The history and detailed physical examination are key to diagnosing this condition. The initial step in the evaluation of nocturnal enuresis is obtaining a history. It is essential to determine whether the enuresis is primary or secondary, its pattern (number of episodes in one night and number of nights per week), and caffeine and evening fluid intake. Also, it is just as important to determine the presence of nocturnal polyuria (elicited by asking the parents if the enuretic episodes involve large amounts of urine), polydipsia, dysuria, urgency, frequency, daytime incontinence, abnormal urinary stream, and constipation.[2] The child that has multiple voiding episodes of variable amounts of urine throughout the night can be presumed to have a component of overactive bladder or one of small capacity. Other pertinent questions include family history of enuresis,[2] history of recurrent urinary tract infections (which may point to underlying bowel or bladder dysfunction), sleep disorders, snoring or a diagnosis of sleep-disordered breathing, and the use of chronic medications, since some drugs, may be associated with secondary enuresis.[3] Patients should have screening for psychological or behavioral disturbances, including attention deficit and hyperactivity disorder and learning disabilities, and obtaining a developmental history is also necessary.[8][2]

The physical exam is unremarkable in most affected children. Clinicians should look for distended bladder, rectal exam consistent with fecal impaction,[2] phallic or meatal anomalies in boys and labial adhesions or urethral anomalies in girls, abnormal muscle tone, sensation, or deep tendon reflexes, and skin changes suggestive of occult spinal dysraphism (tuft of hair or sacral dimples).[2]

The laboratory tests besides a urinalysis are usually unnecessary since this test will show alterations in specific gravity in the case of diabetes insipidus, glycosuria in case of diabetes mellitus, and the presence of nitrites, leukocyte esterase, leukocytes, or bacteria in case of infection.[2] Moreover, the non-monosymptomatic enuresis and lack of response to therapy may warrant additional workups,[2] like renal and bladder ultrasound including measurement of post-void residual volume, measurement of urine flow rate, urodynamics studies, and anorectal manometry.

The treatment of this common condition can be tailored according to the patient's underlying cause, and monitoring of treatment plays in a crucial role in a successful response. After identifying the term, it should ideally be treated early, preferably no later than age 6 years.[7] The treatment choice should be tailored to the patient’s most likely underlying pathophysiology and coexisting disorders,[9] and it is essential to take into account that the patient’s and family’s motivation is a significant factor in the success of the intervention.[7] If the patient suffers from constipation, this problem should be treated first [12], and any behavioral or psychological comorbidities should be addressed as well since their presence negatively affects treatment adherence leading to lower success rates.[12][8][13] The initial approach is to try behavioral modifications, including restriction of fluid intake 2 hours before bedtime and of dairy 4 hours before bedtime (to avoid osmotic diuresis) and voiding before going to bed.[2]

By a slight difference over desmopressin, the most effective therapeutic modality is the alarm system.[7] Estimates of cure rates are at 66% to 70% and, even though it takes longer and requires strict daily usage to achieve results, it offers a much lower relapse rate after discontinuation than pharmacological options.[2] It is believed to work through conditioned response.[14] Parents are advised to make the patient wear underwear instead of diapers, and to wake the patient up when the alarm goes off (i. e. when the device senses moisture) if the child does not wake on his own, and the patient should go to the bathroom when this happens.[2] This treatment works best in monosymptomatic enuresis and in older children who are motivated to achieve dryness.[5] Therapy is considered successful if the patient uses the device without triggering the alarm for one month, which usually requires 3 to 4 months of use.[2]

Pharmacologic therapy is used to help treat the disorder while awaiting natural resolution, rather than as a curative measure.[2] It is considered in case of failure to improve with behavioral modifications and alarm therapy, or if the clinical scenario is highly suggestive of specific underlying pathophysiology that receives targeted medication therapy.

The initial choice is desmopressin acetate,[2] a synthetic ADH analog, which works by reducing urine production, and thus the presence of nocturnal polyuria is a predictor for an excellent response to desmopressin,[6] while patients with associated bladder dysfunction or daytime incontinence usually show no response or only a partial one. Desmopressin is also useful for camps or sleepovers.[15] The favorable response, defined as a 50% decrease in the number of wet nights, is achieved in 60% to 70% of patients, but relapses after discontinuation of therapy are frequent.[2]

Also, combining the desmopressin and alarm system can lead to response rates close to 100%.[3] Desmopressin is taken 30 minutes before bedtime at a starting dose of 0.2 mg, which can be titrated up after 14 days without an adequate response to a maximum of 0.6 mg until achieving the desired effect.[1][2] Treatment should be discontinued for 2 weeks after 6 months to see if enuresis has resolved.[2] In its oral presentation, it is well-tolerated and adverse effects are rare,[2] but it is still advised to avoid fluid intake, or restrict it to 250 mL,[1] one hour before and 8 hours after taking the medication to prevent hyponatremia.[6] Due to a higher incidence of severe adverse effects (mainly those consistent with “water intoxication”), the intranasal formulation does not have approval for use in the treatment of enuresis.[2] It is crucial to keep in mind that treatment with desmopressin should temporarily cease during periods when the patient is at increased risk for electrolyte abnormalities, such as when experiencing fever, gastrointestinal losses, or after vigorous exercise.[2]

Anticholinergic agents are suggested as an add-on therapy to non-responders to desmopressin.[2] Patients with non-monosymptomatic enuresis, with overactive bladder, or with small bladder capacity are more likely to respond.[2] Oxybutynin is the most commonly used one, while tolterodine is not FDA-approved for pediatric patients.[1] The adverse reactions of this group of medications include dry mouth and eyes, constipation, flushing, sedation, and cognitive effects.[15]

Furthermore, the Imipramine, a tricyclic antidepressant, is another pharmacological option that should be reserved for older non-responders to first and second-line treatments. Its mechanism of action has been proposed to involve a central effect at the brainstem level promoting arousal and inhibiting urination, a weak anticholinergic, and detrusor antispasmodic effect, increasing ADH release, and suppressing REM sleep.[2] Its response rate is close to 50%, but only 25% of initial responders remain dry long-term after discontinuation, with lower chances if the medication stops abruptly.[2] Adverse effects are uncommon at therapeutic doses but include cardiac arrhythmia, liver toxicity, central nervous system depression, drug interactions, and accidental overdose.[2][1] Some experts suggest screening for long QT syndrome with an electrocardiogram before initiation of therapy.[1] Parents should be advised to store and lock this medication in a safe place out of reach of children.[15]

The most important to exclude conditions before diagnosing enuresis include

• Bladder dysfunction from infection or neurological conditions,
• Incontinence due to anatomical abnormalities, and
• Polyuria secondary to diabetes mellitus, diabetes insipidus, excessive fluid or diuretic intake, or drugs.

DSM V Criteria

• Recurrent episodes of enuresis, whether intentional or involuntary
• The behavior occurs at least twice a week for a minimum of 3 consecutive months
• The enuresis is associated with significant social distress and poor functioning in school
• The behavior occurs in a child who is at least 5 years
• Behavior is not attributed to any medical condition or medication

Enuresis tends to self-resolve spontaneously, with 15% of affected individuals becoming continent per year.[2]

However, the condition is associated with enormous morbidity. The children are susceptible to emotional and physical abuse. The child often has low self-esteem and has poor academic performance.

Of all the treatments, alarm therapy and treatment with imipramine and desmopressin have the highest success. However, the response is slow and as many as 20% will continue to have enuresis as adults.

Enuresis has been found to negatively impact the child’s and family’s quality of life,[8][5] lead to low self-esteem,[8][7] mood problems,[3] and high levels of stress.[8] The condition also impairs the patient’s ability to socialize with peers normally. Additionally, evidence that effective treatment of enuresis leads to improvement in the quality of life of patients.[8]

Referral to a specialist should be a strong consideration for patients with non-monosymptomatic enuresis since they are more likely to fail standard therapy. Suggestions are that patients who do not respond to treatment after three months should obtain a referral to a specialist.[15]

Families should receive counseling on what are the appropriate and inappropriate behavioral interventions for enuresis. Caregivers should also be informed about the natural history of the condition, the different therapeutic options, and the complications associated with delaying treatment.

Nocturnal enuresis is a very common problem in children, leading to embarrassment, social isolation, and loss of self-esteem. Because many people do not admit to the problem, for fear of embarrassment, the exact incidence remains unknown. Because of its significant negative repercussions on the child, the condition is best diagnosed and managed by an interprofessional team. Nurses can assess the effectiveness of therapy, medication compliance, and counsel the family or caregivers. Pharmacists can verify dosing and counsel on proper administration. Concerns in these areas require communication to the rest of the healthcare team. Only through this type of interprofessional collaboration can patient outcomes achieve their optimal potential. [Level V]

Healthcare providers should actively enquire about enuresis during well-child visits since many families still see it as a disciplinary issue instead of a medical condition. Parents need to understand that punishment has no role in the treatment of this condition and may make the enuresis worse.  The nurse should educate the caregiver on alarm therapy, and the pharmacist should provide information about the drugs, their benefits, and adverse effects.

The children should be evaluated every few months to monitor progress.

An interprofessional approach involving the primary care provider, a urologist in the setting of refractory or non-monosymptomatic cases, nurses, and different specialists in case of comorbidities, including mental health professionals, is the ideal line of action to achieve better outcomes.[8] [Level IV]