Tamsulosin does not increase 1-week passage rate of ureteral stones in ED patients

doi:10.1016/j.ajem.2015.08.006

The American Journal of Emergency Medicine

Volume 33, Issue 12, December 2015, Pages 1721-1724

https://doi.org/10.1016/j.ajem.2015.08.006 Get rights and content

Abstract

Objective

The objective of the study is to determine if tamsulosin initiated in the emergency department (ED) decreases the time to ureteral stone passage at 1 week or time to pain resolution, compared to placebo.

Methods

We performed a prospective, randomized, double-blinded, placebo-controlled trial of tamsulosin vs placebo in ED patients with ureterolithiasis on computed tomography. Patients were identified and enrolled between April 2007 and February 2009 and were randomized to either 0.4 mg of tamsulosin or placebo for 1 week. We contacted participants using a telephone survey on post-ED visit days 1, 2, 3, and 7. The primary outcome was time to stone passage, with secondary outcomes being maximum pain score and amount of pain medication required.

Results

Of the 127 patients enrolled during this study, 15 were lost to follow-up, and 12 required surgical interventions before the 7-day mark, leaving 100 patients for analysis. Of the 100 patients, 53 received tamsulosin and 47 received placebo. There was no difference between groups in percentage of male, mean age, initial serum creatinine, average stone size, stone location, and history of prior stone. The probability that the patient did not pass a stone at 7 days was not different between tamsulosin and placebo, 62.1% (95% confidence interval, 49.1%-75.1%) vs 54.4% (95% confidence interval, 40.3%-68.6%; P = .58). There was no significant difference in the high pain score (P = .12) or hydrocodone/acetaminophen intake (P = .76) between treatment groups at any of the time points.

Conclusion

This study reveals no difference in the proportion of stone passage or high pain score and pain medication utilization at 7 days between tamsulosin and placebo.

Introduction

Renal colic is a common presenting complaint of patients in an emergency department (ED), and ureterolithiasis is a common diagnosis by emergency physicians. The annual incidence of stones and cost of therapy are increasing, and urolithiasis is reported to create $2.1 billion in health care costs in the United States alone [1]. Prior research demonstrates that most stones will pass spontaneously, and stone passage rates tend to be inversely proportional to stone size. A subset of patients with ureterolithiasis requires operative urologic intervention. This contributes to cost as well as morbidity.

Medical expulsive therapy (MET) has been investigated since the 1960s as an alternative to operative management for ureterolithiasis. Many drugs have been investigated, including steroids, nonsteroidal anti-inflammatory drugs, calcium-channel blockers, and α antagonists. Of these studied MET, α-blocker use is supported by the American Urologic Association for its MET properties in patients with ureteral calculi less than 10 mm [2]. This recommendation is level IV, panel/consensus evidence. The theoretical properties, which may make α-blockers effective for MET, include relaxing ureteral smooth muscle, inhibiting ureteral spasms, and dilating the ureteral lumen, which are postulated to facilitate stone passage [3].

Despite tamsulosin's α-blocking properties, which seem to make it ideal for MET, there are conflicting data in the literature, and only a paucity of studies are prospective or randomized controlled clinical trials. Of the 5 prior studies using α-blocker MET, 1 study that was prospective and randomized, but not double blinded or placebo controlled, did not find any added benefit vs standard analgesics [4]. Al-Ansari et al [5] did find benefit in their prospective, randomized, double-blinded, placebo-controlled investigation of distal-only ureterolithiasis. Further studies also suggest a benefit from tamsulosin, but these studies were not blinded or placebo controlled [6], [7], [8].

These studies are further limited, however, in that 2 [6], [7] used MET in combination with corticosteroids and 1 [8] analyzed only distal ureteral stones. To address this question, the aim of this study is to determine if tamsulosin monotherapy initiated in the ED decreases the time to ureteral stone passage compared to placebo. Our secondary objective was to assess whether tamsulosin decreased patient pain severity or medication use during the study period.

Section snippets

Materials and methods

We performed a prospective, randomized, double-blinded, placebo-controlled trial of tamsulosin vs placebo in ED patients with ureterolithiasis visualized on computed tomography at our tertiary care hospital using a convenience sample. Our tertiary care center has an associated emergency medicine residency program as well as annual ED volume is more than 120 000 patients per year with a 30% admission rate. This was institutional review board approved, and all patients provided informed consent.

Results

Of the 127 patients enrolled during this study, 15 were lost to follow-up, and 12 received surgical intervention before the 7-day mark, leaving 100 patients for analysis. Of the 100 patients, 53 received tamsulosin and 47 received placebo. As seen in the Table, analysis of demographics between the 2 groups revealed similarity in percentage of male, mean age, initial serum creatinine, average stone size, stone location, and history of prior stone.

Discussion

This prospective, randomized, double-blinded, placebo-controlled trial demonstrates no statistical difference in the proportion of stone passage at 7 days between tamsulosin and placebo. We observed a lower 1-week passage rate than previous reports in both the tamsulosin and placebo groups. We did not find a statistical difference in high pain score or Vicodin requirements between the 2 groups either. Of note, we identified no difference in the rate of adverse reactions to study drug vs placebo.

Limitations

Our study has several limitations, the most significant being the small sample size. Our enrollment is nonconsecutive, although no bias was recognized in the patients who were enrolled. Patients in our study had an average stone size of 3.8 mm in the control group and 4.0 mm in the treatment group, which is consistent with prior studies, supporting the lack of bias in recruiting. Our study also did not evaluate the amount of nonsteroidal anti-inflammatory drugs used by both groups, which may or

Conclusion

In this first prospective, randomized, double-blinded, placebo-controlled trial of ED patients with documented ureterolithiasis, we did not demonstrate any benefit in the form of early stone expulsion, decreased pain severity, or decreased pain medication use with the administration of tamsulosin. Reviewing our data and the aforementioned quasiexperimental trials addressing this topic, we conclude that a large multicenter randomized controlled trial would be needed to answer this question

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Cited by (10)

Effect of Tamsulosin on Stone Passage for Ureteral Stones: A Systematic Review and Meta-analysis
2017, Annals of Emergency Medicine
Citation Excerpt :
Five studies were duplicates, 5 did not contain sufficient data to analyze in a meta-analysis, and 1 reported 1-week outcomes (versus 3- to 4-week outcomes). Authors for 7 studies were contacted for additional information,8,17-22 and complete data were available in only 8 cases. Agreement between study abstractors was excellent (Cohen’s κ=0.94 [95% CI 0.82 to 1.0]).
Tamsulosin is recommended for patients receiving a diagnosis of a ureteral stone less than 10 mm who do not require immediate urologic intervention. Because of conflicting results from recent meta-analyses and large randomized controlled trials, the efficacy of tamsulosin is unclear. We perform a systematic review and meta-analysis to investigate the effect of tamsulosin on stone passage in patients receiving a diagnosis of ureteral stone.
MEDLINE, EMBASE, and CENTRAL databases were searched without language restriction through November 2015 for studies assessing the efficacy of tamsulosin and using a double-blind, randomized, controlled trial design. Meta-analysis was conducted with a random-effects model and subgroup analyses were conducted to determine sources of heterogeneity.
Eight randomized controlled trials (N=1,384) contained sufficient information for inclusion. The pooled risk of stone passage in the tamsulosin arm was 85% versus 66% in the placebo arm, but substantial heterogeneity existed across trials (I²=80.2%; P<.001). After stratifying of studies by stone size, the meta-analysis of the large stone subgroup (5 to 10 mm; N=514) indicated a benefit of tamsulosin (risk difference=22%; 95% confidence interval 12% to 33%; number needed to treat=5). The meta-analysis of the small stone subgroup (<4 to 5 mm; N=533) indicated no benefit (risk difference=–0.3%; 95% confidence interval –4% to 3%). Neither meta-analysis for the occurrence of dizziness or hypotension showed a significant effect.
Tamsulosin significantly improves stone passage in patients with larger stones, whereas the effect of tamsulosin is diminished in those with smaller stones, who are likely to pass their stone regardless of treatment.
Medical Expulsive Therapy in Urolithiasis: A Review of the Quality of the Current Evidence
2017, European Urology Focus
Citation Excerpt :
These trials were parallel in design, whereby each group of participants was exposed to one of the study intreventions (α-blocker vs placebo [22,23,25,52,57] or α-blocker vs calcium channel blocker vs placebo [24]). They conformed to most of the 37 CONSORT criteria (n = 23 [22]; n = 25 [52]; n = 27 [57]; n = 31 [23,25]; n = 36 [24]). Patients with stones located in any part of the ureter [23,24] or with distal ureteral stones [22,25,52,57] were enrolled.
Medical expulsive therapy (MET) is widely used to promote spontaneous passage of urinary stones. However, there is conflicting evidence on the actual role of MET.
To evaluate the conformance of published randomized controlled trials (RCTs) on MET with the Consolidated Standards for Reporting Trials (CONSORT) criteria, and to clarify the current role of MET in management of urinary stones on the basis of our findings.
We carried out an electronic search of the Cochrane Library, PubMed, and Embase databases for RCTs on MET. For each RCT included, we created a checklist table documenting the minimum essential items that should be included in reports of RCTs according to the CONSORT 2010 statement.
Clinical heterogeneity between pooled studies in terms of the MET given, inclusion criteria, sample size, pre- and post-treatment imaging, and differential follow-up was profound. The overall methodological rigor of the pooled studies was low, as indicated by the moderate to poor conformance of the studies with the CONSORT criteria. The aforementioned reasons may explain the discrepancies found between the supporting results of several meta-analyses and those of well-designed placebo-controlled double-blind studies revealing no benefit from MET. Recent well-designed RCTs have shown no benefit from α-blockers versus placebo. However, on the basis of sensitivity analyses in a recently published meta-analysis, α-blockers may still promote spontaneous expulsion of large stones.
Conflicting data on MET may be explained by clinical heterogeneity and methodological flaws. Urologists must decide whether to follow single, large, well-conducted RCTs or pooled data from meta-analyses. The latter still support selective use of MET for larger urinary stones.
In this review we tested the accuracy of the studies published on various medications given to promote spontaneous passage of stones from the ureter. Although the majority of the studies were not designed properly, there is still some evidence to support medical expulsive therapy.
Tamsulosin for urolithiasis: a review of the recent literature and current controversies
2016, American Journal of Emergency Medicine
In the United States, urolithiasis affects approximately 1 in 11 people, and there is evidence that the prevalence is increasing. A relatively recent treatment strategy for urolithiasis involves using medical expulsive therapy (MET) to increase the likelihood of spontaneous passage of ureteral stones. The 2 leading drug classes for MET are alpha-1-andrenergic receptor blockers and calcium channel blockers. Tamsulosin, an alpha-1-adrenocepter blocking agent, is thought to induce spontaneous stone passage by relaxing ureteral smooth muscle tone. However, tamsulosin has not been proven effective for increasing ureteral stone passage and is not approved by the Food and Drug Administration for this indication. There is a relative paucity of data on the efficacy of tamsulosin for urolithiasis, and of the published results, there are conflicting conclusions from the data. Because of the acute and often severe nature of symptoms from urolithiasis, emergency medicine physicians are frequently the first to diagnose and treat this condition. This has led to tamsulosin being frequently prescribed from the emergency department (ED) for off-label use without the support of high-quality evidence. If tamsulosin is proven effective, its use in the treatment of urolithiasis could offer several important advantages. The number of procedures, length of hospital stay, and health care costs after the initial ED visit could potentially be reduced. Tamsulosin may also increase patient satisfaction by reducing the invasive treatment and decreasing the time to stone passage. This review focuses on the efficacy of tamsulosin based on stone location, after shock wave lithotripsy, compared with other MET drugs and in the acute setting of the ED.
Alpha-blockers: the magic pill for endourology—The great delusion
2024, World Journal of Urology
Is tamsulosin effective for the passage of symptomatic ureteral stones A systematic review and meta-analysis
2019, Medicine (United States)
α-blockers as medical expulsive therapy for ureteric stones: a Cochrane systematic review
2018, BJU International

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^☆: Meetings: Not presented at any national or international meetings.

^☆☆: Clinical Trials number NCT00448123; no grant or financial support.

^★: Conflicts of interest: None for any author.

^★★: Author contribution statement: MR, JH, JZ, RJ, and RS conceived the study and designed the trial. MR, RJ, and RS supervised the conduct of the trial and data collection. RJ and RS managed the data to ensure quality control. RJ and RS provided statistical advice, and the statistical analysis was performed by CC. DB drafted the manuscript, and all authors contributed to its revision. DB, RJ, and RS take responsibility for the article as a whole.

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Original ContributionTamsulosin does not increase 1-week passage rate of ureteral stones in ED patients☆,☆☆,★,★★

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Materials and methods

Results

Discussion

Limitations

Conclusion

J Urol

Eur Urol

Urology

Ann Emerg Med

Am J Emerg Med

J Emerg Med

American Urologic Association Clinical Guideline for Ureteral Calculi

Original Contribution
Tamsulosin does not increase 1-week passage rate of ureteral stones in ED patients☆,☆☆,★,★★