THE JOURNAL OF UROLOGY
Vol. 113, January Printed in U. S.A.
,
Copyright © 1975 by The Williams & Wilkins Co.
TREATMENT WITH PHENOXYBENZAMINE OF UPPER URINARY TRACT COMPLICATIONS CAUSED BY INTRA VESICAL OBSTRUCTION K. STOCKAMP
From the Department of Urology, University of Mainz Medical School, Mainz, West Germany
The pediatric urologist is sometimes confronted with a patient in whom reflux and hydronephrosis persist after repeated attempts at ureteral reimplantation or who appears to be unamenable to such a procedure because of progressive renal deterioriation, finally requiring supravesical urinary diversion . This situation is well known in cases of neurogenic bladder but may also be found in cases of non-neurogenic bladder dysfunction with or without overt intravesical obstruction. ' In a previous report , recently confirmed by Krane and Olsson , it was shown that residual urine and complications of the u ca_ses of neuropathic bladde an_ h e_imp.m.v ed with drugs blockin the ph.a- a.d.ren.e.i:gic receptors. 1 · 3 This th era yjeads....to relaxat ion..of the blaader nec kand the trigone and reduces the infravesica!J5ressure. This therapeutic 7egimen was tried on 5 children without nfililllli!gic.al symptoms but with seD.Q1J.S_uppe1:...t.:i:ae-t- e0m-p 1-i-ca ti ons. MATERIAL AND METHOD
All 5 patients had had a history of urinary tract infection since childhood (see table). Three patients had definitive voiding disorders that had not been considered when the patient was treated previously. To study the detrusor function and a possible elevated bladder outlet resistance, excretory cystomanometry was done using the technique of Kuffer.4 Care was taken to perform this examination when the urinary tract infection was suppressed. Furthermore , each child was examined with a 30-minute excretory urogram , voiding cystourethrogram and determination of residual urine before and 2 weeks after initiation of therapy. Therapy consisted of 0.3 to 0.5 mg . per kg . body weight phenoxybenzamine orally at bedtime . There were no major adverse side effects but 2 P.atients did complain of drowsiness during the first week and 1 of these, a 14-year-old girl, had postural hypotension for several days. Accepted for publication March 8, 1974. 1 Stockamp, K. and Schreiter, F.: Beeinflussung von Harni~_k ontinenz und neµrogener Harnentleerungsstorung uber das sympathische Nervensystem. Actuelle Urol. , 4: 75, 1973. 2 Krane, R. J. and Olsson, C. A.: Phenoxybenzamine in neurogenic bladder dysfunction. I. A theory of micturition. J . Urol., llO: 650, 1973. 3 Krane, R. J. and Olsson, C. A.: Phenoxybenzamine in n_eurogenic bladder dysfunction. II. Clinical considerations. J. Urol., llO: 653, 1973. 'Kuffer, F.: Die Myelomeningocele. Baltimore: The Williams & Wilkins Co ., 1972.
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RESULTS
The cystomanometrical evaluation revealed elevation of intravesical pressure and outlet res istance in all cases, especially marked in the 2 patients who underwent transurethral resection because of overt bladder neck obstruction. Out let resistance was elevated in the 3 patients without visible obstruction. In all cases the phenoxybenzamine therapy led to a depression of the out let resistance and of the intravesical pressure . The 3 older children could start to void easier, 1 of them with a previous frequency reported a normalization, and the other 2 children have been able to void with a strong stream. The diminished bladder capacity in 2 children was elevated remarkably and a previously normal capacity in 1 child remained unchanged. Reduction of the outlet resistance led to residual free voiding a nd th e van ous d~grees of dilatation of the upper urinary trac t w~ relieved ,I~ 4 ureters serious reflux disap?eared co~ pletel twice was funct10nall y iJ:Ep rove m the 2 others., that is reflux did not o~ G~ In 1 of the latter patients a fourth ureteral reimplantation was successful while the child was under therapy (see table) . These 5 children have taken phenoxybenzamine therapy for 3 to 9 months . Two of them had an episode of infection that was readily curable with antibiotics , whereas the remainder have had sterile urine since starting treatment. X-ray controls of the urinary tract revealed stable conditions (figs. 1 to 3). DISCUSSION
The cases described herein clearly reveal the n t_edtor cystomanometnc evah rn ti an of detrusor and bladder outlet functi on in the presen cP of complicating disorders of the up per urinary t ra~. This ~'.'amination may disclose a clinically ~ detectaoleoostruct 10n or a persisting high outlet ~esistan~e after transmetbra) resection. A~ h igh i~travesical ressure leading to detrusor alt erab=
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a functional obstruction Conversely, a primary aetrusor dysfunction may produce a seconclary bTadder neck ohst rnction by means of hypertrophy ~nd contractur!:h_ The thorough examination of our patients gave no hints for neuropathy , although the bladders behaved like neurogenic bladders in regard to an unsuccessful operation. The number of experimental findings, starting
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129
INTRAVESICAL OBSTRUC11ION TREATED WITH PHENOXYBENZAMINE
Review of cases
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Age t .- ex-(yrs.)
Primary Diagnosis
Preced ing Operations
Present S it uation
IntraOutlet Bladder Residual Resistvesical Capacity Urine Dilatation Pressure ance (ml.) (ml.) (mm.Hg) (mm.Hg)
Reflux
Pre- Post- Pre- Post- Pre- Post- Pre- Post- Pre- Post- Pre- PostRx Rx Rx Rx Rx Rx Rx Rx Rx Rx Rx Rx AK-M-2
Urethral valves
KO-M-4
Fibroelastosis Primary megaloureters Bilat. refluxing megaloureters Bilat. Segmental reflux, bladder remegacys- section, 2 x tis It. UCN, 3 x rt. UCN
FS- M-11 AM-F-10
MR-F -14
Cystostomy, 2 Pyelonephritis, preurem ia, reflux and xTUR, lt. nephrectomy hydronephrosis Hydronephrosis, reTUR, rt. nephrectomy sidual urine Pyelonephritis, bi2 x rt. UCN, lat. reflux and hy3 x lt. UCN dronephrosis Rt. reflux, contracted 1 x lt. UCN, 2 x rt. UCN bladder Pyelonephritis, hydronephrosis and rt. reflux, residual
10
5
++
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320 270 150
0
++
+
18
325 330
35
0
+++
!tJ
+ + + !tJ
15
12
150 260
45
5
+
g
+++ +
20
15
350 350 150 40* ++ +
g
+++ ++*
60
21
33
18
44
18
20
9
39
21
27
27
22
45
32
50
80
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urine
* After successful reimplantation under phenoxybenzamine presently free of reflux and residual urine.
FIG. 1. Patient K. 0. A, dribbling overflow bladder, excessive hydronephrosis on left side and non-functioning kidney on right side. B, condition after right ureteronephrectomy and transurethral resection of narrow bladder neck. Note moderate dilatation and high residual urine. C, 10 days after phenoxybenzamine therapy there was diminished dilatation, nearly normal bladder configuration and residual free voiding.
with the work of Learmonth' in 1931 up to the modern concepts of bladder innervation, 6 have established the significance of the sympathetic nerve system in bladder function. Furthermore, as 'Learmonth, J . R.: A contribution to the neurophysiology of the urinary bladder in man. Brain, 54: 147, 1931. 'El-Badawi, A. and Schenk, E. A.: A new theory of the innervation of bladder musculature. Part l. Morphology of the intrinsic vesical innervation apparatus. J. Urol., 99: 585, 1968.
noted by Sundin, 7 the role of the adrenergic innervation gains special importance in regard to neurogenic bladder dysfunction when a growth of the adrenergic neuro-terminals can be observed . This fact explains the surprising good results of therapy with alpha-adrenergic blocking drugs. The egually good results of this therapy in our 5 cases 7 Sundin, T. : Re innervation of the urinary 5ladder. An experimental study in cats. Scand. J. Urol. Nephrol., suppl. 17, 1972.
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STOCKAMP
FIG. 2. Patient F. S. A, condition after 3 ureteral reimplantations on left side and 2 reimplantations on right side with persisting dilatation. B, voiding cystourethrogram shows bilateral reflux. C, note complete relief of dilatation under phenoxybenzamine therapy. D, voiding cystourethrogram under phenoxybenzamine reveals no reflux, only stumps of Boari flap filled on left side.
131
INTRAVESICAL OBSTRUCTION TREATED WITH PHENOXYBENZAMINE
' '' FIG. 3. Patient M. R. A, condition after 3 ureteral reimplantations on right side, 2 on left side and segmental bladder resection. Note hydronephrosis on left side and nearly non-functioning kidney on right side. B, voiding cystourethrography shows excessive reflux into right kidney. C, after phenoxybenzamine therapy there was no more dilatation of upper urinary tract. D, voiding cystourethrogram shows no reflux after fourth reimplantation under phenoxybenzamine.
wit vesical obstruction and without detecta, ble neuro enic com onents indicate a a f;. cally elevated activity of the sympathetic nerve s ~ The proo y means of neurohistolog1cal examination is still lacking. SUMMARY
Five children in whom reflux and progressive hydronephrosis persisted despite multiple surgical attempts or repair are described. In :1,ases
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cystomanometry displayed a marked elevation of the bladder outlet resistance combined with high i"ltravesical pressure values. Therapy with phenoxybenzamine, an alpha-adrenergic blocker, was successful in all cases, restoring a free urine passage of the upper urinary tract and unimpaired voiding preventing urinary diversion which has been considered in some of these children. Although there were no signs of bladder neuropathy, a hyperfunction of the sympathetic innervation as a ,caus~for !cladder complications is discussed .
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