Ibrahim Mokhless, Ab

Section of Pediatric Urology and

Received 18 March 2011; accepteAvailable online 17 November 201

statistically significant (P < 0.001).Conclusions: Medical expulsion therapy for lower ureteric stones is a successful procedure in

2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

The incidence and characteristics of urolithiasis in childrenreflect a wide geographic variation, but stones occur in

e.ic

stone disease is considered endemic in developing nations[1,2]. The natural history of pediatric stone disease is not as

* Corresponding author. Pediatric Urology Unit, Department of Urology, University of Alexandria School of Medicine, Alexandria, Egypt.Tel./fax: 20 203 486 0029.

E-mail address: dr.youssif@gmail.com (M. Youssif).

1477-5131/$36 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.doi:10.1016/j.jpurol.2011.09.008

Journal of Pediatric Urology (2012) 8, 544e548Introduction children of all ages without a clear gender predominancAlthough uncommon in the Western hemisphere, pediatrchildren. Tamsulosin demonstrated no clinically significant adverse effect, while proving tobe a safe and effective treatment option.Results: All patients completed the study and none were excluded due to side effects. Nosignificant differences were found between the groups for age, gender and stone size. Meanpatient age was 8.1 6.8 years. There were 25 females and 36 males. The stone-free ratewas 87.8% in Group I (29/33), compared with 64.2% (18/28) in Group II. A mean stone expulsiontime of 8.2 and 14.5 days was recorded for Group I and II respectively, and this difference wasKEYWORDSTamsulosin;Adrenergic alpha-antagonists;Pediatrics;Urolithiasisren: A prospective randomized study

del-Rahman Zahran, Mohamed Youssif*, Ahmed Fahmy

Endourology, Department of Urology, Alexandria University, Alexandria, Egypt

d 12 September 20111

Abstract Purpose: Based on efficacy demonstrated in the adult population, tamsulosin wasevaluated with regard to facilitating ureteral stone expulsion in children presenting with distalureteric calculi.Patients and methods: A prospective randomized controlled study involving 61 children withdistal ureteric calculi

tests. Non-contrast computerized tomography (NCCT) was

On follow-up, blood pressure values, pain episodes,need for analgesics and time to stone expulsion werenoted. The time for spontaneous passage was defined asthe day the parent reported the passage of a stone and thereport was confirmed by absence of the radiopaque calculion KUB. If a 4-week treatment failed to expel the stone,pain was uncontrolled by medications, or fever was docu-mented as a sign of UTI or worsening hydronephrosis, thendefinitive treatment whether by ESWL or ureteroscopicprocedures was performed.

The primary endpoint was stone-free rate and time tostone passage, determined by KUB or NCCT at 4 weeks. Thesecondary endpoint was incidence of adverse effects duringthe 4-week period. Statistical analyses were carried outusing Fishers exact test and the level of statistical signifi-cance was set at P < 0.05.

Tamsulosin for management of distal ureteral stones 545performed in select cases when indicated. Children wererandomly divided into two groups. Group I (study group of33 children; 18 presented with lower third ureteric calculi

offered a closely monitored trial of spontaneous passage for3e4 weeks prior to definitive therapy, since most studiesdemonstrate stone expulsion in the first 10 days of medicaltherapy, and despite complete ureteral obstruction thekidneys can function without any permanent damage [15].

Spontaneous expulsion of distal ureteral stones dependson several factors, including size, number and location, aswell as associated smooth muscle spasm and ureteraledema. Coll et al. found a linear relationship betweenstone size and spontaneous expulsion [15]. They indicatedthat in adults spontaneous expulsion rates for stones5e7 mm and greater than 8 mm are 60% and 39%, respec-tively. The aims of conservative treatment are preventingmuscular spasms, ureteral edema and possible infections,and reducing pain until spontaneous expulsion occurs[17,18]. Although ureteral stones have been studied

Table 2 Overall results in both groups.

Group I Group II P value

Expulsion rate 87.8% 64.2%

response of alpha-blockers is well known, and higher doses

expulsion rates compared to controls, they observed nosignificant difference between the two doses. Evaluating

[19]. We observed fewer pain episodes and less need for

Tamsulosin for management of distal ureteral stones 547central nervous system side effects such as mild degreesof headache, somnolence and nausea The incidence ofhypotension has been observed to be dose related toa1-antagonists such as terazosin and doxazosin. Thedevelopment of a specific a1A-antagonist with less ofa hemodynamic effect subsequently came about withtamsulosin. Donohoe et al. [25] first reported the use oftamsulosin as primary or second-line therapy in childrentreated with a variety of a1-anatagonists for primarybladder neck dysfunction. They reported excellentsuccess rates with no major adverse effects. The tolera-bility and variable degrees of efficacy of alpha-blockers inadults have been well documented [8e10]. Long-termsafety and efficacy of tamsulosin for treatment ofbladder outlet obstruction in the adult population led usto examine its use in our pediatric population with distalureteric stones. We did not have any child or parentreporting symptoms of postural hypotension, syncope orpalpitation throughout the 4-week duration of treatment.Side effects observed in the study and placebo groups werecomparable and mild, and no patient withdrew because ofthem. Tamsulosin seems to be a safe treatment option forselect children with distal ureteric calculi devoid of anyhemodynamic adverse sequel.

Our study was limited to patients affected by ureteralstones equal to or smaller than 12 mm Al-Ansari et al. [26]evaluated the effectiveness of tamsulosin for treating distalureteral stones in adults and concluded that it is effectivefor stones sized 10 mm or smaller. Our results using tam-sulosin for distal ureteral stones in children parallel theirfindings. Moreover, we observed a decrease in time to stoneexpulsion rate for the treatment group, and the differencewas statistically significant. Few randomized trials havebeen carried out to study the impact of alpha-blockers onthe rate of spontaneous passage of distal ureteral stones inchildren. Aydogdu et al. [27] showed no significant differ-ence in stone expulsion in children after administration ofdoxazosin daily to treat distal ureteral stones of up to10 mm as compared to analgesic alone. This could be

Table 3 Treatment result as categorized by stone size.

10 mm

Expulsion rate: n(%)Group I 16 (94.1) 11 (84.6) 2 (66.6)Group II 11 (87.5) 7 (53.8) 0

Days to expulsion: (mean SD)Group I 7.2 2.0 8.8 0.9 10.6 1.9Group II 10 2.9 16.0 1.9 eexplained by the relatively small size of the stones in thisstudy (6.2 1.1 mm). The mean stone size was more than7.4 mm in both groups of our study population. Differencesin the results could also be attributed to differences inpatients and stone characteristics.

In our study, time to expulsion was significantly shorterin the tamsulosin group. Miller et al. suggested thata pediatric ureter is capable of transporting comparativelylarger fragments after lithotripsy [14]. However, as weincluded children with distal ureteral stones of up to12 mm, the potential benefits of alpha-blockers have beenanalgesics in the treatment group. These results demon-strate that tamsulosin probably decreases the frequency ofphasic peristaltic contractions in the pediatric ureter.

The main limitation of our study is the small number ofpatients, which makes stratification by age and genderdifficult. Placebo control has provided information espe-cially about analgesic needs and frequency of painepisodes. We have demonstrated that tamsulosin therapy inchildren had better results regarding the frequency ofepisodes of renal colic, the need for analgesics, and itstotal dose.

To our knowledge, the present study is the first to showthe efficacy of tamsulosin for spontaneous stone passage ina pediatric population. Tamsulosin proved to be effective infacilitating expulsion of ureteral stones in addition todecreasing time to expulsion.

Conclusion

In this randomized placebo-controlled study, we havedemonstrated that medical expulsion therapy for lowerureteric stones is a successful procedure in children. Tam-sulosin demonstrated no clinically significant adverseeffect, while increasing spontaneous expulsion of distalureteral stones in addition to decreasing time to expulsion,pain episodes, and need for and dose of analgesic in thispediatric population.

Funding

None.

Conflict of interest

None.the dose response has provided important information inour study. Our dose was 0.2 mg daily in children youngerthan 4 years and 0.4 mg daily in older children, which isquite high. Although this dose was safe and tolerable,different doses should be investigated in future studies todetermine optimum dosage and evaluate the dose responsein separate age groups.

Some prospective randomized studies have revealed thatmedical treatment with alpha-blockers of distal ureteralstones in adults decreases the demand for analgesics andreduces patient discomfort associated with stone passagecould possibly demonstrate a significant difference.Although Lojanapiwat et al. [28] showed that low dose(0.2 mg daily) and standard dose (0.4 mg daily) tamsulosinfor distal ureter stones produced significantly higher stonemore pronounced. Another possible reason that resultswere in favor of the tamsulosin group is that the drugdosage used in the study, which was reported to be effec-tive in adults, was well tolerated in children. The dose

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Tamsulosin for the management of distal ureteral stones in children: A prospective randomized studyIntroductionMaterial and methodsResultsDiscussionConclusionFundingConflict of interestReferences