Enuresis Treatment & Management

The most important reason for treating enuresis is to minimize the embarrassment and anxiety of the child and the frustration experienced by the parents. Most children with enuresis feel very much alone with their problem, and they frequently have issues of low self-esteem. ^[20]  Family members with a history of enuresis should be encouraged to share their experiences and offer moral support to the child. The knowledge that another family member had and outgrew the problem can be therapeutic.

Preliminary management focusing on behavioral modification and positive reinforcement is often helpful. The only therapies that have been shown to be effective in randomized trials are alarm therapy and treatment with desmopressin acetate or imipramine. Nonmonosymptomatic enuresis may be more difficult and time-consuming to treat. ^{[21, 22]}

Bladder training has not been shown to be effective. ^[1] With this therapy, the child is asked to ingest large quantities of fluid and to hold the urine in the bladder without voiding until uncomfortable. A therapeutic approach that involves (a) teaching a child not to respond normally to the sensation of a full bladder and (b) prescribing a therapy that is inherently painful is fundamentally without merit. The results of studies that have reported on this therapy either have been methodologically flawed or have demonstrated no significant improvement.

Enuresis is not a surgically treated condition. Treatment usually is not recommended for children younger than 6 or 7 years. However, ectopic ureter and obstructive sleep apnea (OSA) may respond to specific surgical interventions.

Referral to a pediatric otolaryngologist or a pediatric sleep specialist may be appropriate if OSA is suspected.

Patients with primary enuresis (PE) are asked to keep a diary and should return for evaluation on a monthly basis to assess their progress.

A positive attitude and motivation to be dry are important components of treatment. Children with enuresis benefit from a caring and patient parental attitude; punishment has no role whatsoever. A positive approach by the physician is also important for instilling confidence and enhancing compliance. Many children have given up on achieving dryness, and an optimistic attitude must be encouraged. Behavioral modification with positive reinforcement may enhance treatment results. Consistent follow-up is important to assess therapeutic results.

An explanation of the probable cause of the enuresis is important for every family. If a child has no daytime symptoms or has experienced significant dry spells in the past, it is unlikely that a structural abnormality is causing the enuresis. This should be explained to the parents in order to allay any fears about other causes and to reassure them that invasive investigations are not necessary. Parents should be asked to provide specific examples of potential causes that have them worried, so that the physician can address and help relieve these often irrational fears.

Keen attention to a normal daytime voiding pattern is important. The child should be encouraged to void upon awakening, at common transition times and approximately every 1.5-2 hours, before leaving home or school for any reason, and always before bed. With voiding, the child should relax, use optimal posture, and take time to empty the bladder completely.

At school, children should be encouraged to void regularly, at least two or three times daily. A note for the teacher should be written to ensure that the child is allowed regular access to the bathroom. Children should not be expected to wait for scheduled breaks to void. Holding the urine to the last minute must be discouraged.

Children should be instructed to drink liberal amounts during the day and to maintain optimal hydration throughout the entire day. A well-hydrated child is not thirsty when he or she returns home from school and is not thirsty at bedtime. Thirst should be prevented so that a child does not drink excessive amounts in the evening hours before bed. Children who play sports or who are otherwise physically active in the evening after mealtime should be well hydrated for the activity.

Parents should be asked to take the child to the bathroom to void before bedtime. Because this therapeutic measure is designed only to minimize the quantity of fluid in the bladder, full wakefulness is neither necessary nor desirable. Careful monitoring by a parent is necessary for the trip from bed to bathroom and back. Children should go to bed at an hour calculated to offer the optimal number of sleep hours for their age.

If attention to the above preliminary management program for up to 3 months does not result in dryness, then either alarm therapy or pharmacologic therapy should be considered. Because neither therapy has been shown to be consistently superior to the other, the preliminary choice should be dictated by the clinical setting, the family preference, and the experience of the practitioner.

Alarm therapy offers the possibility of sustained improvement of enuresis and should be considered for every patient. It is reported to alleviate bedwetting by increasing nocturnal bladder capacity or by providing enhanced arousal; it does not reduce nocturnal urine output.

Numerous types alarms are available (eg, using sound, vibration, code words, or a combination of a sound and an electrical impulse). The alarm should be attached at bedtime to the underwear or pajamas in a position chosen to permit prompt sensing of wetness. Although most children with enuresis do not awaken to the alarm, they often stop emptying the bladder. When the alarm sounds, a parent must help the child wake to full consciousness and attend to the bathroom to finish voiding. After the sheets and underwear or pajamas are changed, the child should be returned to bed and the alarm reset.

Some successfully treated children replace enuresis with nocturia, and others sleep dry without the need to void at night. Some improve within the first 2 weeks of treatment, and others improve only after several months. A Cochrane review of 56 randomized trials involving 3257 children concluded that alarm therapy is beneficial. ^[17] About two thirds of children on alarm therapy were dry, but about half relapsed, so that only about a third remained dry at 6-month follow-up.

Optimal results occur when the child is well motivated. Older children usually have better developed motivation. Parental motivation and involvement are also important. The parent should believe that the approach is worthwhile and should be prepared to participate every night for at least 3 consecutive months. Close biweekly or monthly follow-up care is important to sustain motivation, troubleshoot technical problems, and otherwise monitor the therapy.

In successfully treated children, alarm therapy should be continued for at least 3 months and for 1 month after sustained dryness (at least 90% dry nights). Relapses are common, developing in 29-66% of children, and sometimes respond to further alarm therapy. If the child is still wet after a minimum of 3 months of consecutive use, alarm therapy can be discontinued and considered unsuccessful. Failure does not preclude future successful treatment once the child is older and more motivated.

Desmopressin acetate

Desmopressin acetate is the preferred medication for treating children with enuresis. A Cochrane review of 47 randomized trials concluded that desmopressin therapy reduces bedwetting; children treated with desmopressin had an average of 1.3 fewer wet nights per week. ^[18]

The tablet and the orally disintegrating tablet (melt) have similar efficacy. The orally disintegrating tablet is not approved for treatment of pediatric enuresis in the United States. The intranasal formulation carries a black box warning from the US Food and Drug Administration (FDA) and is no longer recommended for enuresis, because of the risk for severe hyponatremia that can cause seizures and death. ^[23]

Desmopressin acetate tablets or orally disintegrating tablets should be administered just before bedtime; the agent appears to be effective for about 8 hours. The recommended starting dose for the tablet is 0.2 mg, and the drug can be titrated as necessary to a maximum dose of 0.6 mg. The equivalent starting dose for the orally disintegrating tablet is 120 µg, and the maximum dose is 360 µg.

Desmopressin’s immediate onset of action allows the flexibility of choosing either intermittent administration for special occasions or long-term use to maintain dryness. For long-term use, desmopressin can be prescribed in 3-month quantities and discontinued between prescriptions to determine whether the wetting persists and thus whether continued use is justified.

The safety profile of desmopressin acetate is favorable, and many studies have documented low rates of adverse effects. For the tablet, the incidence of minor adverse events is not significantly different from that for a placebo.

The only serious adverse effect reported in patients with enuresis treated with desmopressin is the development of seizure or other central nervous system (CNS) symptoms due to water intoxication. A review of case reports of water intoxication associated with desmopressin confirmed that excess fluid intake was a feature in at least six of 11 individuals. ^[24]

This serious adverse effect can be prevented by educating the patient not to consume an excess of fluids on any evening in which desmopressin is administered. A maximum of 1 cup of fluid should be offered at the evening meal, no more than 1 cup between mealtime and bedtime, and no fluid at all within the 2 hours preceding bedtime. Early symptoms of water intoxication include headache, nausea, and vomiting. If these symptoms develop, the medication should be discontinued and the child promptly assessed by a physician.

Combination of alarm therapy with desmopressin therapy has been reported to result in dryness not achievable with either therapy alone.

Anticholinergic agents

An anticholinergic medication might be helpful in some patients, especially those with overactive bladder, dysfunctional voiding, or neurogenic bladder. These medications reduce uninhibited detrusor (bladder muscle) contractions, increase the threshold volume of the bladder  at which an uninhibited detrusor contraction occurs, and enlarge the functional bladder capacity.

Oxybutynin chloride and tolterodine are commonly prescribed in this setting. Oxybutynin chloride also has antispasmodic and analgesic properties. Anticholinergic adverse effects include dry mouth, blurred vision, facial flushing, constipation, poor bladder emptying, and mood changes. Constipation as an adverse event is especially problematic in that it might increase the risk for wetting.

Anticholinergic medications should not be administered during a fever, because one anticholinergic effect is a decrease in sweating. Similarly, they should be used with caution in children who exercise or play strenuously, especially on hot days.

Oxybutynin is given in a dose of 2.5-5 mg administered at bedtime. A long-acting preparation is available but has not been approved for use in children. Tolterodine is not approved for pediatric use. Flavoxate, a urinary spasmolytic, might be helpful in some patients with overactive bladder and dysfunctional voiding but is approved only for children older than 12 years.

The combination of desmopressin acetate and oxybutynin chloride might be efficacious in children with overactive bladder or dysfunctional voiding who respond to anticholinergic therapy with improved daytime symptoms but who continue to wet at night. Long-acting preparations of oxybutynin may be more efficacious for combined use with desmopressin and are thus recommended.

Imipramine

A Cochrane review of 64 randomized trials concluded that imipramine is effective in reducing bedwetting; children treated with imipramine had one fewer wet night per week. ^[19] The relapse rate is high when the medication is discontinued. The usual dose, taken 1-2 hours before bedtime, is 25 mg for patients aged 6-8 years and 50-75 mg for older children and adolescents.

Adverse effects include constipation, difficulty initiating voiding, irritability, drowsiness, reduced appetite, and personality changes. Imipramine overdose can be fatal, and a cautionary warning is necessary with every prescription. Because of the unfavorable adverse effect profile ( especially cardiac side effects) and the significant risk of death with overdose, the World Health Organization (WHO) does not recommend imipramine for the treatment of enuresis.

Children should be instructed to drink a liberal amount during the day, to maintain good hydration throughout the day, and to drink enough to prevent thirst when they arrive home from school and at bedtime. Children who play sports in the evening should be optimally hydrated prior to the activity.

Children should be assessed several months after the initial appointment to monitor progress and to fine-tune the treatment recommendations. Children who do not show any improvement, notwithstanding the best efforts of the child and family, should be referred to a pediatric urology or nephrology program for assessment and for determination of whether further investigations are required and whether other treatment options should be implemented.