Does Use of Tamsulosin in Renal Colic Facilitate Stone Passage?

Does Use of Tamsulosin in Renal Colic Facilitate Stone PassageRenal colic is a common ED presentation. Rarely does a day go by that we don’t see a patient rocking and rolling in acute renal colic. Dan Firestone makes an impassioned argument against the use of CT scanning for diagnosis of renal colic so I won’t address that here. Once we make a diagnosis, our primary goal in the ED is pain relief. Then we turn our attention to disposition planning, follow up and outpatient medications. The majority (90%) of stones will pass spontaneously but it would be nice if we could:

  1. increase the passage rate
  2. shorten the time to passage.

This could potentially reduce ED revisits, reduce the number of invasive procedures and make happy patients. So does the use of tamsulosin in renal colic facilitate stone passage?

What Urban Legend Will we Cover Today?

Patients with ANY ureteral stone should be treated with alpha antagonists to facilitate stone passage.

What is the background for the use of alpha antagonists in renal expulsion therapy?

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 (at least in the US) recommend treatment with these agents and tamsulosin is the preferred treatment because it carries a lower side effect profile.

The idea of medical expulsion therapy seems to have entered the EM realm after the publication of a systematic review in Annals of Emergency Medicine in 2007 (17681643). 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 conclusions 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 they were able to find was 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. Putting together a bunch of poor studies does not make a good study.

Despite these limitations, this study appears to have changed practice. Now, though, we have better evidence to guide our decisions.

What other studies have evaluated the use of alpha antagonists to facilitate stone passage?

OneAl-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. (20109697)

Details

  • RDCT of 100 patients
  • Overall stone expulsion 82% vs. 61% giving a 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.

 

TwoHermanns 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. (19375849)

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

 

ThreeFerre RM et al. Tamsulosin for Ureteral Stones in the ED: a Randomized, Controlled Trial. Ann of EM 2009; 54: 432-9. (19200622)

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)

 

FourVincendeau S et al. Tamsulosin hydrochloride vs Placebo for Management of Distal Ureteral Stones. Arch Intern Med 2010; 170(22): 2021-7. (21149761)

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 of the above studies: Clearly, there is disagreement in the literature. None of the studies are ideal. We continue to lack a large, RDCT done on patients presenting to the Emergency Department with renal colic.

Mythbusting

Clinical Bottom Line:

The best evidence we have to date, does not show a significant benefit in the use of tamsulosin in renal colic to facilitate stone passage.

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Anand Swaminathan

Clinical Assistant Professor of Emergency Medicine at Bellvue/NYU
REBEL EM Associate Editor and Author

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  1. Hey everyone. I discussed this issue on EMRAP back in December and received the following comments from one of the listeners who discussed this topic with their urology group. I thought I would share the comment as well as my response:

    EMRAP Listener:

    Here is the response I got from our urology group:

    I listened to the audio report, which refers to some relevant literature, but I think comes to a questionable conclusion in its recommendation.

    The audio report begins be citing two large meta analysis that were conducted in 2006 (Hollingsworth, Lancet) and 2007 (Singh, Annals of Emer Med). Both meta analysis had positive findings in favor of the use of Tamsulosin.

    In the Lancet paper, all but one of the 9 RCTs it referred too were faulty. The Emer Med paper bundled more poor quality trials. The conclusion that good data cannot be drawn from poor designed studies is correct; however the overwhelming evidence suggested utility of use and this has some value.

    The narrator then refers to a couple smaller studies done in 2009 and then one in 2010. This was a study in Urology, a RCT, well designed, not particularly powerful (100 pts) and its conclusions were not supportive. The narrator holds this study as exemplary and uses it to question the blanket use of Tamsulosin in medical expulsion therapy.

    Surprisingly, the narrator fails to mention that the average diameter of stones in the trial, however well designed it was, was 3.1mm. As we know, the spontaneous passage rate for stones like this is 90+ %. I question is applicability to stones between 4 and 10mm.

    Between 2010 and 2014 there were four more small, RCTs looking at the issue. They all had powers around 100, but were designed well (Int J CLin Practive, 2014; Can J Urol, 2010, Int J Urol 2010 and Urology 2010). Criteria were prox stones < 6mm, distal stones 4-10mm, and all ureteral stones < 10mm. All of these RCTs showed a benefit and were not mentioned in the audio report.

    The SUSPEND trial is currently running. It is a well designed prospective RCT, which started in 2011. Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. This is the best study to date and will be powered to over 800 ppl. I think this will give us the answers we seek.

    Until such time, I think for any ureteric stone between 4-10mm, Flomax is useful. It is cheap and low in adverse effects (<4%). As always, medical expulsion therapy has to be tailored to the patient and his/her prior conditions.

  2. Here was my response to the above comment:

    Brook – thanks for sending this to your urology group and for the response. It’s great to get our consultants to weigh in.

    First of all, let me clarify some of my statements and then I’ll discuss the literature pointed out by your group.

    The systematic review data from the Lancet and Ann of EM in 2009 are minimally, if at all, useful. They suffer from the simple fact that if you take a bunch of poorly done studies and throw them together, you get a poor systematic review. The studies going into them had poor methodology making them severely biased.

    I discussed 4 randomized trials since then:
    1. Vincendeau S et al. Arch Int Med 2010. Small study, well-done, small overall stone size (3.1 mm) and showed no benefit. This was a true RDCT.
    2. Hermanns T et al. Eur Urology 2009. small study, okay methodology, small overall stone size (3.9 mm) and showed no benefit. Again, true RDCT.
    3. Ferre RM et al. Ann Emerg Med 2009. small study, non-blinded, small overall stone size (3.6 mm) and showed no benefit. Non-blinding design would favor drug but no benefit anyway.
    4. Al-Ansari A et al. Urology 2010. small study, RDCT that showed benefit. However, the results are suspect. They calculated an 80% power to detect a 25% difference. They did not detect a 25% difference but rather a 21% difference. There study was not powered to determine whether a 21% difference (although this seems big) was statistically significant.

    Overall, I would say that these 4 studies do not prove a benefit to tamsulosin over standard care.

    That brings us to the additional studies pointed out by your group.
    1. Lee SW et al. Int J Clin Practice 2013. Open label trial. The providers and patients knew if they got tamsulosin or not. This introduces serious bias because patients and providers were able to decide that they had failed conservative treatment and wanted to get interventional therapy. I imagine that if you were on tamsulosin and you and your provider knew that you may say “just hold on another couple of days and wait for passage.” Additionally, the authors state that the “procedures” (i.e. imaging) were performed in an “emergency setting.” It’s unclear whether this means they presented to an Emergency Department or they presented to a clinic and were sent for emergent imaging. Applicability to our patients in the ED is unclear. This study is severely flawed and ripe for significant bias and therefore, adds little to the discussion.
    2. Abdel-Meguid TA et al. Can J Urology 2010. This study was an RDCT and the methods were okay. A couple of big points, though. Once again, it is not specified if these patients presented to the ED or not. Aplicability to the ED setting is unclear. It’s additionally unclear if patients were collected consecutively or not. This introduces bias. The methods also do not discuss any power calculation. It’s unclear if the study was adequately powered to detect the difference they found. The group did find a significant difference in passage rate but the flaws above are important to note.
    3. Kaneko T et al. Int J Urology 2010. This was a randomized, open-label trial (similar to the Lee article). It appears this study was not on an ED population as well. They found an improved primary outcome of spontaneous stone passage in the tamsulosin group. Once again, however, the study is ripe for bias as it’s open label. The providers and patients know how they were being treated and could call it quits on conservative management and opt for intervention (and thus failure of the primary endpoint) any time they wanted to. This significant bias again renders the data non-helpful.
    4. The fourth study referenced (Urology 2010) was detailed in my segment (Al-Ansari 2010).

    Where does this leave us? There are no well done, large RDCTs to guide us. The decent evidence we have points to no benefit to the treatment. A host of very poor data shows a benefit but these studies were not performed with any degree of methodological rigor that is acceptable. The SUSPEND trial may be a useful addition although when I reviewed the protocol, it is again unclear whether these are ED patients. However, the methodology appears sound.

    I strongly disagree with the final statement from your urology group. In the absence of robust (or even decent) evidence, we should not be using this medication for ED patients presenting with renal colic. Flomax is not cheap. 30 capsules cost $190.85 or approximately $6.36/pill. Generic tamsulosin isn’t cheap either (30 capsules are 139.23 or $4.63/pill). The side effect profile isn’t too bad but why take a medication if it offers no proven benefit. In this case, any minor adverse effects outweighs benefit as there is no proven benefit.

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