|Year : 2018 | Volume
| Issue : 4 | Page : 202-205
The Efficacy of Tamsulosin as Medical Expulsion Therapy in Ureteric Calculus of <8 mm Size
Nagesha Shivanna1, Abhishek Kumar Singh2, Prateek Jugalkishore Laddha3
1 Aditya Birla Hospital, Pune, Maharashtra, India
2 Department of Urology, Institute of Kidney Diseases and Research Centre, Ahmedabad, Gujarat, India
3 Shri Sathya Sai Institute of Higher Medical Sciences, Prashanthigram, Puttaparthy, Andhra Pradesh, India
|Date of Web Publication||16-Apr-2019|
Dr. Prateek Jugalkishore Laddha
6833/3, Mohar Singh Nagar, St No 8, Hargobind Marg, Ludhiana - 141 008, Punjab
Source of Support: None, Conflict of Interest: None
Introduction: Many conservative medical therapies have been researched and studied for ureteric stones. Alpha 1- Adrenergic blocker Tamsulosin reduces muscle spasm in the ureteric wall, decreases peristalsis below and raises pressure above the stone thus facilitating stone passage. Material and Methods: Patients diagnosed with ureteric stones from OPD, Casualty/Emergency Room and wards were included in the study. The patients were randomized into the study and the control arms. This was a prospective, randomized, controlled, open label clinical trial conducted on patients presenting to tertiary care center in north India with ureteric colic. Study group received Tamsulosin along with the analgesics, whereas the control group received only symptomatic treatment and hydration. Results: There were 29 (52.7%) subjects in the study group and 25 (45.4%) subjects in the control group had a subjective score of over 9 on arrival. The minimum pain score at presentation was 4 in the study group whereas it was 5 in the control group. Majority of the patients received Inj. Morphine after the initial Inj. Diclofenac sodium, 33 (60%) in the study group and 36 (65.45%) from the control group. There were 12 and 11 in the study and the control group who received an additional morphine infusion pump for pain control. The mean number of colic episodes during treatment was 1.75 (SD=1.534) in study group which was marginally less when compared to that of the control group 1.93 (SD=1.138) (P=0.288).In the study group 41 patients had expelled the stone whereas in the control group 30 of them had expelled at the end of study period, the difference was statistically significant (P=0.03). Conclusion: There was decreased pain score, number of colic episodes on treatment and duration of expulsion in the study group as compared to the control group (P >0.05). The difference in the number of patients who expelled the calculus among both the groups was statistically significant (P=0.03) noted in this study.
Keywords: Medical expulsion therapy, tamsulosin, ureteric calculus
|How to cite this article:|
Shivanna N, Singh AK, Laddha PJ. The Efficacy of Tamsulosin as Medical Expulsion Therapy in Ureteric Calculus of <8 mm Size. J Datta Meghe Inst Med Sci Univ 2018;13:202-5
|How to cite this URL:|
Shivanna N, Singh AK, Laddha PJ. The Efficacy of Tamsulosin as Medical Expulsion Therapy in Ureteric Calculus of <8 mm Size. J Datta Meghe Inst Med Sci Univ [serial online] 2018 [cited 2019 Jul 19];13:202-5. Available from: http://www.journaldmims.com/text.asp?2018/13/4/202/256210
| Introduction|| |
Urolithiasis is a global problem spanning all geographic regions with an estimated annual incidence of 1%, prevalence of 3%–5%, and a lifetime risk of 15%–25%.
Stone formation is affected by gender, age, climate, lifestyle, dietary habits, metabolic diseases, congenital abnormality of the urinary tract and geography. Men are more likely to form stones than women. Lifestyle and diet may play a more significant role in stone formation than ethnicity. Geography also seems to be a significant risk factor with a higher prevalence of stone disease in hot, arid, or dry climates. A failed expectant treatment for ureteric calculus may well be complicated with increasing severity of hydronephrosis, deranged renal function or urosepsis and also interventional techniques are not always free of complications and failures. Medical expulsive therapy (MET) has shown to enhance stone expulsion rate, decrease stone expulsion time and decrease the use of analgesics in ureteric calculus. One area in which medical therapy alters the natural history of the stone disease is on the spontaneous passage of ureteral calculi. The two most important factors in predicting the ureteral stone passage are stone size and location. However, even stones that eventually pass may do so with debilitating pain over an unpredictable time interval. Consequently, agents that promote spontaneous stone passage and reduce the symptoms associated with passage are needed. MET has shown to enhance stone expulsion rate, decrease stone expulsion time, and decrease the use of analgesics in lower ureteric calculus. Tamsulosin is the most common agent used in MET along with analgesics. Other agents which can be used are alfuzosin, silodosin, naftopidil, calcium channel blockers, and steroids., Tamsulosin reduces muscle spasm in the ureteric wall, decreases peristalsis below, and raises pressure above the stone thus facilitating stone passage. The use of tamsulosin 0.4 mg daily in patients with distal ureteric stones is clinically safe and cost-effective.
This study aims at the efficacy of MET with tamsulosin in patients with ureteric calculus of up to 8 mm in size and comparing the results with a control group without MET.
| Materials and Methods|| |
A prospective, randomized, controlled, open-label clinical trial was conducted on patients presenting to Christian Medical College Hospital, Ludhiana, with ureteric colic due to ureteral calculus confirmed by non-contrast computed tomography of the kidney, ureters, and bladder (NCCT KUB). Institutional Research Committee and Ethics Committee were obtained before commencement of the study. All the patients presenting to emergency and outpatient department with ureteric colic were screened and recruited for the study after fulfilling the inclusion criteria. The study was conducted from December 01, 2014, to May 31, 2016, and a total of 134 patients were screened of which 24 patients were excluded according to the reasons mentioned in [Figure 1]. All patients having a single ureteric calculus of size ≤8 mm were included in the study. Patients with a stone size more than 8 mm, multiple ureteric stones, stones associated with severe backpressure changes, or elevated serum creatinine values (>1.2 mg/dl) were excluded from the study. Furthermore, patients who were already on other drugs (calcium channel blockers or alpha 1 adrenergic agonists) which can contribute to stone expulsion were excluded from the study.
All patients included in the study executed an informed consent after they are fully informed of the merits and demerits of the study, details of the follow-up protocol and the list of investigations to be undertaken. Patients presenting with acute colic received injection Diclofenac sodium 75 mg i. m. stat. If pain continued injection Morphine 5 mg slow i. v. (5 mg diluted in 5 ml normal saline) stat. Pain pump was used in refractory cases injection ondansetron 4 mg i. v. for nausea and vomiting. All patients underwent NCCT KUB using High-speed PHILIPS 128-slice CT scanner. A detailed informed written consent was taken from all the patients before recruitment for the study. They were explained regarding the study details, investigations required, duration of the therapy, and the follow-up dates. Patients were then divided into two groups which include:
Group I – Patients with ureteric calculus who received MET (study): tablet diclofenac sodium SR 100 mg P. O. PRN/tablet Drotaverine 40 mg P. O PRN and tablet Tamsulosin 0.4 mg P. O. once daily after food along with increased fluid intake for 2 weeks.
Group II – Patients with ureteric calculus who did not receive MET (controls). Patients in the control group received tablet diclofenac sodium 100 mg SR P. O. PRN/tablet Drotaverine 40 mg P. O PRN only along with increased fluid intake for 2 weeks. Block randomization was done according to a predetermined random sequence in blocks of six participants. For each patient, the following variables were recorded: age, gender, stone location, severity of hydronephrosis, and serum creatinine. Patients were followed up with telephonic interviews and in the outpatient department by the end of 2 weeks. X-ray KUB/USG KUB/NCCT KUB was done after 2 weeks to confirm the status of the calculus. For each patient, at the end of 2 weeks the following variables were recorded: stone expulsion, time to stone expulsion, number of episodes of colic, and pain score during the follow-up and side effects of therapy. The data were collected and analyzed using IBM SPSS Software (SPSS Inc. 233 South Wacker Drive, 11th Floor Chicago, IL 60606-6412). The effect of multiple variables on expulsion was analyzed using multiple logistic regressions. The statistical significance of the difference in mean pain score and additional medications required was analyzed using the t-test.
| Results|| |
Most of the participants in the study were in the second and third decades of life (38 and 37, respectively). The number of female participants was less than the males (21 and 89, respectively) during the study. The average age in males and females were 35.83 and 36.23 years, respectively. The mean age among the study and control groups was 36.74 years (standard deviation [SD] - 13.07) and 35.10 years (SD - 12.66), respectively. The mean diameter of calculus in the study and control groups was 4.18 mm (SD - 1.22) and 4.15 mm (SD - 1.06), respectively. In the study group, 41 patients had calculus <5 mm as compared to 38 in the control group. In the study group, 6 (10.91%) patients had calculus in their upper ureter, 11 (20%) patients had in the mid ureter, and 38 (69.09%) patients had calculus in the lower ureter. In the control group, 8 (14.55%), 14 (25.45%), and 33 (60%) patients had calculi in the upper, middle, and lower ureter, respectively. The mean number of colics during treatment was 1.75 (SD = 1.534) in the study group which was marginally less when compared to that of the control group 1.93 (SD = 1.138). However, the difference was statistically not significant (P = 0.288). In the study group, 41 patients had expelled the stone whereas in the control group 30 of them had expelled at the end of the study period, the difference was statistically significant. On univariate and multivariate logistic regression analyses of factors that predict stone expulsion, tamsulosin medication (odds ratio [OR] = 2.44; 95% confidence interval [CI], 1.090–5.465; P = 0.03*) was significant predictor of stone expulsion. Even on multivariate analysis, only tamsulosin remained statistically significant (OR = 2.434; 95% CI, 1.072–5.528; P = 0.033*).
The mean time taken for the expulsion of calculi in the study and control arm was 3.12 and 3.8 days, respectively. The difference in both groups 0.7 was statistically not significant (P = 0.063). Time to spontaneous stone expulsion was evaluated with Kaplan-Meier analysis [Figure 2]. The mean duration of stone expulsion as Kaplan-Meir estimate in the study group was 5.89 days (95% CI, SD 4.56-7.22) and for the control group was 8.43 days (95% CI, SD 7.059-9.814). The gap between the curves showed progressive widening as the days progressed. Giddiness was the major side effect noted during the study accounting for 13 (23.63%) of the study group of participants. There were 3 (5.45%) individuals reported occasional headache. There was no need to stop the drug during the study. A total of six patients underwent URSL after the study, two of them were from the study group, and four were from the control group.
| Discussion|| |
In the present study, the participants were followed up for 2 weeks after initiation of therapy. Al- Al-Ansari et al. in their study found that 41 out of 50 (82%) patients in the study group had passed the stone while in the control group only 28 out of 46 (60.86%) patients had passed the calculus. The average time for stone expulsion was 6.4 ± 2.77 days in the study group whereas it was 9.87 ± 5.4 days in the control group.
Yilmaz et al. in their study found that 23 out of 29 (79.31%) in the study group had expelled the stone while in the terazosin group 22 out 28 (78.57%) patients had passed out the calculus. The number of patients in the doxazosin group who passed the calculus was 22 out of 29 (75.86%) while the same in the control group was 15 out of 28 (53.57%) patients. The average time for stone expulsion in the control, tamsulosin, terazosin, and doxazosin groups were 10.54 ± 2.12, 6.31 ± 0.88, 5.75 ± 0.88, and 5.93 ± 0. 59 days, respectively.
Ahmed and Al-Sayed in their study found that 25 out of 29 (86.20%) patients in the tamsulosin group had passed the calculus while the same in the alfuzosin group was 23 out of 30 (76.66%) patients. The control group had 14 out of 28 patients passing the stone. The average time for stone expulsion in the tamsulosin, alfuzosin, and control group were 7.52 ± 7.06, 8.26 ± 7.34, and 13.9 ± 6.99 days, respectively.
All the studies mentioned above had a weekly follow-up of the patients for 4 weeks. At the end of 4 weeks when the study concluded the patients who did not pass the stone or had persistent symptoms underwent an alternative therapy such as ureteroscopy and stone removal or extracorporeal shortwave lithotripsy. Moreover, Ahmed and Al-Sayed had observed that a few patients in the tamsulosin group had expelled the calculus spontaneously while they were awaiting intervention for stone removal after their study period got over.
The studies mentioned above showed a significant decrease in the number of days taken to expel the stone (an average of 5 days) by the tamsulosin group in comparison to the control arm. The present study showed a similar trend. There was an obvious difference in the number of patients who expelled the stone in the present study (74.54% and 54.54% in the study and control groups, respectively) which was statistically significant (P = 0.03) similar to the other studies.
In a study done by Ramesha et al., mid ureteric calculus in the study group had an expulsion rate of 56.6% as compared to 20% in the control group. In the lower ureter, the expulsion rate was 93.3% and 43.3% in the study group and control group, respectively. Lee et al. noticed an expulsion rate of 74.1% in the study group of upper ureteric calculi as compared to 46.3% in the control group as noted in [Table 1] and [Table 2].
In the present study, the rates of expulsion in the study group were 50%, 72.72%, and 78.94% as compared to 37.5%, 42.85%, and 63.63% in the upper, mid, and lower ureteric calculi of the control group, respectively.
| Conclusion|| |
The findings of the study recommend that alpha antagonist namely tamsulosin can be used as primary modality of treatment in selected patients with ureteric calculus. It decreases the duration of stone expulsion and also reduces the number of colic episodes and severity of pain. It is well tolerated with relatively lesser side effects.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]