Enuresis

Definition and Introduction

Image courtesy of MOJOE Opens in new window Enuresis is the medical term that refers to the involuntary discharge of urine. Although this is the meaning of the word, many clinicians erroneously use the term to refer to urinary incontinence that occurs during sleep (nocturnal enuresis).

Enuresis may occur in diverse forms; below is a brief summary.

1. Primary enuresis refers to urinary incontinence from birth.
2. Secondary enuresis refers to urinary incontinence that develops after the child has been dry for at least 6 months.
3. Diurnal enuresis refers to urinary incontinence that occurs during the day.
4. Mixed enuresis refers to urinary incontinence that occurs day and night.
5. Monosymptomatic enuresis refers to nocturnal enuresis that occurs without any other symptoms.
6. Polysymptomatic nocturnal enuresis refers to nocturnal incontinence that occurs in association with urinary urgency, the sensation that one must urinate immediately, urge incontinence, voiding due to the presence of an urge to void, or staccato voiding and bursts of voiding.

The process by which our bodies’ physiological maturation interacts with daily psychological events as exemplified in our learning to gain control over urinating is complex and rife with opportunity for learning to go wrong. It involves the establishment of a complex communication between our voluntary and involuntary nervous system and our bladder and its surrounding pelvic floor muscles.

The bladder is very elastic and is comprised of smooth muscle fibers that permit its expansion. Silverstein (2004) noted that:

In newborns urination is a spinal cord reflex. During the first or second year of life, bladder capacity increases as well as simultaneous maturation of the central nervous system, resulting in a greater awareness of bladder filing but still an inability to voluntarily control voiding. Voluntary control of voiding is eventually achieved by the coordinated development of:

1. increased bladder capacity,
2. voluntary control over the external sphincter, and
3. central nervous system control over voiding or inhibition of micturition independent of bladder capacity.
(MacKeith, 1972).

Acquisition of urinary continence is a complex physiological process. Normal continence is attained through appropriate voluntary elimination via sphincter release upon the lowering of the bladder neck when it is full and preventing micturation by contraction of pelvic floor muscles which raises the top of the bladder. (Muellner, 1951; Vincent, 1974)

Considered for some time to be primarily a sleep disorder (Wolfish, Pivik, & Busby, 1997), recent research (Nevéus, 2003) indicates that the sleep of enuretic children is quite normal polysomnographically, but it is also very “deep”: Children with enuresis have high arousal thresholds.

Pathogenesis

Clinical treatment and research into childhood enuresis has revealed a variety of possible contributors, including:

• faulty suppression of urine production by the kidneys to the bladder during sleep (Muellner, 1951);

• malfunction or lack of maturation of the bladder, detrusor, and pelvic floor muscles responsible for adjusting the bladder position as it fills and empties (Muellner, 1960);
• neurological signaling between the cortex and the musculature controlling the bladder, especially during sleep (Yeung, Diao, & Spreedhar, 2008);
• anatomical irregularity or immature growth of the bladder resulting in small bladder capacity (Kawauchi et al., 2003);
• an unsuccessful development of operant or classical conditioning control over awakening in time to void appropriately or to not void until awakening (Gaber El-Anany, Maghraby, El-Din Shaker, & Abdel-Moneim, 1999); and
• either infections anywhere in the urinary tract or a significant number of rare anatomical and physiological anomalies that result in the label of mixed enuresis and that require specific medical interventions.

Treatments for nocturnal enuresis have closely followed these general known causes for primary and secondary nocturnal and diurnal enuresis and can be categorized generally as pharmacological, behavioral, and other. Interventions specific to the variety of medical conditions that are associated with mixed enuresis is beyond the scope of this literature.

Demographic Variables

If one parent is enuretic, then enuresis occurs in children with a 40% increase from the general population and with a 70% increase if both parents are enuretic (Bakwin, 1993). By 5 years of age, 85% of children have gained complete diurnal and nocturnal control of urination. The remaining 15% of children gain urinary continence at a rate of approximately 15% per year.

By 12 to 13 years of age, between 2% and 5% of children will continue to have urinary incontinence or primary nocturnal enuresis. The incidence of primary nocturnal enuresis in adults has been reported to range between approximately 1.5% and 3%. Secondary enuresis occurs in approximately 3% to 8% of children between the ages of 5 and 13 years, and spontaneously resolves at approximately the same rate as primary enuresis (Husmann, 1996).

Impact of the Disorder

Estimated to affect 5 to 7 million children in North America, primary nocturnal enuresis is 3 times more prevalent than daytime wetting and occurs 3 times more often in boys. Secondary causes account for less than 25% of cases (Ramakrishnan, 2008); however, treatment efficacy is greatly dependent on proper ruling out of multiple symptoms (R. Butler & Heron, 2006).

Indeed, Van de Walle and Van Laecke (2008) noted the inconsistent reporting of actual participant admission symptoms due to differences in symptoms reported in the Diagnostic and Statistical Manual of the American Psychiatric Association (APA, 1994) and the terminology outlined in the International Children’s Continence Society (Nevéus et al., 2006).

This has resulted in a general lack of clarity as to the relative effects of different treatments on different subpopulations of persons with enuresis. This observation limits all past and current research findings and conclusions and can only be addressed in future research with standardized reporting of a variety of participant symptoms or lack thereof in all research.

It is increasingly being shown that different subgroups of monosyptomatic enuresis may benefit more from different treatments that have been developed for specific patient characteristics and studies should describe those characteristics to arrive at meaningful conclusions regarding the different forms and treatments of enuresis. This review will also suffer from these limitations.

Pharmacological Interventions

1. Impipramine

Imipramine is a tricyclic antidepressant with anticholinergic effects that can affect nocturnal enuresis by reducing muscle tone of the bladder and by lowering arousal levels of deep sleep, especially in the latter third of nighttime sleeping.

Functionally, imipramine increases bladder capacity and assists in arousing the patient. Unfortunately, the effects of imipramine are closely tied to serum levels and the effective dosage to achieve an effective serum level has been shown to vary as much as 700% from one person to another (Fritz, Rockney, & Yeung, 1994). Additionally, some have reported negative side effects, such as upset stomach, and potentially fatal cardiac arrhythmias can be produced by higher dosages of imipramine (Husmann, 1996).

Less than two wet nights per month have been reported with impipramine for 20%–36% of patients, but cure rate is the same as for no treatment when medication is stopped (Kardash, Hillman, & McGinley, 1970; Martin, 1971; Monda & Husmann, 1995). Most recently Nevéus & Tullus (2008) reported on a trial of imipramine compared to placebo and tolterodine. Although better than placebo, tolterodine was not as effective as imipramine, which resulted in a mean of only 7.8 +/- 5.1 wet nights in a 2–week period with 25 children.

Imipramine is not reliably effective at eliminating monosymptomatic nocturnal enuresis and is the same as placebo for curing enuresis once medication is stopped. Reports of some side effects and the danger of overconsumption causing heart disrythmia reduce its attractiveness as a treatment.

2. Desmopressin

Desmopressin is an analog of the natural pituitary hormone vasopressin acetate, which is responsible for reducing urinary production while we sleep and is believed to be at fault in many monosymptomatic nocturnal enuresis cases (Rittig, Knudsen, Norgaard, Pedersen, & Djurhuus, 1989).

Desmopressin produces an antidiuretic effect resulting in more reabsorption of water by the kidney, more concentrated volume of urine entering the bladder, and overall lower urine production. Its effects are only observed as long as the medication is taken.

Common Behavioral Interventions

1. Urine Alarm

The urine alarm (bell and pad apparatus) is probably the most well-known and most researched treatment for enuresis. Mowrer first examined it in 1938, and since then studies of its effectiveness have led to the identification of strengths and weaknesses of this technique in the treatment of enuresis.

Variations in implementation have been developed to allow it to be used in a variety of different settings, with a variety of different individuals, and to enhance its effectiveness.

In general, the urine alarm consists of a moisture-sensitive switch that closes, setting off the alarm, in the presence of moisture (i.e., urine). For nocturnal enuresis, the moisture sensor is often placed inside the child’s pajamas or under the bed sheets and is activated when the child urinates.

In cases of diurnal enuresis the child usually wears the device inside of his or her under wear. The development of a silent but vibrating alarm has also allowed it to be utilized for cases of diurnal enuresis without the public embarrassment of an audible alarm (Ruckstuhl, 2003).

2. Retention Control Training

Many studies have shown a correlation between enuresis and a reduced functional bladder capacity (De Wacher, Vermande., De Moerloose, & Wyndaele, 2002). For example, Hallman (1950) assessed the bladder capacity of 192 children by giving them a large amount of water and then instructing them to refrain from voiding for as long as possible.

Their urine outputs were then measured over the next 4–6 hours and the largest void was used as a measure of functional bladder capacity. This original finding was then confirmed by subsequent studies (Esperanca & Gerrard, 1969; Starfield, 1967), and has been shown to be true both diurnally and nocturnally (Troup & Hodgson, 1971).

These findings have led to a treatment approach that involves requiring individuals to drink more fluid and then delay urination for an increasingly longer time to remediate the disparate functional bladder capacities of enuretic individuals, but does not directly train skills that may be associated with nocturnal continence. This approach assumes that the correlation between enuresis and functional bladder capacity is causal, meaning that continence problems are seen as a direct result of a smaller functional bladder capacity.

3. Positive Practice

Positive practice has been a common element of treatment in both diurnal and nocturnal enuresis. It involves the repeated practice of going to the bathroom and sitting on the toilet numerous times, in the absence of the urge to urinate. In the case of diurnal enuresis this is often conducted many times throughout the day and the child is required to interrupt ongoing activities to go to the bathroom a specified number of times.

In the case of nocturnal enuresis, the child is required to lie in bed for a specified period of time and then get up out of bed, go to the bathroom, and sit on the toilet. This is often done during waking hours before going to bed and is practiced repeatedly in a given time period. Such practices may also be implemented contingent on an incident of wetting behavior. When the child has an accident they are required to repeat the practice of going to the bathroom and sitting on the toilet.

When an accident has occurred, positive practice is often combined with procedures that involve the restitution of the surrounding environment. This means that the child is required to change clothes or pajamas, clean themselves, clean up the area where urination occurred (for example, remove bedding and replace with clean bedding, and perhaps even do laundry that includes bedding or clothing that contacted urine). These procedures have also been referred to as “Responsibility Training” (Friman & Jones, 1998) and “Cleanliness Training” (Azrin, Sneed, & Foxx, 1974).

4. Stream Interruption Exercises

Stream interruption exercises consist of practice in the initiation and then terminaton of urine flow during a urinary episode. This approach is derived from the treatment of incontinence in women where they are required to contract and relax Kegel muscles in the pelvic floor. As these are the same muscles utilized to stop the flow of urine, this approach seems to be relevant to the treatment of enuresis and is often included as part of a treatment package for enuresis (Friman & Jones, 1998).

5. Waking Schedule

Waking schedules are only applicable to the treatment of nocturnal enuresis and typically involve waking the child at some predetermined interval and guiding them to the bathroom (Azrin et al., 1974). The initial interval until waking may be based on the typical period from the onset of sleep until an incident of wetting occurs.

Waking may occur throughout the night, for example, every hour, or may just occur at the critical time before wetting. These awakenings are then systematically faded out by awakening the child progressively less or earlier in the evening until they can go the bathroom before bed and stay dry until morning. This fading is typically based on a criterion of dry nights.

6. Positive Reinforcement

A number of procedures based on the principle of reinforcement have been utilized in the treatment of enuresis, often used in conjunction with other approaches. Positive reinforcement is often viewed not as a method by which to cure enuresis, but as a way to increase or maintain participation.

Children are often allowed to select items that they would like to earn. Then conditioned reinforcers, such as tokens, points, stars, and so forth, are delivered for appropriate continence-related behaviors and later exchanged for the larger, significant preferred item or activity selected by the child (Friman & Jones, 1998; Harris & Purohit, 1977; Lassen & Fluet, 1979; Paschalis, Kimmel, & Kimmel, 1972; Popler, 1976). Other reinforcement-based procedures have delivered preferred items such as food, toys, or activities directly following appropriate voiding or other continence-related behaviors (LeBlanc, Carr, Crossett, Bennett, & Detweiler, 2005; Samaan, 1972). Reinforcement procedures have been utilized in the treatment of both diurnal and nocturnal enuresis.

7. Dry Bed Training

A combination of many of the aforementioned treatment was first utilized by Azrin et al. (1974). Their treatment package, dry bed training (DBT), included increased fluid intake, scheduled awakenings and reduced intensity of prompts to waken, positive practice, reinforcement of appropriate voiding, use of the urine alarm, wetness awareness (some children need training in discriminating that they have wet underwear or wet bed sheets), and cleanliness or responsibility training.

The addition of reinforcement for appropriate behaviors and other contingencies such as those described Dry Bed Training (DBT) provide a treatment that is consistently effective in a short period of time with few relapses. Parents, given some minimal level of instruction and supervision, can effectively implement DBT.