Enuresis

See Also

Definitions

Enuresis
1. Inability to control Urinary Bladder, resulting in unintentional urination at an age where Bladder control would be expected
Nocturnal Enuresis
1. Involuntary Bedwetting at least twice weekly in children age 5 years and over
Daytime Enuresis (Diurnal Enuresis)
1. Involuntary loss of urine control during the daytime, awake hours, at an age where Bladder control would be expected

Epidemiology
Prevalence of Enuresis

Age 2 years: 82%
Age 3 years: 49%
Age 4 years: 26%
Age 5 years: 15-25%
Age 7 years: 5-10%
Age 12 years: Boys: 8%; Girls 4%
Age 18 years: Boys: 1%: Girls rare

Types
Enuresis

Monosymptomatic Enuresis (70 to 85%)
1. Nighttime Bed Wetting without other symptoms
2. Primary Monosymptomatic Enuresis (80%)
  1. Persistent Nocturnal Enuresis, with no history of 6 months continuous dry nights
  2. Causes
    1. Sleep arousal disorder
      1. Difficult to arouse with normal Bladder cues
      2. Typically with fragmented or nonrestorative sleep
    2. Nocturnal Polyuria
      1. Decreased renal concentrating function with large volume voids (e.g. inadequate pituitary ADH release at night)
      2. Large liquid volume ingestion or solute (sugar or salt) ingestion before bed
    3. Bladder dysfunction
      1. Low Bladder storage capacity
      2. Detrussor overactivity
3. Secondary Monosymptomatic Enuresis (20%)
  1. Relapse of Nocturnal Enuresis after previously continuously dry at night >6 months
  2. Typically associated with new psychosocial stressors or pathological medical or behavioral condition (see secondary causes below)
  3. Causes
    1. Acute Renal Failure
    2. Constipation
    3. Diabetes Insipidus
    4. New onset Diabetes Mellitus
    5. Emotional stress
    6. Urinary Tract Infection
Non-monosymptomatic Enuresis (15 to 30%)
1. Associated with more significant abnormalities
2. Criteria (any of the following)
  1. Daytime lower urinary tract symptoms (e.g. Dysuria, urgency, frequency, incomplete emptying, straining to void) or
  2. Daytime Incontinence (Diurnal Enuresis) or
  3. Dysuria or
  4. Holding maneuvers (e.g. leg crossing)
3. Causes
  1. Chronic Kidney Disease
  2. Constipation
  3. Diabetes Mellitus
  4. Overactive Bladder
  5. Spinal Dysraphism
  6. Neurologic disorder
  7. Urethral sphincter dysregulation
  8. Urinary tract malformation or obstruction
4. Associated Conditions
Timing
1. Nocturnal Enuresis only (80%)
2. Nocturnal and diurnal (20%)

Pathophysiology

Maturation delay
1. Enuresis Prevalence decreases with age
2. "Bladder full" signal does not yet work
  1. Inability to awaken in response to the stimulus of a full Bladder
Other predisposing factors
1. Excessive nighttime urine production
2. Decreased Bladder functional capacity
Strong association with Family History
1. Gene markers on Chromosome 5, 12, 13 and 22
2. Contrast with baseline risk of Enuresis without a Family History: 15%
3. Both parents with Enuresis: 77% chance of Enuresis
4. One parent with Enuresis: 44% chance of Enuresis
  1. Relative Risk if Father with Enuresis: 7.1
  2. Relative Risk if mother with Enuresis: 5.2

Risk Factors

Family History of Nocturnal Enuresis (up to 44 to 77% risk)
Male (up to 30%, double the risk of girls)
Adenotonsillar Hypertrophy
Attention Deficit Hyperactivity Disorder
Bladder dysfunction
Constipation
Daytime Enuresis (Diurnal Enuresis)
Developmental Delay
Emotional Stress
Encopresis
Sleep Deprivation

Causes
Secondary (3%)

Bladder Dysfunction or unstable Bladder (3-5%)
Medically treatable
1. Urinary Tract Infection, especially in girls (18 to 60% of cases)
2. Diabetes Insipidus
3. Diabetes Mellitus
4. Hyperthyroidism
5. Sickle Cell Anemia
6. Fecal Impaction or Constipation often with comorbid Encopresis and treatment resistance (33-75% of cases)
7. Overactive Bladder or dyfunctional voiding (<41% of cases)
Surgically treatable
1. Ectopic Ureter
2. Lower Urinary Tract Obstruction
3. Neurogenic Bladder (e.g. Spinal Dysraphism)
4. Bladder calculus or foreign body
5. Obstructive Sleep Apnea secondary to large adenoids (10 to 54% of cases)
Psychiatric illness (in only 20%)
1. More common in enuretic girls
2. Suggested by Enuresis both night and day
3. More likely if Enuresis persists in older child
Regressive Enuresis (occurs after being dry)
1. Associated with stressful environmental event

History

Voiding History
1. Consider a two week voiding diary or chart
2. Does child meet DSM-IV criteria for Enuresis above?
3. Has the child ever been dry for a 6 month period? (primary or secondary)
4. Is there daytime Enuresis? (complicated Enuresis)
5. Characterize the Enuresis
  1. How many days per week?
  2. How many times per night?
  3. What time of night does Enuresis occur?
  4. Are the nocturnal voiding volumes large or small?
  5. How large in volume is the voluntary first morning void?
Impacts and Treatment History
1. How disruptive is the Enuresis to the child and family?
  1. How motivated is the child and their family in working toward a resolution?
2. What treatment measures have already been tried?
  1. Positive reinforcement
  2. Scheduled waking
  3. Witholding liquids at bedtime
  4. Bed-Wetting Alarm
Urinary Tract Infection symptoms (Non-monosymptomatic Enuresis)
1. Dysuria
2. Urinary urgency
3. Urinary Frequency
4. Hesitancy
Functional Bladder disorder or neurogenic Bladder signs (Non-monosymptomatic Enuresis)
1. Frequent Urination with voids >7 per day
2. Urine urgency
3. Withholding urine until last minute
4. Wets more than once nightly
5. Small volumes from incomplete emptying
6. Dribbling, straining to obtain even a weak urine stream
7. Recurrent Urinary Tract Infections
8. Spinal Dysraphism (poor anal tone, sacral skin changes)
9. Obstruction risks
  1. Labial adhesions
  2. Abnormal Urethra (e.g. Hypospadias, meatal stenosis, Phimosis)
Bowel habit changes
1. Infrequent or difficult stool passage
2. Encopresis
3. Constipation with hard stools at a frequency of <4 times per week
Nocturnal Polyuria
1. Enuresis on only a few nights per week
2. Voids large volumes when Enuresis occurs
3. Soaked absorbant underpants or voids large first-morning void despite Enuresis?
4. Excessive water intake prior to bed?
5. Weight loss associated with polydipsia and Polyuria (Diabetes Mellitus)?
Other related history
1. Birth complications
2. Neurologic disorders (motor disorders, Learning Disorders, Developmental Delay)?
3. Genitourinary surgeries
4. Family History of Enuresis
5. Behavioral problems
6. Snoring and Daytime Somnolence (Obstructive Sleep Apnea)
7. Sickle Cell Anemia
8. Failure to Thrive (e.g. Diabetes Mellitus, Diabetes Insipidus, renal disease)

Examination

Examination is typically normal in Monosymptomatic Enuresis
Height and weight
1. Evaluate for Growth Delay or Failure to Thrive (e.g. Diabetes Mellitus, Chronic Kidney Disease)
Head and Neck Exam
1. Evaluate for Tonsillar Hypertrophy (and consider enlarged adenoids) suggestive of pediatric Sleep Apnea
Abdominal and flank exam
1. Costovertebral Angle Tenderness (CVA Tenderness)
2. Abdominal masses
3. Bladder enlargement
Genitourinary exam and Rectum
1. Males
  1. Hypospadias, meatal stenosis, Phimosis
2. Females
  1. Labial adhesions
3. Sexual abuse signs
  1. Excoriations at the perineum or perianal region
  2. Prepubertal Vulvovaginitis
4. Rectum
  1. Fecal Impaction or signs of soiling (Constipation, Encopresis)
  2. Decreased sphincter tone (may be comorbid with neurogenic Bladder)
Back exam
1. Dimple, hair tuft, Lipoma or other skin findings in the midline superior to the gluteal cleft (Spinal Dysraphism signs)
Neurologic Exam
1. Gait Evaluation for neurologic deficits
2. Lower limb motor weakness or reflex abnormality
3. Developmental Delay
4. Attention Deficit Hyperactivity Disorder findings

Labs

Urinalysis
1. Signs of Urinary Tract Infection
2. Urine Specific Gravity
3. Urine Glucose
Other labs to consider
1. Fingerstick Blood Sugar
2. Basic metabolic panel including Renal Function

Imaging

Consider as indicated
Renal Ultrasound and Bladder Ultrasound
1. Indicated for suspected urinary tract malformation or Chronic Kidney Disease
MRI Lumbar Spine
1. Indicated for suspected Spinal Dysraphism

Diagnosis
Enuresis (DSM-IV Classification)

Repeated voiding of urine into bed or clothes
1. Involuntary or intentional
Clinically Significant criteria (one of the following)
1. Twice weekly for at least 3 consecutive weeks
2. Significant distress
3. Impaired functioning
Age 5 years or older
Secondary cause not present
1. Medication (e.g. Diuretics)
2. Diabetes Mellitus
3. Spina bifida
4. Seizure Disorder

Management
Referral Indications

Non-monosymptomatic Enuresis
Recurrent Urinary Tract Infection
Urinary tract malformations
Prior pelvic surgery
Neurologic disorders (e.g. neurogenic Bladder)
Failure to respond after age 7 years old to adequate trial of bed alarm and Desmopressin
Psychiatric disorder
Dysfunctional voiding (or urinary tract malformation)
Chronic Kidney Disease

Management
General

Discussion topics
1. Reassure parents with age-related norms
2. Counsel family regarding conflict surrounding Enuresis
Assess for organic causes (see above)
1. Complete history and physical with Urinalysis
  1. No further evaluation necessary if normal results
2. Treat reversible underlying causes
  1. Constipation
    1. Consider pediatric gastroenterology Consultation for Encopresis
  2. Acute Urinary Tract Infection
    1. Consider imaging and Consultation for Recurrent Urinary Tract Infection
  3. Obstructive Sleep Apnea
    1. Consult regarding Tonsillar or adenoid hypertrophy
  4. Diabetes Mellitus
3. Obtain Consultation for complicated secondary causes (esp. Non-monosymptomatic Enuresis)
  1. See referral indications above

Management
Non-Pharmacologic Therapies

Indicated for monosymptomatic Enuresis (no secondary disorder suspected)
General Recommendations
1. Enlist support and cooperation of child
2. Older children launder their own soiled clothes
  1. Should not be punishment
  2. Allows child's participation and responsibility
Appropriate Bladder Training
1. Scheduled voiding times every 3 to 4 hours while awake (especially in evening)
2. Bed-Wetting Alarm (Enuresis Alarm)
  1. Indicated in Nocturnal Enuresis at least 1-2 times weekly typically in a child age 6 years and older
  2. Most effective treatment for Nocturnal Enuresis (in highly motivated children and their families)
  3. Requires use often for up to 15 weeks for full effect
    1. Reevaluate at 2-3 weeks after starting
    2. Consider other therapy if no effect by 6 weeks (consider re-trial every 2 years despite failed prior trial)
    3. May discontinue after 2 weeks of consecutive dry nights (restart if relapse)
  4. Parents and children must be motivated for success
    1. Parents often need to sleep in same room with child initially to assist awakening to the alarm
    2. Child may need to be awakened and carried to bathroom to finish voiding
3. Behavior Modification (Urotherapy)
  1. Visualization techniques
  2. Void just before bedtime
  3. Limit fluids 1 to 2 hours before bedtime
    1. Drink most of fluids in the morning and afternoon
    2. Target total fluid per day at 30-50 ml/kg/day
    3. Avoid Caffeine
  4. Scheduled awakening during night to void
    1. Some experts do not recommend
4. Positive reinforcement system
  1. Charts the child's progress of dry nights
  2. Given stickers on calendar or points per dry night
Avoid harmful measures
1. Waking child repeatedly during the night to void
  1. Interferes with sleep
  2. Aggravates child and parent
2. Punishing or shaming the child for wetting the bed
3. Intimidating the child or lowering his self esteem
4. Postponing the child's bedtime to decrease Bedwetting

Management
Pharmacologic Therapies

Try to avoid medications if possible
1. Medications are only effective briefly
2. Drug tolerance is common
3. Symptoms are exacerbated after drug is discontinued
4. Adverse effects are common
5. If used, avoid in under age 6 years
Medications: Primary Nocturnal Enuresis
1. dDAVP (Desmopressin, ADH)
  1. Indicated as first line medication when Bed Wetting alarm and Behavior Modification do not control symptoms
  2. Typical dose: 0.2 mg taken 30 to 60 minutes before bedtime
    1. May increase nightly dose by 0.2 mg every 14 days up to a maximum dose of 0.6 mg nightly
    2. Tablets may be split or crushed
    3. Reassess response every 2 weeks
      1. Discontinue if no effect by 2 weeks
      2. If continued, consider tapering off after 3 months
    4. May also consider for intermittent use on overnights or summer camp
  3. Restrict fluid intake to 250 ml in the evening and NO fluid from 1 hour before taking dDAVP until 8 hours after
    1. Risk of Hyponatremia with excessive free water intake
  4. Nasal form is no longer approved for Enuresis due to Hyponatremia (Water Intoxication)
    1. Hyponatremia can also occur with oral form, but less commonly
    2. Robson (2007) J Urol 178(1):24-30. [PubMed]
  5. Effective in children with nocturnal Polyuria (but high relapse rate)
    1. Not effective in low nighttime Urine Output or small Bladder capacity
    2. Also with increased efficacy when combined with Bed-Wetting Alarm (Enuresis Alarm)
  6. Adverse effects
    1. Hyponatremia or Water Intoxication is rare (may present with Headache, Vomiting, Seizures)
    2. Avoid in renal disease, Electrolyte abnormalities, Polyuria and polydipsia
  7. Hold dDAVP when increased fluid intake is needed
    1. Febrile illness
    2. Nausea, Vomiting or Diarrhea
    3. Sports participation
2. Imipramine (or Desipramine)
  1. Indicated as second-line agent when Bed Wetting alarm and Desmopressin fail to control Nocturnal Enuresis
  2. Start at 10 mg orally nightly given one hour before bedtime
    1. Avoid in age <6 years
    2. Age 6 to 12 years: May increase dose by 10 mg every 1-2 weeks as needed (maximum 50 mg per night)
    3. Age >12 years: May increase dose by 10 to 25 mg every 1-2 weeks as needed (maximum 75 mg per night)
  3. Monitoring
    1. Reassess efficacy after one month (may be combined with Desmopressin if inadequate effect)
    2. Consider 1-2 week drug holiday every 3 months to maintain efficacy
  4. Efficacy
    1. Imipramine is as effective as Desmopressin
    2. Acts both centrally and as an antispasmodic
  5. Adverse effects (higher rate when compared with dDAVP)
    1. Not first line due to cardiac ventricular Arrhythmia risk (avoid in QT Prolongation, cardiac sudden death Family History)
    2. Psychosis (e.g. Hallucinations, mania)
    3. Extrapyramidal Side Effects
    4. Antidepressant Withdrawal (taper dose by 50% every 1-2 weeks when discontinuing)
Medications: Urge Incontinence or Diurnal Enuresis
1. Oxybutynin (Ditropan)
  1. Indicated as a third line agent in refractory monosymptomatic Nocturnal Enuresis
    1. Typically combined with Desmopressin or Imipramine
  2. Oxybutynin Immediate Release
    1. Indicated in children age 5 years or older with primarily nighttime symptoms
    2. Dose: 2.5 mg orally nightly given one hour before bed
      1. May increase dose to 5 mg after one week
  3. Oxybutynin Extended Release (Ditropan XR)
    1. Indicated in children age 6 years or older with day and night symptoms
    2. Dose: 5 mg orally nightly given at the same time each day
      1. May increase dose by 5 mg weekly up to a maximum of 20 mg daily
  4. Monitoring
    1. Reevaluate efficacy after 1 to 2 months (effects may be delayed)
    2. Consider in combination with dDAVP (typically inadequate effect as monotherapy)
    3. Consider tapering after every 3 months after effective dose reached
    4. New symptoms may suggest Anticholinergic adverse effects
      1. Dysuria may indicate Urinary Retention
      2. Recurrent Nocturnal Enuresis after dry period may indicate Constipation
  5. Adverse Effects
    1. Anticholinergic side effects
    2. Psychosis (e.g. Hallucinations)
    3. Seizures
    4. Sinus Tachycardia

Course

Annual spontaneous resolution rate of Nocturnal Enuresis: 14-15%
Severe Enuresis (every night, heavy Urine Output and daytime symptoms) is less likely to spontaneously resolve

Complications

Lower self esteem
Lower self confidence
Decreased quality of life
Rangel (2021) Int Braz J Urol 47(3): 535-41 [PubMed]

References