Provoked Enuresis-like Episodes in Healthy Children 7 to 12 Years Old

0022-5347/96/1561-0210$03.00/0 UROLOGY Copyright 0 1996 by AMERICAN UROLOGICAL ASSOCIATION, INC.

Vol. 156,210-213, July 1996 Printed in U . ~ . A

THE JOURNAL OF

PROVOKED ENURESIS-LIKE EPISODES IN HEALTHY CHILDREN 7 TO 12 YEARS OLD JOHN KIRK, PETER VESTERGAARD RASMUSSEN, S0REN RITTIG AND JENS CHR. DJURHUUS From the Institute of Experimental Clinical Research, University of Aarhus and Urological Department K, Skejby University Hospital, Aarhus, Denmark

ABSTRACT

Purpose: We evaluated whether a water load before bedtime provoked enuresis episodes in healthy children with no previous enuresis. We also studied pelvic floor activity during a n enuresis episode and the completeness of bladder emptying, attempted to identify a possible trigger mechanism for nocturnal enuresis, and investigated any age and sex differences regarding the frequency of provoked enuresis episodes. Materials and Methods: We evaluated 55 healthy volunteers (22 girls and 33 boys) 7 to 12 years old who were dry from age 5 years and had no urological or other complaints. Subjects were admitted to the hospital for 4 consecutive nights. Night 1 was for adaptation without a water load. On nights 2 to 4, 25 ml./kg. body weight of water were given orally half an hour before bedtime. During the night pelvic floor activity was monitored, and the time and volume of enuresis and nocturia episodes were noted. Results: In 17 subjects 28 enuresis-like episodes were provoked, generally comprising incomplete voidings with large residual volumes mostly in younger children and in boys. Enuresis and nocturia episodes were provoked at a volume specific for each individual without a relation t o the bladder filling rate. Conclusions: Our results support the hypotheses that nocturnal polyuria is a n important pathogenetic factor in enuresis and that arousal failure can be provoked in nonenuretic subjects. KEY WORDS:enuresis, polyuria, bladder

Development of urinary control is a process of maturation. Infants have an automatic bladder with no bladder control but by age 4% years most children have acquired complete day and night bladder control.' Nevertheless, a significant proportion of children have delayed acquisition of complete bladder control, especially at night. In a population of 7-yearold children J h e l i n et al found a 6.4% rate of nocturnal enuresis with boys more often enuretic than girls.2Hellstrom noted a nearly identical prevalence in 7 to 8-year-old children with enuresis in approximately 7% of girls and 11 to 12%of boys.3 Others have reported that monosymptomatic bedwetting is benign with a high spontaneous cure rate of approximately 15%a n n ~ a l l yHowever, .~ approximately 1 to 2% of the young adult population continue to have enuresis.5.6 Studies of the pathophysiology of monosymptomatic bedwetting have not pinpointed differences in sleep pattern and arousal between normal and enuretic children,7 and enuresis episodes are without relation to any specific sleep stage.8 Nmgaard found that lower urinary tract function in patients with monosymptomatic enuresis is usually nomal.7 Electromyography activity of the pelvic floor is generally not detectable during voiding9 and in enuretic patients the pelvic floor muscle pattern is silent during bladder filling leading to enuresis, in contrast to normal increasing activity during bladder filling leading to arousal and nocturia.7 Studies have also shown that a large proportion of patients with monosymptomatic enuresis have high urine output at night.7.10.11 Nighttime polyuria has been associated with low plasma levels of the antidiuretic hormone,10 and it has been hypothesized that excretion of a large quantity of poorly concentrated urine results in overfilling the bladder and, thereby, enuresis. In animal studies Blok et a1 demonstrated that an increasing fluid load through the ureter causes unstable bladder contractions by stimulating the pen-junctional part Accepted for publication January 26, 1996.

of the bladder.12 Also, increased diuresis is followed by an increased incidence of unstable contractions in patients with bladder instability.13 This bladder activating factor may have a role in the enuresis provoking mechanism, although bladder instability is infrequent in monosymptomatic enuresis.7 In a pilot study we investigated whether high urine output at night may cause nocturnal enuresis in normal nonenuretic children.14 Six of 10 children had enuresis-like episodes after induction of nocturnal polyuria. However, the mechanisms behind this latent lack of nighttime bladder control in normal children are unclear. The aims of our present study were to elucidate whether enuresis episodes may be provoked by water diuresis at night in healthy children with previously acquired bladder control, to evaluate whether any provoked enuresis episode is a normal coordinated voiding with complete bladder emptying, and to investigate the possibility of age and sex differences regarding the frequency of provoked enuresis episodes. MATERIAL AND METHODS

We evaluated 55 healthy volunteers (22 girls and 33 boys) 7 to 12 years old (median age 10) with an even distribution over this age range. Median weight was 33.6 kg. (range 23.8 to 58.9) and median height was 142 cm. (range 125 to 163). The distribution of these values between girls and boys is indicated in the table. All subjects were dry from age 5 years. None of the children had urological or other complaints, and none was taking medication. Health was confirmed by a complete physical examination, including post-void suprapubic ultrasound to exclude bladder emptying difficulties, a questionnaire, a blood test (plasma sodium, potassium, albumin, creatinine, urea, hematocrit, carbon dioxide and osmolality), urine samples (sodium, potassium, creatinine and osmolality) and a urine culture.

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PROVOKED ENURESIS-LIKE EPISODES IN HEALTHY CHILDREN Distribution of age, sex, body weight and height of 55 healthy volunteers Median Kg. Body Wt. (range)

Pt. Age (yrs.) 7 8 9 10 11 12

Totals

No. Girls 3 3 6 4 2 4 22

No. Boys 5 4 5 6 8 5 33

Median Cm. Ht. (range)

Girls

Bow

Girls

33.5 (24.0-36.5) 31.7 (26.0-34.5) 28.0 (24.8-42.9) 35.8 (33.2-45.3) 42.6 (40.7-44.5) 39.9 (35.7-58.9) 34.8 (24.0-58.9)

25.5 (23.a30.0) 26.5 (26.0-29.0) 32.7 (28.6-33.4) 41.3 (30.4-45.3) 39.8 (32.5-43.1) 44.7 (33.1-51.0) 33.4 (23.&51.0)

128 (125-137) 132 (129-137) 131 (125-142) 146 (143-149) 155 157 (150-163) 140 (125-163)

-

Boys

129 (126-132) 129 (127-135) 138 (137-141) 147 (134-152) 148 (142-156) 151 (147-157) 142 (126-157)

The study was approved by the Local Ethical Committee of Aarhus County. The children were admitted to the hospital for 4 consecu90 loo tive nights. During the day they were home with free fluid 50 access. On the 4 evenings 1-hour urine production from 7 to 8 p.m. and urine osmolality were recorded to establish a baseline value for hydration status before water load. Night 1a t the hospital was for adaptation without a water load. On nights 2 to 4 the children were given 25 ml./kg. body weight of water orally half an hour before bedtime. For all 4 nights the children wore an enuresis sensor and pad for estimation of urine volume in case of enuresis. When the pad weighed 5 gm. more by morning, an episode of incontinence/enuresis was recorded. The enuresis alarm device was placed where the children were unable to hear it. Pelvic floor activity was documented on all 4 nights by 2 disposable surface electromyography electrodes placed on the perianal skin at the 2 and 10 o’clock positions. Another similar electrode was placed on the thigh as a grounding plate. Electromyography activity was recorded continuously on a personal 10 computer. Sampling frequency was 65 Hz., low pass cutoff was 20 Hz. and high pass cutoff was 5 kHz. When an enuresis or nocturia episode was observed, the time and urine volume were noted. If the child did not 4 1 2 3 awaken spontaneously after an enuretic episode, helshe was Study night asked to void 5 to 10 minutes later. Post-enuretic voided volume was recorded and osmolality was evaluated. Bladder FIG.1. Number of nocturia (white bars) and enuresis (hatched filling rate before a nocturia or enuresis episode was esti- bars) episodes on 4 study nights. mated from the voided volume, total enuresis volume (enuresis volume plus post-enuretic residual volume) and time since the last voiding. On all 4 nights morning urine volume difference in the number of enuresis episodes between boys and osmolality were measured for all 55 children. and girls did not reach significance (p = 0.095). There was a Results are reported as median values with ranges. For nonsignificant tendency toward decreasing frequency of enanalyses of correlation between variables Pearson’s correla- uresis episodes with increasing age, especially after age 10 tion test was done. An analysis of variance model was used years. In most of the 17 children 1or 2 enuresis episodes were for statistical analyses of the variation in median nocturnal provoked during the 3 water loading nights, although 1child urine production during the 4 study nights. A Pearson chi- had 3 episodes and 1 had 4. During nights 2 to 4 all but 1 square test was performed for comparison of sex distribution child with provoked enuresis had enuresis and nocturia epibetween boys and girls with p <0.05 considered significant. sodes, and there was no significant variation in the number of enuresis or nocturia episodes. The majority of enuresis RESULTS episodes occurred during the first part of the night a t beAll 55 children completed the study. Baseline 1-hour urine tween 1 and 3 hours of sleep (median 100 minutes) and only production and osmolality before water loading did not differ 2 occurred late at night. The relationship between median total enuresis volume significantly among study nights. Median nocturnal urine production increased significantly (p <0.001) after fluid prov- (enuresis volume plus post-enuresis residual volume) and ocation on nights 2 to 4 (median 26.6, 25.1 and 23.4 ml.kg. median nocturia volume for the subjects with enuresis is body weight, respectively) compared to night 1without fluid shown in figure 2, A. There was a highly significant correlation between the 2 volumes (R = 0.861, p <0.001). No signifprovocation (median 5.5 ml./kg. body weight). Overall during the 165 water loading nights there were icant correlation was found between bladder filling rates 224 nocturia episodes, including 80 in 51 cases, 79 in 53 and before a nocturia or enuresis episode (fig. 2, B ) .All but 1child 65 in 49 on nights 2 to 4, respectively (fig. 1).Median urine had a post-enuretic residual volume after the enuresis epivolume was 369 ml. (48 to 938). There were 28 enuresis sodes (median 240 ml., range 0 to 6231, and an inverse episodes, including 7 in 7 cases, 11in 11and 10 in 8 on nights relationship between voided enuresis volume and post2 to 4, respectively. Median urine volume was 40 ml. (5 to enuresis residual volume was observed (R = -0.459, ~ 0 0 )No . reaction to the water load was observed in 1case on p = 0.014, fig. 3). In 11 of the 14 evaluable enuresis episodes pelvic floor nights 2 and 3, and in 2 on night 4. The 28 enuresis episodes occurred in 17 ofthe 55 children (31%), including 6 in 4 of the activity was silent during bladder filling leading to enuresis. 22 girls (18%)and 22 in 13 of the 33 boys (39%).However, the In 2 enuresis episodes increased activity was observed during

1

PROVOKED ENURESIS-LIKE EPISODES IN HEALTHY CHILDREN

212

11

8

800 -

8

10

2 100 -

1 0

, , m , , , , , , , ~ , , I , , , , I , , , , ~ , , , , I , , , , ,

0

~ ~ ~ ~ ~ ~ " ~ ~ " ~ ~ " ~ " ' l ~ ~ ' ~ ~ ' ~ ' l ' ' ' " ' ' ~ ~ l ~

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P 0.0 E

-20

2

0

8

10

12

14

18

18

20

22

24

26

28

-4.0

Enuresr e w e

FIG.3. Enuresis (white bars) and post-enuretic residual (hatched bars) volumes of 28 enuresis episodes. No post-enuretic residual volume was obsened in enuresis episode 21. U-uol, urine volume.

bladder filling and in 1pelvic floor activity fluctuated before the enuresis episode. During the enuresis episode bursts of pelvic muscle activity were noted in most cases followed by a decrease in pelvic floor activity 2 to 3 minutes after the enuresis episode started. Figure 4 shows typical electromyography activity during an enuresis episode. During bladder filling leading to nocturia episodes no marked increase in pelvic floor activity was observed. However, there was pelvic muscle silence during the entire voiding, in contrast to the enuresis episodes. DISCUSSION

Our study demonstrates that it is possible to provoke voiding during sleep in healthy children with otherwise matured bladder function. These enuresis-like episodes were observed mainly in the younger age groups and predominantly in boys. Episodes were characterized by incomplete bladder emptying and a high degree of consistency concerning total bladder volume resulting in enuresis and nocturia, respectively. Because of incomplete bladder emptying and bursts of pelvic floor activity during the enuresis episodes, our findings do not fully comply with the definition of an enuresis episode,7 and they question whether these episodes are real equivalents of enuresis episodes.

0:40:00

0:40:10

0:40:20

0:40:30

0:40:40

0:40:50

0:41:00

0:41:10

Time (h:rn:s)

FIG.4. Pelvic floor electromyography activity during enuresis episode with time at which enuresis sensor was activated (arrow). h:m:s, hours, minutes, seconds.

In a pilot study we noted nonsignificant variation in the frequency of provoked enuresis-like episodes in a 6-day study period (no enuresis-like episodes on day 1but some on successive days).'* Consequently the first night in this study was for adaptation without fluid provocation. The water load was tolerated by most children, although a few had difficulty consuming the large amount of fluid in a short time. Response to the water load was consistent from nights 2 to 4, and nighttime urine output was more than doubled by fluid provocation and resulted in overfilling the bladder capacity in all children. On all 3 nights with fluid provocation we observed a n equal number of enuresis and nocturia episodes, and nighttime urine output was almost 25 ml./kg. body weight (the amount given to the children), indicating equilibrium the following day. In a number of studies enuresis has been associated with high urine output at night.5~10 Nogaard showed that bladder capacity and firnction are normal in enuretic compared to normal children during daytime urodynamics and nighttime artificial bladder filling, and enuresis volume seems to be closely related to bladder capacity on daytime c y s t o m e t ~ . ~ Others have shown that bladder capacity in patients with

PROVOKED ENURESIS-LIKE EPISODES IN HEALTHY CHILDREN

213

CONCLUSIONS enuresis is smaller than in healthy controls.15 We provoked 28 enuresis-like episodes and none of the episodes comprised A water load just before bedtime producing nighttime polynormal coordinated voidings, judging from the bursts of pel- uria can provoke enuresis-like episodes in healthy dry chilvic muscle activity during the episodes. Interestingly enure- dren. Also, enuresis-like and nocturia episodes seem to be sis volumes were generally small but varied greatly. In all triggered by a specific bladder volume characteristic of each but 1 case a large post-enuretic voided volume followed the individual, whereas the bladder filling rate seems not to be a enuresis-like episode, which was usually larger than the enure- major pathogenetic factor in provoked nocturnal enuresis. sis volume (fig. 3). These findings are not consistent with the The finding that most enuresis-like episodes were provoked general conception of a n enuresis episode. An explanation for in the younger age groups indicates that bladder control is a these different findings could be that the bladder in healthy process of maturation, and immature pathways in the central volunteers usually does not become over distended during nervous system may contribute to manifest or latent enurethe night. In the present study intended over distension may sis. Subject age and sex distribution of the enuresis-like have provoked unstable bladder contractions followed by a episodes and the finding that most enuresis-like episodes burst of pelvic muscle activity. However, to our knowledge no occurred during the first hours of sleep indicate that the studies have confirmed that enuresis is without residual mechanism in spontaneous and provoked enuresis may be volume. similar. Numerous definitions of nocturnal enuresis have been proposed through the years. A few authors have defined enuresis volume and the completeness of emptying the bladder during REFERENCES enuresis, and agree that enuretic patients void completely 1. Muellner, S. R.: Development of urinary control in children: during ~ l e e p . ~ .To ~ ' ;our knowledge no studies to date have some aspects of the cause and treatment of primary enuresis. incorporated measurements of post-enuretic residual volume J.A.M.A., 172:1256, 1960. with ultrasound. Our findings may indicate that total blad2. Jarvelin, M. R., Vikevainen-Tervonen, L., Moilanen, I. and der emptying does not always occur during enuresis episodes Huttunen, N. P.: Enuresis in seven-year-old children. Acta but similar studies are needed in children with monosympPaed. Scand., 77: 148, 1988. tomatic nocturnal enuresis. 3. Hellstrom, A.-L.: Dysfunctional bladder in children. Studies in As shown in figure 2, A, there was a highly significant euidemiolow and urotherapv. Gothenburg- University, Thesis, correlation between total enuresis and nocturia volumes. Goteborg, Sweden, p.1, 1990. This finding led to the hypothesis that bladder filling to a 4. Forsythe, W. I. and Redmond, A.: Enuresis and spontaneous specific volume for each individual results in an enuresis or cure rate. Study of 1129 enuretics. Arch. Dis. Child., 4 9 259, 1974. nocturia episode. This specific bladder volume may provide 5. McLain, L. G.: Childhood enuresis. Curr. Probl. Ped., 9 1, 1979. information to the voiding center in the central nervous sys6. Fergusson, D. M., Honvood, L. J. and Shannon, F. T.: Factors tem via the sensory output from the bladder. When this related to the age of attainment of nocturnal bladder control: information is transmitted to the cerebral voiding center a a n 8-year longitudinal study. Pediatrics, 78: 884, 1986. nocturia episode occurs, but when there is a lack of trans7. Norgaard J. P.: Pathophysiology of nocturnal enuresis. Scand. J . mission to the cerebrum or the pathways are immature, the Urol. Nephrol., suppl., 140 1, 1991. full bladder will not be noticed and a n enuresis episode will 8. Mikkelsen, E. J. and Rapoport, J. L.: Enuresis: psychopathology, occur. Also, pelvic floor activity in these otherwise dry indisleep stage, and drug response. Urol. Clin. N. Amer., 7: 361, viduals, which caused interruption of the enuresis episode 1980. 9. Fowler, C. J.:Pelvic floor neurophysiology. In: Manual of Clinical resulting in incomplete bladder emptying, indicates a n alNeurophysiology. Butterworth: Heinemann, pp. 1-20, 1992. most intact sensory pathway. Watanabe and Azuma concluded that enuretic patients 10. Rittig, S., Knudsen, U. B., N ~ r g a a r dJ, . P., Pedersen, E. B. and Djurhuus, J. C.: Abnormal diurnal rhythm of plasma vasopreshave a low frequency of unstable bladder contractions during sin and urinary output in patients with enuresis. Amer. J. daytime cystometry.17 On the other hand, during cystometry Physiol., part 2, 256 F664, 1989. performed at night they reported more frequent unstable 11. Puri, V. N.: Urinary levels of antidiuretic hormone in nocturnal contractions than during the day.17 Experimental animal enuresis. Indian Ped., 17: 675, 1980. data suggest that an increased rate of bladder filling can 12. Blok, C., Coolsaet, B. L. R. A,, Mansour, M. and Razzouk, A,: provoke bladder contractions,12 which could hypothetically Dynamics of the ureterovesical junction: interaction between diuresis and detrusor instability a t the ureterovesical junction contribute to initiation of a n enuresis episode. However, we in pigs. J. Urol., 136 1123, 1986. found no significant relationship between bladder filling rates before enuresis or nocturia episodes, contradicting the 13. van Venrooij, G. E. P.M., Kamphuis, E. T. and Wolthagen, M. J. H. M.: Diuresis cystometry versus filling cystometry: the theory that the rate of bladder filling is a pathogenetic factor diagnostic value of diuresis cystometry in patients with frein enuresis (fig. 2, B ) . quency, urgency, and/or urge incontinence complaints. NeurEnuresis-like episodes were provoked with several similarourol. Urodynam., 6 29, 1987. ities to classic enuretic episodes. Both conditions are induced 14. Rasmussen, P. V., Kirk, J., Borup, K., N ~ r g a a r d ,J. P. and by high urine flow; most provoked enuresis-like episodes Djurhuus, J. Chr.: Enuresis nocturna can be provoked in noroccur during the first 2 hours of sleep, mimicking the premal children by increasing the nocturnal urine output. Scand. ponderance of monosymptomatic nocturnal enuresis during J. Urol. Nephrol., in press. the early hours of sleep;'R the frequency of enuresis-like 15. Starfield, B.: Functional bladder capacity in enuretic and nonenuretic children. J . Ped., 70 777, 1967. episodes decreased with increasing age, and the preponderance of provoked enuresis-like episodes in boys mimicked the 16. HjalmBs, K.: Urinary incontinence in children: suggestions for definitions and terminology. Scand. J. Urol. Nephrol., suppl., spontaneous resolution of nocturnal enuresis and the prepon141: 1, 1992. derance of enuresis in boys.":j However, our study may also 17. Watanabe, H. and Azuma, Y.:A proposal for a classification indicate that normal children are able to respond shortly system of enuresis based on overnight simultaneous monitorafter the initiation of voiding with interruption of voiding. ing of electroencephalography and cystometry. Sleep, 12:257, Whether this ability is part of the normal development of 1989. bladder control, which is absent in children with nocturnal 18. N ~ r g a a r d ,J. P.. Hansen, J . H., Nielsen, J . B., Rittig, S. and Djurhuus, J . C.: Nocturnal studies in enuretics. A polygraphic enuresis, remains to be determined. Also, future studies are study of sleep-EEG and bladder activity. Scand. J. Urol. Nephneeded to elucidate the factors responsible for the arousal rol.. S U.. D D ~ . .125 73. 1989. mechanism after critical bladder filling occurs. I