Pediatric Nephrology
Pediatr Nephrol (1992) 6:428-432 9 IPNA 1992
Original article Lower urinary tract function after exstrophy closure Jean G. Hollowelll*, Patrick D. Hill2, Patrick G. Duffy 1, and Philip G. Ransleyl 1Department of Urology, Hospital for Sick Children, Great Ormond Street, London, UK 2 Department of Medical Physics, Institute of Urology, London, UK Received November 27, 1991; received in revised form and accepted March 10, 1992
Abstract. Twenty-eight children with bladder exstrophy, prior to surgery for continence, underwent a urodynamic evaluation, cystogram, ultrasound and dimercaptosuccinic acid scan, to define parameters of lower urinary tract function that are a risk for upper tract damage and/or impair development of bladder capacity. The bladders in 7 of 28 demonstrated no storage function [leak pressure)LP) = 0]; but storage parameters could be measured in the other 21. Their LP was 10-35 c m H 2 0 ; 17 of 21 revealed involuntary contractions and 7 of 21 had an end-fill pressure greater than 10 c m H20. Bladder capacity was better in those with a higher LP and those with no involuntary contractions. The 4 patients with bilateral hydronephrosis (3 of whom also had bilateral multiple scars) were among the 6 with LP greater than 30 cm H20. Of the 7 with an end-fill pressure greater than 10 c m H20, 5 had upper tract damage. Involuntary contractions may impair development of capacity. A L P of greater than 30 cm H20 is a risk factor for upper tract damage and an end-fill pressure greater than 10 cm H20 may also be a factor.
Key words: Exstrophy - Paediatric urodynamics - Renal scarring - Hydronephrosis
Introduction Over the last 15-20 years management of bladder exstrophy has altered from urinary diversion to staged reconstruction of the lower urinary tract for most children. The first stage of reconstruction is bladder closure, preferably in the neonatal period. Penile repair and urethral construc-
*Present address: Ttflane University School of Medicine, Children's Hospital, 200 Henry Clay Avenue, New Orleans, LA 70118, USA Correspondence to: J. G. Hollowdl
tion in the males is usually performed around 1 year of age. Continence surgery is commenced at 3 - 5 years of age. Evolution of new surgical techniques now enable successful anatomical closure of the lower abdominal wall, bladder and urethra, greatly improving the cosmetic result [1- 3]. However, achieving adequate bladder capacity and eventually, urinary control, without bladder augmentation, while preserving renal function, still remains one of the most daunting challenges in paediatric surgery. Most of the children with bladder exstrophy are born with normal upper tracts. Following closure, almost all demonstrate vesicoureteral reflux and a large proportion have hydroureteronephrosis. Pyelonephritis and renal scarfing is reported in up to 25%-50% of the children [4-5]. Development of bladder capacity during the period between closure and continence surgery is very variable, and failure to develop adequate capacity has been an indication to proceed to early augmentation, as part of the initial continence procedure [6, 7]. The aetiology of upper tract damage and the factors limiting bladder development following closure have been poorly understood. The development of upper tract damage due to abnormal function of the neurogenic bladder has been well documented [8, 9]. The relationship of bladder dysfunction to progressive renal damage in boys who have had posterior urethral valve ablation has also been studied [10]. Surprisingly, little attention has been given to bladder function, or dysfunction, in exstrophy. This is at least partly due to several suppositions regarding lower tract function following closure. When the everted bladder is initially closed, there is no attempt to create outflow resistance, and it is generally assumed that the closed detrusor actually serves as a conduit rather than providing storage function. Therefore parameters of storage such as compliance, contractility and leak pressure, as well as the standard technique for evaluating these parameters (filling and voiding cystometrograms), have been presumed inapplicable to the exstrophy bladder. With these presumptions, upper tract damage has been primarily attributed to urethral stricture and the mainstay of treatment for hydronephrosis and recurrent urinary
429 tract infections has b e e n urethral dilatation and/or intermittent catheteris ation [ 11]. A preliminary study of f u n c t i o n of the closed exstrophy bladder carried out i n this department demonstrated that in the majority, during the period b e t w e e n bladder closure and c o n t i n e n c e surgery, the bladder did provide storage function and that compliance, contractility and leak pressure could be measured [12]. This study has b e e n extended to define those parameters of lower tract function likely to impair d e v e l o p m e n t of bladder capacity and/or present a risk to the upper tracts. The relationship b e t w e e n physiological bladder pressure and upper tract damage was examined.
Table 1. Bladder capacity following exstrophy closure No. of patients
Capacity (ml) Range
Group 1, LP = 7 cm H20
10-60
Group 2, LP = 10-25 cm H20 A. Stable B. Active Group 3, LP >25 cm H20 A. Stable B. Active
4 9 -
Mean 45
110-250 55- 165
156 100
7a
50-270
142
LP, Leak pressure a The child who was only 17 months was eliminated from this analysis
Patients and methods Twenty-eight children with classical bladder exstrophy were evaluated, including 10 females and 18 males, aged 1.5-11 years (median 6 years). All males in the group had undergone urethral construction at least 9 months prior to the time of study. For all of the children the urine was sterile at the time of study. Of the 28 children, (25%) had a history of at least one urinary infection. However, this should not be interpreted as meaning that the other 75% had maintained sterile urine since bladder closure. Since urinary infection mimics other illnesses in children, the urine is not always evaluated. When it is evaluated it may not always be properly collected, cultured and reported. Therefore, retrospectively obtaining a history of urinary infection in a group such as this is not reliable for reporting the true incidence of bacteriuria. Evaluation of bladder function consisted of monitoring each child for approximately 2 - 6 h during multiple natural fill and void/leak cycles in the sitting and supine positions. The child was allowed to move about on the couch but not on and off the couch due to positioning of the transducers. Bladder pressure was recorded via a 5 CH Infant Cystofix~placed suprapubically under general anaesthesia at least 2 days prior to the bladder function study. Intra-abdominal pressure (measured via a rectal catheter), bladder pressure and subtracted (detrusor) pressure were simultaneously recorded throughout the study using the Ormed UIS 5000 system2. All studies were performed by the same individual. Bladder activity during illling was described as active if there were involuntary contraetions generating bladder pressure greater than or equal to 15 cm H20. Otherwise it was considered stable. End-fill pressure, defined as the maximum baseline bladder pressure reached during natural fill, was recorded as an estimate of compliance. Leak pressure was defined as the minimumtotal bladder pressure (whether from detrusor activity or increased intra-abdominal pressure) during natural filling which resulted in leakage. It should be noted that this is similar to, but not exactly the same as, the leak point pressure, defined as the bladder pressure resulting in leakage during artificial filling and with a catheter in the urethra, and for a patient population with neurogenic bladders due to myelomeningocele [ 13]. Cystograms were performed on all children under general anaesthesia at the time of placement of the suprapubic catheter. The bladder was filled with contrast through an 8-Fr urethral catheter under fluoroscopy until the pressure was 25 -30 cm H20. Cystogram capacity was defined as the total volume of contrast instilled with an adjustment for an estimate of upper tract volume in those with reflux. Renal ultrasound examinations and dimercaptosuccinic acid (DMSA) seans were performed to assess the upper tracts, except in 4 patients in which the cystogram revealed reflux into a renal pelvis and calyces that were not dilated and not distorted.
1Cystofix minipaed CH5, B. Braun, Melsungen AG, Germany 20rmed UIS 5000, Lectromed, Letchworth, Garden City, Hertfordshire, UK
Table 2. Bladder capacity following exstrophy closure for each age group Age (years)
3-4 4-5 5-6 6-7 >7
(n = 5) (n = 8) (n = 4) (n = 4) (n = 6)
Capacity (ml) Range
Mean
10-120 10-165 30-250 40-250 10-270
64 88 123 125 114
Results L o w e r tract f u n c t i o n Of the 28 children, 7 retained small amounts ( 1 0 - 6 0 ml) of urine but leaked frequently without any m e a s u r a b l e increase in bladder pressure (leak pressure = 0). Their lower tracts can best be described as serving as a conduit, and contractility and c o m p l i a n c e could not be measured. The other 21 demonstrated storage function with well-defined filling cycles and a leak pressure of 1 0 - 3 5 c m H20. The cystograms demonstrated bilateral vesicoureteral reflux in 18 of these 21 (85%), unilateral reflux in 2 and no reflux in 1 child.
Bladder activity. Of these 21 children, 17 revealed involuntary contractions and 4 revealed stable bladders. I n most of the 17, the pressures generated from the i n v o l u n t a r y contractions were very variable i n amplitude. The maxim u m amplitude ranged from 15 to 140 c m H20. The amplitude of the contractions did not relate to the leak pressure. The m a x i m u m amplitude was not greater than 40 c m H 2 0 in some with a leak pressure of 30 c m H20, whereas some of those with a leak pressure of only 10 c m H 2 0 produced contractions which generated pressures up to 80 c m H20. End-fill pressure. Baseline bladder pressures of less than 8 c m H 2 0 were m a i n t a i n e d by 14 children throughout the study. The other 7 demonstrated a gradual rise in bladder
430 Table 3. Upper tract damage following closure
No. of patients
Group 1 LP = 0 Group 2 LP = 10-25 Group 3 LP >25
Dilatation on ultrasound
Scars on DMSA scan Unilaterala
Bilateralb
7
None
1
None
12c
None
3
None
4
~1
3
8
DMSA, Dimercaptosuccinicacid The 5 with unilateral scan-ing did not have hydronephrosis b The 3 with bilateral scars were among the 4 in that group with hydronephrosis. The 1 with dilatation but no scars was the 17-month-old child
One child was eliminated from this analysis becanse she had developed hydronephrosis immediately following perimreteral Teflon injection 2 years previously (vesicoureteral obstruction confirmed by diethylene triamine penta-acetic acid scan) and it had not progressed since then
pressure with end-fill pressures of 1 2 - 1 5 cm H 2 0 in 6 and up to 30 c m H 2 0 in 1 child. O f these 7 children, 4 had a leak pressure between 10 and 25 cm H 2 0 and the other 3 had a leak pressure greater than 25 c m H20.
Upper tracts (Table 3)
Leakage. The leak pressure for these 21 children ranged from 10 to 30 cm H20. In the 17 with involuntary contractions, most of the leakage resulted from detrusor activity. However, 8 of these 17 also leaked small amounts with increases in intra-abdominal pressure. In the 4 with stable bladders, the leak pressure was exceeded by increases in intra-abdominal pressure but, interestingly, only when the bladder was near full (near the previously determined cystogram capacity). Pressures of the same or greater magnitude did not cause leakage throughout most of the filling cycle. (In 7 of the 21 children, the pressure resulting in leakage was generated by a combination of an elevated baseline bladder pressure and a transient rise in pressure.)
Bladder capacity Bladder capacity (measured from the cystogram under general anaesthesia) was analysed with respect to leak pressure (measured during the cystometrogram) in order to determine if higher leak pressure promoted better development of capacity (Table 1). The cystogram capacity was used for this correlation because this measure of capacity was obtained independently of the bladder function study. The 1 child who was less than 3 years of age (17 months) was eliminated from this analysis. Capacity was poor in all of those with no resistance to leakage. Among the other 20, capacity was best for the group with stable bladders. For those with involuntary contractions, capacity was better in the group with a leak pressure greater than 25 cm H20. Capacity was also analysed with respect to age (Table 2). A wide range of capacity was seen for each age group. The mean for each group suggests that capacity may increase with age up to 5 years, but not beyond that. When the groups in Table 1 were adjusted to eliminate the potential bias of age, only group 3 was affected, with mean capacity increasing from 142 ml to 225 ml.
Several different components of lower urinary tract function, including leak pressure, end-fill pressure and bladder activity, were examined to determine those parameters which are associated with upper tract damage. O f the 6 children (in group 3) with a leak pressure of 30 cm H20 or greater, 4 had bilateral hydronephrosis, and 3 of these 4 had apparent bilateral diffuse scarring on D M S A scan. Seven children had an end fill-pressure greater than 10 cm H20. Three of these also had a leak pressure greater than or equal to 30 cm H20, and all of these had bilateral renal damage, included in the group mentioned above. Of the other 4, 2 had diffuse defects on D M S A scan which were limited to one kidney, and 2 had normal D M S A images. Only 3 children demonstrated abnormal DMSA images who did not have a leak pressure of 30 cm H20 or greater and/or an end-fill pressure greater than 10 cm H20. The defects in these 3 children were relatively minor. Of these 3 children, 2 had only a single unilateral scar and the other had scars limited to the upper pole of one kidney (indicating segmental scars). Surprisingly, neither the presence nor amplitude of involuntary contractions was associated with upper tract damage.
Discussion
This study of patients with a closed exstrophy bladder aimed to define the parameters of lower tract function likely to impair development of bladder capacity and/or present a risk to the upper tracts. Vesicoureteral reflux and urinary infection are common factors in the development of renal scars and are common problems in exstrophy management. However, only a minority of children with exstrophy develop significant renal damage. Therefore it is important to look for factors which are more specific to those with upper tract damage. This study focused on bladder and urethral function. End-fill pressure was noted to be an "estimate" of compliance. Strictly speaking, compliance is defined as the
431
change in volume per unit change in pressure and is a curve, not a numerical value [14]. End-fill pressure adequately describes compliance in cases where there is minimal change in bladder pressure throughout filling (i. e. the compliance curve is a horizontal line). In cases where compliance varies markedly during filling, reporting only end-fill pressure may actually be misleading. Because only 1 patient in this study had a significant rise in pressure during filling, end-fill pressure was felt to be an adequate description of compliance for the group. However, it may not be valid to apply the norms for end-fill pressure determined by artificial fill cystometrograms [15] to this study, because natural fill may yield lower end-fill pressure. While it is probably valid to label those with an end-fill pressure greater than 10 cm H20 as having "abnormal" compliance, the degree of abnormality may be underestimated with natural filling. In addition, some of those with an end-fill pressure less than 10 cm H20 may not have "normal" compliance as defined by artificial fill studies. Another consideration regarding compliance in this group is that because the majority demonstrate vesicoureteral reflux, end-fill pressure probably reflects compliance of the upper tracts as well as bladder compliance. Regarding the technique employed, although we have no objective data to indicate that natural fill and not using a urethral catheter are superior, we favour this method for several reasons. First, natural fill eliminates the potential artifacts due to the unphysiological rate of fill and unphysiological temperature of artificially instilled fluid, and the requirement of a second catheter for filling. These are factors which may be particularly important in small bladders. Secondly, when a catheter is in the urethra, a higher bladder pressure is probably required for leakage (i. e. a higher leak pressure recorded). This is suggested by the observation that almost none of the children leaked around the urethral catheter when the bladder was filled to a pressure of 25 cm H20 during cystography, although most of them leaked during physiological monitoring at bladder pressures less than 25 cm H20. This could be attributed to the artificial filling or the general anaesthesia, but it is most likely due to the 8-Fr catheter in the urethra [16]. Most importantly, one should realise that if different methods of evaluation are used the parameters relating to upper tract damage, as determined in this study, may not be applicable. Another preference regarding technique is not to perform cystoscopy at the time of placement of the suprapubic lines for this study. Several children who underwent cystoscopy complained of bladder irritability, persisting 2 days after the cystoscopy, when the bladder function study was to be performed. They were, of course, eliminated from this analysis. Also, the value of routine cystoscopy is questionable. The functional significance of a stricture is unknown until the leak pressure is measured. Some strictures may promote development of capacity without increasing the risk of upper tract damage. In contrast, an absence of tight anatomical strictures does not guarantee that the patient has a safe leak pressure. Although all children in this study were catheterised with an 8-Fr urethral catheter for the cystogram, 6 of 28 children had a leak pressure greater than or equal to 30 cm H20.
Higher leak pressures appear to promote better development of capacity. A leak pressure of less than 10 cm H20 resulted in very poor capacity. Within a given range of leak pressure above 10 cm H20, capacity was greater in those with stable bladders. This finding indicates that it is valuable to identify involuntary contractions early in the course of management. Anti-cholinergics may decrease bladder activity and thereby promote development of capacity. The children identified as having involuntary contractions in this study are currently undergoing a trial with anti-cholinergic therapy. Although the risk of adverse side effects from oxybutynin is low, there are two potential problems for this particular group of children of which one should be aware. Alleviating the contractions would appear to eliminate the primary mechanism of bladder emptying, which may increase the risk of infections. Also decreased detrusor activity in those with a high leak pressure may allow high baseline bladder pressures to be maintained. Thus children treated with anti-cholinergics should be carefully monitored and their parents should be informed of the potential risks as well as the fact that their efficacy in this particular setting has not yet been determined. If medical therapy does not prove to be effective for the abnormal detrusor activity, then at the time of initial continence surgery a clam cystoplasty in addition to bladder neck surgery should be considered. Alternatively, one could hypothesise the abnormal detrusor activity may be altered by the bladder neck surgery. However, a study of bladder function after bladder neck surgery (although in a group of children who had not been evaluated prior to the surgery) revealed involuntary contractions in half of the patients [12]. This finding does not encourage optimism that detrusor activity isfavourably altered by the surgery. Several components of bladder and urethral function, including bladder activity, compliance and leak pressure, were examined to identify parameters associated with upper tract damage. The transient elevations in bladder pressure due to involuntary contractions did not appear to present risk to the upper tracts. Hypocompliance resulting in even mild increases in physiological bladder pressure may increase the chance of developing renal scars. This factor will need to be further explored in future studies. These data do indicate that a leak pressure of 30 cm H20 or greater is a significant risk factor for upper tract damage. It is intriguing that leak pressure is the component of lower tract function which is associated with upper tract damage, because this measurement does not correspond to the bladder pressure at which the child actually "lives". The majority of children maintained a low baseline bladder pressure throughout filling, and leakage resulted from very transient elevations in bladder pressure generated by involuntary contractions. Furthermore, because leak pressure was defined as the minimum pressure at which leakage occurred, this did not define the maximum bladder pressure(s) experienced. Although some of the children leaked small amounts at relatively low bladder pressure, they also experienced contractions which generated pressures at the upper end of the spectrum seen in this study. The importance of leak pressure measurement may be that it defines the pressure which can potentially be maintained. For those
432
children whose leakage normally occurs as a result of contractions, it may be envisaged that during periods of relative bladder activity, such as may possibly occur during sleep, bladder pressures equal to the magnitude of the leak pressure may be generated and maintained. This could conceivably explain why higher leak pressure is a risk factor for upper tract damage. Therapy for those children in whom a high leak pressure is identified must be individualised. Although procedures effective in reducing leak pressure (i. e. urethral dilatation, etc.) may be necessary in some children, one must bear in mind that while a high leak pressure may present risk to the upper tracts it appears to promote development of bladder capacity. Ureteroneocystomies, routinely performed in conjunction with continence surgery, may be indicated earlier in some cases where a high leak pressure is identified. However, this procedure should be performed with the understanding that reflux in this setting is not primary reflux but is associated with abnormal bladder function. For many children with high leak pressure, closer surveillance, prophylactic antibiotics and/or intermittent chatheterisation may be the most appropriate management. The lower urinary tract does function as a storage organ in the majority of children following exstrophy closure. Compliance, contractility and leak pressure can be measured meaningfully and provide information important in following the upper tracts and development of bladder capacity. Monitoring during natural filling is the preferred method of evaluation. Acknowledgements. We thank Sister Brid Carr for her assistance with these studies and Mr. Larry Watkinson for his support in information technology. The support for J. G. H. from Action Research and St. Peter's Research Trust is gratefully acknowledged.
References 1. Ansell JS (1979) Surgical treatment of exstrophy of the bladder with emphasis on neonatal primary closure: personal experience with 28 consecutive cases treated at the University of Washington Hospitals from 1962 to 1977: techniques and results. J Urol 121:650-653 2. Osterling JE, Jeffs RD (1987) The importance of a successful initial bladder closure in the surgical management of classical bladder exstrophy: analysis of 144 patients treated at the Johns Hopkins Hospital between 1975 and 1985. J Urol 137:258-262 3. Ransley PG, Duffy PG, Wollin M (1988) Bladder exsu'ophy closure and epispadias repair. In: Spitz L, Nixon HH (eds) Operative surgery (paediatric surgery). Butterworths, London, pp 620-632 4. Turner WR, Ransley PG, Williams DI (1980) Patterns of renal damage in the management of vesical exstrophy. J Urol 124:412-415 5. Mesrobian HJ, Kelalis PP, Kramer SA (1988) Long-term follow-up of 103 patients with bladder exstrophy. J Urol 139:719 - 722 6. Hollowell JG, Ransley PG The surgical management of incontinence in bladder exstrophy. Br J Urol (in press) 7. Gearhart JP, Jeffs RD (1988) Augmentation cystoplasty in the failed exstrophy reconstruction. J Urol 139: 790-793 8. Wang SC, McGuire EJ, Bloom DA (1988) A bladder pressure management system of myelodysplasia - clinical outcome. J Urol 140: 1499-1502 9. Bauer SB, Hallett M, Khoshbin S, Lebowitz RL, Winston KR, Gibson S, Colodney A, Retik AB (1984) Predictive value of urodynamic evaluation in newborns with myelodysplasia. JAMA 252: 650-652 10. Parkhouse HF, Barratt TM, Dillon M J, Duffy PG, Fay J, Ransley PG, Woodhouse CRJ, Williams DI (1988) Long-term outcome of boys with posterior urethral valves. Br J Uro162: 59-62 11. Jeffs RD, Lepor HL (1986) Management of the exstrophy-epispadias complex and urachal anomalies. In: Walsh PC, Gittes RF, Perlmutter AD, Stamey TA (eds) Campbell's urology, vol 2, 5th edn. Saunders, Philadelphia, p 1900 12. Hollowell JG, Hill PD, Duffy PD, Ransley PG (1991) Bladder function and dysfunction in exstrophy and epispadias. Lancet 338: 926-928 13. Bloom DA, McGuire EJ (1989) Practical management of children with myelomeningocele. Dial Pediatr Urol 12:3 - 4 14. Abrams P, Blalvas JG, Stanton SL, Andersen JT (1988) The standardisation of terminology of lower tract function. Scand J Urol Nephrol [Suppl] 114:5 - 2 6 15. Hjalmas K (1988) Urodynamics in normal infants and children. Scand J Urol Nephrol [Suppl] 114:20-27 16. Decter RM, Harpster L (1991) Pitfalls in determination of the leak point pressure (abstract). Proceedings of the 60th Meeting of the American Academy of Pediatrics, p 60
Literature abstract Arch Dis Child (1991) 66: 1284-1286
Covert bacteriuria: long term follow up V. K. Aggarwal, K. Verrier Jones, A. W. Asscher, C. Evans, and L. A. Williams In a longitudinal prospective study 58 schoolgirls with covert bacteriuria were followed up for an average of 11.2 years (range 8.8 to 13.5 years). Intravenous urography was carried out at the start of the study (aged 4 to 11 years) and after completion of the follow up period (aged 14.8 to 22.3 years). After random allocation 27 of these girls received intermittent treatment for covert bacteriuria for the first four years and the control group received no treatment. The effect of covert bacteriuria, treatment, vesicoureteric reflux, and reflux nephropathy at presentation on the final
renal length, progression of scarring, and development of new scars was analysed. No new scars were found in girls with bilaterally normal kidneys. In gifts with reflux nephropathy, three kidneys showed progression of existing scars and two kidneys developed new scars. It was shown that final renal length was not influenced by vesicoureteric reflux or treatment, but reduced renal length at final assessment was associated with the presence of kidney scarring at initial assessment.
Pediatr Nephrol (1992) 6:428-432 9 IPNA 1992
Original article Lower urinary tract function after exstrophy closure Jean G. Hollowelll*, Patrick D. Hill2, Patrick G. Duffy 1, and Philip G. Ransleyl 1Department of Urology, Hospital for Sick Children, Great Ormond Street, London, UK 2 Department of Medical Physics, Institute of Urology, London, UK Received November 27, 1991; received in revised form and accepted March 10, 1992
Abstract. Twenty-eight children with bladder exstrophy, prior to surgery for continence, underwent a urodynamic evaluation, cystogram, ultrasound and dimercaptosuccinic acid scan, to define parameters of lower urinary tract function that are a risk for upper tract damage and/or impair development of bladder capacity. The bladders in 7 of 28 demonstrated no storage function [leak pressure)LP) = 0]; but storage parameters could be measured in the other 21. Their LP was 10-35 c m H 2 0 ; 17 of 21 revealed involuntary contractions and 7 of 21 had an end-fill pressure greater than 10 c m H20. Bladder capacity was better in those with a higher LP and those with no involuntary contractions. The 4 patients with bilateral hydronephrosis (3 of whom also had bilateral multiple scars) were among the 6 with LP greater than 30 cm H20. Of the 7 with an end-fill pressure greater than 10 c m H20, 5 had upper tract damage. Involuntary contractions may impair development of capacity. A L P of greater than 30 cm H20 is a risk factor for upper tract damage and an end-fill pressure greater than 10 cm H20 may also be a factor.
Key words: Exstrophy - Paediatric urodynamics - Renal scarring - Hydronephrosis
Introduction Over the last 15-20 years management of bladder exstrophy has altered from urinary diversion to staged reconstruction of the lower urinary tract for most children. The first stage of reconstruction is bladder closure, preferably in the neonatal period. Penile repair and urethral construc-
*Present address: Ttflane University School of Medicine, Children's Hospital, 200 Henry Clay Avenue, New Orleans, LA 70118, USA Correspondence to: J. G. Hollowdl
tion in the males is usually performed around 1 year of age. Continence surgery is commenced at 3 - 5 years of age. Evolution of new surgical techniques now enable successful anatomical closure of the lower abdominal wall, bladder and urethra, greatly improving the cosmetic result [1- 3]. However, achieving adequate bladder capacity and eventually, urinary control, without bladder augmentation, while preserving renal function, still remains one of the most daunting challenges in paediatric surgery. Most of the children with bladder exstrophy are born with normal upper tracts. Following closure, almost all demonstrate vesicoureteral reflux and a large proportion have hydroureteronephrosis. Pyelonephritis and renal scarfing is reported in up to 25%-50% of the children [4-5]. Development of bladder capacity during the period between closure and continence surgery is very variable, and failure to develop adequate capacity has been an indication to proceed to early augmentation, as part of the initial continence procedure [6, 7]. The aetiology of upper tract damage and the factors limiting bladder development following closure have been poorly understood. The development of upper tract damage due to abnormal function of the neurogenic bladder has been well documented [8, 9]. The relationship of bladder dysfunction to progressive renal damage in boys who have had posterior urethral valve ablation has also been studied [10]. Surprisingly, little attention has been given to bladder function, or dysfunction, in exstrophy. This is at least partly due to several suppositions regarding lower tract function following closure. When the everted bladder is initially closed, there is no attempt to create outflow resistance, and it is generally assumed that the closed detrusor actually serves as a conduit rather than providing storage function. Therefore parameters of storage such as compliance, contractility and leak pressure, as well as the standard technique for evaluating these parameters (filling and voiding cystometrograms), have been presumed inapplicable to the exstrophy bladder. With these presumptions, upper tract damage has been primarily attributed to urethral stricture and the mainstay of treatment for hydronephrosis and recurrent urinary
429 tract infections has b e e n urethral dilatation and/or intermittent catheteris ation [ 11]. A preliminary study of f u n c t i o n of the closed exstrophy bladder carried out i n this department demonstrated that in the majority, during the period b e t w e e n bladder closure and c o n t i n e n c e surgery, the bladder did provide storage function and that compliance, contractility and leak pressure could be measured [12]. This study has b e e n extended to define those parameters of lower tract function likely to impair d e v e l o p m e n t of bladder capacity and/or present a risk to the upper tracts. The relationship b e t w e e n physiological bladder pressure and upper tract damage was examined.
Table 1. Bladder capacity following exstrophy closure No. of patients
Capacity (ml) Range
Group 1, LP = 7 cm H20
10-60
Group 2, LP = 10-25 cm H20 A. Stable B. Active Group 3, LP >25 cm H20 A. Stable B. Active
4 9 -
Mean 45
110-250 55- 165
156 100
7a
50-270
142
LP, Leak pressure a The child who was only 17 months was eliminated from this analysis
Patients and methods Twenty-eight children with classical bladder exstrophy were evaluated, including 10 females and 18 males, aged 1.5-11 years (median 6 years). All males in the group had undergone urethral construction at least 9 months prior to the time of study. For all of the children the urine was sterile at the time of study. Of the 28 children, (25%) had a history of at least one urinary infection. However, this should not be interpreted as meaning that the other 75% had maintained sterile urine since bladder closure. Since urinary infection mimics other illnesses in children, the urine is not always evaluated. When it is evaluated it may not always be properly collected, cultured and reported. Therefore, retrospectively obtaining a history of urinary infection in a group such as this is not reliable for reporting the true incidence of bacteriuria. Evaluation of bladder function consisted of monitoring each child for approximately 2 - 6 h during multiple natural fill and void/leak cycles in the sitting and supine positions. The child was allowed to move about on the couch but not on and off the couch due to positioning of the transducers. Bladder pressure was recorded via a 5 CH Infant Cystofix~placed suprapubically under general anaesthesia at least 2 days prior to the bladder function study. Intra-abdominal pressure (measured via a rectal catheter), bladder pressure and subtracted (detrusor) pressure were simultaneously recorded throughout the study using the Ormed UIS 5000 system2. All studies were performed by the same individual. Bladder activity during illling was described as active if there were involuntary contraetions generating bladder pressure greater than or equal to 15 cm H20. Otherwise it was considered stable. End-fill pressure, defined as the maximum baseline bladder pressure reached during natural fill, was recorded as an estimate of compliance. Leak pressure was defined as the minimumtotal bladder pressure (whether from detrusor activity or increased intra-abdominal pressure) during natural filling which resulted in leakage. It should be noted that this is similar to, but not exactly the same as, the leak point pressure, defined as the bladder pressure resulting in leakage during artificial filling and with a catheter in the urethra, and for a patient population with neurogenic bladders due to myelomeningocele [ 13]. Cystograms were performed on all children under general anaesthesia at the time of placement of the suprapubic catheter. The bladder was filled with contrast through an 8-Fr urethral catheter under fluoroscopy until the pressure was 25 -30 cm H20. Cystogram capacity was defined as the total volume of contrast instilled with an adjustment for an estimate of upper tract volume in those with reflux. Renal ultrasound examinations and dimercaptosuccinic acid (DMSA) seans were performed to assess the upper tracts, except in 4 patients in which the cystogram revealed reflux into a renal pelvis and calyces that were not dilated and not distorted.
1Cystofix minipaed CH5, B. Braun, Melsungen AG, Germany 20rmed UIS 5000, Lectromed, Letchworth, Garden City, Hertfordshire, UK
Table 2. Bladder capacity following exstrophy closure for each age group Age (years)
3-4 4-5 5-6 6-7 >7
(n = 5) (n = 8) (n = 4) (n = 4) (n = 6)
Capacity (ml) Range
Mean
10-120 10-165 30-250 40-250 10-270
64 88 123 125 114
Results L o w e r tract f u n c t i o n Of the 28 children, 7 retained small amounts ( 1 0 - 6 0 ml) of urine but leaked frequently without any m e a s u r a b l e increase in bladder pressure (leak pressure = 0). Their lower tracts can best be described as serving as a conduit, and contractility and c o m p l i a n c e could not be measured. The other 21 demonstrated storage function with well-defined filling cycles and a leak pressure of 1 0 - 3 5 c m H20. The cystograms demonstrated bilateral vesicoureteral reflux in 18 of these 21 (85%), unilateral reflux in 2 and no reflux in 1 child.
Bladder activity. Of these 21 children, 17 revealed involuntary contractions and 4 revealed stable bladders. I n most of the 17, the pressures generated from the i n v o l u n t a r y contractions were very variable i n amplitude. The maxim u m amplitude ranged from 15 to 140 c m H20. The amplitude of the contractions did not relate to the leak pressure. The m a x i m u m amplitude was not greater than 40 c m H 2 0 in some with a leak pressure of 30 c m H20, whereas some of those with a leak pressure of only 10 c m H 2 0 produced contractions which generated pressures up to 80 c m H20. End-fill pressure. Baseline bladder pressures of less than 8 c m H 2 0 were m a i n t a i n e d by 14 children throughout the study. The other 7 demonstrated a gradual rise in bladder
430 Table 3. Upper tract damage following closure
No. of patients
Group 1 LP = 0 Group 2 LP = 10-25 Group 3 LP >25
Dilatation on ultrasound
Scars on DMSA scan Unilaterala
Bilateralb
7
None
1
None
12c
None
3
None
4
~1
3
8
DMSA, Dimercaptosuccinicacid The 5 with unilateral scan-ing did not have hydronephrosis b The 3 with bilateral scars were among the 4 in that group with hydronephrosis. The 1 with dilatation but no scars was the 17-month-old child
One child was eliminated from this analysis becanse she had developed hydronephrosis immediately following perimreteral Teflon injection 2 years previously (vesicoureteral obstruction confirmed by diethylene triamine penta-acetic acid scan) and it had not progressed since then
pressure with end-fill pressures of 1 2 - 1 5 cm H 2 0 in 6 and up to 30 c m H 2 0 in 1 child. O f these 7 children, 4 had a leak pressure between 10 and 25 cm H 2 0 and the other 3 had a leak pressure greater than 25 c m H20.
Upper tracts (Table 3)
Leakage. The leak pressure for these 21 children ranged from 10 to 30 cm H20. In the 17 with involuntary contractions, most of the leakage resulted from detrusor activity. However, 8 of these 17 also leaked small amounts with increases in intra-abdominal pressure. In the 4 with stable bladders, the leak pressure was exceeded by increases in intra-abdominal pressure but, interestingly, only when the bladder was near full (near the previously determined cystogram capacity). Pressures of the same or greater magnitude did not cause leakage throughout most of the filling cycle. (In 7 of the 21 children, the pressure resulting in leakage was generated by a combination of an elevated baseline bladder pressure and a transient rise in pressure.)
Bladder capacity Bladder capacity (measured from the cystogram under general anaesthesia) was analysed with respect to leak pressure (measured during the cystometrogram) in order to determine if higher leak pressure promoted better development of capacity (Table 1). The cystogram capacity was used for this correlation because this measure of capacity was obtained independently of the bladder function study. The 1 child who was less than 3 years of age (17 months) was eliminated from this analysis. Capacity was poor in all of those with no resistance to leakage. Among the other 20, capacity was best for the group with stable bladders. For those with involuntary contractions, capacity was better in the group with a leak pressure greater than 25 cm H20. Capacity was also analysed with respect to age (Table 2). A wide range of capacity was seen for each age group. The mean for each group suggests that capacity may increase with age up to 5 years, but not beyond that. When the groups in Table 1 were adjusted to eliminate the potential bias of age, only group 3 was affected, with mean capacity increasing from 142 ml to 225 ml.
Several different components of lower urinary tract function, including leak pressure, end-fill pressure and bladder activity, were examined to determine those parameters which are associated with upper tract damage. O f the 6 children (in group 3) with a leak pressure of 30 cm H20 or greater, 4 had bilateral hydronephrosis, and 3 of these 4 had apparent bilateral diffuse scarring on D M S A scan. Seven children had an end fill-pressure greater than 10 cm H20. Three of these also had a leak pressure greater than or equal to 30 cm H20, and all of these had bilateral renal damage, included in the group mentioned above. Of the other 4, 2 had diffuse defects on D M S A scan which were limited to one kidney, and 2 had normal D M S A images. Only 3 children demonstrated abnormal DMSA images who did not have a leak pressure of 30 cm H20 or greater and/or an end-fill pressure greater than 10 cm H20. The defects in these 3 children were relatively minor. Of these 3 children, 2 had only a single unilateral scar and the other had scars limited to the upper pole of one kidney (indicating segmental scars). Surprisingly, neither the presence nor amplitude of involuntary contractions was associated with upper tract damage.
Discussion
This study of patients with a closed exstrophy bladder aimed to define the parameters of lower tract function likely to impair development of bladder capacity and/or present a risk to the upper tracts. Vesicoureteral reflux and urinary infection are common factors in the development of renal scars and are common problems in exstrophy management. However, only a minority of children with exstrophy develop significant renal damage. Therefore it is important to look for factors which are more specific to those with upper tract damage. This study focused on bladder and urethral function. End-fill pressure was noted to be an "estimate" of compliance. Strictly speaking, compliance is defined as the
431
change in volume per unit change in pressure and is a curve, not a numerical value [14]. End-fill pressure adequately describes compliance in cases where there is minimal change in bladder pressure throughout filling (i. e. the compliance curve is a horizontal line). In cases where compliance varies markedly during filling, reporting only end-fill pressure may actually be misleading. Because only 1 patient in this study had a significant rise in pressure during filling, end-fill pressure was felt to be an adequate description of compliance for the group. However, it may not be valid to apply the norms for end-fill pressure determined by artificial fill cystometrograms [15] to this study, because natural fill may yield lower end-fill pressure. While it is probably valid to label those with an end-fill pressure greater than 10 cm H20 as having "abnormal" compliance, the degree of abnormality may be underestimated with natural filling. In addition, some of those with an end-fill pressure less than 10 cm H20 may not have "normal" compliance as defined by artificial fill studies. Another consideration regarding compliance in this group is that because the majority demonstrate vesicoureteral reflux, end-fill pressure probably reflects compliance of the upper tracts as well as bladder compliance. Regarding the technique employed, although we have no objective data to indicate that natural fill and not using a urethral catheter are superior, we favour this method for several reasons. First, natural fill eliminates the potential artifacts due to the unphysiological rate of fill and unphysiological temperature of artificially instilled fluid, and the requirement of a second catheter for filling. These are factors which may be particularly important in small bladders. Secondly, when a catheter is in the urethra, a higher bladder pressure is probably required for leakage (i. e. a higher leak pressure recorded). This is suggested by the observation that almost none of the children leaked around the urethral catheter when the bladder was filled to a pressure of 25 cm H20 during cystography, although most of them leaked during physiological monitoring at bladder pressures less than 25 cm H20. This could be attributed to the artificial filling or the general anaesthesia, but it is most likely due to the 8-Fr catheter in the urethra [16]. Most importantly, one should realise that if different methods of evaluation are used the parameters relating to upper tract damage, as determined in this study, may not be applicable. Another preference regarding technique is not to perform cystoscopy at the time of placement of the suprapubic lines for this study. Several children who underwent cystoscopy complained of bladder irritability, persisting 2 days after the cystoscopy, when the bladder function study was to be performed. They were, of course, eliminated from this analysis. Also, the value of routine cystoscopy is questionable. The functional significance of a stricture is unknown until the leak pressure is measured. Some strictures may promote development of capacity without increasing the risk of upper tract damage. In contrast, an absence of tight anatomical strictures does not guarantee that the patient has a safe leak pressure. Although all children in this study were catheterised with an 8-Fr urethral catheter for the cystogram, 6 of 28 children had a leak pressure greater than or equal to 30 cm H20.
Higher leak pressures appear to promote better development of capacity. A leak pressure of less than 10 cm H20 resulted in very poor capacity. Within a given range of leak pressure above 10 cm H20, capacity was greater in those with stable bladders. This finding indicates that it is valuable to identify involuntary contractions early in the course of management. Anti-cholinergics may decrease bladder activity and thereby promote development of capacity. The children identified as having involuntary contractions in this study are currently undergoing a trial with anti-cholinergic therapy. Although the risk of adverse side effects from oxybutynin is low, there are two potential problems for this particular group of children of which one should be aware. Alleviating the contractions would appear to eliminate the primary mechanism of bladder emptying, which may increase the risk of infections. Also decreased detrusor activity in those with a high leak pressure may allow high baseline bladder pressures to be maintained. Thus children treated with anti-cholinergics should be carefully monitored and their parents should be informed of the potential risks as well as the fact that their efficacy in this particular setting has not yet been determined. If medical therapy does not prove to be effective for the abnormal detrusor activity, then at the time of initial continence surgery a clam cystoplasty in addition to bladder neck surgery should be considered. Alternatively, one could hypothesise the abnormal detrusor activity may be altered by the bladder neck surgery. However, a study of bladder function after bladder neck surgery (although in a group of children who had not been evaluated prior to the surgery) revealed involuntary contractions in half of the patients [12]. This finding does not encourage optimism that detrusor activity isfavourably altered by the surgery. Several components of bladder and urethral function, including bladder activity, compliance and leak pressure, were examined to identify parameters associated with upper tract damage. The transient elevations in bladder pressure due to involuntary contractions did not appear to present risk to the upper tracts. Hypocompliance resulting in even mild increases in physiological bladder pressure may increase the chance of developing renal scars. This factor will need to be further explored in future studies. These data do indicate that a leak pressure of 30 cm H20 or greater is a significant risk factor for upper tract damage. It is intriguing that leak pressure is the component of lower tract function which is associated with upper tract damage, because this measurement does not correspond to the bladder pressure at which the child actually "lives". The majority of children maintained a low baseline bladder pressure throughout filling, and leakage resulted from very transient elevations in bladder pressure generated by involuntary contractions. Furthermore, because leak pressure was defined as the minimum pressure at which leakage occurred, this did not define the maximum bladder pressure(s) experienced. Although some of the children leaked small amounts at relatively low bladder pressure, they also experienced contractions which generated pressures at the upper end of the spectrum seen in this study. The importance of leak pressure measurement may be that it defines the pressure which can potentially be maintained. For those
432
children whose leakage normally occurs as a result of contractions, it may be envisaged that during periods of relative bladder activity, such as may possibly occur during sleep, bladder pressures equal to the magnitude of the leak pressure may be generated and maintained. This could conceivably explain why higher leak pressure is a risk factor for upper tract damage. Therapy for those children in whom a high leak pressure is identified must be individualised. Although procedures effective in reducing leak pressure (i. e. urethral dilatation, etc.) may be necessary in some children, one must bear in mind that while a high leak pressure may present risk to the upper tracts it appears to promote development of bladder capacity. Ureteroneocystomies, routinely performed in conjunction with continence surgery, may be indicated earlier in some cases where a high leak pressure is identified. However, this procedure should be performed with the understanding that reflux in this setting is not primary reflux but is associated with abnormal bladder function. For many children with high leak pressure, closer surveillance, prophylactic antibiotics and/or intermittent chatheterisation may be the most appropriate management. The lower urinary tract does function as a storage organ in the majority of children following exstrophy closure. Compliance, contractility and leak pressure can be measured meaningfully and provide information important in following the upper tracts and development of bladder capacity. Monitoring during natural filling is the preferred method of evaluation. Acknowledgements. We thank Sister Brid Carr for her assistance with these studies and Mr. Larry Watkinson for his support in information technology. The support for J. G. H. from Action Research and St. Peter's Research Trust is gratefully acknowledged.
References 1. Ansell JS (1979) Surgical treatment of exstrophy of the bladder with emphasis on neonatal primary closure: personal experience with 28 consecutive cases treated at the University of Washington Hospitals from 1962 to 1977: techniques and results. J Urol 121:650-653 2. Osterling JE, Jeffs RD (1987) The importance of a successful initial bladder closure in the surgical management of classical bladder exstrophy: analysis of 144 patients treated at the Johns Hopkins Hospital between 1975 and 1985. J Urol 137:258-262 3. Ransley PG, Duffy PG, Wollin M (1988) Bladder exsu'ophy closure and epispadias repair. In: Spitz L, Nixon HH (eds) Operative surgery (paediatric surgery). Butterworths, London, pp 620-632 4. Turner WR, Ransley PG, Williams DI (1980) Patterns of renal damage in the management of vesical exstrophy. J Urol 124:412-415 5. Mesrobian HJ, Kelalis PP, Kramer SA (1988) Long-term follow-up of 103 patients with bladder exstrophy. J Urol 139:719 - 722 6. Hollowell JG, Ransley PG The surgical management of incontinence in bladder exstrophy. Br J Urol (in press) 7. Gearhart JP, Jeffs RD (1988) Augmentation cystoplasty in the failed exstrophy reconstruction. J Urol 139: 790-793 8. Wang SC, McGuire EJ, Bloom DA (1988) A bladder pressure management system of myelodysplasia - clinical outcome. J Urol 140: 1499-1502 9. Bauer SB, Hallett M, Khoshbin S, Lebowitz RL, Winston KR, Gibson S, Colodney A, Retik AB (1984) Predictive value of urodynamic evaluation in newborns with myelodysplasia. JAMA 252: 650-652 10. Parkhouse HF, Barratt TM, Dillon M J, Duffy PG, Fay J, Ransley PG, Woodhouse CRJ, Williams DI (1988) Long-term outcome of boys with posterior urethral valves. Br J Uro162: 59-62 11. Jeffs RD, Lepor HL (1986) Management of the exstrophy-epispadias complex and urachal anomalies. In: Walsh PC, Gittes RF, Perlmutter AD, Stamey TA (eds) Campbell's urology, vol 2, 5th edn. Saunders, Philadelphia, p 1900 12. Hollowell JG, Hill PD, Duffy PD, Ransley PG (1991) Bladder function and dysfunction in exstrophy and epispadias. Lancet 338: 926-928 13. Bloom DA, McGuire EJ (1989) Practical management of children with myelomeningocele. Dial Pediatr Urol 12:3 - 4 14. Abrams P, Blalvas JG, Stanton SL, Andersen JT (1988) The standardisation of terminology of lower tract function. Scand J Urol Nephrol [Suppl] 114:5 - 2 6 15. Hjalmas K (1988) Urodynamics in normal infants and children. Scand J Urol Nephrol [Suppl] 114:20-27 16. Decter RM, Harpster L (1991) Pitfalls in determination of the leak point pressure (abstract). Proceedings of the 60th Meeting of the American Academy of Pediatrics, p 60
Literature abstract Arch Dis Child (1991) 66: 1284-1286
Covert bacteriuria: long term follow up V. K. Aggarwal, K. Verrier Jones, A. W. Asscher, C. Evans, and L. A. Williams In a longitudinal prospective study 58 schoolgirls with covert bacteriuria were followed up for an average of 11.2 years (range 8.8 to 13.5 years). Intravenous urography was carried out at the start of the study (aged 4 to 11 years) and after completion of the follow up period (aged 14.8 to 22.3 years). After random allocation 27 of these girls received intermittent treatment for covert bacteriuria for the first four years and the control group received no treatment. The effect of covert bacteriuria, treatment, vesicoureteric reflux, and reflux nephropathy at presentation on the final
renal length, progression of scarring, and development of new scars was analysed. No new scars were found in girls with bilaterally normal kidneys. In gifts with reflux nephropathy, three kidneys showed progression of existing scars and two kidneys developed new scars. It was shown that final renal length was not influenced by vesicoureteric reflux or treatment, but reduced renal length at final assessment was associated with the presence of kidney scarring at initial assessment.
