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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 8  |  Issue : 2  |  Page : 69-74

Study of the effect of Tamsulosin in the spontaneous expulsion of ureteric calculi


1 Department of Surgery, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India
2 Department of Urology, Kilpauk Medical College, Chennai, Tamil Nadu, India
3 Department of Anaesthesia and Critical Care Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India
4 Department of Urology, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India

Date of Web Publication30-May-2019

Correspondence Address:
Dr. Jay Prakash
205, Roma Pearl Apartment, AECS layout, Bengaluru, Karnataka - 560 037
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ais.ais_39_18

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  Abstract 


Background: To increase the expulsion rate and reduce the analgesic requirement, there is a great deal of enthusiasm for adjuvant pharmacological interventions which is non-invasive and cost-effective. Tamsulosin shortens hospital stay, decreases operative interference. Tamsulosin increases stone expulsion rate and decreases expulsion time and has been shown to be safe and cost effective. The aim was to study the effect of Tamsulosin in the spontaneous expulsion of calculi in the ureter and to study the side effects of use of Tamsulosin for ureteric stones.
Patients and Methods: A prospective, randomized controlled study was conducted to compare the effect of Tamsulosin between two groups. This study included a total of 50 patients, 25 patients were chosen randomly and advised to take plenty of oral fluids and treated with NSAIDs (Diclofenac sodium) and the other 25 patients were treated with Tamsulosin (alpha blocker) 0.4mg HS for one month along with oral fluids and NSAIDs (Diclofenac sodium). The patients were then observed weekly and ultrasound scan was repeated after 15 days to look for any passage of calculi. If the stone was passed successfully, it was confirmed with ultrasonography. After one month if treatment failed, conservative management was discontinued and the patient was advised surgery. Independent t-test and Chi-square test' was the test of significance.
Results: Majority of the patients were in the age group of 20-40 yrs. The mean size of the calculus was 7.18 mm on the right side and 6.62 mm on the left side. Out of the 25 patients who were on alpha 1 blocker (Tamsulosin) 16 patients had passed the calculi and 9 patients had no results with a success rate of 64%. In the 25 patients who were not on Tamsulosin 6 patients passed the calculi and 19 patients did not pass the calculi.
Conclusion: Tamsulosin is an effective and safe drug in the management of calculi in the ureter and should be considered before ureteroscopy or extracorporeal lithotripsy for uncomplicated ureteral calculi.

Keywords: Alpha 1 blocker, Tamsulosin, Ureteric stones


How to cite this article:
Ravikumar, Guptha SA, Kurabalakota S, Prakash J, Parachuri S, Karthik A S. Study of the effect of Tamsulosin in the spontaneous expulsion of ureteric calculi. Arch Int Surg 2018;8:69-74

How to cite this URL:
Ravikumar, Guptha SA, Kurabalakota S, Prakash J, Parachuri S, Karthik A S. Study of the effect of Tamsulosin in the spontaneous expulsion of ureteric calculi. Arch Int Surg [serial online] 2018 [cited 2019 Aug 24];8:69-74. Available from: http://www.archintsurg.org/text.asp?2018/8/2/69/259462




  Introduction Top


Urinary calculus disease is one of the three most common urological diseases. It affects about 12% of the world population and has become a worldwide health problem. It affects 1%-5% of the population in Asia, Europe, North America, and Saudi Arabia.[1] Of all the urinary tract stones, 20% are ureteral stones, of which 70% are found in the lower third of ureter.[2] Previously reported that about 50% of patients with a history of urinary stones will have a recurrence of a second stone forming within the next 10 years.[3],[4],[5] Males are more commonly afflicted than females (male: female = 3:1). Increased testosterone levels in men, which might cause an increased oxalate production by the liver, and protective increased urinary citrate concentrations in women have been cited as causes for the male predominance.[6],[7] The etiology of the stones, however, has remained obscure. Various studies over time have shown that the cause of urinary stones to be multifactorial.

Stones do not usually form in the ureter but drop down from the pelvicalyceal system while they are still small. They tend to increase in size as they remain in the urinary passage. Most stones, smaller than 5 mm, pass spontaneously.[8] The transport of stones from the kidney into the bladder and their movement through the ureter is accompanied by three basic factors: spasm of smooth muscles, submucosal edema, and pain.

For the treatment of urinary stones, location (upper, mid, and lower) and the size of the stone as well as stone composition and complications are determining factors. Treatment options are divided into the following groups: observation and medical expulsive therapy (MET), extracorporeal shock wave and lithotripsy, retrograde ureteroscopy, open or laparoscopic stone removal, or percutaneous antegrade ureteroscopy.

The incidence of spontaneous passage of ureteric calculi, smaller than 4 and 4–6 mm, experienced rates of spontaneous passage of 80% and 59%, respectively.[9] The management of these stones is usually conservative in the first instance because of the high spontaneous passage rate. The accurate prediction of stone passage may prevent unnecessary intervention and therefore possible complications.

The treatment that can be offered to the patient depends on many factors, such as the size of the stone, obstruction, infection, and site of impaction. Nonsteroidal anti-inflammatory drugs (NSAIDs) form the core of treatment for acute renal colic, which acts by inhibiting prostaglandin synthesis and is the commonly used drug.[10]

Calcium, channel blocker, alpha blockers, phosphodiesterase type 5 inhibitors, and corticosteroid are most commonly used drugs as MET. In recent time, MET with alpha antagonist is in practice. Tamsulosin, which is commonly used in the treatment of bladder outflow obstruction, was chosen for this study as it acts on alpha 1a and alpha 1d receptor subtypes in the ureter due to its alpha I receptor blocker action. It also acts on the smooth muscles of the ureter causing its relaxation and prevents spasm, and acts on the C fibers blocking pain conduction. It has recently been demonstrated that specific adrenoceptor subtypes (alpha1a, alpha 1b, and alpha1d) are prevalent in the detrusor and the intramural part of the ureter; however, the distal part of the ureter is more dense with alpha 1a and alpha 1d adrenergic receptors. Stimulation of these receptors inhibits the basal tone, ureteral contractions, and the peristaltic wave frequency. The opposite effects have been seen by its antagonist. Tamsulosin has equal affinity on both receptor, i.e. alpha 1a and alpha 1d. The alpha 1d is the most common receptor in the ureter and mainly concentrated in the distal ureter.

This study is taken up to assess the possible role of alpha 1-antagonist, tamsulosin, for facilitating spontaneous expulsion of distal ureteral stones.


  Patients and Methods Top


After approval from the Institutional Ethical Committee, a prospective randomized controlled study was conducted in the department of surgery between the period of January 2014 and December 2015. The study conformed to the Helsinki declaration (World Medical Association, 1995). Written informed consent from each patient was taken before enrolment in the study. This observational study was conducted on 50 patients with age >20 years, calculus in the ureter with stone size 6–10 mm, and stones at multiple sites, and patients with post-extra corporeal shock wave lithotripsy with steinstrasse was also included. The exclusion criteria were patients on any other antihypertensive alpha-blocker drug and congenital abnormality detected in the ultrasonography (USG).

These patients were divided into two groups A and B and the randomization was done by odd-even method. Group A (25 patients) patients were treated with tamsulosin (alpha blocker) 0.4 mg HS for 1 month along with oral fluids, nonsteroidal anti-inflammatory drugs (NSAIDs) (diclofenac sodium), intravenous (IV) fluids, and antiemetic. Group B (25 patients) patients were chosen randomly and advised to take plenty of oral fluids and treated with NSAIDs (diclofenac sodium), IV fluids, and antiemetic.

Routine investigations, such as complete blood count, routine examination of urine, renal function test, X-ray KUB, and USG KUB, were done at the beginning of the treatment. The patients were then observed for 4 weeks and asked for any history of the passage of calculi, and USG was repeated to look for any passage of calculi. The findings were recorded and the patients were monitored and followed up for a period of 1 month. If the stone was passed successfully, it was confirmed with USG. After 1 month if treatment failed, conservative management was discontinued and the patient has advised surgery.

Statistical analysis

Data were entered into Microsoft excel data sheet and was analyzed using EPI info 7 version software. Categorical data were presented in the form of frequencies and proportions. “Chi-square test” and “Independent t-test” were the test of significance. Continuous data were represented in the form of mean and standard deviation. P value <0.05 was considered as statistically significant.


  Results Top


In total, 17 males (68%) and 8 females (32%) in group A and 16 males (64%) and 9 females (36%) in group B were included in the study. The mean age of group A was 36.60 ± 13.8 year and that of group B was 35.20 ± 17.7 year. Overall, 24 (48%) patients had right ureteric calculus and 26 (52%) patients had left ureteric calculus and the mean size of the calculus was 7.18 mm on the right side and 6.62 mm on the left side, whereas the mean size of the stone in group A and group B was 7.08 and 6.94 mm, respectively. [Table 1] summarizes the demographic and clinical characteristics of patients, which show that there was no statistical significant difference between the two groups in age, gender, laterality, and size of the stone. Stones were found in upper ureter in 7 cases in group A and in 6 cases in group B, in middle ureter in 3 cases in group A and in 4 cases in group B, and in lower ureter in 15 cases each in groups A and B. This distribution is not significant (P = 1.000) and attributed to randomization.
Table 1: Demographic and clinical characteristics

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[Table 2] shows the expulsion of calculi among the groups. In the study, during the follow-up, 22 subjects expelled the calculi, of which 16 were in group A and 6 were in non-tamsulosin group. About 32 patients failed to pass the calculi. This observation was statistically significant at P value 0.004. Hence, it can be said that with tamsulosin treatment, expulsion of ureteric calculi was higher.
Table 2: Expulsion of calculi among the groups

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[Table 3] states that the overall expulsion of calculi was higher in the first 2 weeks with group A (tamsulosin therapy), and 12 patients out of 16 patients (75%) who expelled calculi while on tamsulosin therapy did so in the first 2 weeks of the treatment. This was statistically significant with P = 0.029. However, in 9 patients in group A and 19 patients in group B after the end of the fourth week, expulsion of the stone was not seen as shown in [Figure 1]. [Table 4] shows the number of passing the stone in relation to size and intervention in different studies and the present study. [Table 5] shows the size of stones (in mm) and its locations among groups. In group A, by the end of 7 days, four patients had passed calculus. By the end of 14 days, eight more patients had passed calculus. By the end of 21 days, two more patients had passed calculus, and after the end of 28 days, another two patients had passed calculus. Patients who were not on treatment with alpha 1 blocker were also followed up every week for 4 weeks. By the end of 7 days, one patient had passed calculus; by the end of 14 days, another patient had passed calculus; by the end of 21 days, two more patients passed calculus; and by the end of 28 days, another patient passed calculus. Nineteen patients did not pass calculus.
Table 3: Mean time for calculi expulsion among groups

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Figure 1: Shows expulsion of calculi with time

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Table 4: The number of passing stone with relation to size and intervention in different studies

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Table 5: Size of stones (in mm) and locations among groups

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  Discussion Top


One of the most common urological diseases is urolithiasis. Among all urinary tract stones, 20% are ureteral stones, of which 70% are found in the lower third of the ureter.[11] The influencing factors for spontaneous expulsion are stone size, location, number, structure, ureteral spasm, mucosal inflammation or edema, and also ureteral anatomy. Therefore, the use of medical therapy is justifiable to reduce edema, reduce spasm, and relax the smooth muscles for stone expulsion.[12],[13] Active intervention and conservative wait and watch approaches are the current therapeutic options for ureteral stones. The efficacy of mini-invasive therapies, such as extracorporeal shock wave lithotripsy and ureterorenoscopy, has been proven by several studies.[9],[14] Although such procedures are effective, they are not free from risk or inconvenience and have consequent implications such as lowering the quality of life, high cost, and suspension of regular activities.[15] According to the published data, the distal ureteric expulsion rate of stone with the watchful waiting approach is 25%–54% with a mean expulsion time of >10 days and considerable analgesic requirement, even for stones <4 mm. To increase the expulsion rate and reduce the analgesic requirement, there is a great deal of enthusiasm for adjuvant pharmacological interventions.[16] Sigala et al.[17] found that α-1D and α-1A adrenoceptors are present in significantly larger amounts than α-1B adrenoceptors in the human ureter. Therefore, clinical studies have been conducted to investigate the effect of the combined α-1A and α-1D-selective antagonist tamsulosin on distal ureteral stone expulsion. Most of these studies showed that tamsulosin treatment improves the expulsion rate of medium-sized (3–10 mm) stones.

In the present study, we also observed an expulsion rate of 64% with tamsulosin, which was better than the expulsion rates in historical controls used in earlier studies of 43% and 30.2%. Thus, tamsulosin may be used as a noninvasive and cost-effective alternative to interventional approaches. In our study, majority of the patients were in the age group of 20–40 years. The mean age group was 36.11 years in females and 35.84 years in males. The most common age reported by previous studies for the presentation of ureteric calculi is between 20 and 40 years.[18],[19]

Our study included 17 females (34%) and 33 males (66%). Most of the studies have reported a male to female ratio between 3:1 and 2:1. Ketabchi AA et al.[19] reported that in group A, the number of males and females were 37 and 10, whereas in group B, males and females were 40 and 15, respectively. Males and those with a family history of the stone disease are three times more likely to be afflicted than others for a urinary stone disease.[20] It has been attributed to the protective effect of estrogen against stone formation in premenopausal women, owing to enhanced renal calcium absorption and reduced bone resorption.[21]

In our study, 13 (26%) calculi were found in upper ureter, 7 (14%) in mid-ureter, and 30 (60%) in lower ureter. An incidence of 27% of calculi in the upper one-third of the ureter, 12% in the middle one-third of the ureter, and 61% in the lower one-third of the ureter has been reported.[6] The probability of spontaneous ureteral stone passage is directly related to the distance of the ureter to be traversed and inversely related to stone size.[6],[9] Hence, the spontaneous passage of lower ureteric calculi is more likely and also the effect of tamsulosin on lower ureteric calculi is more than the calculi in other ureteral sites. This was observed even in our study with spontaneous passage higher in patients with lower ureteric calculi.

In our study, mean size of the calculus was 7.18 mm on the right side and 6.62 mm on the left side. Kumar et al.[22] reported that the mean size of the calculus was 6.9 mm in group A and 7.1 mm in group B. In the absence of external ureteral compression or internal narrowing, the width of the stone is the most significant measurement affecting the likelihood of stone passage.[6] In this study, 24 patients had calculus on the right side and 26 patients had calculus on the left side. Ahmed et al.[23] showed that in a series of 87 patients, 44 patients had stone on the right side and 43 patients on the left side. Most of the series found calculi with equal frequency on either side.

In our study, 10% of patients came in the first week after the appearance of symptoms, 26% came in the second week, and 64% patients came in the third and fourth weeks after the appearance of symptoms. It is reported that the duration of symptoms varies from 3 h to 5 years. Morse et al.[6] studied that 80% of the patients came within 1 month of onset of symptoms and 4% gave a history of ≥1 year. In our study, 100% (50 patients) had complaints of loin pain, 20% (10 patients) had complaints of vomiting, 8% (4 patients) had hematuria, 0% had the fever, and 14% (7 patients) had complaints of burning micturition. Pain, nausea/vomiting, hematuria, burning micturition/urgency/frequency of micturition, and oliguria were the most common symptoms. Abdel-Kader et al.[24] reported that 74% had loin pain, 26% of patients had the fever, and renal pain in a study of 23 patients with ureteric calculi.

The stimulation of alpha 1 adrenergic receptors increases ureteral peristaltic frequency, smooth muscle tones, and contractile force, resulting in ureteral spasm and decreased ureteral flow.[2] So, alpha 1 adrenergic receptor antagonists decrease this ureteral spasm to increase the ureteral flow. In this study of 50 patients diagnosed to be having ureteric calculi, 25 patients were started on alpha 1 blocker drug (tamsulosin) for 1 month and 25 patients were given only NSAIDS and plenty of fluids. Out of the 25 patients who were on alpha 1 blocker (tamsulosin), 16 patients passed the calculi and 9 patients did not, with a success rate of 64%. In the 25 patients who were not on tamsulosin, 6 patients passed the calculi and 19 patients did not pass the calculi.

Side effects were minimal in our study, probably because of the younger study population, short follow-up period, and the lack of any associated comorbidities. Out of 50 patients, 3 patients in group A complained of giddiness and 2 had headache. Diarrhea and retrograde ejaculation are also the complications of tamsulosin; none of our patients complained of retrograde ejaculation. In this study, patients were treated on the in-patient and out-patient basis too and the mean duration of stay in the hospital was 2 days. In this study, follow-up was done every week for a period of 4 weeks. The patients were asked to pass urine in a filter and identify the passage of calculi. Ultrasonography was done weekly for all the patients. Patients who were not on treatment with alpha 1 blocker were also followed up every week for 4 weeks.

In conclusion, for the management of small ureteric calculi of size 6–10 mm, particularly those <8 mm and those in the distal third of ureter tamsulosin therapy should be considered. It increases and hastens the expulsion of stone by spasmolytic action with reduced mean days and also decreases the analgesic dose with minimal side effect. However, further large prospective randomized control trials are required to validate these promising and statistically significant results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Hochreiter WW, Danuser H, Perrig M, Studer UE. Extracorporeal shock wave lithotripsy for distal ureteral calculi: What a powerful machine can achieve. J Urol 2003;169:878-80.  Back to cited text no. 14
    
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Bensalah K, Pearle M, Lotan Y. Cost-effectiveness of medical expulsive therapy using alpha-blockers for the treatment of distal ureteral stones. Eur Urol 2008;53:411-8.  Back to cited text no. 15
    
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Ahmad H, Azim W, Akmal M, Murtaza B, Mahmood A, Nadim A, et al. Medical expulsive treatment of distal ureteral stone using Tamsulosin. J Ayub Med Coll Abbottabad 2015;27:48-50.  Back to cited text no. 18
    
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