COMPARATIVE EFFECTIVENESS OF TAMSULOSIN VERSUS STANDARD MEDICAL THERAPY FOR MEDICAL MANAGEMENT OF SMALL URETERIC STONES.
Objective: To investigate and compare the effectiveness of tamsulosin versus standard medical therapy (SMT) for conservative management of ureteric stones in terms of time needed for stone expulsion, reduction in pain episodes and stone expulsion rates.
Methodology: This was a prospective non-blinded, non-randomised controlled study conducted at Urology Unit, LRH Peshawar, from July 2015 to June 2016. 50 patients were included, 25 patients in Group 1 (SMT) and 25 patients in Group 2. All patients were selected consecutively from the outpatient department with a stone size a$?10 mm. In Group 1, patients were prescribed adequate oral analgesics while Group 2 patients were given tamsulosin plus analgesics for pain relief on as need basis. Data was obtained about symptoms duration, stone size, stone location, total pain episodes and the time to passage of stone.
Results: There were 35 (70%) males and 15 (30%) females with a ratio of 2.3:1. Overall mean age was 31.84 +-5.64 years; range was 22 to 42 years; and mean duration of symptoms was 6.64 +-1.48 days. The overall mean stone size was 5.94 +-1.46 mm (range 4 mm to 9 mm). Significant differences were detected in total pain episodes (mean pain episodes for group 1= 3.64 and group 2= 1.6, p<0.0001) and stone passage time (mean passage time for group 1= 17.52 +-7.22 days and group2 = 10.44 +- 5.64 days, p <0.0001).
Conclusions: Tamsulosin effectively reduce the time needed for spontaneous expulsion of ureteric stones. It increases the rate of stone passage and importantly reduces the number of pain episodes.
KeyWords: Tamsulosin, Ureteric stones, Medical expulsive therapy.
Renal tract stones are known to mankind for millennia. They are associated with considerable morbidity and if untreated can lead to obstructive renal failure1. The lifetime prevalence in the Middle Eastern countries is estimated at 20-25% as compared to the 5-10% prevalence in western communities. Men (124 per 100,000) are several times more affected than women (36 per 100,000)2,3. Moreover, the recurrence rate ranges between 50-80% during a 10-year period4. The majority (97%) of renal tract stones are encountered in the ureter and kidneys while 3% are found in the bladder and urethra4,5. A number of treatment methods have been evaluated in the medical literature, ranging from conservative watchful waiting6, laser7 and shockwave lithotripsy8 to invasive procedures like laparoscopic9, endoscopic or open procedures10.
Most of these procedures are indicated depending primarily upon factors contributed by the stone, anatomy of the renal tract, comorbids, personal preferences or a combination of these11,12. Medical expulsive therapy (MET) for ureteric stones has recently received a reappraisal among the medical and conservative options during the initial 6 weeks of presentation13. Studies have shown that MET effectively reduces the time to passage of the stone while also reducing the number of colic episodes12-14. MET is also dependent upon the size of the stone (a$?10 mm) and renal tract anatomy as well as the preference of the patient. It has also been suggested that smaller stones (a$?5 mm) have higher rates of expulsion (75-80%) with MET while stones between 5 to 10 mm size have moderate rates of passage (45-50%)14.
The Canadian Urological Association (CUA) guidelines15 for ureteric stone management states that MET should be considered as a viable option in stones a$?10 mm in order to shorten the passage interval and pain episodes. However, they have cited a large randomised controlled trial by Pickard et al16 where they have concluded that MET does not reduce the need for additional therapies for stone retrieval. Similarly, other studies have also concluded that MET might not be helpful or altogether useless17. On the other hand, large reviews of RCTs have shown that MET is highly effective in at least shortening the passage interval and pain episode13,15. In order to find answers for the currently ongoing controversy regarding MET, especially the use of tamsulosin versus conservative therapy, we aimed to conduct a prospective study where we hope to determine the effectiveness of MET as compared to SMT.
The role of tamsulosin is to increase the rate of expulsion of small ureteric stones and will be thus benefitting the patients presenting with severe renal colic.
This was a prospective non-randomised study conducted at Urology Unit, LRH Peshawar, from July 2015 to June 2016. The institute's ethical committee approval was obtained before commencing the study. Informed consent was taken from all patients before inclusion in the study. After thorough clinical assessment the patients were investigated with ultrasonography of the renal tract. Stone size and location were determined using high frequency ultrasonic probe. All other relevant investigations were ordered from the hospital laboratory such as full blood counts, urea and creatinine, serum electrolytes and urine microscopy. Two treatment arms were created; group 1 and group 2. Patients in group 1 were prescribed with analgesics (diclofenac sodium 50 mg TID) with gastroprotection (oral ranitidine 150 mg BID). Patients in group 2 were prescribed with analgesics and gastroprotection as for group 1, but additionally they were prescribed with Tamsulosin (400 ug once daily in the morning).
Patients who presented with concomitant features of urinary tract infection (UTI) were also treated with antibiotics (ciprofloxacin 500 mg BID) in both groups. Fifty patients with age 16 or above having small primary ureteric stone of size 1-10 mm were included in the study. While patients having abnormal renal function tests, severe complicated UTI or evidence of moderate to severe dilation of the renal tract (ureter, pelvis, kidney) on ultrasonography were excluded. All patients were followed-up for 4-week time (28 days), with complete clinical and ultrasonographic assessment of the stone position or presence/absence thereof, every week in the outpatient department. Data was collected about patient demographics such as age, gender and comorbids. Symptoms duration was noted along with ultrasonographic location and size of the stone along the ureter.
Parameters recorded during follow-up were status of the stone (passed/not passed), time to stone passage (in days/weeks), total pain episodes, hospitalisation (if required) and complications of the drug treatment as well as the stone. All patients who failed to pass stone during the study period or who developed severe complications due to ureteral stones were managed according to their clinical findings. The data was coded and entered in a digital chart. At the conclusion of the study, the data was imported to SPSS version 22.0. Qualitative data was presented in frequencies and percentages while continuous data was presented as mean +-SD. Analysis was done for all the predictor and outcome variables (mean total pain episode, mean stone passage time, stone passage rate and complications) and the data was stratified according to treatment method given. The Shapiro-Wilk test and the Smirnov-Kolmogorov tests were used to assess the normality of the available data before applying special tests.
An independent samples t-test was used to ascertain mean difference between the predictor and outcome variables according to the treatment given. In case assumptions for the parametric tests were violated, a Mann-Whitney U test was conducted to ascertain a statistically significant difference. In all tests a p-value of a$?0.05 was considered significant.
Table 1: Treatment-group wise outcome
Clinical Variable###Group 1(SMT)###Group 2(MET)###Significance
Mean Total Pain Episodes###3.64 +- 0.995###1.60 +- 0.707###P <0.0001
Mean Stone Passage Time(days)###17.52 +- 7.23###10.44 +- 5.64###P <0.0001
Stone Passage Rate(N, %)###19(76%)###23(92%)###P = 0.24
Nasal Congestion(N, %)###None###3(12%)
Postural Hypotension(N, %)###None###2(8%)
Sexual Dysfunction(N, %)###None###2(8%)
Table 2: Expulsion rates for the two treatment arms
Time###Group 1: n(%)###Group 2: n(%)
Table 3: The independent samples t-test for comparison of mean difference between the two treatment groups
Clinical Variable###t###df###Sig.(2-tailed)###Mean Difference###Std. Error###95% CI of Difference
Stone Passage Time###3.860###45.328###.05), and there was no homogeneity of variances, as assessed by Levene's test for equality of variances. There were no significant differences in stone sizes or pain duration between the treatment groups. Significant differences were detected in total pain episodes (mean pain episodes for group 1= 3.64 and group 2= 1.6, p <0.0001) and stone passage time (mean passage time for group 1= 17.52 +-7.22 days and group 2= 10.44 +-5.64 days, p <0.0001) as is shown in Table 2 , Figure 1 and Figure 2.
Distributions of the passage rates for group 1 and group 2 were not significantly different for the two treatment groups. Passage rates for group 1 (mean rank= 27.50) and group 2 (mean rank= 23.5) were not significantly different, U= 262.50, z= -1.528, p= 0.13.
Ureteric stones bear significant morbidity due to its high prevalence and occurrence in younger age population13. Such a high prevalence of morbidity due to stones warrant particular focus in establishing effective, rapid and financially affordable treatment methods. The most significant effects of MET are to shorten the stone passage time and to reduce the number of pain episodes till the stone is cleared. Our main aim was to analyse these two variables. We therefore noted a significant effect of MET on the duration of stone expulsion as compared to SMT (mean difference= 7.08 days, 95% CI, 3.387 to 10.773, p <0.0001). These findings are concurrent with the findings of numerous randomised studies6,19-21. A large Cochrane database review by Campschroer et al19 has shown that MET significantly reduces stone expulsion time as well as the number of pain episodes. The CUA guidelines15 recommend that MET must be primarily used to shorten stone passage interval and reducing the number of pain episodes.
Reduction in the number of pain episodes translates into lesser requirement for oral or parenteral analgesia and reduced number of AandE visits22. We included adult patients with primary episodes of colic and radiologically proven location within the ureter. We, however, taken in consideration all locations of stone within the ureter. Many studies have shown the efficacy of MET in distal ureteric stones with primary aim of improving stone expulsion rates. Ahmad et al23 has shown an effective stone expulsion rate of more than 85% for tamsulosin group while only 55% rate for patients without tamsulosin treatment. Other features of this study are also in agreement with our study where majority (73.46%) of stones in MET group were cleared during the first two weeks of start of treatment whereas only 30% of stones in control group passed during the first two weeks23.
In our study, about 44% of stones were passed during the initial 14 days for SMT where as 80% of stones passed in the MET group during the same period (p 10 mm in size, these factors do not have any prognostic role14. We studied the effects of symptoms duration on passage time and did not find any correlation between the two (Spearman's R2: -0.18, p= 0.21).
However, it is important to note that stone size had negative correlation with duration of symptoms (R2: -0.029, p = 0.84). It was also noted that stone location within the ureter did not have any association with the expulsion rate (p= 0.57, Z= -0.56, Mann-Whitney U= 148). One of the negative effects of alpha blockers are their systemic effects such as retrograde ejaculation, nasal congestion and postural hypotension. Though we noted these complications in a minority of our patients, they should be kept in mind, and if significantly affecting lives of the patients, alpha blockers should be withdrawn or replaced with another agent. Ibrahim et al19 in a prospective RCT found side effects of tamsulosin in 13% of patients while 15% of patients with alfuzosin had these side effects19. As mentioned earlier, these side effects did not lead to stopping of the MET as they were of minor degree. Randomised clinical trials with larger sample sizes are required to effectively answer questions regarding MET.
Small ureteric stones can be easily managed using medical expulsive therapy by utilising the specific alpha1 blocking agents. The most significant effect of this therapy was shortening of time to stone expulsion and decrease in the number of pain episodes. Stone expulsion rates remains the same across conservative therapy and medical expulsive therapy.
We recommend to consider MET in all patients with ureteric stones of a$?10 mm, especially those who want to opt for medical management. Moreover, MET should not be limited to distal ureteric stones only, unless the stones are too large and/or the renal tract is significantly dilated or there are high chances of renal damage.
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|Author:||Khan, Aya; Ahmad, Tanveer; Khan, Ismail; Khattak, Ikram Ullah|
|Publication:||Journal of Postgraduate Medical Institute|
|Date:||Sep 30, 2018|
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