Comparison of the efficacy of tamsulosin and solifenacin on stone expulsion and pain relief after extracorporeal shock wave lithotripsy for lower ureteral stones
Abstract】Objective To analyze and compare the efficacy of tamsulosin and solifenacin on stone expulsion and pain relief after extracorporeal shock wave lithotripsy for lower ureteral stones. Methods 120 patients with lower ureteral stones were randomly divided into 4 groups, 30 patients in each group, with stones of 0.5-1.1 cm in diameter. no antispasmodic measures were taken in the control group except lithotripsy; Solinacin group was given 5 mg, 1 time/d; tamsulosin group was given tamsulosin 0.2 mg, 1 time/d, and tamsulosin combined with solinacin treatment group was: solinacin 5 mg, 1 time/d + tamsulosin The observation period of treatment did not exceed 2 weeks in each patient. The results were 24 cases (80.0%) in the control group, 26 cases (83.3%) in the solifenacin group, 28 cases (93.3%) in the tamsulosin group, and 29 cases (96.7%) in the combination treatment group, who had their stones expelled within 2 weeks. The differences were statistically significant in the tamsulosin group, and in the combination treatment group compared with the control group. The difference was statistically significant in the combination treatment group compared with the solifenacin and tamsulosin groups. The mean time to stone removal in each group was (7.6±3.7) d, (6.3±2.5) d, (4.4±2.3) d, and (3.5±2.2) d. The difference was statistically significant in the combination therapy group, which was shorter than the control group, and in the tamsulosin group compared with the control group, which was shorter than the other groups. In terms of analgesic drug use and relief of bladder irritation signs, there were significant differences between the solifenacin and combination treatment groups compared to the control group. Conclusion After extracorporeal shock wave lithotripsy for lower ureteral stones, tamsulosin and solifenacin are safe and effective in assisting stone removal, shortening stone removal time, relieving pain and improving symptoms, and tamsulosin combined with solifenacin is more effective in treatment.
[Keywords] Ureteral stones; tamsulosin; solifenacin.
CombinationSolifenacinandTamsulosinforthetreatmentoflowerureteralcalculiafterextracorporealshockwavelithotripsy
GongDaxin,JiangZhenming,LiZhenhua,LiuXiankui,LiZeliang,BiJianbin,KongChuize.DepartmentofUrology,theFirstAffiliatedHospital ChinaMedicalUniversity,Shenyang,110001,China
[Abstract]. ObjectivetoevaluatetheeffencyofcombinationSolifenacinandTamsulosinforthetreatmentoflowerureteralcalculiafterextracorporealshockwavelithotripsy .Methods120patientsrandomlyassignedto4groups(eachgroup30)withthecalculidiameterrangefrom0.5to1.1cm. Thecontrolgroupdidnotperformanyantispasmtreatmentexceptforextracorporealshockwavelithotripsy. TheSolifenacingroupadministeredSolifenacin5mg,onceperday. theTamsulosingroupadministeredTamsulosin0.2mg,onceperday. ThecombinationgroupadministeredSolifenacin5mg,onceperday+Tamsulosin0.2mg,onceperday. theobservationdurationdidnotexceed2weeks. ResultsThesuccessfulstoneexpulsionratewithin2weekswere80.0%,83.3%,93.3%and96.7%inthecontrolgroup,Solifenacingroup, Tamsulosingroupandcombinationgrouprespectively.StasticaldifferencesweresignificantbetweentheTamsulosingroup, thecombinationgroupandthecontrolgroup.StasticaldifferencesweresignificantbetweenthecombinationgroupandtheTamsulosingroup, theSolifenacingroup.Thesuccessfulstoneexpulsiondurationwere(7.6±3.7)d,(6.3±2.5)d,(4.4±2.3)d,(3.5±2.2)dinthecontrolgroup, Solifenacingroup,Tamsulosingroupandcombinationgrouprespectively.StasticaldifferencesweresignificantbetweentheTamsulosingroup, thecombinationgroupandthecontrolgroup. StasticaldifferenceswerealsosignificantfortheuseofanalgesicsandreliefofbladderirritationbetweentheSolifenacingroup, thecombinationgroupandthecontrolgroup. ConclusionsItisdemonstratedtheTamsulosinandSolifenacinaresafeandeffectiveforthetreatmentoflowerureteralcalculiafterextracorporealshockwavelithotripsy .Itcansignificantlyimprovethestoneexpulsionrate,reliefthepain.thecombinationofTamsulosinandSolifenacincanprovideabetterprognosis.
【Keywords】lowerureteralcalculi；Tamsulosin；Solifenacin
Renal colic caused by lower ureteral stones is one of the most commonly encountered emergencies in urology clinics, and some cases can be treated with extracorporeal shock wave lithotripsy. In some cases of ureteral stones, acute renal colic occurs during stone evacuation after extracorporeal shock wave lithotripsy treatment. Treatment can be taken after antispasmodic and analgesic treatment. In recent years, α1-blockers have been reported to relieve pain and promote stone expulsion. m-blockers can relieve ureteral spasm and improve symptoms. In order to evaluate the therapeutic effect of the combined application of the two, from November 2009 to May 2010, 120 patients with lower ureteral stones undergoing extracorporeal shock wave lithotripsy were selected for clinical observation to observe the adjuvant effect of α1 receptor blocker tamsulosin and M receptor blocker solifenacin on lower ureteral stones after extracorporeal shock wave lithotripsy (ESWL) and their effect on the symptoms of renal colic relief.
Data and Methods
1. Clinical data: 120 patients, including 100 males and 20 females, were diagnosed with lower ureteral stones with a diameter of 0.5-1.1 cm by ultrasound, CT or KUB, excluding patients with significant hydronephrosis (collecting system separation >2.5 cm), severe fever (temperature >38℃), multiple kidney stones, renal failure, pregnancy and lactation. The patients were randomly divided into 4 groups, control group, solifenacin group, tamsulosin group, and combination group, with 30 cases in each group. The basic information of each group is shown in Table 1. the mean age, gender ratio, and stone size of the patients in the 4 groups were compared, and the differences were not statistically significant (P>0.05).
Table 1: The basic situation of each group of ureteral stones
Group
Number of cases
Male: Female
Age (years)
Mean age (years)
Stone diameter (mm)
Control group
30
25:5
19-65
38±12
5.5±1.7
Solifenacin group
30
26:4
18-66
41±15
5.6±1.5
Tamsulosin group
30
24:6
20-67
42±11
5.8±1.4
Joint group
30
25:5
21-63
39±13
5.7±1.8
*The difference was not significant when comparing between the groups.
2. treatment method The control group was treated with extracorporeal shock wave lithotripsy (ESWL) only, and the other groups were given 5 mg, 1 time/d in addition to extracorporeal shock wave lithotripsy; tamsulosin 0.2 mg, 1 time/d in the tamsulosin group, and tamsulosin combined with solifenacin in the tamsulosin treatment group: solifenacin 5 mg, 1 time/d + tamsulosin 0.2 mg, 1 time/d. All patients were required to drink about 2 L of water per day during the treatment period. During the treatment period, all patients needed to drink about 2L of water per day. during the treatment period, the pain was classified into 4 grades by combining with WHO pain grading criteria. 0 without any discomfort in the kidney and ureteral travel area. grade 1 (mild pain) continuous or intermittent vague pain in the kidney and ureteral travel area, but tolerable and able to live a normal life with undisturbed sleep. grade 2 (moderate pain): significant renal and ureteral colic, unbearable, requiring Grade 3 (severe pain): pain is severe and unbearable, requiring analgesics, and sleep is severely disturbed. If renal and ureteral colic occurs and requires treatment, non-steroidal analgesics can be given, and if it cannot be relieved, dulcolax 1mg/kg can be administered intramuscularly. The observation period of treatment for each patient was no more than 2 weeks. During the treatment period, stones were observed and collected daily, side effects of lithotripsy drugs were recorded, ultrasound and CT or KUB were reviewed weekly, and drug treatment was terminated after imaging confirmed complete stone expulsion. For those who had not expelled the stones in 2 weeks, ESWL was performed again.
3. Statistical treatment SPSS13.0 software was applied to perform independent sample t-test and one-way ANOVA on the data of the three groups, and P<0.05 was considered statistically significant difference.
Results
The relief of renal and ureteral pain and bladder irritation signs after extracorporeal shock wave lithotripsy of ureteral stones by solifenacin and tamsulosin is shown in Table 2.
Table 2 Comparison of pain divisions in each group of ureteral stones
Group
Grade 0
Grade 1
Grade 2
Grade 3
Bladder irritation
Analgesic drug use
Control group
8
10
6
6
12
13
Solifenacin group
13
12
3
2
6#
5#
Tansolosin Group
11
12
4
3
10$ 9$ Joint group
15
12
2
1
4&
3&
#:compared with control group, P<0.05$:compared with control group, P>0.05&:compared with other groups, P<0.05
Comparison of ureteral stone elimination rates within 2 weeks is shown in Table 3.
Table 3 Comparison of stone elimination in ureteral stones in each group
Group
Number of cases
Number of expulsion cases
Lithotripsy rate (%)
Number of days of stone evacuation
Control group
30
24
80.0
7.6±3.7
Solifenacin group
30
25
83.3#
6.3±2.5#
Tamsulosin group
30
28
93.3$ 4.4±2.3$ Combined group
30
29
96.7&
3.5±2.2&
#:compared with control group, P>0.05$:compared with control group, P<0.05&:compared with other groups, P<0.05
The difference in stone evacuation rate between solifenacin group, tamsulosin group, and combination group compared with control group was statistically significant (P<0.05). The mean time to stone evacuation was shorter in the tamsulosin group and the combination group compared with the control group, and the difference was statistically significant (P<0.05). There were 2 cases of mild decrease in blood pressure on tamsulosin, which were tolerated without withdrawal, and 10 cases of dry mouth, 2 cases of blurred vision and 1 case of constipation on solifenacin, all of which did not require discontinuation of treatment.
Discussion
Ureteral stones account for 20% of urolithiasis, and 70% of ureteral stones are located in the lower ureter. Conservative treatment is preferred for ureteral stones, and when conservative treatment is ineffective, extracorporeal shock wave lithotripsy or ureteroscopic surgery can be performed [1]. After extracorporeal shock wave lithotripsy, it can cause ureteral edema and stone fragments can stimulate the ureter, causing spasm, which affects stone expulsion and may aggravate pain.
A large number of M receptors and α1 receptors are distributed on the ureter. α1 receptors can cause an increase in ureteral contraction force and peristaltic frequency. α1 receptor blockers can reduce smooth muscle tone, decrease the amplitude and frequency of smooth muscle contraction, lower the pressure in the lumen, and increase the rate of fluid delivery. In addition, α1 receptor blockers
There are three subtypes of α1 receptors, α1a, α1b, and α1d, with α1d predominating in the distal ureter. Tamsulosin is well tolerated, has fewer side effects, and is highly selective for urinary α1a and α1d receptors. It can relax the smooth muscle of the ureteral segment and promote stone expulsion, while relieving pain and reducing the use of analgesic drugs, and is a commonly used drug in the treatment of ureteral stones. There have been several reports showing significant differences in tamsulosin in promoting stone expulsion compared to controls [2,3]. deSio et al. reported a group of 96 studies with 90% stone clearance and 4.4 days of stone expulsion [4].
For stones less than 5 mm in diameter, only a small number of studies showed significant significance for α1 receptor blockers, while for stones larger than 5 mm in diameter, most studies showed significant stone removal [5-7].
In the present study, we showed that there was a significant difference in stone evacuation rate and time to stone evacuation in the tamsulosin-treated group compared to the control group (P<0.05), but there was no significant difference in the relief of bladder irritation signs and the use of analgesic drugs.
Choline receptor blockers, which can relax smooth muscle and release the spasm of blood vessels, ureter and bile duct, are more widely used in clinical practice as smooth muscle relaxants. Studies have shown that M2, M3 and M5 receptors are widely distributed on the ureter [8]. Solifenacin is a highly selective M receptor blocker, mainly acting on M3 receptors, with a strong urological selectivity, and is commonly used to treat overactive bladder disorders. Since M3 receptors are also distributed on the ureter, solifenacin also has a relaxing effect on M3 receptor-mediated ureteral constriction. Ureteral stones treated by lithotripsy can cause local edema and stone fragments can cause spasm of ureteral smooth muscle. The M-blocker solifenacin can relieve ureteral smooth muscle spasm and bladder irritation and reduce the use of analgesic drugs. Our data showed that in the solinacin treatment group, bladder irritation was significantly lower than that in the tamsulosin group and the control group, and the difference was statistically significant (P<0.05), and it also had a significant effect on pain relief and could significantly reduce the use of analgesic drugs. The results showed that the use of solifenacin alone had no significant effect on stone expulsion rate and stone expulsion time.
The combination of solifenacin and tamsulosin can exert both α1-blocker and M-blocker effects to maximize the effect on the relief of spasm of ureteral smooth muscle and the dilation of ureter. The results showed that the combined treatment group showed significant differences in the relief of bladder irritation signs, the use of pain medication, the time of stone removal and the rate of stone removal, compared with the other treatment groups.
The side effects associated with both drugs during treatment were mild and tolerated without the need for discontinuation of treatment.
This study shows that tamsulosin and solifenacin are safe and effective in assisting stone removal after extracorporeal shock wave lithotripsy for lower ureteral stones, shortening stone removal time, relieving pain, and improving symptoms, and that tamsulosin combined with solifenacin is more effective in treatment.