Nocturia

Nocturia is waking one or more times at night to void, each void preceded and followed by sleep. Clinically significant nocturia is two or more voids per night, which affects quality of life and increases risk of falls, fractures and mortality in older people.

• The prevalence rises with age: about 20 to 30 percent of those aged 20 to 30 years have one or more voids per night; over 80 percent of people over 80 years.
• Pathophysiology falls into four groups:
  • Nocturnal polyuria: nocturnal urine output exceeding 33 percent of the 24 hour volume in those over 65 (more than 20 percent in young adults and 25 to 33 percent in the middle aged). Causes: heart failure, venous insufficiency with leg oedema (fluid mobilisation on lying down), obstructive sleep apnoea (atrial natriuretic peptide release), loss of circadian rhythm of antidiuretic hormone, diabetes mellitus (osmotic diuresis), hypercalcaemia, evening alcohol and caffeine, excessive evening fluid, diuretics taken late, chronic kidney disease, nephrogenic diabetes insipidus, nocturnal hypertension.
  • Global polyuria (24 hour urine volume more than 40 mL/kg): diabetes mellitus, diabetes insipidus (central or nephrogenic), primary polydipsia, hypercalcaemia, hypokalaemia, lithium therapy, osmotic agents.
  • Reduced bladder capacity or overactive bladder: detrusor overactivity, bladder outlet obstruction (benign prostatic enlargement), interstitial cystitis, bladder stones or tumour, urinary tract infection, neurogenic bladder, radiation cystitis, pelvic organ prolapse.
  • Sleep disorders: obstructive sleep apnoea, insomnia, restless legs, pain, depression, anxiety (the person wakes then voids).
  • Mixed: very common.
• Medicines: diuretics (furosemide, bumetanide, thiazides if taken late), lithium, SGLT2 inhibitors, calcium channel blockers (fluid retention), selective serotonin reuptake inhibitors, alcohol, caffeine.

• Waking to void: record number of voids, volumes, timing. Ask about daytime frequency, urgency, incontinence, stream, hesitancy, terminal dribble, thirst, daytime polydipsia, snoring, daytime sleepiness, leg swelling, orthopnoea, weight change, medications, alcohol, caffeine and evening fluid intake.
• Red flags: visible haematuria, weight loss, bone pain, severe thirst, new neurological symptoms, severe lower urinary tract symptoms with retention, pelvic mass.
• Examination: blood pressure (including nocturnal if possible), BMI, oedema, signs of heart failure, abdominal examination (bladder), digital rectal examination in men (prostate size, nodule), pelvic examination in women (prolapse, atrophy), neurological examination.

• Frequency volume chart or 3 day bladder diary: record time and volume of each void and fluid intake; calculate:
  • 24 hour urine volume (polyuria if more than 40 mL/kg or more than 2.8 L in adults).
  • Nocturnal polyuria index (night volume divided by 24 hour volume) above 33 percent in over 65s (above 20 percent in under 35s).
  • Maximum voided volume (small functional bladder capacity if under 200 to 250 mL).
• Urinalysis (glucose, protein, blood, nitrites), urine culture if indicated.
• Bloods: urea, creatinine, eGFR, electrolytes, calcium, glucose and HbA1c, full blood count, thyroid function, and in men PSA after counselling.
• Further tests: B-type natriuretic peptide or echocardiography if heart failure suspected; sleep study if sleep apnoea suspected (snoring, witnessed apnoeas, Epworth score above 10); renal tract ultrasound with post-void residual; urodynamics if bladder outlet obstruction or neurogenic bladder suspected; water deprivation test or desmopressin test if suspected diabetes insipidus.

• Treat the cause: heart failure optimisation; diabetes control; continuous positive airway pressure for sleep apnoea; treat infection; manage benign prostatic enlargement; treat overactive bladder.
• Lifestyle: restrict fluids for 2 to 4 hours before bedtime (without becoming dehydrated overall); reduce evening caffeine and alcohol; salt restriction (target below 6 g per day, reducing a high intake reduces nocturia); leg elevation or compression stockings in the afternoon (1 hour with legs elevated at about 4 pm) to mobilise oedema before bedtime; take diuretics in the morning (or no later than 4 to 6 hours before sleep); empty the bladder before sleep; avoid sleeping late in the day; improve sleep hygiene.
• Drug therapy by cause:
  • Nocturnal polyuria: desmopressin acetate oral lyophilisate (melt) 25 micrograms (women) or 50 micrograms (men) sublingually one hour before bed (Noqdirna); or desmopressin tablets 100 to 200 micrograms at night (off label for nocturia). Contraindications: hyponatraemia or history of it, heart failure, uncontrolled hypertension, eGFR under 50 mL/min, syndrome of inappropriate antidiuretic hormone secretion, concurrent loop or thiazide diuretics, glucocorticoids, polydipsia, age over 65 requires caution (check sodium at baseline, at 3 days and at 1 month after starting, and after dose changes; stop if sodium below 130 mmol/L). Limit fluid intake from 1 hour before to 8 hours after dosing.
  • Furosemide 20 to 40 mg orally at about 4 to 6 pm (6 hours before bedtime), to promote the diuresis before sleep in heart failure or oedema (monitor potassium, sodium, renal function).
  • Overactive bladder: solifenacin 5 mg orally daily, increased to 10 mg; or mirabegron 50 mg orally daily (25 mg if eGFR 15 to 29; avoid with uncontrolled hypertension; monitor blood pressure); anticholinergics are best avoided in dementia or the elderly at risk of falls (anticholinergic burden); vibegron 75 mg daily is an alternative.
  • Benign prostatic enlargement: tamsulosin 400 micrograms orally at night (alternatively alfuzosin 10 mg modified release once daily, or doxazosin 1 mg at night titrated to 4 to 8 mg; caution orthostatic hypotension and floppy iris syndrome before cataract surgery) with or without finasteride 5 mg orally daily (or dutasteride 500 micrograms daily) for prostate volume above 30 to 40 mL.
  • Nocturia with diabetes: optimise glycaemic control, review SGLT2 inhibitor timing.
  • Insomnia: sleep hygiene and cognitive behavioural therapy for insomnia first; avoid benzodiazepines in older adults.
• Review at 2 to 4 weeks and after sodium check if using desmopressin.
• Refer to urology for haematuria, retention, suspected malignancy or failed medical therapy; sleep clinic for suspected apnoea; cardiology for heart failure.