Garjae D. Lavien, MD
Michael J. Naslund, MD
BASICS
DESCRIPTION
• Nocturia is a symptom describing an individual who awakens at night one or more times to void. Each void is preceded and followed by sleep.
• Can negatively impact quality of life.
– Can be associated with depression, daytime fatigue, and increased orthopedic morbidity among the elderly.
• Underlying etiologies of nocturia
– Nocturnal polyuria:
The rate of urine output is excessive only at night and total 24-hr output is within normal limits.
– Reduced bladder capacity
– 24-hr polyuria
– Sleep disorder
EPIDEMIOLOGY
Incidence
• The incidence of nocturia and total number of voiding episodes increases with age
– Overall: 28%
– Age >60: 41%
• Body mass index >29: 36%
• Black and Hispanic > White
Prevalence
• Higher prevalence in women than men among young adults
• Higher prevalence in men than women among elderly population groups
RISK FACTORS (1)
• Advanced age
• Diuretic usage
• Lower urinary tract dysfunction
• Cardiac disease
• Obesity, sleep apnea
Genetics
None
PATHOPHYSIOLOGY
• 24-hr polyuria:
– Excessive total urine production where the total 24-hr urinary volume >40 mL/kg)
– Diabetes mellitus:
Secondary to polydipsia and osmotic diuresis from hyperglycemia
– Diabetes insipidus:
Under-secretion (central) or impaired response (nephrogenic) to ADH
– Medications:
Lithium, diuretics, caffeine, nephrotoxic medications
– Hypercalcemia: Can cause osmotic diuresis
– Hyperaldosteronism
– Psychogenic polydipsia
• Nocturnal polyuria
– Relative increased production of urine at night that is often offset by lowered daytime urine production resulting in normal 24-hr urine volume.
– Age-related loss of the normal diurnal secretion of vasopressin, resulting in increased nocturnal urine output.
– Peripheral edema:
Fluid that accumulates in the lower extremities when upright during the day is mobilized when supine at night, due to an increase in GFR and excretion.
Conditions: CHF, liver disease, nephrotic syndrome, hypoalbuminemia, venous insufficiency, lymphedema, lower extremity injury/swelling.
– Sleep apnea:
Transient periods of hypoxia lead to increased pulmonary vascular resistance and secretion of atrial natriuretic peptide, a potent diuretic.
– Medications: Poorly timed/dosed diuretics that exert maximal effect during sleeping hours.
– Excessive fluid intake prior to bedtime, resulting in a physiologic large volume excretion.
• Reduced bladder capacity
– Nonneurogenic or Neurogenic OAB (over active bladder)
– Inflammatory: UTI, radiation cystitis, bladder calculi, interstitial cystitis
– Neoplastic: Bladder cancer, prostate cancer, extrinsic compression from pelvic masses
– Traumatic: Spinal cord injury, urethral stricture, injury to pelvic nerves or bladder, foreign body within bladder
– Obstructive; BPH, urethral stricture
ASSOCIATED CONDITIONS
• Bladder outlet obstruction
• OAB: Idiopathic and neurogenic
• Detrusor hyperactivity with impaired contractility
• Radiation cystitis
• Diabetes mellitus
• Psychogenic polydipsia
• Depression
• Obesity
• See also “Pathophysiology”
GENERAL PREVENTION
• Avoid excessive evening fluid intake, alcohol, and caffeine
• Closely monitor and control the underlying conditions that cause nocturia
DIAGNOSIS
HISTORY
• Number of times getting up at night to urinate from time of going to bed until time of waking in the morning
• Degree of bother assessment
• Differentiate between awakening due to the urge to void vs. awakening due to other sleep disturbances
• Fluid intake habits
• Timing, volume
• Caffeine and alcohol consumption
• Previous pelvic surgery or radiation
• Daytime fatigue and depression
• Review of medications known to contribute to nocturia: such as diuretics, excessive calcium supplementation, antacids, or lithium.
• Swelling of lower extremities
PHYSICAL EXAM
• Global or focal neurologic deficits
• Digital rectal: Assess anal tone, prostate exam in men
• Pelvic exam in women: Anterior prolapse causing retention, urethral diverticulum, atrophic vaginitis causing irritative urinary symptoms
• Lung auscultation for rales, crackles
• Dependent edema, pedal edema
• Suprapubic distension consistent with urinary retention
• Obesity and a wide neck circumference raises the possibility of sleep apnea
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis: Low specific gravity (polyuria), RBCs (rule out stones, bladder cancer, foreign body, etc.), proteinuria (nephrotic syndrome), glucosuria (diabetes mellitus), pyuria (UTI)
• Urine culture: UTI
• Urine osmolality: Dilute low values suggest inappropriate excretion of ADH or excess intake of water
• PSA if indicated
• Serum electrolytes: Hypokalemia with diuretic use, CHF, or hyperaldosteronemia
Imaging
• Bladder US with PVR volume for suspected urinary retention, especially if considering antimuscarinics
• Renal US may demonstrate hydronephrosis in cases of urinary retention or poorly compliant bladders
Diagnostic Procedures/Surgery
• Voiding diaries
– All voiding episodes and volumes should be recorded for a 24-hr period; the time the patient actually goes to sleep and awakens for the day should also be noted.
– Nocturnal urine volume (NUV) is the total volume of urine voided during the night (the 1st morning void is included in this sum since it represents urine excreted during sleep hours).
– Nocturnal polyuria index (NPi): NUV divided by the total volume voided over the 24-hr period:
NPi >33% = nocturnal polyuria
– Nocturnal Bladder Capacity index (NBCi)
– NBCi = (NUV/Maximal volume per void)–1
NBCi >0 suggests that the nocturnal bladder capacity cannot store the amount of urine made at night.
• Urodynamics
– Helpful when empiric treatment for overactive bladder (OAB) or bladder outlet obstruction has failed to improve nocturia
• Polysomnographic sleep studies: Differentiate between sleep disorder and true nocturia
Pathologic Findings
N/A
DIFFERENTIAL DIAGNOSIS
• Sleep disorders:
– Most patients awaken due to the sleep disturbance, but recall this as an awakening to void.
– May need polysomnography
• Urologic
– Bladder outlet obstruction, OAB, incomplete bladder emptying.
• Nonurologic:
– Renal failure, idiopathic nocturnal polyuria, diabetes mellitus, central diabetes insipidus, nephrogenic diabetes insipidus, primary polydipsia, hypercalcemia, drugs, autonomic failure, obstructive sleep apnea.
TREATMENT
GENERAL MEASURES
• Nocturnal polyuria secondary to diuretics
– Change to afternoon dosing to induce an early evening diuresis rather than a nocturnal diuresis
• Treatment of underlying condition associated with nocturia
MEDICATION
First Line
• Antimuscarinics are appropriate for reduced voided volumes.
• Men only: α-blocker alone or combined with a 5-α-reductase inhibitor (only modest benefit) (2)[A].
Second Line
• DDAVP for nocturia associated with nocturnal polyuria (3)[B]:
– Dosing: 0.01 mg PO; titrate up to 0.04 mg.
– DDAVP has a high risk of hyponatremia.
– Greatest risk seen in men >65 yr old.
SURGERY/OTHER PROCEDURES
Sacral neuromodulation for nocturia secondary to reduced voided volumes is associated with refractory daytime frequency and urgency (4)[B].
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• Behavioral training:
– Pelvic floor muscle exercises, +/– biofeedback: More effective than both drug therapy and placebo in treatment of nocturia associated with daytime urgency and urge incontinence (5)[A]
• CPAP for obstructive sleep apnea
Complementary & Alternative Therapies
None
ONGOING CARE
PROGNOSIS
Although it is often difficult to completely eliminate episodes of nocturia, characterizing nocturia according to cause-specific etiologies allows for cause-specific treatment.
COMPLICATIONS
• Traumatic falling accidents, including hip fractures, from rising from sleep to urinate
• DDAVP can lead to hyponatremia
• Urinary retention secondary to antimuscarinics
FOLLOW-UP
Patient Monitoring
• Bladder sonography with PVR as needed, particularly when treating men with antimuscarinics
• Repeat 24-hr voiding diaries
• Regular monitoring of serum electrolytes with DDAVP, starting 3 days after initiation of treatment
Patient Resources
• Medline Plus — Excessive Urination at Night
http://www.nlm.nih.gov/medlineplus/ency/article/003141.htm
REFERENCES
1. Fitzgerald MP, Litman HJ, Link CL, et al. The association of nocturia with cardiac disease, diabetes, body mass index, age and diuretic use: Results from the BACH survey. J Urol. 2007;177:1385–1389.
2. Johnson TM 2nd, Burrows PK, Kusek JW, et al. The effect of doxazosin, finasteride and combination therapy on nocturia in men with benign prostatic hyperplasia. J Urol. 2007;178:2045.
3. Mattiasson A, Abrams P, Van Kerrebroeck P, et al. Efficacy of desmopressin in the treatment of nocturia: A double-blind placebo-controlled study in men. BJU Int. 2002;89:855.
4. Van Kerrebroeck PE, van Voskuilen AC, Heesakkers JP, et al. Results of sacral neuromodulation therapy for urinary voiding dysfunction: Outcomes of a prospective, worldwide clinical study. J Urol.2007;78:2029.
5. Johnson TM 2nd, Burgio KL, Redden DT, et al. Effects of behavioral and drug therapy on nocturia in older incontinent women. J Am Geriatr Soc. 2005;53:846.
ADDITIONAL READING
• Cornu JN, Abrams P, Chapple CR, et al. A Contemporary assessment of nocturia: definition, epidemiology, pathophysiology, and management—a systematic review and meta-analysis. Eur Urol.2012;62;877–890.
• Weiss JP, Blaivas JG, Bliwise DL, et al. The evaluation and treatment of nocturia: a consensus statement. BJU Int. 2011;108:6–21.
See Also (Topic, Algorithm, Media)
• Bladder Outlet Obstruction
• Diabetes Mellitus
• Incontinence, Adult Female
• Incontinence, Adult Male
• Neurogenic Bladder
• Nocturia Algorithm 
• Nocturnal Polyuria
• Overactive Bladder
• Urgency, Urinary (Frequency and Urgency)
• Urodynamics
• Voiding Diary (see Section VII: Reference Tables)
CODES
ICD9
• 596.59 Other functional disorder of bladder
• 788.42 Polyuria
• 788.43 Nocturia
ICD10
• N31.9 Neuromuscular dysfunction of bladder, unspecified
• R35.1 Nocturia
• R35.8 Other polyuria
CLINICAL/SURGICAL PEARLS
• The etiology of nocturia is not prostate or bladder related in the majority of men. Poor sleep pattern and fluid consumption/mobilization need to be considered.
• A voiding diary is extremely helpful to determine the cause of nocturia.