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PEDIATRIC UROLOGY
Written by:
Stephen R. Shapiro, M.D.
Generally, enuresis is defined as the involuntary discharge of urine that occurs during sleep at night (enuresis nocturnal). Daytime wetting is generally referred to as diurnal enuresis. Primary (or continuous) enuresis refers to a child who has never been consistently dry. Secondary (or onset) enuresis refers to a child who has been reliably dry for a reasonably long period, such as 6 months to 1 year, and then starts wetting again. Considerable confusion exists as to the criteria that should be used to describe a child as a nocturnal enuretic. It is usually defined in terms of age and statistical prevalence. By defining it as bedwetting in the child in whom the act of voiding otherwise occurs in the normal way, one can avoid considering the minimum age or frequency of the act. Another practical solution is to define nocturnal enuresis as night wetting in the school age child. How often does the child have to wet the bed to be considered as enuretic? This author has defined it as wetting often enough to disturb the parent and child and to cause them to seek professional help. The prevalence of bedwetting decreases with increasing age. At each age, boys wet the bed more often than girls in most series, although in some series the ratio has been closer to 1:1 prior to puberty. In adolescence, boys outnumber girls by as much as 3.5:1. The maximum diminution of wetting occurs between the ages of 1 ½ to 4 ½ years. Between 10 and 15% of children over 5 years of age have a bedwetting problem. It is not entirely clear how many of these children will spontaneously cease wetting the bed by the age of 12. One estimate is that 50% will still be wetting the bed by age 12. Another study of 1,129 enuretic children showed that between the ages of 5 and 9, 14% became dry each year, between 10 and 14, 16%, and, between 15 and 19, a further 16%. This high spontaneous cure rate must be balanced against claims for cures, old or new, by drugs, treatments or operations. Of further interest is the fact that even enuresis diurnal shows a high spontaneous remission rate with age. Andersen and Petersen studied 133 enuretic children aged 4 to 15 years. They found that boys, especially young boys aged 4 to 6, usually fell into the category of children with primary enuresis without behavioral disturbances. Girls, in particular those ages 7 to 10, predominated in the group of children with primary enuresis and behavioral disturbances, as well as those children with secondary enuresis, with or without behavioral disturbances. While this study may be significant, it is unclear what this means for treatment and the results of treatment. The study of Whiteside and Arnold, suggesting that urodynamic studies are normal in patients with nocturnal enuresis and abnormal in patients with nocturnal plus diurnal enuresis, is interesting but will require confirmation, which it is unclear how many of the patients studied were children and how many were adults; in addition, many males were excluded from the study. At present, it is probably best to consider that most enuretic children fall into 2 categories from the urodynamic point of view; either they have small bladders, or they are deep sleepers with normal bladder function. There is clearly some overlap between these groups. Enuresis is a worldwide problem. Treatments have varied from punishments with beatings and threats, frequent rouses at night, medicines and herbs, to some treatments which are probably as sensible as some of our modern treatments, such as tying a frog around the child's waist. The urgency syndrome described by Vincent is not infrequently seen among enuretic females. It is characterized by unpredictable attacks of a sudden urge to micturate, the patient immediately externally compressing the urethra in order to prevent outflow of urine. It is difficult to determine exactly the prognosis, since these children are rarely specifically referred to in most series on enuresis. Families of lower socioeconomic and educational levels have a higher reported prevalence of enuresis. This association becomes more significant as the child gets older. Also there is an increased incidence of enuresis among institutionalized children. Heredity plays a role in enuresis. The closer the genetic relationship, the higher the concordance for enuresis. There is definitely a family incidence of enuresis. The etiology for enuresis is unknown but there is not lack of theories. There is a widespread belief that enuresis is a psychogenic problem. Numerous excellent psychiatric studies have documented that enuresis is not a etiologically homogeneous condition. In most cases, even with secondary enuresis, there will prove to be no demonstrable pathology or psychopathology. Although emotional disorders are more common in bedwetters in children who are dry, most children who wet the bed are nevertheless, normal. The nature of the association between emotional disorder and enuresis remains uncertain in the genesis of secondary enuresis. Because of the many factors shared by disturbed enuretic children and disturbed non-enuretic children, the relationship is unlikely to be simple. Some have suggested that stress and anxiety in the third and fourth year of life play an important part in the etiology of enuresis and that this effect persists into adolescence. Kolvin and Taunch feel that enuresis is due to a maturational delay. MacKeith argues that maturational delay may be the explanation fro bedwetting in children under 5 but not in those over 5. Another idea is that enuresis is due to a poor or deficient learning of a habit pattern. The converse of this states that the longer the habit of nocturnal enuresis wetting persists, the more difficult it is for the patient to achieve nighttime control of urination, with or without treatment. It is also stated that the chance of cure is increased when the treatment is started early in childhood. However, there is little evidence to support either of these points of view, especially in view of the high spontaneous cure rate of enuresis. The smaller bladder capacity of enuretics, which has been demonstrated at all ages, seems to figure prominently in most theories on the etiology of enuresis and, also, affects various therapeutic regimens. A urinary infections is relatively uncommon in enuretic females. An infection must always be ruled out in these cases. However, treatment of the infection does not vary often result in cure of the enuresis. Much has been written regarding the relationship of various sleep patterns and the electroencephalogram enuretics. It seems that enuretic episodes generally occur as the child is arousing from non-REM Stage III or IV sleep prior to entering an REM period. Adolescents and young adults are more likely to be enuretic when arousing from non-REM Stages I or II. It appears that enuresis can occur in any sleep phase except REM (Rapid Eye Movement) sleep. Forty to 70% of children with primary enuresis may show an EEG tracing that could be confused with a seizure disorder in a child with an appropriate history for seizures. Abnormal EEGs are less common in secondary enuresis. The abnormal EEG in an enuretic child has no prognostic significance, and enuresis is clearly not an epileptic equivalent. In fact, the study should not be done for this disorder unless there is a history of seizures. Most parents of enuretic children will state that their child sleeps deeply. This is difficult to measure scientifically and, accordingly, hard to confirm. However, this factor is probably of tremendous significance, if not in the etiology, then in the perpetuation of the disorder. Various allergies have been proposed as the etiological factor of some enuretics. The hypothesis is that the reaction to the various inhaled allergens is expressed as bladder irritability and small bladder capacity. Siegel has shown rather conclusively that there is no relationship between respiratory allergy and enuresis. Food allergies have also been suggested. Various dietary regimens have been proposed but, in general, the most common foods to avoid are said to be cows milk and dairy products, chocolate, cola drinks, eggs, citrus fruits and juices, tomatoes and tomato products. In balance, however, there is really no evidence to suggest that allergy plays a role in the cause or cure of enuresis. Urethral/vaginal reflux has been suggested a s cause for secondary enuresis. This concept is not widely accepted. Somewhat more realistic is the suggestion by Sachdev and Howards that a number of cases of secondary enuresis may be due to pinworm infestation (Enterobius vermicularis). The prevalence of this problem as a cause of secondary enuresis is not clear at this time. However, it would seem practical to check all children with secondary enuresis, especially girls, for pinworm infestation. Obstructive uropathy has been saved for last purposely in this discussion of the etiology of enuresis. From a casual review of the literature, the reader can determine the incidence of obstructive lesions of the urinary system as the cause for enuresis to be totally nonexistent or as high as and occurrence of 95%. Mahony and Leferte have been the strongest advocates of obstructive urophathy as the cause for enuresis. When one looks critically at the types of lesions that are diagnosed as the factor responsible for the enuresis, the nature of the lesion is most unimpressive. In fact, one may even go so far as to describe them as nebulous and ill defined. The diagnosis of distal urethral stenosis prevails in little girls and meatal stenosis and posterior urethral valves prevail among boys with enuresis. Although posterior urethral valves without obstructive urophathy can undoubtedly be a cause of enuresis in occasional cases, the prevailing opinion is that the burden of proof is upon the surgeon to prove the relationship. Avoiding cystourethrogram, documenting dilation of the posterior urethra is probably the best evidence, since the author has had 2 cases with normal flow rates. However, in both cases, there had been bilateral hydronephrosis. It is unlikely that urethral obstructions have anything to do with enuresis in the vast majority of cases. In summary, then, most children become dry at night between the ages of 2 and 4 years. Dryness is a natural development, which seems to emerge in the absence of any training. Clearly, adverse factors during this period may impair the acquisition and security of subsequent dryness. How extensive should the evaluation of children with enuresis be? The history should be quite extensive. It is important to determine how frequently the child voids during the daytime. One must know whether the enuresis is primary or secondary. The maximal bladder capacity can be measured simply by having the child hold his urine as long as possible and then void into a volumetrically measured receptacle. Whether the enuresis is diurnal nocturnal or any combination of these 2 should be determined also. The family history is important. Was the mother or father a bedwetter? At what age did they stop bedwetting? It never ceases to amaze me how a mother who stopped bedwetting at age 12 can bring in a child at the age of 4 and wonder why he is still wetting the bed. Details regarding the urinary stream should be obtained. Does the child void with a good urinary stream? Is there any straining to void? Has there been any history of urinary tract infections? What about siblings? When did they stop wetting the bed? The physical examination should aim to rule out diabetes mellitus or insipidus. Accordingly, a urine specific gravity must be determined. Neurological examination should rule out any evidence for neurogenic vesical dysfunction. Evidence for myelodysplasia should be sought. The rectal examination is essential, and should determine the rectal tone. Perinatal sensation must be normal. The sacrum usually can be palpated, and this maneuver will rule out sacral agenesis. Children with the so call occult neurogenic bladder (non-neurogenic bladder), will usually have a history of both enuresis and encopresis. In addition, in most cases, there is a history of urinary tract infection. The combination of enuresis and encopresis usually suggests a psychological problem. As with enuresis, the encopresis may be primary or secondary. In a sample of 700 4-year-olds. Newson found that encopresis occurred in 31 children, and in only 18 was it severe or persistent. Organic pathology should be ruled out in these cases. The urine should be tested thoroughly. A specific gravity and microscopic urinalysis, as well as urine culture is probably in order. The urine specific gravity is required to rule out diabetes. The IVP and voiding cystourethrogram is clearly not indicated in all cases. The return in terms of abnormal studies will be quite small unless there is some suggestion of pathology in the history and physical examination, whether or not the author obtains these studies is determined by the history and physical examination as well as the anxiety level of the parents and the age of the child. The older the child, the more important it is to obtain these studies. Certainly, by the age of 12, these studies become imperative. Another approach is to wait until a trial of one of the various therapeutic regimes has failed, then obtain the studies. Alternatively, if there is an extremely high anxiety level, a normal IVP and voiding cystourethrogram, although rather expensive, can definitely serve to allay these anxieties. Individual judgements will obviously be required. There are numerous therapeutic regimens available. However, in terms of scientific approach, there are only 2 primary approaches. These consist of drug therapy and conditioning treatment. Most general practitioners and pediatricians who screen these patients have developed their own approach to therapy. Retention control training is probably the simplest measure that can be employed. Increased in functional bladder capacity have been shown to correlate positively with decreased bedwetting. The method employed is that of Muellner and Kimmel and Kimmel. The method is characterized by gradual increase in the retention interval, up to 30 minutes, delivery of reinforcers at the end of the interval, and reinforcement contingent upon liquid intake. The theory upon which this method is based appears very sound, but there does not seem to be well-defined pattern of changes that accompanies the onset of retention control training by which the child. s progress can be measured. The long-term effects of retention control training also remain in question. Follow-up data, extending 6 months or more beyond treatment, are available for only 3 of the 141 subjects that are currently available in the literature for review. The data available do not provide strong support for retention control training as a useful treatment procedure for enuresis. The so-called positive reinforcement approach, described by Marshall, et al combines principles and techniques derived from 2 psychotherapeutic conceptions: 1) reality therapy which emphasizes the patient. s assuming responsibility for his own behavior and 2) techniques of positive reinforcement and response shaping from behavior modification therapy. In essence a progress record is kept and a star is placed on the calendar when the child is dry. Another aid in overcoming enuresis in this method is the technique of response shaping. The alarm clock can be set so that the child awakens and empties his bladder at longer and longer intervals at night. In addition, the sensation awareness technique of Muellner and Kimmel and Kimmel is also employed. This technique is time consuming and difficult to evaluate objectively. What little data does exist suggests that the method leaves little to be desired over merely reassuring the parents that the child will eventually outgrow the enuresis. Other techniques, which are notably unsuccessful, include lifting the child prior to bedtime, severe fluid restrictions and punishment contingencies. On the other hand, simply placing the child on the toilet during the night can be more effective; also, lifting can be slightly effective if it is staggered, rather than performed at the same time. The preventive approach, in essence consists of determining the underlying anxieties with regard to enuresis. This is a form of supportive psychotherapy. All attempts at coercive toilet training must be eliminated. The child's anxiety must be reduce as well. A sense of optimism definitely is helpful. If the parents are willing to wait, it is my opinion that this is the best therapeutic approach. Therefore, when I see a younger child, who only wets the bed at night, I encourage the parents to wait as long as possible before embarking upon a therapeutic regimen. On the other hand, if the child is wetting during the daytime, as well, then this becomes not merely a family problem, but also a social problem. It is interesting to note that the child that wets the bed is really ill and rarely upset with himself. This is in accordance with our current concept that enuresis is not really a disease, but rather a developmental problem which may assume social significance. I prefer to put off therapy as long as possible. I don not believe that earlier therapy will prevent teenage enuretics. Time is on the side of a physician who is awaiting a spontaneous cure. I am amazed at the present-day attitudes that children seem to have in our area towards enuresis. Not only does the bedwetting not bother the child, but also it does not seem to bother the child's friends. Most of the patients that I see readily admit that their friends are aware of the fact that they wet the bed at night. There seems to be an increased tolerance for this sort of problem as compared to some years ago. Accordingly, the pressure for early treatment should be less important. Without doubt, the best form of therapy is the conditioning treatment of enuresis. This form of therapy is so effective that children living in residential homes have responded favorably to it. This form of therapy has not been popular in the United States because the apparatus required has been cumbersome, expensive and difficult to obtain. With the availability of less expensive and more efficient devices, however, this should be the first line of therapy in the future. It has obvious advantages over drug therapy. Complications have been minimal. Obviously, burns have occurred with more complicated, older devices. However, with newer, battery-operated devices, burns should become only of historical interest. Currently I am testing a remarkable new device made by Nytone Medical Products, Inc. 2424 South 900 West, Salt Lake City, UT 84119. Since the current in the device is less that 1 ma, and since the device is battery operated, it is almost inconceivable that burns could occur. Another distinct advantage of this device over older devices is that the alarm goes off as soon as the child begins wetting, since the device is clipped onto the front of the child's underpants. This is a distinct advantage as compared to the bee and pad systems which were previously employed. The idea of a wristwatch is clearly of great appeal to a child. In my initial series, the device has had a greater than 80% success rate in unselected cases. Device that shock the genitals and lower abdomen are clearly to be avoided. More complicated and more expensive devises are less desirable for obvious reasons. I believe that this device, manufacture by the Nytone Company, and other similar devices will open up a new era in the therapy of bedwetters. With easy access to such a device, there is really little reason for most enuretic children to be even seen by a physician before giving this device a trial. If such were the case, then the medical profession could give one big sign of relief and turn its attention to the hard core cases which should be the ones primarily seen by physicians. There are some ways to make behavior therapy somewhat more effective. One technique consists of so-called dry-bed training. This procedure uses a urine alarm apparatus but adds such features as training and inhibiting urination, positive reinforcement for correct urination, training and rapid awakening, in creased fluid intake increased social motivation in being non-enuretic, self-correction of accidents and practice in toileting. After 1 all-night training session, there is rapid control of the bedwetting. Another useful technique is over learning. Over learning consists of requiring the patient to increase his fluid intake immediately prior to bedtime so that additional stress is imposed on the bladder detrusor muscle. There is not question that over learning reduces the relapse rate. In the usual situation, conditioning therapy, with enuresis alarms can be 40 to 80% effective. The relapse rate varies from 20 to 40% and relapses are generally cured by another course of therapy, except in a few exceptional circumstances. With the Nytone Enuresis Alarm, approximately 3 to 6 months are required for total cure. An initial response is usually seen within the first 7 to 10 days. Rarely is psychotherapy indicated in children with enuresis. An occasional child with overt behavior disorder problems is an obvious candidate. The use of self-hypnosis, however, may be applicable in many cases. Olness, et al, report a 75% cure rate using this simple technique in susceptible children. However, due to the specialized nature of the technique, it is unlikely to be widely practiced. The standard form of drug therapy for enuresis now is the use of the tricyclic antidepressants. Tofranil (imipramine hydrochloride) is the mainstay of therapy. It has been proven effective by numerous double-blind studies. It is generally reserve for use in children over the age of 5. A dose of 25 mg. For children under 12, and a dose of 50 mg. For those over 12, is usually sufficient. However, a dose of 75 mg. Is sometimes required in older children. A dose of 100 mg. Has occasionally been referred to in the literature, but runs the added risk of an increased incidence of side effects and complications. The commonest reason for having to stop the drug is the onset of mood or sleep disturbance as the dose is increased. The mechanism of action of imipramine is unknown. The drug definitely has an anticholinergic action, as well as a specific effect on the bladder detrusor (beta-stimulatory). In addition, the central effects of imipramine, in terms of antidepressant action, and its effect on the electroencephalogram, must also be considered. The drug also has an antihistaminic effect. Because it is so highly fat-soluble, it is well distributed in the tissues. However, there are several problems associated with the use of this drug. Some serious complications have been reported. These include rare cases of agranulocytosis and include rare cases of agranulocytosis and various side effects, such as difficulty in urination, atropine0like affects, liver injury, dermatitis, insomnia, agitation, injury, dermatitis, insomnia, agitation, loss of appetite, and personality changes. Electro cardiographic abnormalities have not occurred when less that 5 mg./kg. Has been employed. In general, the therapeutic dose for enuresis is usually in the range of 1 to 2 mg./kg. Sudden death of a child receiving an unusually large single bedtime dose of 14.7 mg./kg. Has occurred. Two hundred and fifty milligrams has been responsible for the death of a 2-year-old, and 750 mg. Was lethal to a 16-year-old adolescent. Doses as small as 10mg./kg. Will usually cause toxicity, and 20 mg./kg will definitely cause toxicity. Accordingly, warning must be given to all parents that this drug must be kept out of reach of children. The drug should only be prescribed in childproof bottles. Unfortunately, although Tofranil can achieve a success rate of 60 to 80%, while the child is taking the drug, there is a very high relapse rate as soon as the drug is discontinued. The overall cure rate is probably as low as 30%. Accordingly, Tofranil can really only be viewed as symptomatic therapy and not really curative. Similar results are obtained with the various derivatives of the tricyclic antidepressants, such as Elavil (amitriptyline hydrochloride) and its congeners. Some other drugs are now currently available that can be effective in the symptomatic therapy of enuresis. Anticholinergic drugs available in the past, such as Pro-Banthine and tincture of belladonna, have rarely been effective. However, the new drug, Ditropan (oxybutynin chloride), does seem to be more effective. It definitely seems worth trying in the child with a small bladder capacity who has not responded to conditioning therapy. Other drugs which have been tried, but which have not been proven to be successful in the treatment of enuresis by double-blind studies, include the alpha sympathetic drugs (amphetamine and ephedrine), the monoamine oxidase inhibitors, the major tranquilizers, pituitary snuff, and anticonvulsants. Other tranquilizers, such as chlordiazepoxide (Librium), have also been unsuccessful. Diuretics should, theoretically, be successful if given early enough and if they result in volume depletion and oliguria. In a similar fashion desmopressin (D.D.A.V.P.) Which is a synthetic analog of antidiuretic hormone, has been employed in the treatment of enuresis. Intranasal installation of 5 to 10 mcg. Gives a prolonged antidiuretic response, lasting approximately 11 hours. The drug has definitely proven effective in approximately two-thirds of cases. Effectiveness can be increased by raising the dose to 40 mcg. Whether this is safe or not remains to be determined. The expense of D.D.A.V.P., and its limited action in treating a symptom rather than the disease, will clearly limit its use to special situations, such as a child going on a holiday or on a school trip. In addition, the relationship of antidiuretic hormone activity to the problem of enuresis should be further investigated. The problem of adult enuretics is beyond the scope of this discussion. In summary, then, in most cases the physician will be dealing with a child with primary or secondary enuresis in whom there is a normal physical examination and a negative urinalysis and urine culture. Even in girls, only 1 in 10 to 20 enuretics will have a urinary tract infection. A thorough history and physical examination is required to rule out organic pathology. Many parents and children, especially in the 4 to 6-year-old age group, will be content with reassurance that there is a good probability of spontaneous cure in the next year or 2. In children with diurnal enuresis, treatment is probably required at and age if the child is going to school. With pure nocturnal enuresis, which accounts for more than two-thirds of cases, a decision whether or not to treat must depend on the family situation and the relationship between the parents and the child. Conditioning therapy would appear to be the primary treatment of choice. In our hands, this has effected cure of diurnal as well as nocturnal enuresis. Drug therapy must be viewed as merely symptomatic
treatment and cannot be expected to result in cure in more than on-third
of the cases. On the other hand, permanent cure can be expected in more
than two-thirds of the cases after the first trial of conditioning
therapy. Complicated urodynamic evaluations are certainly not indicated in
the assessment of most enuretics. Similarly, with a negative history and a
normal physical examination, the intravenous urogram and voiding
cystourethrogram may be reserved until after failure of a therapeutic
regimen. Most patients will be cured by a combination of tincture of time
and therapeutic measures described previously.
University of
California, Davis School of Medicine Reprinted from UROLOGY TIMES, Vol. 6, No. 2, February, 1978.
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