocturnal polyuria with obstructive sleep apnoea: continuous positive airway pressure.

Bladder outlet obstruction in men. Tamsulosin 400 micrograms orally once daily after food (or alfuzosin 10 mg once daily), with finasteride 5 mg orally once daily or dutasteride 0.5 mg once daily for enlarged prostate (full effect at 6 months), and surgery for refractory symptoms.

Overactive bladder and reduced capacity. Bladder training, antimuscarinics (solifenacin 5 to 10 mg daily; tolterodine 2 mg twice daily; avoid oxybutynin in older adults) or mirabegron 25 to 50 mg daily (check blood pressure), with post-void residual monitoring.

Genitourinary syndrome of menopause and prolapse. Vaginal oestrogen (estradiol 10 microgram pessary daily for 2 weeks then twice weekly), pelvic floor training, and gynaecology care.

Diabetes and diabetes insipidus. Glycaemic control (including review of sodium glucose cotransporter 2 inhibitors), desmopressin for central diabetes insipidus (100 to 200 micrograms orally two to three times daily, with sodium monitoring), and treatment of nephrogenic causes.

Insomnia and sleep disorders. Cognitive behavioural therapy for insomnia, management of restless legs (iron replacement for ferritin under 75 micrograms/L; gabapentin 300 mg at night or pramipexole 0.125 mg 2 to 3 hours before bed), pain control, and treatment of depression.

Sleep apnoea. Positive airway pressure, mandibular advancement device, weight loss, and positional therapy.

Heart failure and oedema. Diuretic timing and dose adjustment, compression, and cardiology care.

Monitoring. Frequency volume chart at 4 to 6 weeks, sodium after starting desmopressin, renal function and potassium with diuretics, blood pressure, post-void residual with antimuscarinics, and falls review.

Referral and escalation. Urology for obstruction, haematuria, suspected malignancy, and refractory symptoms. Cardiology for heart failure. Sleep medicine for obstructive sleep apnoea. Endocrinology for diabetes insipidus and hypercalcaemia. Geriatrician for frail older adults with falls.

Admission criteria. Hyponatraemia with symptoms, retention with renal impairment, decompensated heart failure, or severe hyperglycaemia or hypercalcaemia.

Discharge and safety netting. Advise on timing of fluids and drugs, and nocturnal safety. Return for headache, nausea, confusion, drowsiness (hyponatraemia), blood in urine, retention, new leg swelling or breathlessness, or worsening symptoms.