0022-5347 /79/1223-0373$02.00/0 Vol. 122, September Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
ASSOCIATION OF URINARY TRACT INFECTION AND REFLUX WITH UNINHIBITED BLADDER CONTRACTIONS AND VOLUNTARY SPHINCTERIC OBSTRUCTION STEPHEN A. KOFF, JACK LAPIDES AND DANIEL H. PIAZZA From the Department of Surgery, Section of Urology, University of Michigan Medical Center, Ann Arbor, Michigan
ABSTRACT
We studied 53 neurologically normal children with recurrent urinary tract infection who were found to have bladder-sphincter incoordination characterized by voluntary sphincteric constriction during involuntary uninhibited bladder contraction. Increased intravesical pressure was documented during these events and was associated with vesicoureteral reflux in nearly 50 per cent of the children and with abnormalities of the ureteral orifice in 30 per cent of those without reflux. We hypothesize that increased intravesical pressure causes urinary infection in these children and produces a spectrum of intravesical anatomic distortion that predisposes to vesicoureteral reflux. In a prospective uncontrolled study treatment of the uninhibited bladder contractions allowed 58 per cent of the patients to maintain sterile urine without subsequent antimicrobial therapy after cure of the initial infection. A major problem in pediatric urology relates to difficulty in identifying a cause for most urinary tract infections and in preventing recurrence. As a result, much attention has been directed towards the diagnosis and treatment of obstructive lesions in the lower urinary tract, for example the bladder neck and urethra, which have seemed to be responsible for infection. Recent advances in urodynamic knowledge have demonstrated that obstructive lesions in the lower urinary tract are not necessarily anatomic and that incoordination between the bladder and urinary sphincter can produce pathophysiologically significant obstruction. 1- 5 Similar advances in urodynamic technique now mal:e accurate identification of bladder and sphincter disturbances feasible, even in children. 4- 7 In an attempt to determine the relationship between detrusor-sphincter dysfunction and urinary infection, during the last 3 years all children with recurrent urinary tract infection have undergone complete neurourological testing as part of the routine evaluation. Of these patients 53 have been identified with bladder-sphincter incoordination characterized by voluntary sphincter obstruction during uninhibited bladder contractions. Herein we present the clinical and urodynamic features of this group and the preliminary results of a prospective treatment protocol. MATERIALS AND METHODS
Of 363 children studied during the last 3 years 53 neurologically normal patients with uninhibited bladder contractions were identified and comprise this clinical study group. There were 48 girls and 5 boys, ranging in age from 2.5 to 17 years. All children had been toilet trained and treated previously with multiple courses of antibacterials. Many had had prior urologic investigation and treatment including urethral dilation. In addition to a careful history of voiding and wetting problems, each patient underwent physical examination, urinalysis and culture, voiding cystourethrography, excretory urography (IVP), cystoscopy and combined cystometry and periurethral striated muscle electromyography. The combined cystometric-electromyographic study was done in all children under light nitrous oxide anesthesia and was repeated while awake in those children who would cooperate according to previously described techniques. 7 · 8 A carbon dioxide cystometer with a small caliber urethral catheter was used to measure intravesical pressure and Accepted for publication December 15, 1978.
volume. Saline was substituted for carbon dioxide when voiding dynamics were to be assessed. Direct measurement of the electrical activity in the striated muscles of the urinary sphincter was made with monopolar needle electrodes and a TECA TE4 multichannel recording electromyograph.* Uninhibited contractions were confirmed when necessary by the intravenous administration of propantheline. A urodynamic study was performed at least once in all patients. When voluntary urinary obstruction was diagnosed during uninhibited bladder contraction patients were placed on a similar, uncontrolled, prospective treatment protocol aimed at the infection and the uninhibited bladder activity. All children received 2 to 3 weeks of culture-specific antibiotics and in those with higher grades of reflux (grades III and IV) long-term low dose antibiosis was used. In children with mild reflux (grades I and II) a cautious attempt was made to wean them from antibiotics. Urinalysis and culture were done at 6-week intervals in all patients with reflux to exclude infection. In children without reflux antibiotics were discontinued after initial therapy, and urinalysis and culture were obtained at 2 to 3month intervals. Recurrence of infection was treated in all patients with long-term antibiosis. Uninhibited bladder contractions were treated with anticholinergic drugs in an attempt to reduce the intensity and frequency of the involuntary contractions without interfering with normal micturition, as has been described previously. 9 Dosage was based on body weight and then adjusted according to the symptomatic response and side effects. In general, high doses, often equaling the recommended adult dose, were required and used in all but the smallest child. In addition, frequent voiding and fluid reduction were used to reduce further the frequency of involuntary bladder contraction. RESULTS
All children were normal neurologically and none had bladder emptying problems or a residual urine >25 ml. In 22 children (42 per cent) febrile episodes, including sepsis and clinical pyelonephritis, were recorded. Urinary incontinence was noted in 36 patients (68 per cent), 5 of whom had nocturnal enuresis alone. The remaining 31 children had daytime and nighttime wetting often associated with urgency, frequency and precipitate micturition. During episodes of extreme urgency 6 girls *
373
TECA Corp., 220 Ferris Ave., White Plains, New York.
374
KOFF, LAPIDES AND PIAZZA
assumed a characteristic squatting position similar to a curtsy. In 17 children (32 per cent) there was no history of nocturnal or diurnal enuresis (table 1). There was no difference in the incidence or pattern of urinary incontinence in children with or without vesicoureteral reflux (table 2). Voiding cystourethrography was used to study 96 renal units and in 40 (25 patients) reflux was identified and graded according to established criteria (table 3). IO In nearly two-thirds of the cases the reflux was mild (grades I and II). An IVP was done in all patients and disclosed renal damage in 9 kidneys, which was characterized by focal parenchymal scarring. Damage occurred only in systems with reflux. Cystoscopic examination of 94 of the ureteral orifices studied by cystography revealed that 45 were normal and 49 were abnormal according to the criteria of Lyon and associates. 11 The appearance of the ureteral orifices is correlated with the occurrence of reflux in table 4. Abnormalities of the orifice predominated in children with vesicoureteral reflux (84 per cent). However, in children without reflux nearly one-third (30 per cent) of the ureteral orifices were abnormal. Obvious trabeculation was noted at cystoscopy in 20 children and was significantly more common in those without reflux. Bladder diverticula in the presence of trabeculation were noted in 4 children. No child demonstrated a clinically significant vesical neck contracture, urethral narrowing or meatal stenosis and in none was an anatomic outflow obstruction identified.
TABLE
All children demonstrated uninhibited bladder contractions during combined cystometry and periurethral striated muscle electromyography. The bladder volume at which these contractions occurred ranged from 50 to 150 ml. In some children multiple small contractions preceded a powerful sustained contraction, while in others a single strong contraction occurred unheralded. During the awake studies most children experienced a sense of urgency coincident with the onset of the uninhibited contraction. Each child was instructed specifically not to void during bladder filling even when urgency was perceived. A characteristic abrupt and intense increase in the activity of the periurethral muscles occurred during the uninhibited contraction as the child tightened the sphincter to maintain continence (see figure). However, the uninhibited contraction continued with increasing intravesical pressure and could not be suppressed or dampened. This resulted in higl;i. intravesical pressures often exceeding 150 cm. water. When the child was instructed to void a striking change in the periurethral activity occurred with abrupt cessation of sphincter contraction. With the catheter removed at this point voiding usually proceeded normally to completion with full coordination between bladder contraction and sphincter relaxation. In no patient was a residual urine >25 ml. recorded. The aforementioned treatment protocol produced a marked symptomatic improvement in 30 of the 36 incontinent children, such that daytime frequency, urgency and precipitate micturiTABLE
1. Children with uninhibited bladders
Symptom
No. Pts.
Recurrent infection Febrile episodes Incontinence: Day and night Night only No incontinence
(%)
53 22 36 31 5 17
3. Children with uninhibited bladders and reflux* I II
100 42 68
9
III
16 12
IV
3
* 25 patients and 40 renal units. 32 TABLE
TABLE 2.
Symptom
Reflux
No Reflux
16 12 4
20 19 1 8
9
4. Cystoscopic findings Reflux
Incontinence in children with and without reflux
Wetting: Day and night Night only No incontinence
No. Units
Grade of Reflux
Orifices: Grade 0 Grades 1 and 2 Grade 3 Trabeculation Diverticula
6
2~) 84% 6
2
No Reflux 39 1; ) 30%
14 2
UNINHIBITED BLADDER SPHINCTER CONTROL
c,,
:c E E uJ O!:
::,
V,
Vl UJ O!:
c..
50
VOLUME (ml)
EMG Schematic representation of awake cystometry and sphincter electromyography in child with uninhibited bladder activity and voluntary sphincteric obstruction. Note intense sphincter constriction during unsuppressible involuntary detrusor contraction.
URINARY TRACT INFECTION AND REFLUX
tion were virtually eliminated (no more than 1 accident per week). All children who performed the squatting maneuver were freed from this ritual. In 3 children with daytime and nighttime wetting only the daytime symptoms improved with anticholinergic drug therapy, while 3 other children with only nocturnal enuresis had no improvement in the pattern of wetting. The average period of followup on therapy was 1.3 years with no one followed
THE JOURNAL OF UROLOGY
Copyright© 1979 by The Williams & Wilkins Co.
ASSOCIATION OF URINARY TRACT INFECTION AND REFLUX WITH UNINHIBITED BLADDER CONTRACTIONS AND VOLUNTARY SPHINCTERIC OBSTRUCTION STEPHEN A. KOFF, JACK LAPIDES AND DANIEL H. PIAZZA From the Department of Surgery, Section of Urology, University of Michigan Medical Center, Ann Arbor, Michigan
ABSTRACT
We studied 53 neurologically normal children with recurrent urinary tract infection who were found to have bladder-sphincter incoordination characterized by voluntary sphincteric constriction during involuntary uninhibited bladder contraction. Increased intravesical pressure was documented during these events and was associated with vesicoureteral reflux in nearly 50 per cent of the children and with abnormalities of the ureteral orifice in 30 per cent of those without reflux. We hypothesize that increased intravesical pressure causes urinary infection in these children and produces a spectrum of intravesical anatomic distortion that predisposes to vesicoureteral reflux. In a prospective uncontrolled study treatment of the uninhibited bladder contractions allowed 58 per cent of the patients to maintain sterile urine without subsequent antimicrobial therapy after cure of the initial infection. A major problem in pediatric urology relates to difficulty in identifying a cause for most urinary tract infections and in preventing recurrence. As a result, much attention has been directed towards the diagnosis and treatment of obstructive lesions in the lower urinary tract, for example the bladder neck and urethra, which have seemed to be responsible for infection. Recent advances in urodynamic knowledge have demonstrated that obstructive lesions in the lower urinary tract are not necessarily anatomic and that incoordination between the bladder and urinary sphincter can produce pathophysiologically significant obstruction. 1- 5 Similar advances in urodynamic technique now mal:e accurate identification of bladder and sphincter disturbances feasible, even in children. 4- 7 In an attempt to determine the relationship between detrusor-sphincter dysfunction and urinary infection, during the last 3 years all children with recurrent urinary tract infection have undergone complete neurourological testing as part of the routine evaluation. Of these patients 53 have been identified with bladder-sphincter incoordination characterized by voluntary sphincter obstruction during uninhibited bladder contractions. Herein we present the clinical and urodynamic features of this group and the preliminary results of a prospective treatment protocol. MATERIALS AND METHODS
Of 363 children studied during the last 3 years 53 neurologically normal patients with uninhibited bladder contractions were identified and comprise this clinical study group. There were 48 girls and 5 boys, ranging in age from 2.5 to 17 years. All children had been toilet trained and treated previously with multiple courses of antibacterials. Many had had prior urologic investigation and treatment including urethral dilation. In addition to a careful history of voiding and wetting problems, each patient underwent physical examination, urinalysis and culture, voiding cystourethrography, excretory urography (IVP), cystoscopy and combined cystometry and periurethral striated muscle electromyography. The combined cystometric-electromyographic study was done in all children under light nitrous oxide anesthesia and was repeated while awake in those children who would cooperate according to previously described techniques. 7 · 8 A carbon dioxide cystometer with a small caliber urethral catheter was used to measure intravesical pressure and Accepted for publication December 15, 1978.
volume. Saline was substituted for carbon dioxide when voiding dynamics were to be assessed. Direct measurement of the electrical activity in the striated muscles of the urinary sphincter was made with monopolar needle electrodes and a TECA TE4 multichannel recording electromyograph.* Uninhibited contractions were confirmed when necessary by the intravenous administration of propantheline. A urodynamic study was performed at least once in all patients. When voluntary urinary obstruction was diagnosed during uninhibited bladder contraction patients were placed on a similar, uncontrolled, prospective treatment protocol aimed at the infection and the uninhibited bladder activity. All children received 2 to 3 weeks of culture-specific antibiotics and in those with higher grades of reflux (grades III and IV) long-term low dose antibiosis was used. In children with mild reflux (grades I and II) a cautious attempt was made to wean them from antibiotics. Urinalysis and culture were done at 6-week intervals in all patients with reflux to exclude infection. In children without reflux antibiotics were discontinued after initial therapy, and urinalysis and culture were obtained at 2 to 3month intervals. Recurrence of infection was treated in all patients with long-term antibiosis. Uninhibited bladder contractions were treated with anticholinergic drugs in an attempt to reduce the intensity and frequency of the involuntary contractions without interfering with normal micturition, as has been described previously. 9 Dosage was based on body weight and then adjusted according to the symptomatic response and side effects. In general, high doses, often equaling the recommended adult dose, were required and used in all but the smallest child. In addition, frequent voiding and fluid reduction were used to reduce further the frequency of involuntary bladder contraction. RESULTS
All children were normal neurologically and none had bladder emptying problems or a residual urine >25 ml. In 22 children (42 per cent) febrile episodes, including sepsis and clinical pyelonephritis, were recorded. Urinary incontinence was noted in 36 patients (68 per cent), 5 of whom had nocturnal enuresis alone. The remaining 31 children had daytime and nighttime wetting often associated with urgency, frequency and precipitate micturition. During episodes of extreme urgency 6 girls *
373
TECA Corp., 220 Ferris Ave., White Plains, New York.
374
KOFF, LAPIDES AND PIAZZA
assumed a characteristic squatting position similar to a curtsy. In 17 children (32 per cent) there was no history of nocturnal or diurnal enuresis (table 1). There was no difference in the incidence or pattern of urinary incontinence in children with or without vesicoureteral reflux (table 2). Voiding cystourethrography was used to study 96 renal units and in 40 (25 patients) reflux was identified and graded according to established criteria (table 3). IO In nearly two-thirds of the cases the reflux was mild (grades I and II). An IVP was done in all patients and disclosed renal damage in 9 kidneys, which was characterized by focal parenchymal scarring. Damage occurred only in systems with reflux. Cystoscopic examination of 94 of the ureteral orifices studied by cystography revealed that 45 were normal and 49 were abnormal according to the criteria of Lyon and associates. 11 The appearance of the ureteral orifices is correlated with the occurrence of reflux in table 4. Abnormalities of the orifice predominated in children with vesicoureteral reflux (84 per cent). However, in children without reflux nearly one-third (30 per cent) of the ureteral orifices were abnormal. Obvious trabeculation was noted at cystoscopy in 20 children and was significantly more common in those without reflux. Bladder diverticula in the presence of trabeculation were noted in 4 children. No child demonstrated a clinically significant vesical neck contracture, urethral narrowing or meatal stenosis and in none was an anatomic outflow obstruction identified.
TABLE
All children demonstrated uninhibited bladder contractions during combined cystometry and periurethral striated muscle electromyography. The bladder volume at which these contractions occurred ranged from 50 to 150 ml. In some children multiple small contractions preceded a powerful sustained contraction, while in others a single strong contraction occurred unheralded. During the awake studies most children experienced a sense of urgency coincident with the onset of the uninhibited contraction. Each child was instructed specifically not to void during bladder filling even when urgency was perceived. A characteristic abrupt and intense increase in the activity of the periurethral muscles occurred during the uninhibited contraction as the child tightened the sphincter to maintain continence (see figure). However, the uninhibited contraction continued with increasing intravesical pressure and could not be suppressed or dampened. This resulted in higl;i. intravesical pressures often exceeding 150 cm. water. When the child was instructed to void a striking change in the periurethral activity occurred with abrupt cessation of sphincter contraction. With the catheter removed at this point voiding usually proceeded normally to completion with full coordination between bladder contraction and sphincter relaxation. In no patient was a residual urine >25 ml. recorded. The aforementioned treatment protocol produced a marked symptomatic improvement in 30 of the 36 incontinent children, such that daytime frequency, urgency and precipitate micturiTABLE
1. Children with uninhibited bladders
Symptom
No. Pts.
Recurrent infection Febrile episodes Incontinence: Day and night Night only No incontinence
(%)
53 22 36 31 5 17
3. Children with uninhibited bladders and reflux* I II
100 42 68
9
III
16 12
IV
3
* 25 patients and 40 renal units. 32 TABLE
TABLE 2.
Symptom
Reflux
No Reflux
16 12 4
20 19 1 8
9
4. Cystoscopic findings Reflux
Incontinence in children with and without reflux
Wetting: Day and night Night only No incontinence
No. Units
Grade of Reflux
Orifices: Grade 0 Grades 1 and 2 Grade 3 Trabeculation Diverticula
6
2~) 84% 6
2
No Reflux 39 1; ) 30%
14 2
UNINHIBITED BLADDER SPHINCTER CONTROL
c,,
:c E E uJ O!:
::,
V,
Vl UJ O!:
c..
50
VOLUME (ml)
EMG Schematic representation of awake cystometry and sphincter electromyography in child with uninhibited bladder activity and voluntary sphincteric obstruction. Note intense sphincter constriction during unsuppressible involuntary detrusor contraction.
URINARY TRACT INFECTION AND REFLUX
tion were virtually eliminated (no more than 1 accident per week). All children who performed the squatting maneuver were freed from this ritual. In 3 children with daytime and nighttime wetting only the daytime symptoms improved with anticholinergic drug therapy, while 3 other children with only nocturnal enuresis had no improvement in the pattern of wetting. The average period of followup on therapy was 1.3 years with no one followed
