Is There a Role for Tamsulosin After Shock Wave Lithotripsy in the Treatment of Renal and Ureteral Calculi?

Introduction

U rolithiasis is a disease that affects 12% of the world population. ^1,2 It can create pain, hematuria, infection, fever, nausea, and vomiting. ³

The goal of treating ureteral calculi is to achieve complete stone clearance with minimal morbidity for the patient. Shock wave lithotripsy and ureteroscopy have become standards of care for ureteral calculi. ⁴

The rate of spontaneous stone passage depends mainly on stone size and location. ^{5 –7} Although most ureteral stones pass spontaneously, the pain and cost associated with repeated episodes of renal colic are substantial. ⁸ Medical expulsive therapy for urolithiasis has gained increasing attention in the last years. ⁹ Various medications, such as nifedipine (a calcium antagonist) glyceryl trinitrate, prostaglandin synthesis inhibitors, antibiotics, and corticosteroid agents, have been investigated as spasmolytic agents that would promote the expulsion of ureteral stones, both in watchful waiting patients and those with post extracorporeal shock wave lithotripsy (ESWL). ^{10 –12}

Unfortunately, there is no uniformity in the regimes or inclusion criteria in these trials. Different agents' doses, duration of treatment, and adjunctive drugs as well as variability in stone size and location criteria make comparison between trials difficult. ¹³

Alpha 1A, 1B, and 1D adrenoceptor subtypes are localized in human ureter irrespective of location. The expression levels of subtypes are altered according to level of ureter and subtype. ¹⁴

Alpha-1 blockers decrease the tension, release the spasm of smooth muscles, and, thus, lessen the obstruction and irritation symptoms in the lower urinary tract. ¹

So recently, alpha1-adrenergic blockers have been noted by urologists.

Tamsulosin is an alpha1-adrenergic antagonist that bears with patients and has at least one side effect on blood pressure, so we can use this drug without titration dose.

The tamsulosin displays selectivity for alpha 1A and 1D adrenoceptors. ¹⁵

Due to restriction of articles and investigations about effectiveness of tamsulosin, we planned to use this drug, as adjunctive therapy, to verify its role in renal and ureteral stone fragments expulsion after ESWL treatment.

Materials and Methods

This study was a placebo-controlled, randomized, double-blind clinical trial prospectively performed between February 2008 and September 2009 on 150 patients with renal and ureteral stones referred to our ESWL center.

Patients enrolled in our study had a renal or ureteral stone that was 4 to 20 mm. Patients were excluded from the study if they had any of the following: recent open or endoscopic surgical intervention, radiolucent calculus, elevated serum creatinin (>1.5 mg/dL), urinary tract infection, high-grade hydronephrosis, peptic ulcer, concomitant treatment with calcium antagonists and/or alpha-adrenergic antagonists, hypotension, coagulopthy, urinary congenital anomalies, severe skeletal malformation, severe obesity, pregnancy, aortic or renal artery aneurysm, and if they were children.

All patients were evaluated before ESWL with plain radiography of the kidney, ureter, and bladder (KUB), intravenous urography and renal ultrasonography. Complete blood count, urine culture, renal profile, coagulation, and pregnancy tests were conducted.

All patients were treated with the Storz lithotriptor-Made in Germany.

We performed ESWL in all patients under mild intravenous sedation. We did not use general anesthesia. The intensity of waves was one to three, and the rate of waves was about 4000 Hz.

After ESWL, all patients were randomly assigned to two groups (placebo and case). The drugs administration was started immediately after ESWL and was continued for a maximum of 30 days. For all patients, Gentamicine 80 mg intramuscularly 30 minutes before ESWL and Ofluxacine 200 mg per 12 hours for 5 days after ESWL were administered. Also if pain occurred after ESWL, we used Meperidine 50 mg intramuscularly.

We recommended all patients to drink a minimum of 2 L water or liquid daily.

Group 1 (n = 75) received 0.4 mg tamsulosin once a day, and control group (group 2) received a placebo tablet once a day.

Follow-up included examination, U/C, renal ultrasonography, and KUB after ESWL.

After the following up of the patients and performing all the steps, the data were studied with SPSS 17 with chi-square and student's t-test.

Results

Our study was a placebo–controlled, randomized, double-blind clinical trial with 150 patients. 141 patients completed the study (71 patients from control group and 70 patients from case group). Nine patients were excluded from analysis due to discontinued drug consumption (two patients in placebo group and three patients in case group) and the migration of patients (two patients in placebo group and two patients in case group).

Both groups were comparable in their baseline demographic aspects (Table 1).

There was no statistically significant difference between the 2 groups with regard to location of stone, their sex, and age.

The mean stone size in the control group was 12.88 mm and in the case group was 13.22 mm.

We used the Storz Lithotriptor for ESWL in all patients under mild intravenous sedation. We did not use general anesthesia. The intensity of waves was one to three, and the rate of waves was about 4000 Hz.

The overall stone clearance rate was 60.5% (43 patients) in the control group and 71.4% (50 patients) in the case group; and the difference was not statistically significant (p = 0.116).

Finally, the remaining 39.4% in the control group and 28.6% in the case group did not discharge the stone fragments within 12 weeks after beginning medical therapy and were tried on other treatments.

Based on age, the patients were divided into three groups: The first group included those who were 20–40 years old; the second group included those who were 40–60 years old; and the third group included those who were 60–80 years old. Most of the patients were between 40 and 60 years old in all the groups.

The time of stone passage in 14 of 43 patients happened between the 20th and 30th day after ESWL in the control group (32.6%) and in 25 of 50 patients, between the 10th and 20th day after ESWL in the case group (50%). There was a statistically significant difference between the case and control groups (p = 0.002), and the time of stone passage can show the efficacy of the tamsulosin treatment.

Discussion

Urolithiasis is a disease that affects 12% of the world population. ^1,2 If stones do not pass spontaneously, the least invasive method of treatment is ESWL. ¹⁶

Medical expulsive therapy for urolithiasis has gained increasing attention in the last years. ⁹ Various medications such as nifedipine and corticosteroid agents have been investigated as spasmolytic agents that would promote the expulsion of the ureteral stones, both in watchful, waiting patients and patients with post ESWL. ^{10 –12} Alpha-1 blockers decrease the tension, release the spasm of smooth muscles, and, thus, lessen the obstruction and irritation symptoms in the lower urinary tract. ¹

According to the significance of this matter and the restriction of these investigations in Iran, we tried to study about tamsulosin efficacy with definite dosage (0.4 mg) on stone discharge after ESWL.

Gravina et al ¹⁷ in 2005 evaluated the role for tamsulosin based on the success rate of ESWL and found that tamsulosin with ESWL is more effective than ESWL alone in the patients with renal stones. The results of the study by Naja et al ¹⁸ in 2008 have shown that tamsulosin facilitates earlier clearance of fragments after ESWL to renal calculi and helps reduce the severity of the pain.

Dr. Mauro in 2008 suggested that adjunctive tamsulosin therapy combined with ESWL is safe and effective in enhancing stone clearance in patients with renal stones 10–24 mm in diameter. ¹⁹

Graves et al ²⁰ indicated that adjunctive medical therapy with tamsulosin after ESWL on distal ureteral stones does not affect the success and stone-free rate and the passage time of fragments but adjunctive administration of tamsulosin can reduce the total analgesic consumption after an ESWL procedure in the specific subgroup of patients with stone.

In the study done by Thomas Hermans in 2009, tamsulosin treatment does not improve the stone expulsion rate in patients with distal ureteral stone <7 mm, but their study showed that patients may benefit from supportive analgesic effect. ²¹ Bhagat et al ²² demonstrated that tamsulosin with SWL improved stone clearance, particularly with the larger stones, improved the outcome of steinstrasse, and reduced the need for intervention. Our study was designed to prospectively indicate the impact of tamsulosin after ESWL on the clearance of renal and ureteral stones. The clinical success was 71.4% and 60.56% for the tamsulosin and the control groups, respectively. Despite having a higher amount of stone passage in the case group in relation to the control group, it was not a statistically significant difference.

This study showed that stone fragments expulsion is faster in the case group in relation to the control group, and it was a statistically significant difference.

Further, some studies have pointed out the efficacy of stone location in the results of using the drug forcefully on the ureter in the rate of stone passage after ESWL. ¹

This result is not seen in our study, perhaps due to the low rate of the ureter stone in our study; and we do not have any significant statistical results.

Finally, according to the earned results and older studies with similar goals, we can arrive at a positive relationship between using tamsulosin and shortage of time of stone expulsion due to ESWL.

It is recommended to encourage more studies with more cases that result in more benefits and practical aspects of this project with regard to patient healing and treatment.

Conclusion

The results of our study have shown that the use of tamsulosin improved stone clearance but not with a statistically significant difference, and tamsulosin facilitates earlier clearance of fragments after ESWL to renal and ureteral calculi.