SGEM#230: Tamsulosin – You’ve Lost that Loving Feeling – For Renal Colic

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Date: September 17th, 2018

Reference: Meltzer, A. et al. Effect of Tamsulosin on Passage of Symptomatic Ureteral Stones: A Randomized Clinical Trial. JAMA Internal Med, 2018.

Guest Skeptics: Dr. Tony Seupaul, Professor and Chair, University of Arkansas for Medical Sciences Department of Emergency Medicine. Dr. Daniel Holleyman, Chief Resident at University of Arkansas for Medical Sciences Emergency Medicine Residency.

Case: A 51-year-old man presents to the emergency department (ED) with five-hour history of acute onset left flank pain. The pain comes in waves, radiates into his left groin and is associated with nausea and vomiting. He noticed darkening of his urine, but does not have dysuria, fever, testicular pain, or penile discharge.

You work him up and the urine analysis shows large blood, negative nitrites, negative bacteria. CT abdomen/pelvis without contrast is done which identifies a 7mm radiopaque stone in the left distal ureter. The patient receives 15mg ketorolac IV (SGEM#175) because you know there is a ceiling to the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs). His pain improves significantly, and he is ready for discharge. He is given a referral to Urology for follow up of his ureteral stone, a prescription for oral antiemetics, and advised to take over-the-counter (OTC) NSAIDs. He asks if there is anything he could do or take to help the stone pass faster?

Background: We have covered renal colic many times on the SGEM. This has included the medical expulsive therapy using alpha blockers, lidocaine for pain control, pushing IV fluids or diuretics to pass stones, ultrasound vs. CT scans for diagnosis, and even acupuncture vs. morphine for renal colic pain.

SGEM#4: Getting Un-Stoned (Renal Colic and Alpha Blockers)
SGEM#32: Stone Me (Fluids and Diuretics for Renal Colic)
SGEM#71: Like a Rolling Kidney Stone
SGEM#97: Hippy Hippy Shake – Ultrasound Vs. CT Scan for Diagnosing Renal Colic
SGEM#154: Here I Go Again, Kidney Stone
SGEM#202: Lidocaine for Renal Colic?
SGEM#220: Acupuncture Morphine for Renal Colic

The SGEM bottom lines on the management of renal colic from those previous episodes were as follows:

Expulsive therapy is unnecessary for ureteric stones < 5mm.
You don’t need to push fluids (oral/IV) or use diuretics to pass kidney stones.
There is some weak evidence that Tamsulosin MAY help passage of larger stones (5 to 10 mm).
Bedside emergency department ultrasound is safe and has several advantages over CT for the diagnosis of kidney stones.
Lidocaine cannot be recommended for the treatment of renal colic at this time.
The evidence does not support the claim that acupuncture is superior to morphine for renal colic.

Clinical Question: Does initiation of Tamsulosin at the time of diagnosis in ED patients with symptomatic ureteral stones less than 9mm increase the rates of stone passage in the following 28 days?

Reference: Meltzer, A. et al. Effect of Tamsulosin on Passage of Symptomatic Ureteral Stones: A Randomized Clinical Trial. JAMA Internal Med, 2018.

Population: Emergency Department patients older than 17 years of age with symptomatic ureteral stone less than 9mm as determined by CT
- Excluded: There were 19 exclusions that can be found in the ClinicalTrial.gov website NCT00382265
Intervention:Tamsulosin 0.4mg daily for 28 days
Comparison: Placebo
Outcome:
- Primary: Passage of the stone within 28 days, determined by visualization or physical capture of the stone by patient
- Secondary: Assessment of stone passage by follow up CT; number who crossed-over to open-label Tamsulosin; proportion who returned to work; rate of surgical procedures; rate of hospitalization; percentage returning to the ED; duration of analgesic medication use; time to passage of stone.

Authors’ Conclusions: “Tamsulosin did not significantly increase the stone passage rate compared with placebo. Our findings did not support the use of Tamsulosin for symptomatic urinary stones smaller than 9mm. Guidelines for medical expulsive therapy for urinary stones may need to be revised.”

Quality Checklist for Randomized Clinical Trials:

The study population included or focused on those in the emergency department. Yes
The patients were adequately randomized. Yes. They used the simple urn randomization with site stratification.
The randomization process was concealed. Unsure
The patients were analyzed in the groups to which they were randomized. Yes
The study patients were recruited consecutively (i.e. no selection bias). Yes
The patients in both groups were similar with respect to prognostic factors. Yes
All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes
All groups were treated equally except for the intervention. Yes
Follow-up was complete (i.e. at least 80% for both groups). Yes
All patient-important outcomes were considered. Unsure
The treatment effect was large enough and precise enough to be clinically significant. No

Key Results: The study included 267 patients randomized to Tamsulosin and 245 patients randomize to placebo. The mean age was roughly 41 with just over ¼ being female. The mean diameter of urinary stones was 3.8mm (with a standard deviation of 1.4mm) with about ¼ being 5mm or greater. Just over 2/3 of stones were in the distal ureter, ureterovesicular junction (UVJ) or bladder.

No difference in stone passage at 28 days

Primary Outcome: At 28 days, stone passage rate was 49.6% for Tamsulosin and 47.3% for placebo (RR 1.05 [95% CI 0.87 to 1.27] P= 0.60)
Secondary Outcomes:
- No difference between treatment groups for any of the secondary outcomes.
- Treatment adverse effects were also similar with the exception of ejaculatory dysfunction in men was more common in the Tamsulosin group (18.2% in Tamsulosin group vs. 7.4% in placebo group P=0.007).

We think this is a well-designed multi-center, randomized, double-blinded, placebo-controlled trial in ED patients at various different urban EDs, representing different (but not all) US geographic regions. This study has not differed from recent conclusions on Tamsulosin use in symptomatic ureteral stones. For stones <9mm, there just isn’t convincing evidence that stones are passed any faster. This study represents a strong addition to the literature on the lack of benefit of medical expulsive therapy (MET).

1) Consistency with Prior Trials: This trial cited a stone passage rate of only 50% at 28 days. The prior two trials we reviewed, Furyk and Pickard, the stone passage rate was >80% at 28 days. In the Meltzer trial, stone passage was primarily measured by patient report, either visualization or capture of the stone in 28d.

Compared to the Furyk and Pickard trials which used absence of stone on CT and absence of need for additional intervention, respectively.

So they weren’t really comparing apples to apples. Additionally, in Phase 2 of the Meltzer trial, absence on CT was a secondary outcome, which had a smaller sample size, but had passage rates of 83.6% and 77.6% (tamsulosin v placebo).

Other factors to consider are sampling bias due to history of stone, not getting a CT initially, location of stone, etc.

2) Systematic Review Meta-Analysis of Stones <5mm? Why are we still talking about this? While it would be an error to make a logical leap based on this study alone, (after all, this study was powered for ALL stones <9mm), considering the theoretical benefit that Tamsulosin confers, one would think that the pooled evidence for its benefit in stones <5mm is pretty damning. Pooling of the subgroups from several trials would be interesting to see reported in a SRMA.

3) Subgroup Analysis of 5-9mm Stones: Is the subgroup of stones 5-8mm worthy of studying on its own? The large majority of stones in this study were <5mm. If the goal of this study is to prove the inefficacy of Tamsulosin in stones <9mm, it would have been nice to see an even distribution of all stone sizes. Also considering that the urologic guidelines specifically delineate between <5mm and >5mm, it would make sense to focus on this group. Increasing the power to analyze this group would be beneficial. That being said, a four-year enrolment period at six different EDs yielded 512 patients. Of the total population, 133 had stones 5-8mm. Prevalence may be low enough for this subgroup that further studies would be difficult. Previous studies recommending Tamsulosin in the 5-10mm subgroup were underpowered and are discussed in SGEM#154.

4) Urology Guidelines: The discussion at hand is whether the urologic guidelines are based on the best evidence. This paper would suggest that they are not, and it recommends revision of said guidelines. As emergency medicine physicians we find ourselves in a position to advocate for our patients and do what is in their best interest. Many EM attendings I have spoken to state that they know what the evidence suggests, but they also know that many urologists will not consider further intervention until a course of MET has been done. EM physicians feel that their hands are tied, and they must prescribe Tamsulosin so that their patients do not have potential delays in care.

5) Consultant Relations: We must have professional discussions with our all our colleagues. Maintaining trustworthy and respectful relationships is extremely important. This can pave the way for intelligent conversations about the latest scientific evidence on Tamsulosin. Try to avoid tribalism with the Urologists and do not be rude when discussing medical expulsive therapy. Consider inviting them to Grand Rounds to discuss how the literature can be applied so patients with renal colic get the best care possible based on the best evidence.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusions about avoiding the prescription of Tamsulosin for ureteral stones <9mm.

SGEM Bottom Line: Medical Expulsive Therapy is not recommended for ureteral stones <9mm.

Case Resolution: The patient is not prescribed Tamsulosin at discharge. He does follow-up with a Urologist three weeks after his ED visit. He continued to have pain for a week after his visit, which was partially controlled with NSAIDs. The patient believes he passed the stone but did not visualize the stone. A kidney-ureter-bladder (KUB) x-ray is performed in clinic, which does not identify a ureteral stone, and the patient is advised to follow up as needed.

Dr. Anthony Seupaul

Clinical Application: There are many discussions to be had with our Urology colleagues to determine the allocation of resources in the best interests of our patients. The guidelines published by the American Urological Association should also reflect the latest research. In female patients with stones 5-9mm, perhaps Tamsulosin could be used with less risk, but the current literature does not support its routine use. Otherwise, uncomplicated stones <9mm can be treated conservatively.

What Do I Tell My Patient? The evidence supporting the use of Tamsulosin for kidney stones is very weak. In men, like you, there could be a risk of ejaculatory dysfunction while taking this medicine. Some urologists still like to have their patients try a course of this medicine. When you see the Urologist in follow-up they may still prescribe Tamsulosin, even though we do not recommend it at this time.

Keener Kontest: Last weeks’ winner was Dr. Kirsten Johannessen a PGY2 EM resident at Beaumont Trenton in Michigan. She knew the name of the 1957 landmark legal case about informed consent was SALGO v. LELAND STANFORD JR UNIVERSITY BOARD OF TRUSTEES

Listen to the SGEM podcast on iTunes to hear this the new keener question. If you know the answer send an email to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

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