1. Nocturnal Enuresis Elizabeth H. Kwon, MD, MPH

2. DEFINITIONS In 2006, the International Children’s Continence Society published new standardization for the terminology of enuresis to help clarify day and night wetting.

3. Incontinence Incontinence is defined as the uncontrollable leakage of urine that may be intermittent or continuous and occurs after continence should have been achieved. Continuous incontinence  constant urine leakage (eg. Ectopic ureter, iatrogenic damage to external sphincter ) Intermittent incontinence  urine leaking in discrete amounts during day, night, or both.

4. Definitions continued Enuresis  any urinary wetting that occurs during the night Daytime incontininence  urinary leakage that occurs during the day (no longer called diurnal enuresis) Dysfunctional voiding  inappropriate muscle contraction during voiding that is usually associated with constipation and is referred to as dysfunctional elimination syndrome.

5. PRIMARY NOCTURNAL ENURESIS Nocturnal wetting in a child who has never been dry on consecutive nights for longer than 6 months in children ages 6 and older. SECONDARY NOCTURNAL ENURESIS -New-onset nighttime wetting on consecutive nights after a 6-month or greater period of dryness. -Usually not due to an organic cause. -In some cases, a stressful event, such as a birth of a sibling, a move or the death of a parent or grandparent, is the source. -Should be evaluated and treated like primary without need for additional lab work or studies.

6. Epidemiology of Nocturnal Enuresis AGE: –7 years old: 10%-15 % prevalence –Each subsequent year, 15% of bed wetters become dry –By 15 years of age, only about 1% of adolescents remain enuretic

7. Epidemiology of Nocturnal Enuresis SEX: –Nocturnal enuresis: Boys>girls –Daytime wetting: Girls>boys SOCIOECONOMIC –Enuresis occurs more frequently in lower socioeconomic populations and in larger families

8. Etiology of Nocturnal Enuresis Only 3% of nocturnal enuresis has an organic etiology Examples of organic symptoms: –Polyuria Diabetes insipidus Diabetes mellitus Isothenuria (Sickle Cell Disease) Alcohol, caffeine, medications Habit polydispsia

9. Examples of organic symptoms (cont’d): –Urgency/Frequency UTI bladder calculus from hypercalciuria or bladder foreign body fecal impaction (impinges on bladder’s space) leading to incomplete bladder filling lower urinary tract obstruction, neurogenic bladder or dysfunctional voiding leading to incomplete bladder emptying \

10. Sleep Apnea can cause enuresis Recent studies have shown that patients with sleep apnea have increased atrial natriuretic factor which inhibits the renin- angiotensin-aldosterone pathway leading to increased diuresis. Tonsillectomy, adenoidectomy or both have been shown to cure enuresis significantly in this group of patients.

11. Etiology of Nocturnal Enuresis Since only 3% of nocturnal enuresis is caused by an organic disease state, most nocturnal enuresis is caused by a multifactorial combination of the following: –Genetics –Sleep arousal dysfunction –Urodynamics –Nocturnal Polyuria –Psychological Components –Maturational Delay

12. Genetics –If both parents were bedwetters-->77% chance offspring would have enuresis –If one parent was a bedwetter--> 45% chance offspring would have enuresis –If neither parent--> 15% chance –Concordance for enuresis is 68% for identical twins vs 36% for fraternal twins –Thus, parental age of resolution often predicts when the child’s enuresis should resolve.

13. Sleep Arousal Dysfunction By age 5, most (85%) children can associate between the presence of a full bladder and the sensation in the brain from a full bladder. Daytime urination control is achieved first followed by the ability to wake up in the night to the sensation of a full bladder. Anecdotally, parents report that the bedwetting episodes occur with their children who are difficult to arouse from sleep. However sleep studies HAVE NOT found an association from sound sleep cycles and bedwetting.

14. Nocturnal Polyuria There are some children who may have an abnormal circadian release of ADH. Normally, based on circadian rhythms, nocturnal urine production is approximately 50% less than daytime urine production but this may be altered in some children who suffer from enuresis. Nocturnal polyuria may also be exacerbated by caffeine, alcohol, medications, irregular drink intake, staying up late or its most common cause—habit polydipsia. The patient must try to modify these factors.

15. Psychological Factors Children with ADHD have a 30% increased chance for enuresis vs. controls. Enuresis itself clearly also increases psychosocial problems for the enuretic child such as poor self-esteem, family stress and social isolation. Enuretic children have lower self-esteem than children with chronic, debilitating illnesses. Important to assess the psychosocial symptoms in the patient and family to decide on the aggressiveness of treatment.

16. Bladder Dysfunction Nocturnal enuresis patients have both –Smaller-than normal functional bladder capacities at night –Higher bladder instability at night compared with during the day based on urodynamic studies. Thus diminished bladder capacity and abnormal urodynamics may play a role in some nocturnal enuresis patients.

17. Maturational Delay Children with enuresis have more –fine and gross motor delays, –Perceptual dysfunction –Speech defects. However, most enuretic children eventually are cured with or without treatment.

18. Maturational Delay Thus, maturational delay as a hypothesis for the cause of enuresis may be the most unifying of theories. Perhaps the best way to think about the cause of nocturnal enuresis is a delay in the –maturation of CNS recognition pathways to full bladder sensation, –maturation of circadian rhythms –maturation of nocturnal ADH surges, & –maturation of size of the bladder and bladder stability

19. Evaluation of Nocturnal Enuresis Who should be evaluated? Usually, enuresis at 5 years old concerns parents. It does not concern children usually until around age 7… So generally, at age 6, evaluation should start.

20. History 1) Primary or Secondary 2) Family history 3) Symptoms- Polyuria, Polydipsia, Urgency, Frequency, Dysuria, Abnormal Urine Stream, Constant wetness 4) PMHX- UTI, Bowel complaints (15 % with enuresis have encopresis), Sleep Apnea Symptoms, Sleep Disorders, Developmental delay, ADHD

21. Evaluation of Nocturnal Enuresis Physical Exam—most will have a normal exam –Genitalia Ectopic ureter, labial adhesions, urethral abnormalities, traumatized urethra –Abdomen Distended bladder vs. fecal impaction –Upper airway Mouth breathing secondary to adenoidal hypertrophy –Neurologic Lumbrosacral exam to r/o overlying midline defect (sacral dimples, hair patches, vascular birthmarks) Gait, muscle tone, strength, DTRs and cremasteric, anal, abdominal reflexes. –Direct observation of urinary stream if hx. suggests abnormality.

22. Evaluation of Nocturnal Enuresis Laboratory Tests ( for all workups ) –Urinalysis +/- glucosuria  r/o diabetes mellitus <1.015 specific gravity--r/o diabetes insipidus –Urine Culture if screening UA shows signs of UTI Radiographic tests ( only if has history of UTI ) –Voiding Cystourethrogram and Renal Ultrasound-- if symptoms or signs suggest urinary tract obstruction or neurogenic bladder or history of UTI –Bladder Ultrasonography (pre- and post- voiding)-- to rule out partial emptying Sleep studies (if indicated by history) –To rule out sleep disorders or sleep apnea

23. Management Principles Primary Goal: protect the child’s self-esteem “ I knew that bedwetting was a) wicked and b) outside my control….It was therefore possible to sin without knowing you committed it, without wanting to commit it, and without being able to avoid it….The double beating was a turning point for it brought home to me for the first time the harshness of the environment into which I had been flung…. I had a conviction of sin and folly and weakness such as I don’t remember to have had before.” --George Orwell

24. Management Principles In general: No punishment. Parents should be REASSURED that bedwetting is due to maturational delay and is not intentional. At ages 6-8 y.o. emotional harm can come from being different. Children at this age are often embarrassed and ashamed. They are at an age when peers begin to sleep away from home. It is a family secret. Thus, targeted intervention should be at age 8 at the latest and prior to that should parents/children request it.

25. Management Principles If there is any other comorbid conditions that can lead to enuresis, they must be treated first… –constipation--stool softeners to have daily bowel movements –urinary tract infection---prophylactic antibiotics –sleep apnea—adenoidectomy and tonsillectomy

26. Treatment At ages 6 or 7 all that may be needed to decrease the psychological burden on child and family is to: -describe the condition, -provide medical explanations, -discuss the family history of enuresis -outline its age-specific prevalence However, after age 6, if children and family are bothered by the enuresis and request further intervention, treatment options should be discussed and begun. At age 8, interventions should be actively encouraged since enuresis is having at least a negative effect on the child’s self esteem.

27. Treatment For maximum efficacy of the treatment program the child must accept and be motivated to comply with treatment AND the parent must also fully support the child and the treatment program. Otherwise the treatment is likely to fail and may lead only to further frustration and disappointment.

28. Treatment of Nocturnal Enuresis MOTIVATIONAL THERAPY 1 ) MAKE SURE THE CHILD WANTS TO DO THIS –Remove responsibility from parent –If the child does not want to do the treatment—then wait til he/she is ready to be an active participant 2)MAKE THE GOAL: WAKE UP EACH NIGHT AND USE THE TOILET & forget “hold it til morning” and “make less urine” –The smaller the bladder, the more important to learn to wake up. –The child must do three things: 1)wake up by himself, 2)find the toilet and 3)urinate there.

29. Motivational Treatment(cont’d) 2)MAKE THE TOILET EASY ACCESS –Nightlight in bathroom –Portable potty in child’s bedroom –Bucket or bottle for boys 4)AVOID EXCESS FLUIDS 2 HOURS QHS –No caffeine -- Normal fluid intake is fine 5) LIMIT DAIRY 4 hours QHS -- to decrease urine output from osmotic diuresis 6)EMPTY BLADDER PRIOR TO BEDTIME –Parental reminders or signs 7)NO DIAPERS OR PULLUPS –Maintain message: no wetting bed –Makes morning cleanup harder and thus, increase motivation to wake up at night. –Use plastic protective mattress cover.

30. MotivationalTreatment (cont’d) 8)INCLUDE CHILD IN MORNING CLEANUP –Make child strip sheets, stick it in the washing machine and replace new sheets in a nonpunitive fashion—it’s just part of the natural consequence of bedwetting. –Be sure child takes shower to prevent odor 9)REMIND PARENTS TO PROVIDE ENCOURAGEMENT TO THE CHILD –Provide information sheets to help parents –Parents must remind and support children with the belief that they will eventually be dry 10) USE A DIARY/CHART –Reward the child for a dry night--including for waking up and going to the bathroom

31. Motivational Treatment (cont’d) Success rates with only motivational treatment: –25% completely cured –70% have a decrease in number of wet nights –Once cured—relapse rate is low. –If unsuccessful after 3 to 6 months, a different treatment program should be tried.

32. Enuresis Alarms Alarms are small, portable alarms worn on the body at bedtime that provide an audio or tactile alarm in response to wetness—likely a conditioned response Goal is to “beat the buzzer” and wake up when the bladder feels full before the alarm goes off

33. Enuresis Alarms <>

34. Enuresis Alarms (Cont’d) REASONS FOR FAILURE (20-30%) –Parents d/c too soon—must thoroughly counsel parent in advance the need to be motivated and to use nightly x 3 months for effective treatment. –Child does not hear alarm— try tactile alarm parents must hear the alarm themselves and wake the child up and walk with them to the bathroom. Do not carry child to toilet—the child must be at least somewhat awake for success. –Child is scared of dark--use nitelight/flashlight –Child does not want to use alarm – then use other techniques.

35. Enuresis Alarms (Cont’d) Success is when the child has not triggered the alarm for 1 month because he/she has remained dry. ADVANTAGES –Highest cure rate (~70%) / relapse(~10%) retx. –No adverse effects DISADVANTAGES --Time-consuming-- need to use 2-3 months --Needs motivated parents to keep reminding --Not covered by medical insurances  costs $80- $100 --May disturb sleep for all family

36. Pharmacologic Therapy Used to treat---not to cure while awaiting natural resolution from maturation. 2 MAIN MEDICATIONS: –DDAVP – Imipramine

37. DDAVP (Desmopressin) is the FIRST LINE CHOICE –Mechanism of action: Synthetic analogue of ADH. Decreases urine production by increasing distal tubule water resorption and urine concentration overnight. –Comes in nasal pump and tablets  Nasal pump not recommended for treatment of enuresis secondary to reports of severe hyponatremia leading to seizures and death. –Use tablets for enuresis

38. DDAVP (cont’d) –Dosage: start at 2mg. (one tablet). Increase 2 mg. q 2weeks (max. of 6 mg. qhs) -- Must limit H20 intake to prevent risk of hyponatremia –Duration of action: 9 hours (try to wake kids who sleep longer than that to see if that helps efficacy) –Efficacy: “Either works or it doesn’t”—since it only controls one factor  the volume of nocturnal urine output

39. DDAVP (cont’d) –Problem: 94.3% relapse (since it is only a treatment not a cure) –Side effects: rare –Contraindications: habit polydipsia (hyponatremia)—, hypertension or heart disease –Cost: Expensive but covered by medicaid/insurance –General use: Increase dose every 2 weeks to minimal effective dose, use for 6 months. Then try off for 2 weeks to see if patient has outgrown the problem.

40. Pharmacologic Tx. (Cont’d) IMIPRAMINE –Mechanism of action: anticholinergic effect increases bladder capacity and norardrenergic effect decreases bladder detrusor excitability –Dosage: 25 mg 1 hour qhs (max. 50 mg for 6-12y.o. and 75mg. for >12 y.o.) –Efficacy: 10-60% but relapse rate off tx. is 90% –Disadvantages: low toxic/therapeutic ratio easy to overdose (#1 fatal poisoning in Britain) OD sx.:ventricular tachycardia, coma, seizures Mild side effects found in 20% of patients on correct dose: anxiety, nervousness, constipation, crying, dizziness, dry mouth and anorexia. –Cost: Inexpensive--$5/month

41. Pharmacologic Tx. (Cont’d) How to use pharmacologic treatments? 1)Intermittent use for children> 8 years old for special occasions (camp, trips, vacations) 2)Nightly therapy 3) Combination therapy Use for children>8 years old with frequent enuresis (>4x/week) Children with frequent enuresis and their parents may become disillusioned by frequent rings of the alarm and lack of rapid improvement. Since there is an earlier increase in the number of dry nights, combination tx. may increase motivation.

42. Pharmacologic Tx. (Cont’d) Combination Treatment –Study by Bradbury and Meadow 36 patients used 40mcg. DDAVP qhs until success or maximum of 6 weeks in combo with alarm. 35 patients used alarm alone until success or til the end of the study period. Success (14 consecutive dry nights) rate was significantly greater for the combo tx. (n=27 ) versus the single tx. group (n=13) Same number of relapses (2 wet nights in two weeks after dry for 4 weeks) seen during 6 month period. Similar success and relapse rates in 30 children subgrouped as having family or behavior problems.

43. Conclusions Physiologic nocturnal enuresis is a primary care pediatrician problem, and most do not need urology referral or expensive enuresis programs. AGE –RELATED TREATMENTS <8years—motivational and alarm only with intermittent medication >8 years– continuous medication OR combination alarm and medication If patients relapse after being dry for 1 month, then try again with the prior effective therapy.