Date:  April 11, 2014 

Guest Skeptics: Dr. Anthony (Tony) Seupaul Chairman of the Department of Emergency Medicine, University of Arkansas for Medical Sciences and Dr. Joshua Hughes one of his star residents.

Case Scenario: A 36 yr old previously healthy white male that comes into the emergency department mid morning one Sunday after about 10 hours of right flank pain he describes as sharp/stabbing and that has progressively become worse since onset.

He says that over the last couple of hours he has felt that it is radiating down towards his groin. He has been “sick to his stomach” but has not vomited. He denies seeing any blood in his urine and has not experienced any pain with urination.

He denies any diarrhea. He has not had any fever that he knows of. He denies any previous pain like this and denies any history of previous kidney stones. He took 400 mg of ibuprofen last night with only some temporary pain relief.

CT stone protocol shows a 0.3 cm non-obstructive stone in right proximal to mid ureter. No evidence of hydronephrosis or hydroureter.

Question: Is tamsulosin safe and effective for the expulsion of ureteral stones?

Background: We have covered renal colic before on the SGEM. Episode#4: Getting Unstoned (Renal Colic and Alpha Blockers) looked at a tamsulosin for expulsion of distal ureteral stones. It was a multicentreed, randomized, double-blind trial that did not show benefit. Now it was only a small study of 129 patients recruited form 6 french hospitals in over five years.

The other episode was #32: Stone Me (Fluids and Diuretics for Renal Colic). It was a Cochrane Systematic Review done by BEEM founder Dr. Andrew Worster. They were looking for studies on high volume IV/oral fluids or diuretic use to aid with passing kidney stones. Only two small studies met inclusion criteria. The conclusion was no reliable evidence was available to support the use of these treatments.

We have been waiting for s Cochrane Systematic Review from Zue et al promised in 2010. Well it has not been published yet but we have another systematic review.

Article: Lu Z et al. Tamsulosin for ureteral stones: a systematic review and meta-analysis of a randomized control trial. Urologia Internationalis 2012

  • Population:  2,763 patients with ureteral stones in 29 trials
  • Intervention: Either tamsulosin 0.2 mg (5 trials) or 0.4 mg daily (25 trials)
  • Comparison: Tamsulosin v control; Tamsulosin plus standard therapy v control; low dose v standard dose tamsulsoin; tamsulosin v ESWL (standard therapies included ketorolac, diclofenac, hydration, cotrimoxazole, and ibuprofen)
  • OutcomeThe primary outcome was overall ureteral stone expulsion rate

Authors’ Conclusions: “Tamsulosin is a safe and effective medical expulsive therapy choice for ureteral stones. It should be recommended for most patients with distal ureteral stones before stones are 10 mm in size. In future, high-quality multicenter, randomized and placebo- controlled trials are needed to evaluate the outcome.” 

Quality Check List for Systematic Reviews:checklist-cartoon

  1. Was the clinical question is sensible and answerable. Agree
  2. Was the search for studies was detailed and exhaustive. Agree
  3. Were primary studies were of high methodological quality.  Disagree
  4. Were the assessments of studies were reproducible. Unsure
  5. Were the outcomes were clinically relevant. Agree
  6. Was there low statistical heterogeneity for the primary outcome.  Disagree     
  7. Was the treatment effect was large enough and precise enough to be clinically significant. Yes

Key Results:

  • Stone expulsion Rate (29 studies)
    • Significant benefit overall
    • Tamsulosin vs control (RR 1.33, 95%CI 1.23-1.44)
  • Subgroup analysis
    • tamsulosin 0.4mg alone vs. control (RR1.51, 95%CI 1.34-1.69)
    • tamsulosin 0.4mg with standard therapy vs. control (RR 1.41, 95%CI 1.19-1.67)
    • No further improvement when comparing 0.4mg group with the 0.2mg tamsulosin group
    • No difference between tamsulosin and other alpha-blockers
  • Stone Expulsion Time (16 studies)
    • tamsulosin 0.4mg vs. control (WMD -3.40, 95% CI -4.50 to -2.29)
    • tamsulosin 0.4mg with standard therapy vs. control (WMD -3.61, 95% CI -5.08 to -2.14)
    • No significant difference between the 0.4mg tamsulosin groups and the 0.2mg tamsulosin group for stone expulsioin
    • No difference between tamsulosin and other alpha-blockers

Screen Shot 2014-04-10 at 9.35.32 PM

Evidence Based Medicine Stuff:

  • Weighted Mean Difference: “The weighted mean could be calculated for groups before and after an intervention (like blood pressure lowering), and the weighted mean difference would be the difference between start and finish values. For this, though, the difference would usually be calculated not as the difference between the overall start value and the overall final value, but rather as the sum of the differences in the individual studies, weighted by the individual variances for each study.”
  • 220px-FunnelplotFunnel Plots: These are a visual tool for investigating bias in meta-analysis. Publication bias is only one of a number of possible causes of funnel-plot asymmetry. They actually look like a funnel. The larger studies will be closer to the average while smaller studies should show a greater spread from the average. Asymmetry of treatment effect and study size can suggest the possibility publication bias. Cochrane Collaboration has a learning module on publication bias if you would like to read more.
Dr. Anthony Seupaul

Dr. Anthony Seupaul

Comments: The review attempted to answer a sensible question. Literature search was appropriate and covered a significant range of sources without language bias.

However, only published studies were sought which may have introduced publication bias as the funnel plot implied.

There was variability in the methodological quality among the studies with a range of high and poor quality and a high number of  comparisons, which the authors themselves indicated as a limitation. The meta-analysis suffered from significant heterogeneity.

This systematic review draws similar conclusions to early randomized control data touting the benefits of medical expulsion therapy.  The majority of these trials enrolled patients from urology clinics where the average stone size exceeded 5mm.

The Bottom Line: Tamsulosin is useless in most ED patients with ureteral colic unless their stone size exceeds at least 4mm.

Dr. Joshua Hughes

Dr. Joshua Hughes

Case Resolution: You treat the patients pain/vomiting with a dose of IM ketorolac, morphine, and ondansetron. You return after the CT scan to see the patient looking much more comfortable lying on the stretcher. He states he still feels some pain but it is much improved.

You let him know the results of the CT and inform him that he will probably pass the stone on his own. You write him prescription for analgesia and antiemetics. You also arrange a follow up with a urologist and provide him with strict return precautions. He thanks you and you leave the room.

Clinical Application: Clinical application at this point is reasonable in patients with large stones due to the suggestion of increased clearance and fewer pain episodes and the relative safety of the the intervention.

What Do I Tell Patients: I would reserve conversation with ED patients unless stone size is known.  Emergency Medicine physicians do see a reasonable number of patients with large renal calculi.  For these patients, I would recommend the use of tamsulosin 0.4 mg for at least 2 weeks with urologic follow up.

Keener Kontest: There is no keener contest winner at this time because we are recording this early. If you want to play the Keener Kontest this week then listen to the podcast for the question. Email me your answer at TheSGEM@gmail.com with “keener” in the subject line. The first person to correctly answer the question will receive a cool skeptical prize.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.