Medical Expulsion Therapy with Tamsulosin in Ureteral Colic

Author: Anand Swaminathan, MD, MPH (Asst Professor/APD, NYU/Bellevue)

Edited by: Alex Koyfman, MD (@EMHighAK), Brit Long, MD (@long_brit, EM Chief Resident at SAUSHEC, USAF)

Intro: Renal colic is a common ED presentation. Rarely does a day go by that we don’t see a patient rocking and rolling in acute ureteral colic. There are a number of areas within this disorder of active discussion, debate, and research. Among these are the use of CT scanning, using low-dose CT scans, and medical expulsion therapy (MET). MET is the use of medications (typically calcium channel blockers or tamsulosin) to 1) increase the passage rate and 2) shorten the time to passage. This could potentially reduce ED revisits, reduce the number of invasive procedures, and make happy patients. This post will focus on the role of tamsulosin for MET in renal colic.

Clinical Question: Is tamsulosin effective in increasing the spontaneous passage rate of ureteral stones and/or in decreasing the pain associated with this disorder?

The pathophysiologic basis for this treatment is that alpha antagonists inhibit contraction of ureteral muscles responsible for ureterospasm allowing for an increased rate of stone propagation. Alpha 1-adrenergic receptors are concentrated in the distal ureter, and as a result, it is distal stones that that should theoretically benefit most. Many urologists recommend treatment of patients with nephrolithiasis with tamsulosin based on studies from the early 2000s.

MET seems to have entered the EM realm after the publication of a systematic review in Annals of Emergency Medicine in 2007 (Singh 2007). This review concluded that the results:

“are encouraging for the use of an alpha-antagonist or calcium channel blocker to facilitate stone expulsion of moderately sized distal ureteral calculi; however, because of the limitation of methodologic quality with the studies reviewed, a large, well-done, randomized clinical trial is needed to confirm these results before uniform adoption can be recommended.”

The caveat at the end of their conclusion is vital but appears to have been initially glossed over by many providers (myself included). The reason for this disclaimer was that the quality of the studies included in this systematic review were poor: randomization, blinding, and follow-up were all markedly sub-optimal.

This is a great example of systematic reviews and meta-analyses only being as good as the original studies that go into them. I always use the haircut analogy. I wouldn’t let a 5 year-old cut my hair. I also wouldn’t let five 5 year-olds cut my hair because five 5 year-olds don’t make a 25 year-old. Similarly, putting together a bunch of poor studies does not make a good study.

Despite these limitations, this systematic review, as well as others published around the same time, changed management. Now, though, we have better evidence to guide our decisions. Let’s take a quick perusal of that literature.

Al-Ansari et al. Efficacy of Tamsulosin in the Management of Lower Ureteral Stones: A Randomized Double-blind Placebo-controlled Study of 100 Patients. Urology 2010; 75: 4-8.

Details

  • RDCT of 100 patients
  • Overall stone expulsion 82% vs. 61% giving an RR = 2.93 for tamsulosin
  • Stones < 5 mm benefited more
  • Shorter time to expulsion and less pain medication use

Limitations + Problems

  • It’s unclear if these were Emergency Department patients
  • It’s unclear what the primary outcome is
  • Patients discharged on parenteral diclofenac (not standard care for us)

This is the only randomized trial to show a benefit to tamsulosin but there are some major issues. The passage rate for stones < 5 mm is considerably lower in the placebo group (69%) than what has been typically described (Segura 1997). Additionally, the authors do not make it clear what the primary outcome was meant to be. It is possible that a number of outcomes were assessed and the ones that were statistically significant were reported.

Hermanns T et al. Is There a Role for Tamsulosin in the Treatment of Distal Ureteral Stones of 7 mm or less? Results of Randomised, Double-Blind, Placebo-Controlled Trial. European Urology 2009; 407-12.

Details

  • RDCT of 100 patients
  • Primary endpoint – stone passage @ 21 days – 86.7% vs. 88.9% (non-significant difference)
  • Secondary endpoint – time to passage and pain medication use (non-significant difference)

Limitations + Problems

  • Time to passage data missing for 1/3 of patients
  • Outpatient study
  • Majority of stones < 5 mm

Ferre RM et al. Tamsulosin for Ureteral Stones in the ED: a Randomized, Controlled Trial. Ann of EM 2009; 54: 432-9.

Details

  • RCT in the Emergency Department of 80 patients
  • Primary outcome – stone passage @ 14 days – 77.1% vs 64.9% (non-significant difference)
  • Secondary outcomes – time to passage, pain scores, renal colic episodes, return visits to the ED (no significant differences)

Limitations + Problems

  • No placebo and no blinding (this tends to favor the drug, though)
  • Mean stone size was small (3.6 mm)

Vincendeau S et al. Tamsulosin hydrochloride vs Placebo for Management of Distal Ureteral Stones. Arch Intern Med 2010; 170(22): 2021-7.

Details

  • RDCT in the Emergency Department of 129 patients
  • Primary outcome – time to expulsion – no statistically significant difference
  • Secondary outcome – passage at 42 days – non-significant difference

Limitations + Problems

  • Patients all admitted to urology

Summary: Clearly, there is disagreement in the literature up to this point. None of these studies are ideal but the preponderance of the evidence points towards the disutility of these agents. For years we had been hoping for a large, well-done RDCT to give us stronger evidence one way or another and now, we have it…

Picard R et al. Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial. Lancet 2015.

Details

  • RDCT performed in 24 UK hospitals including 1167 patients (379 patients receiving nifedipine, 378 patients receiving tamsulosin and 379 patients receiving placebo)
  • Primary outcome – Need for urologic intervention to facilitate stone passage at 4 weeks after randomization – No statistically significant difference between the three groups

Strengths: This was a large, multicenter study with excellent methods and follow up (only 1.2% of patients lost). Additionally, 25% of the patients had “larger” stones (> 5 mm)

Author’s Conclusion: “Tamsulosin 400 μg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic.”

Bottom Line: The Picard study represents the highest quality evidence on the utility (or in this case, the lack thereof) for tamsulosin in the treatment of ureteral colic. Based on this data and that of the other randomized trials reviewed here, tamsulosin should not be standard care for patients presenting with ureteral colic.

References / Further Reading

  1. Singh A et al. A Systemic Review of Medical Therapy to Facilitate Passage of Ureteral Calculi. Ann of EM 2007; 50: 552-63.
  2. Al-Ansari et al. Efficacy of Tamsulosin in the Management of Lower Ureteral Stones: A Randomized Double-blind Placebo-controlled Study of 100 Patients. Urology 2010; 75: 4-8.
  3. Segura JW, Preminger GM, Assimos DG, et al; The American Urological Association. Ureteral Stones Clinical Guidelines Panel summary report on the management of ureteral calculi. J Urol. 1997;158(5):1915-1921.
  4. Hermanns T et al. Is There a Role for Tamsulosin in the Treatment of Distal Ureteral Stones of 7 mm or less? Results of Randomised, Double-Blind, Placebo-Controlled Trial. European Urology 2009.
  5. Ferre RM et al. Tamsulosin for Ureteral Stones in the ED: a Randomized, Controlled Trial. Ann of EM 2009; 54: 432-9.
  6. Vincendeau S et al. Tamsulosin hydrochloride vs Placebo for Management of Distal Ureteral Stones. Arch Intern Med 2010; 170(22): 2021-7.
  7. Picard R et al. Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial. Lancet 2015.
  8. http://www.ncbi.nlm.nih.gov/pubmed/23349418

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